Association of Adverse Childhood Experiences and Resilience With Depression and Anxiety During Pregnancy
This was a retrospective cohort study of pregnant individuals in the Kaiser Permanente Northern California system who were screened for adverse childhood experiences and resilience as part of standard prenatal care at about 16 weeks of gestation. Overall, 14,625 pregnancies were included; 17.0% had newly identified depression; 9.8% had newly identified depression symptoms; and 8.9% had newly identified anxiety during the pregnancy with no known preexisting diagnosis. We found that adverse childhood experiences and low resilience were independently associated with newly identified depressive disorders, depression symptoms, and anxiety disorders during pregnancy. When adverse childhood experiences and resilience were modeled in combination, the greatest odds of each outcome occurred in individuals with a combination of four or more adverse childhood experiences and low resilience (vs no adverse childhood experiences and high resilience): depression adjusted odds ratio (aOR) 6.43 (95% CI, 5.23-7.90), depression symptoms aOR 9.49 (95% CI, 7.50-12.0), and anxiety disorder aOR 4.79 (95% CI, 3.81-6.02). Routine screening for adverse childhood experiences and resilience may identify individuals at risk of developing prenatal depression and anxiety, allowing faster resource linkage and potentially improved maternal and child outcomes.
Authors: Watson, Carey R;Eaton, Abigail;Campbell, Cynthia I;Alexeeff, Stacey E;Avalos, Lyndsay A;Ridout, Kathryn K;Young-Wolff, Kelly C
Obstet Gynecol. 2024 May 01;143(5):707-710. Epub 2024-02-29.
Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System
To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.
Authors: Mitro, Susanna D;Xu, Fei;Lee, Catherine;Zaritsky, Eve;Waetjen, L Elaine;Wise, Lauren A;Hedderson, Monique M
Obstet Gynecol. 2024 May 01;143(5):619-626. Epub 2024-03-28.
Maternal treatment with selective serotonin reuptake inhibitors during pregnancy and delayed neonatal adaptation: a population-based cohort study
Selective serotonin reuptake inhibitor (SSRI) use is common in pregnancy. It is associated with delayed neonatal adaptation. Most previous studies have not adjusted for the severity of maternal mental health disorders or examined the impact of SSRI type and dosage. We examined whether treatment with SSRIs in late pregnancy (after 20 weeks) is associated with delayed neonatal adaptation independent of maternal depression and anxiety. Retrospective population-based birth cohort of 280 090 term infants born at 15 Kaiser Permanente Northern California hospitals, 2011-2019. Individual-level pharmacy, maternal, pregnancy and neonatal data were obtained from electronic medical records. Dispensed maternal SSRI prescription after 20 weeks of pregnancy. Delayed neonatal adaptation defined as a 5 min Apgar score ≤5, resuscitation at birth or admission to a neonatal intensive care unit for respiratory support. Secondary outcomes included each individual component of the primary outcome and more severe neonatal outcomes (pulmonary hypertension, hypoxic-ischaemic encephalopathy and seizures). 7573 (2.7%) infants were exposed to SSRIs in late pregnancy. Delayed neonatal adaptation occurred in 11.2% of exposed vs 4.4% of unexposed infants (relative risk 2.52 (95% CI 2.36 to 2.70)). After multivariable adjustment, there was an association between SSRI exposure and delayed neonatal adaptation (adjusted OR 2.14 (95% CI 1.96 to 2.32)). This association was dose dependent. Escitalopram and fluoxetine were associated with the highest risk of delayed neonatal adaptation. Infants exposed to SSRIs have increased risks of delayed adaptation in a type and dose-dependent relationship, pointing toward a causal relationship.
Authors: Cornet, Marie-Coralie;Wu, Yvonne W;Forquer, Heather;Avalos, Lyndsay A;Sriram, Achyuth;Scheffler, Aaron W;Newman, Thomas B;Kuzniewicz, Michael W
Arch Dis Child Fetal Neonatal Ed. 2024 Apr 18;109(3):294-300. Epub 2024-04-18.
Health Care for Autistic Children: A Public Health Perspective
Autism has been the subject of large-scale public health investment. These investments are increasingly shifting toward mitigating the lifelong disability and impairment associated with autism. Key efforts include bolstering screening schedules, accelerating the path to diagnosis and early entry into evidence-based therapies, and providing preventive management of common co-occurring conditions. Enhancing their implementation will necessitate addressing neurodiversity and health equity. Pediatric primary care teams continue to be important stewards in population-level initiatives to promote autistic health. To thrive in this role, these providers will benefit from specific educational and logistical supports from the health care system.
Authors: Ames, Jennifer L;Davignon, Meghan N;Hayes, Elizabeth A;Croen, Lisa A
Pediatr Clin North Am. 2024 Apr;71(2):111-125. Epub 2024-02-02.
Pregnancy outcomes in a diverse US Lupus Cohort
Although the population of patients with systemic lupus erythematosus (SLE) is racially and ethnically diverse, many study populations are homogeneous. Further, data are often lacking on critical factors, such as antiphospholipid antibodies (aPLs). We investigated live birth rates in patients with SLE at Kaiser Permanente Northern California, including race and ethnicity and aPL data. Electronic health records of pregnancies with outcomes observed from 2011 to 2020 were identified among patients with SLE. Prevalent SLE was defined as two or more International Classification of Diseases-coded visits seven or more days apart before the last menstrual period. We summarized patient characteristics, medication orders, health care use, and medication use. Pregnancy outcomes (live birth, stillbirth, spontaneous abortion, ectopic pregnancy, and molar pregnancy) were presented overall and stratified by race and ethnicity, aPL status, and nephritis history. We identified 657 pregnancies among 453 patients with SLE. The cohort was diverse, reflecting the Northern California population (27% Asian, 26% Hispanic, 26% Non-Hispanic White, 13% Non-Hispanic Black, 5% multiracial, and approximately 2% Pacific Islander and Native American). Approximately 74% of observed pregnancies ended in live birth, 23% resulted in spontaneous abortion, 2% were ectopic or molar pregnancies, and <1% were stillbirths. There was limited variability in live births by race and ethnic group (72%-79%), aPL status (69.5%-77%), and nephritis history (71%-75%). Our findings are consistent with previous studies; however, some methodologic differences may yield a range of live birth rates. We found that approximately 74% of pregnancies in patients with SLE ended in live birth, with modest variability in spontaneous abortion by race and ethnicity, nephritis history, and aPL status.
Authors: Simard, Julia F;Liu, Emily F;Chakravarty, Eliza;Rector, Amadeia;Cantu, Miranda;Kuo, Daniel Z;Shaw, Gary M;Druzin, Maurice L;Weisman, Michael H;Hedderson, Monique M
Arthritis Care Res (Hoboken). 2024 Apr;76(4):526-530. Epub 2024-02-06.
Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women’s Health Across the Nation (SWAN)
To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women’s Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.
Authors: Hedderson, Monique M;Capra, Angela;Lee, Catherine;Habel, Laurel A;Lee, Jennifer;Gold, Ellen B;Badon, Sylvia E;Mitro, Susanna D;El Khoudary, Samar R
Diabetes Care. 2024 Apr 01;47(4):676-682.
Gestational thyroid hormones and autism-related traits in the EARLI and HOME studies
Thyroid hormones are essential for neurodevelopment. Few studies have considered associations with quantitatively measured autism spectrum disorder (ASD)-related traits, which may help elucidate associations for a broader population. Participants were drawn from two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI), enrolling pregnant women who already had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study, following pregnant women from the greater Cincinnati, OH area. Gestational thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured in mid-pregnancy 16 (±3) weeks gestation serum samples. ASD-related traits were measured using the Social Responsiveness Scale (SRS) at ages 3-8 years. The association was examined using quantile regression, adjusting for maternal and sociodemographic factors. 278 participants (132 from EARLI, 146 from HOME) were included. TSH distributions were similar across cohorts, while FT4 levels were higher in EARLI compared to HOME. In pooled analyses, particularly for those in the highest SRS quantile (95th percentile), higher FT4 levels were associated with increasing SRS scores (β = 5.21, 95% CI = 0.93, 9.48), and higher TSH levels were associated with decreasing SRS scores (β = -6.94, 95% CI = -11.04, -2.83). The association between TSH and SRS remained significant in HOME for the 95% percentile of SRS scores (β = -6.48, 95% CI = -12.16, -0.80), but not EARLI. Results for FT4 were attenuated when examined in the individual cohorts. Our results add to evidence that gestational thyroid hormones may be associated with ASD-related outcomes by suggesting that relationships may differ across the distribution of ASD-related traits and by familial likelihood of ASD.
Authors: Zhong, Caichen;Croen, Lisa A;Lyall, Kristen;et al.
Autism Res. 2024 Apr;17(4):716-727. Epub 2024-03-04.
Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study
Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [β -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.
Authors: Aris, Izzuddin M;Ferrara, Assiamira;Zhu, Yeyi;Chehab, Rana F;ECHO Awardees and Cohorts,;et al.
Am J Clin Nutr. 2024 Mar 01.
Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample
Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.
Authors: Zheng, Shuting;Ferrara, Assiamira;Environmental influences on Child Health Outcomes,;et al.
JCPP Adv. 2024 Mar;4(1):e12198. Epub 2023-09-20.
Open-source code to extend early-onset sepsis calculator accessibility
Authors: van der Weijden, Bo M;Janssen, Sanne W C M;Benitz, William E;Kuzniewicz, Michael W;Puopolo, Karen M;Plötz, Frans B;Achten, Niek B
Lancet Digit Health. 2024 Mar;6(3):e153. Epub 2024-01-22.
Behavior reallocations within 24-h movement profiles and change in cardiometabolic biomarkers during pregnancy
The goal of this study was to investigate associations of reallocations within 24-h movement profiles and changes in cardiometabolic biomarkers from early to late pregnancy. In 137 individuals with prepregnancy overweight/obesity, waking movement was measured using wrist-worn accelerometers, sleep was self-reported, and biomarkers were measured in fasting serum samples at 12 and 32 weeks’ gestation. We used compositional isotemporal substitution models. On average, biomarkers increased 21%-83% across pregnancy. For those with guideline-recommended moderate/vigorous-intensity physical activity (MVPA) in early pregnancy, reallocating 30 min from MVPA to sleep, sedentary behavior, or light-intensity physical activity (LPA) was associated with a 0.6 mmol/L greater increase in total cholesterol (95% CI: -0.1 to 1.2) and a 0.7 mmol/L greater increase in low-density lipoprotein (LDL) cholesterol (95% CI: 0.1 to 1.3) from early to late pregnancy. For those with low MVPA in early pregnancy, reallocating 30 min from sleep, sedentary behavior, or LPA to MVPA was associated with a 0.6 mmol/L lower increase in total cholesterol (95% CI: -1.3 to 0.1) and a 0.8 mmol/L lower increase in LDL cholesterol (95% CI: -1.4 to -0.1) from early to late pregnancy. There were no associations with change in glucose, insulin, homeostatic model assessment for insulin resistance, very low-density lipoprotein, or high-density lipoprotein cholesterol, triglycerides, or free fatty acids. Maintaining or achieving a 24-h movement profile with guideline-recommended amounts of MVPA may be beneficial for reducing pregnancy-induced increases in total and LDL cholesterol.
Authors: Badon, Sylvia E;Ferrara, Assiamira;Gabriel, Kelley Pettee;Dooley, Erin E;Quesenberry, Charles P;Avalos, Lyndsay A;Hedderson, Monique M
Obesity (Silver Spring). 2024 Mar;32(3):623-632. Epub 2024-01-28.
History of multifetal gestation and long-term maternal mortality
Multifetal gestation could be associated with higher long-term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long-term maternal mortality in a racially diverse U.S. We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959-1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all-cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all-cause and cause-specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all-cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all-cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all-cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). In a cohort with over 50 years of follow-up, history of multifetal gestation was not associated with all-cause mortality, but may be associated with a lower risk of premature mortality.
Authors: Mitro, Susanna D;Grantz, Katherine L;et al.
Paediatr Perinat Epidemiol. 2024 Mar;38(3):219-226. Epub 2023-11-15.
Prevalence of maternal hyperglycemic subtypes by race/ethnicity and associations between these subtypes with adverse pregnancy outcomes: Findings from a large retrospective multi-ethnic cohort in the United States
With the two-step gestational diabetes mellitus (GDM) screening approach, hyperglycemic subtypes can be identified. We aimed to investigate racial/ethnic differences in the prevalence of hyperglycemic subtypes and to examine the associations between these subtypes and adverse pregnancy outcomes. In this retrospective cohort, 11,405 pregnancies were screened using the two-step approach. Hyperglycemic subtypes included: pregnancy-impaired glucose intolerance-I (PIGT-I), PIGT-II, GDM-I (abnormal post-load glucose only), and GDM-II (abnormal fasting & post-load glucose). Modified Poisson regressions with robust error variance were used to estimate age-adjusted prevalence ratios (PR) of hyperglycemic subtypes and multivariable-adjusted risk ratios (RR) of adverse pregnancy outcomes. The prevalence of hyperglycemic subtypes was higher in Asians (PIGT-I: 1.51 [95% confidence interval 1.35-1.69]; PIGT-II: 2.18 [1.78-2.68]; GDM-I: 2.55 [2.10-3.10]; GDM-II: 1.55 [1.08-2.21]) and Hispanics (PIGT-I: 1.32 [1.16-1.50]; PIGT-II: 2.07 [1.67-2.57]; GDM-I: 1.69 [1.35-2.13]; GDM-II: 2.68 [1.93-3.71]) than non-Hispanic Whites (NHW). Despite low GDM prevalence, Japanese and Koreans had higher PIGT prevalence than NHW. PIGT-II was positively associated with hypertensive disorders of pregnancy (1.19 [1.02-1.38]), large-for-gestational age (1.73 [1.37-2.18]), and preterm birth (PB, 1.33 [1.05-1.68]). PIGT-I (1.23 [1.04-1.45]) and GDM-I (1.56 [0.87-1.71]) were positively related to PB. The prevalence of hyperglycemic subtypes varies by race/ethnicity and they have distinct health implications.
Authors: Liu, Xinyue;Janzen, Carla;Zhu, Yeyi;Seamans, Marissa;Fei, Zhe;Nianogo, Roch;Chen, Liwei
Diabetes Res Clin Pract. 2024 Mar;209:111576. Epub 2024-02-14.
Maternal education prospectively predicts child neurocognitive function: An environmental influences on child health outcomes study
A large body of research has established a relation between maternal education and children’s neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children’s, adolescents’, and young adults’ neurocognitive functions (N = 2,688; Mage = 10.32 years; SDage = 4.26; range = 3-20 years). Moreover, we examined the differential effects of perinatal maternal education and changes in maternal education across development on executive function and language performance. Perinatal maternal education was positively associated with children’s later overall neurocognitive function. This longitudinal relation was stronger for language than executive function. In addition, increases in maternal education were related to improved language performance but were not associated with executive functioning performance. Our findings support perinatal maternal education as an important predictor of neurocognitive outcomes later in development. Moreover, our results suggest that examining how maternal education changes across development can provide important insights that can help inform policies and interventions designed to foster neurocognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Authors: Morales, Santiago;Ferrara, Assiamira;Elliott, Amy J;et al.
Dev Psychol. 2024 Feb 26.
Mobile app activity engagement by cancer patients and their caregivers informs remote monitoring
Mobile phone applications (“apps”) are potentially an effective, low-burden method to collect patient-reported outcomes outside the clinical setting. Using such apps consistently and in a timely way is critical for complete and accurate data capture, but no studies of concurrent reporting by cancer patient-caregiver dyads have been published in the peer-reviewed literature. This study assessed app engagement, defined as adherence, timing, and attrition with two smartphone applications, one for adult cancer patients and one for their informal caregivers. This was a single-arm, pilot study in which adult cancer patients undergoing IV chemotherapy or immunotherapy used the DigiBioMarC app, and their caregivers used the TOGETHERCare app, for approximately one month to report weekly on the patients’ symptoms and wellbeing. Using app timestamp metadata, we assessed user adherence, overall and by participant characteristics. Fifty patient-caregiver dyads completed the study. Within the one-month study period, both adult cancer patients and their informal caregivers were highly adherent, with app activity completion at 86% for cancer patients and 84% for caregivers. Caregivers completed 86% of symptom reports, while cancer patients completed 89% of symptom reports. Cancer patients and their caregivers completed most activities within 48 h of availability on the app. These results suggest that the DigiBioMarC and TOGETHERCare apps can be used to collect patient- and caregiver-reported outcomes data during intensive treatment. From our research, we conclude that metadata from mobile apps can be used to inform clinical teams about study participants’ engagement and wellbeing outside the clinical setting.
Authors: Yunis, Reem;Fonda, Stephanie J;Aghaee, Sara;Kubo, Ai;Davis, Sharon W;Liu, Raymond;Neeman, Elad;Oakley-Girvan, Ingrid
Sci Rep. 2024 Feb 09;14(1):3375. Epub 2024-02-09.
Association Between Neighborhood Deprivation in Early Pregnancy and Gestational Diabetes Mellitus
To evaluate whether having a pregnancy in a deprived neighborhood was associated with an increased risk of gestational diabetes mellitus (GDM) compared with having a pregnancy in the least-deprived neighborhoods. This was a retrospective observational cohort study of pregnant individuals within Kaiser Permanente Northern California from 2011 to 2018 with residential history from prepregnancy through 24 weeks of gestation and clinical data from prepregnancy through delivery. The primary outcome was a diagnosis of GDM. Neighborhood deprivation was characterized with an index aggregating multiple indicators of Census tract-level sociodemographic information. Mediation analysis using inverse odds ratio weighting estimated the mediation effects of prepregnancy body mass index (BMI), gestational weight gain, smoking tobacco, and illegal drug use before GDM diagnosis. Overall, 214,375 pregnant individuals were included, and 11.3% had a diagnosis of GDM. Gestational diabetes prevalence increased with neighborhood deprivation from 10.0% in the lowest Neighborhood Deprivation Index quintile to 12.7% in the highest quintile. Compared with pregnant individuals in the least deprived neighborhoods (quintile 1), pregnant individuals in quintiles 2-5 had elevated risk of GDM (relative risk [95% CI]) when adjusted for maternal age, parity, insurance type, and residential history (quintile 2, 1.17 [1.10-1.23]; quintile 3, 1.38 [1.30-1.46]; quintile 4, 1.54 [1.45-1.63]; quintile 5, 1.71 [1.62-1.82]). There was a dose-response relationship between relative risk of GDM and increasing quintile of neighborhood deprivation (P for trend <.001). Prepregnancy BMI mediated 45.8% (95% CI, 40.9-50.7%) of the association. Other potential mediators were found to mediate a small if not negligible proportion of this association (2.4-3.6%). Neighborhood deprivation was associated with GDM, and a considerable proportion of this relationship was mediated by prepregnancy BMI.
Authors: Liu, Emily F;Ferrara, Assiamira;Sridhar, Sneha B;Greenberg, Mara B;Hedderson, Monique M
Obstet Gynecol. 2024 Feb 01.
Risk of postpartum readmission after hypertensive disorder of pregnancy and variation by discharge antihypertensive medication prescription
Patients with hypertensive disorders of pregnancy have a high rate of postpartum readmission. We evaluated whether type of antihypertensive medication prescribed at discharge was associated with postpartum readmission after a hypertensive disorder of pregnancy. A retrospective cohort of 57,254 pregnancies with hypertensive disorders of pregnancy that began between 2012-2018 in the electronic obstetric database of Kaiser Permanente Northern California. Postpartum readmissions occurred within 6 weeks of discharge from the delivery hospitalization. Cox regression models evaluated associations between type of antihypertensive medication prescription at discharge (none, labetalol only, nifedipine only, two or more antihypertensive medications) with postpartum readmission, adjusted for type of hypertensive disorder of pregnancy, final inpatient systolic and diastolic blood pressures, age, body mass index, mode of delivery, insurance status, race/ethnicity, delivery facility, comorbidity score, smoking, preterm delivery, parity, and neighborhood deprivation index. Among eligible patients with a hypertensive disorder of pregnancy, 1696 (3.0%) were readmitted within 6 weeks. Approximately 86% of patients were discharged without antihypertensive medication; among those discharged with a prescription for antihypertensive medication, most were prescribed either labetalol only (54%) or nifedipine only (30%). Unadjusted readmission risk was highest among patients discharged with labetalol only (7.6%), lower for patients discharged with nifedipine only (3.6%) or two or more antihypertensive medications (3.2%), and lowest for those discharged without a prescription for antihypertensive medication (2.5%). In adjusted models, compared to discharge without antihypertensive medication, discharge on labetalol only was associated with 63% (hazard ratio: 1.63; 95% confidence interval: 1.41, 1.88) greater incidence of postpartum readmission, while discharge on nifedipine only or on two or more antihypertensive medications were associated with 26% and 47% lower incidence of postpartum readmission, respectively (hazard ratios: 0.74 (95% confidence interval: 0.59, 0.93); 0.53 (95% confidence interval: 0.38, 0.74), respectively). There was no strong evidence to suggest that the effect of discharge antihypertensive medication type on incidence of readmission varied by race and ethnicity (interaction p=0.88). Results indicating an elevated risk for labetalol were consistent in models excluding patients with pre-pregnancy hypertension. Discharge on nifedipine alone or multiple antihypertensive medications (versus no medication) were associated with lower incidence of readmission, while discharge on labetalol alone was associated with elevated readmission incidence. Large-scale, prospective research to compare effectiveness of commonly prescribed hypertension medications at discharge is warranted.
Authors: Mitro, Susanna D;Hedderson, Monique;Xu, Fei;Forquer, Heather;Baker, Jennifer M;Kuzniewicz, Michael W;Greenberg, Mara
Am J Obstet Gynecol. 2024 Jan 25.
Metabolomic data presents challenges for epidemiological meta-analysis: a case study of childhood body mass index from the ECHO consortium
Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility. The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework. We used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure. Only 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P < 0.05) with offspring BMI z-scores at age 2 years in a meta-analytic framework including at least two studies: arabinose (Coefmeta = 0.40 [95% CI 0.10,0.70], Pmeta = 9.7 × 10-3), guanidinoacetate (Coefmeta = - 0.28 [- 0.54, - 0.02], Pmeta = 0.033), 3-ureidopropionate (Coefmeta = 0.22 [0.017,0.41], Pmeta = 0.033), 1-methylhistidine (Coefmeta = - 0.18 [- 0.33, - 0.04], Pmeta = 0.011), serine (Coefmeta = - 0.18 [- 0.36, - 0.01], Pmeta = 0.034), and lysine (Coefmeta = - 0.16 [- 0.32, - 0.01], Pmeta = 0.044). No associations were robust to multiple testing correction. Despite including three cohorts with large sample sizes (N > 100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.
Authors: Prince, Nicole;Zhu, Yeyi;Kelly, Rachel S;et al.
Metabolomics. 2024 Jan 24;20(1):16. Epub 2024-01-24.
Barriers to Healthcare for Latinx Autistic Children and Adolescents
To understand the ways in which autistic Latinx children experience disparities in diagnosis, healthcare, and receipt of specialty services. 417 individuals who identified as Latinx caregivers of autistic children who were members of the same integrated healthcare system in Northern California were surveyed. Responses were analyzed using the child’s insurance coverage (Government or Commercial) and caregiver’s primary language (Spanish or English). Compared to the commercially-insured, government-insured participants accessed several services at a higher rate and were less likely to cite the high cost of co-pays as a barrier. There were no significant differences in service access by language status, but Spanish speakers were more likely to cite health literacy as a barrier to receiving care.
Authors: Grosvenor, Luke P;Cohen, Ryan J;Gordon, Nancy P;Massolo, Maria L;Cerros, Hilda J;Yoshida, Cathleen K;Ames, Jennifer L;Croen, Lisa A
J Autism Dev Disord. 2024 Jan 17.
Reproductive Health Care in Adolescents with Autism and Other Developmental Disabilities
Adults with developmental disabilities often have less access to reproductive health services than adults without these disabilities. However, little is known about how adolescents with developmental disabilities, including autism, access reproductive health care. We aimed to characterize the utilization of reproductive health care services among autistic adolescents and adolescents with other developmental disabilities in comparison with typically developing adolescents. We conducted a cohort study of a sample of adolescents who were continuously enrolled members of Kaiser Permanente Northern California, an integrated healthcare system, from ages 14 to 18. The final analytic sample included 700 autistic adolescents, 836 adolescents with other developmental disabilities, and 2187 typically developing adolescents who sought care between 2000 and 2017. Using electronic health records, we obtained information on menstrual conditions, use of obstetric/gynecological care, and prescriptions of hormonal contraception. We compared utilization between groups using chi-squared tests and covariate-adjusted risk ratios estimated with modified Poisson regression. Autistic adolescents and adolescents with other developmental disabilities were significantly more likely to have diagnoses of menstrual disorders, polycystic ovary syndrome, and premenstrual syndrome than typically developing adolescents. These two groups also were less likely than typically developing peers to visit the OB/GYN or to use any form of hormonal contraception, including oral contraception, hormonal implants, and intrauterine devices. Adolescents in all three groups accessed hormonal contraception most frequently through their primary care provider, followed by an OB/GYN provider. Autistic adolescents and adolescents with other developmental disabilities are less likely than their typically developing peers to visit the OB/GYN and use hormonal contraception, suggesting possible care disparities that may persist into adulthood. Efforts to improve access to reproductive healthcare in these populations should target care delivered in both pediatric and OB/GYN settings.
Authors: Ames, Jennifer L;Anderson, Meredith C;Cronbach, Emily;Lee, Catherine;Giwa Onaiwu, Morénike;Vallerie, Amy M;Croen, Lisa A
Am J Obstet Gynecol. 2024 Jan 11.
Maternal Pre-Pregnancy BMI, Breastfeeding, and Child BMI
Breastfeeding practices may protect against offspring obesity, but this relationship is understudied among women with obesity. We describe the associations between breastfeeding practices and child BMI for age z-score (BMIz), stratified by maternal BMI. We analyzed 8134 dyads from 21 cohorts in the Environmental Influences on Child Health Outcomes Program. Dyads with data for maternal pre-pregnancy BMI, infant feeding practices, and ≥1 child BMI assessment between the ages of 2 and 6 years were included. The associations between breastfeeding practices and continuous child BMIz were assessed by using multivariable linear mixed models. Maternal pre-pregnancy BMI category prevalence was underweight: 2.5%, healthy weight: 45.8%, overweight: 26.0%, and obese: 25.6%. Median child ages at the cessation of any breastfeeding and exclusive breastfeeding across the 4 BMI categories were 19, 26, 24, and 17 weeks and 12, 20, 17, and 12 weeks, respectively. Results were in the hypothesized directions for BMI categories. Three months of any breastfeeding was associated with a lower BMIz among children whose mothers were a healthy weight (-0.02 [-0.04 to 0.001], P = .06), overweight (-0.04 [-0.07 to -0.004], P = .03), or obese (-0.04 [-0.07 to -0.006], P = .02). Three months of exclusive breastfeeding was associated with a lower BMIz among children whose mothers were a healthy weight (-0.06 [-0.10 to -0.02], P = .002), overweight (-0.05 [-0.10 to 0.005], P = .07), or obese (-0.08 [-0.12 to -0.03], P = .001). Human milk exposure, regardless of maternal BMI category, was associated with a lower child BMIz in the Environmental Influences on Child Health Outcomes cohorts, supporting breastfeeding recommendations as a potential strategy for decreasing the risk of offspring obesity.
Authors: Shipp, Gayle M;Zhu, Yeyi;Ferrara, Assiamira;program collaborators for Environmental influences on Child Health Outcomes,;et al.
Pediatrics. 2024 Jan 01;153(1).
Inflammatory Conditions During Pregnancy and Risk of Autism and Other Neurodevelopmental Disorders
Maternal inflammation can result from immune dysregulation and metabolic perturbations during pregnancy. Whether conditions associated with inflammation during pregnancy increase the likelihood of autism spectrum disorder (ASD) or other neurodevelopmental disorders (DDs) is not well understood. We conducted a case-control study among children born in California from 2011 to 2016 to investigate maternal immune-mediated and cardiometabolic conditions during pregnancy and risk of ASD (n = 311) and DDs (n = 1291) compared with children from the general population (n = 967). Data on maternal conditions and covariates were retrieved from electronic health records. Maternal genetic data were used to assess a causal relationship. Using multivariable logistic regression, we found that mothers with asthma were more likely to deliver infants later diagnosed with ASD (odds ratio [OR] = 1.62, 95% CI: 1.15-2.29) or DDs (OR = 1.30, 95% CI: 1.02-1.64). Maternal obesity was also associated with child ASD (OR = 1.51, 95% CI: 1.07-2.13). Mothers with both asthma and extreme obesity had the greatest odds of delivering an infant later diagnosed with ASD (OR = 16.9, 95% CI: 5.13-55.71). These increased ASD odds were observed among female children only. Polygenic risk scores for obesity, asthma, and their combination showed no association with ASD risk. Mendelian randomization did not support a causal relationship between maternal conditions and ASD. Inflammatory conditions during pregnancy are associated with risk for neurodevelopmental disorders in children. These risks do not seem to be due to shared genetic risk; rather, inflammatory conditions may share nongenetic risk factors with neurodevelopmental disorders. Children whose mothers have both asthma and obesity during pregnancy may benefit from earlier screening and intervention.
Authors: Croen, Lisa A;Ames, Jennifer L;Qian, Yinge;Alexeeff, Stacey;Ashwood, Paul;Gunderson, Erica P;Wu, Yvonne W;Boghossian, Andrew S;Yolken, Robert;Van de Water, Judy;Weiss, Lauren A
Biol Psychiatry Glob Open Sci. 2024 Jan;4(1):39-50. Epub 2023-10-11.
Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression
Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.
Authors: Jacobson, Melanie H;Avalos, Lyndsay A;Ferrara, Assiamira;Environmental Influences on Child Health Outcomes Consortium,;et al.
JAMA Psychiatry. 2024 Jan 01;81(1):67-76.
A mixture of urinary phthalate metabolite concentrations during pregnancy and offspring Social Responsiveness Scale (SRS) scores
Phthalates are a group of chemicals with ubiquitous exposure worldwide. Exposures to phthalates during pregnancy may play a role in autism spectrum disorder (ASD) etiology by disrupting hormone levels or directly impacting fetal neurodevelopment. However, there is little research quantifying the aggregate effect of phthalates on child ASD-related behaviors. We used data from two prospective pregnancy and birth cohorts-the Health Outcomes and Measures of the Environment (HOME) and the Early Autism Risk Longitudinal Investigation (EARLI). HOME is a general population cohort while participants in EARLI were at higher familial risk for ASD. Using quantile g-computation and linear regression models, we assessed the joint and individual associations of a mixture of six phthalate metabolites during pregnancy with child ASD-related traits measured by Social Responsiveness Scale (SRS) scores at ages 3-8 years. Our analyses included 271 participants from HOME and 166 participants from EARLI. There were imprecise associations between the phthalate mixture and SRS total raw scores in HOME (difference in SRS scores per decile increase in every phthalate = 1.3; 95% confidence interval [CI] = -0.2, 2.8) and EARLI (difference in SRS scores per decile increase in every phthalate = -0.9; 95% CI = -3.5, 1.7). The cohort-specific effect sizes of the pthalates-SRS associations were small and CIs were imprecise. These results suggest that if there are associations between phthalate metabolites during pregnancy and child SRS scores, they may differ across populations with different familial liabilities. Further studies with larger sample sizes are warranted.
Authors: Yu, Emma X;Braun, Joseph M;Lyall, Kristen;Hertz-Picciotto, Irva;Fallin, M Daniele;Croen, Lisa A;Chen, Aimin;Xu, Yingying;Yolton, Kimberly;Newschaffer, Craig J;Hamra, Ghassan B
Epidemiology. 2024 Jan 01;35(1):84-93. Epub 2023-10-11.
Mixture of air pollution, brominated flame retardants, polychlorinated biphenyls, per- and polyfluoroalkyl substances, and organochlorine pesticides in relation to vitamin D concentrations in pregnancy
Over two-thirds of pregnant women in the U.S. have insufficient 25(OH)D (Vitamin D) concentrations, which can adversely impact fetal health. Several pollutants have been associated with 25(OH)D, but have not been considered in the context of chemical co-exposures. We aimed to determine associations between a broad mixture of prenatal environmental chemical exposures and 25(OH)D concentrations in mid-pregnancy. Stored mid-pregnancy serum samples were assayed from 421 women delivering live births in Southern California in 2000-2003. 25(OH)D, six BFRs, eleven polychlorinated biphenyls (PCBs), six per- and polyfluoroalkyl substances, and two organochlorine pesticides were detected in ≥60% of specimens. Gestational exposures to airborne particulate matter ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5), nitrogen monoxide (NO), nitrogen dioxide (NO2), and ozone concentrations were derived from monitoring station data. Bayesian Hierarchical Modeling (BHM) and Bayesian Kernel Machine Regression (BKMR) analyses estimated overall mixture and individual chemical associations accounting for co-exposures and covariates with mean 25(OH)D levels, and BHM was used to estimate associations with insufficient (<75 nMol/L) 25(OH)D levels. Non-mixture associations for each chemical were estimated with linear and logistic models. PM10 [BHM estimate: -0.133 nmol/l 95% Credible Interval (-0.240, -0.026)] was associated with lower 25(OH)D in BHM and BKMR. Higher quantiles of combined exposures were associated with lower 25(OH)D, though with wide credible intervals. In non-mixture models, PM10, PM2.5, NO, and NO2 were associated with lower concentrations, while O3 and PBDE153 were associated with higher 25(OH)D and/or lower insufficiency. While some chemicals were associated with increased and others with decreased 25(OH)D concentrations, the overall mixture was associated with lower concentrations. Mixture analyses differed from non-mixture regressions, highlighting the importance of mixtures approaches for estimating real-world associations.
Authors: Berger, Kimberly;Ames, Jenn;Croen, Lisa A;Pearl, Michelle;et al.
Environ Pollut. 2024 Jan 01;340(Pt 2):122808. Epub 2023-11-03.
Training the next generation of delivery science researchers: 10-year experience of a post-doctoral research fellowship program within an integrated care system
Learning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence-based care. Most existing postdoctoral training programs, such as NIH-funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10-year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system. In 2012, the Kaiser Permanente Northern California Division of Research designed and implemented a 2-year postdoctoral Delivery Science Fellowship research training program to foster research expertise in identifying and addressing barriers to evidence-based care within health care delivery systems. Since 2014, 20 fellows have completed the program. Ten fellows had PhD-level scientific training, and 10 fellows had clinical doctorates (eg, MD, RN/PhD, PharmD). Fellowship alumni have graduated to faculty research positions at academic institutions (9), and research or clinical organizations (4). Seven alumni now hold positions in Kaiser Permanente’s clinical operations or medical group (7). This delivery science fellowship program has succeeded in training graduates to address delivery science problems from both research and operational perspectives. In the next 10 years, additional goals of the program will be to expand its reach (eg, by developing joint research training models in collaboration with clinical fellowships) and strengthen mechanisms to support transition from fellowship to the workforce, especially for researchers from underrepresented groups.
Authors: Grant, Richard W;Schmittdiel, Julie A;Liu, Vincent X;Estacio, Karen R;Chen, Yi-Fen Irene;Lieu, Tracy A
Learn Health Syst. 2024 Jan;8(1):e10361. Epub 2023-03-21.
Agreement Between Self-reports and Urine Toxicology Measures of Illicit Methamphetamine and Cocaine Use During Early Pregnancy
This study aimed to assess agreement between self-report and urine toxicology measures assessing use of 2 illicit simulants (methamphetamine and cocaine) during early pregnancy. This cross-sectional study of 203,053 pregnancies from 169,709 individuals receiving prenatal care at Kaiser Permanente Northern California between January 1, 2011, and December 31, 2019, assessed agreement ( κ , sensitivity, and specificity) between self-reported frequency and urine toxicology measures of methamphetamine and cocaine early in pregnancy. Prenatal use of the illicit stimulants was rare according to toxicology (n = 244 [0.12%]) and self-report measures (n = 294 [0.14%]). Agreement between these measures was low ( κ < 0.20). Of the 498 positive pregnancies, 40 (8.03%) screened positive on both measures, 204 (40.96%) screened positive on toxicology tests only, and 254 (51.00%) screened positive by self-report only. Relative to toxicology tests, sensitivity of any self-reported use was poor with 16.39% (95% confidence interval [CI], 11.75%-21.04%) of pregnancies with a positive toxicology test self-reporting any use in pregnancy. Relative to self-report, sensitivity of toxicology tests was also poor with 13.61% (95% CI, 9.69%-17.52%) of pregnancies who self-reported any use having positive urine toxicology tests. The sensitivity improved slightly at higher frequencies of self-reported use: daily, 17.50% (95% CI, 5.72%-29.29%); weekly, 25.00% (95% CI, 11.58%-38.42%); and monthly or less, 11.06% (95% CI, 6.89%-15.23%). Specificity was high (>99%), reflecting the high negative rate of use. Findings suggest that using self-report and toxicology measures in combination likely provides the most accurate information on methamphetamine and cocaine use in early pregnancy. Findings also highlight the need to provide supportive nonstigmatizing environments in which pregnant individuals feel comfortable disclosing substance use without fear of punishment.
Authors: Sujan, Ayesha C;Avalos, Lyndsay A;Young-Wolff, Kelly C;Young-Wolff, Kelly C;et al.
J Addict Med. 2024 Jan-Feb 01;18(1):28-32. Epub 2023-10-05.
Gestational diabetes mellitus and risk of neurodevelopmental disorders in young offspring: does the risk differ by race and ethnicity?
Previous studies examined the associations of gestational diabetes mellitus with autism spectrum disorder and attention deficit hyperactivity disorder. However, the associations between gestational diabetes mellitus and other neurodevelopmental disorders, such as the common speech/language disorder and developmental coordination disorder, are rarely studied, and whether the associations vary by race/ethnicity remains unknown. This study aimed to examine the associations of gestational diabetes mellitus with individual neurodevelopmental disorders in young offspring, and to investigate whether the associations vary by race/ethnicity. This retrospective cohort study (Glucose in Relation to Women and Babies’ Health [GrownB]) included 14,480 mother-offspring pairs in a large medical center in the United States from March 1, 2013 to August 31, 2021. We ascertained gestational diabetes mellitus using the validated ICD (International Classification of Diseases) codes (ICD-9: 648.8x; ICD-10: O24.4x), and identified neurodevelopmental disorders (speech/language disorder, developmental coordination disorder, autism spectrum disorder, and other neurodevelopmental disorders [attention deficit hyperactivity disorder, behavioral disorder, intellectual disability, and learning difficulty]) and their combinations using validated algorithms. We compared the hazard of neurodevelopmental disorders during the entire follow-up period between offspring born to mothers with and without gestational diabetes mellitus using multivariable Cox regression models. Among all mothers, 19.9% were Asian, 21.8% were Hispanic, 41.0% were non-Hispanic White, and 17.3% were of other/unknown race/ethnicity. During the median follow-up of 3.5 years (range, 1.0-6.3 years) after birth, 8.7% of offspring developed at least 1 neurodevelopmental disorder. Gestational diabetes mellitus was associated with a higher risk of speech/language disorder (adjusted hazard ratio, 1.59 [95% confidence interval, 1.07-2.35]), developmental coordination disorder (2.36 [1.37-4.04]), autism spectrum disorder (3.16 [1.36-7.37]), other neurodevelopmental disorders (3.12 [1.51-6.47]), any neurodevelopmental disorder (1.86 [1.36-2.53]), the combination of speech/language disorder and autism spectrum disorder (3.79 [1.35-10.61]), and the combination of speech/language disorder and developmental coordination disorder (4.22 [1.69-10.51]) among offspring born to non-Hispanic White mothers. No associations between gestational diabetes mellitus and any neurodevelopmental disorders or their combinations were observed among offspring born to mothers of other racial/ethnic groups. We observed an elevated risk of neurodevelopmental disorders among young offspring born to non-Hispanic White mothers with gestational diabetes mellitus, but not among other racial/ethnic groups.
Authors: Liu, Xinyue;Zhu, Yeyi;Seamans, Marissa;Nianogo, Roch;Janzen, Carla;Fei, Zhe;Chen, Liwei
Am J Obstet Gynecol MFM. 2024 Jan;6(1):101217. Epub 2023-11-07.
Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program
Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations. In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.
Authors: Oh, Jiwon;Ames, Jennifer L;Croen, Lisa A;Ferrara, Assiamira;Zhu, Yeyi;program collaborators for Environmental influences on Child Health Outcomes,;et al.
Environ Health Perspect. 2024 Jan;132(1):17004. Epub 2024-01-24.
Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis
Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted. Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic.
Authors: Francis, Ellen C;Zhu, Yeyi;ADA/EASD PMDI,;et al.
Commun Med (Lond). 2023 Dec 18;3(1):185. Epub 2023-12-18.
Maternal obesity and childhood asthma risk: Exploring mediating pathways
Growing evidence for the effect of maternal obesity on childhood asthma motivates investigation of mediating pathways. To investigate if childhood body mass index (BMI), gestational weight gain (GWG) and preterm birth mediate the association of maternal obesity on childhood asthma risk. We used electronic medical records from mother-child pairs enrolled in Kaiser Permanente Northern California integrated healthcare system. Children were followed from their birth (2005-2014) until at least age 4 (n = 95,723), age 6 (n = 59,230) or age 8 (n = 25,261). Childhood asthma diagnosis at each age was determined using ICD-9/10 codes and medication dispensings. Prepregnancy BMI (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese [≥30] kg/m2 ) were defined using height and weight measurements close to the last menstrual period date. Child's BMI (Centers for Disease Control and Prevention BMI-for-age percentiles: underweight [<5th], normal [5th-85th], overweight [85th-95th], obese [>95th]) were obtained using anthropometric measurements taken the year preceding each follow-up age. GWG (delivery weight-prepregnancy weight) was categorised based on Institutes of Medicine recommendations (inadequate, adequate, excessive). Implementing first causal inference test (CIT) then causal mediator models (to decompose the natural direct and indirect effects), we examined the potential mediating effect of childhood BMI, GWG, and preterm birth on the association between prepregnancy BMI (continuous and categorical) and childhood asthma. Overall, risk of childhood asthma increased as prepregnancy BMI increased (age 4 risk ratio: 1.07, 95% confidence interval: 1.04, 1.09, per 5 kg/m2 increase in BMI; similar for age 6 and 8). CIT identified childhood BMI and preterm birth, but not GWG as potential mediators. Causal mediation models confirmed childhood BMI, but not preterm birth, as having a partial mediating effect. Results were similar for age 6 and 8, and when continuous mediators (instead of binary) were assessed. Childhood overweight/obesity has a modest mediating effect on the association between prepregnancy BMI and childhood asthma.
Authors: Rosenquist, Natalie A;Richards, Megan;Ferber, Jeannette R;Strickland, Matthew J;Ryu, So Young;Burkin, Heather;Weber, Ann M;Li, De-Kun;Darrow, Lyndsey A
Paediatr Perinat Epidemiol. 2023 Dec 06.
Associations between COVID-19-related family hardships/distress and children’s Adverse Childhood Experiences during the pandemic: The Environmental influences on Child Health Outcomes (ECHO) program
Economic hardships imposed by the pandemic could have implications for children’s experiences of adversity in the home, or Adverse Childhood Experiences (ACEs). This observational cohort study examined associations between COVID-19-related hardships and distress (e.g., job loss, caregiver stress) and the cumulative number of child ACEs reported by caregivers during the pandemic (i.e., March 1, 2020-February 28, 2022). The study included children (N = 4345; median age = 6.0 years, interquartile range = 4-9 years) and their parents/caregivers who participated in the NIH-funded Environmental influences in Child Health Outcomes (ECHO) Program. We described socio-demographic characteristics and pandemic-related family hardships/distress and cumulative child ACE scores reported during pre-pandemic and pandemic periods. We used negative binomial regression models to evaluate associations between pandemic-related family hardships and cumulative child ACE scores reported during the pandemic. Each caregiver-reported hardship/distress was associated with higher child ACE scores reported during the pandemic. After accounting for pre-pandemic child ACE scores, moderate and severe symptoms of pandemic-related traumatic stress among caregivers were associated with 108 % and 141 % higher child ACE scores reported during the pandemic, respectively, compared with no or low caregiver symptoms. In addition, finance-related stress during the pandemic was associated with 47 % higher child ACE scores. After adjusting for pre-pandemic child experiences of neglect, most sources of stress remained significantly associated with higher child ACE scores reported during the pandemic, particularly severe/very severe symptoms of pandemic-related traumatic stress among caregivers. Findings held for children with no known pre-pandemic ACEs. This research suggests that caregivers experiencing financial hardships and those with severe pandemic-related traumatic stress may require additional support systems during stressful events.
Authors: Thierry, Karen L;Ferrara, Assiamira;program collaborators for Environmental influences on Child Health Outcomes,;et al.
Child Abuse Negl. 2023 Dec;146:106510. Epub 2023-11-01.
Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort
Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort. We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using weighted correlation network analysis and common networks using consensus network analysis across four visits using linear mixed-effects models with the adjustment of false discover rate. Multiple triglycerides (TG) were positively associated with birth weight (BW), BW Z-score, length and head circumference, while some cholesteryl ester (CE), phosphatidylcholine (PC), sphingomyelines (SM), phosphatidylethanolamines (PE), and lysophosphatidylcholines (LPC 20:3) families were inversely associated with BW, length, abdominal and head circumference at different GWs. Longitudinal trajectories of TG, PC, and glucosylcermides (GlcCer) were associated with BW, and CE (18:2) with BW z-score, length, and sum of skinfolds (SS), while some PC and PE were significantly associated with abdominal and head circumference. Modules of TG at GW 10-14 and 15-26 mainly were associated with BW. At GW 33-39, two networks of LPC (20:3) and of PC, TG, and CE, showed inverse associations with abdominal circumference. Distinct trajectories within two consensus modules with changes in TG, CE, PC, and LPC showed significant differences in BW and length. The results demonstrated that longitudinal changes of TGs during early- and mid-pregnancy and changes of PC, LPC, and CE during late-pregnancy were significantly associated with neonatal anthropometry. National Institute of Child Health and Human Development intramural funding.
Authors: Song, Yiqing;Lu, Ruijin;Yu, Guoqi;Rahman, Mohammad L;Chen, Liwei;Zhu, Yeiyi;Tsai, Michael Y;Fiehn, Oliver;Chen, Zhen;Zhang, Cuilin
EBioMedicine. 2023 Dec;98:104881. Epub 2023-11-24.
Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy
Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.
Authors: Brown, Susan D;Kiernan, Michaela;Ehrlich, Samantha F;Zhu, Yeyi;Hedderson, Monique M;Daredia, Saher;Feng, Juanran;Millman, Andrea;Quesenberry, Charles P;Ferrara, Assiamira
Prev Med Rep. 2023 Dec;36:102456. Epub 2023-10-04.
Perinatal Hypoxic-Ischemic Encephalopathy: Incidence Over Time Within a Modern US Birth Cohort
Recent studies suggest that the incidence of perinatal hypoxic-ischemic encephalopathy (HIE) may be increasing in developed countries. However, this observed increase may be due to increased ascertainment and increased treatment with therapeutic hypothermia rather than an increase in disease burden. In a US population-based cross-sectional study, we determined the incidence of perinatal HIE over time. The study population included all 289,793 live-born infants ≥35 weeks gestational age born at 15 Kaiser Permanente Northern California hospitals between 2012 and 2019. Perinatal HIE was defined as the presence of both neonatal acidosis (i.e., cord blood pH < 7 or base deficit ≥10, or base deficit ≥10 on first infant gas) and neonatal encephalopathy confirmed by medical record review. Hospital discharge diagnoses of HIE were determined by extracting International Classification of Disease diagnostic codes for HIE assigned upon hospital discharge. The population incidence of perinatal HIE was 1.7 per 1000. Although the incidence of perinatal HIE did not change significantly, both hospital discharge diagnoses of HIE and treatment with therapeutic hypothermia increased significantly during the study period. The sensitivity and positive predictive value of a hospital discharge diagnosis of HIE for identifying perinatal HIE confirmed by chart review were 72% and 79%, respectively. During the study years, the incidence of perinatal HIE remained stable despite increases in hospital discharge diagnoses of HIE and in the use of therapeutic hypothermia. Our findings underscore the importance of applying stringent diagnostic criteria when diagnosing this complex condition.
Authors: Cornet, Marie-Coralie;Kuzniewicz, Michael;Scheffler, Aaron;Forquer, Heather;Hamilton, Emily;Newman, Thomas B;Wu, Yvonne W
Pediatr Neurol. 2023 Dec;149:145-150. Epub 2023-08-31.
Neonatal Outcomes Associated with In Utero Cannabis Exposure: A Population-Based Retrospective Cohort Study
The full spectrum of associations between in utero cannabis exposure and adverse neonatal outcomes is still unclear. This study evaluates associations between in utero cannabis exposure and neonatal outcomes. This population-based retrospective cohort study of singleton births among Kaiser Permanente Northern California members (January 1, 2011- July 31, 2020) included parent-infant dyads in which the pregnant parent was screened for cannabis use as part of standard prenatal care, generally upon entrance into care. Data were ascertained from electronic health records. Generalized estimating equation models were adjusted for sociodemographic characteristics, other non-cannabis prenatal substance use, medical and mental health comorbidities, and adequacy of prenatal care. In utero cannabis exposure was defined as self-report since becoming pregnant and/or a positive urine toxicology test for cannabis at any time during pregnancy (yes/no; primary) and frequency of use (self-report daily, weekly, ≤ monthly, never, unknown; secondary). Neonatal outcomes included low birth weight (LBW), small for gestational age (SGA), preterm birth, neonatal intensive care unit (NICU) admission, and infant respiratory support. Of 364,924 infants, 22,624 (6.2%) were exposed to cannabis in utero. After adjustment for potential confounders including in utero exposure to other substances, in utero exposure to cannabis was associated with greater odds of LBW (adjusted odds ratio [aOR],1.20; 95%CI, 1.12-1.28), SGA (aOR, 1.24; 95%CI, 1.18-1.30), preterm birth (<37 weeks; aOR,1.06; 95%CI, 1.00-1.13), and NICU admission (aOR,1.06; 95%CI, 1.01-1.11). There was a suggestive association with early preterm birth (<34 weeks; aOR, 1.11; 95%CI, 1.00-1.23, P=.055), but no significant association with respiratory support (aOR,1.07; 95%CI, 0.97-1.18). Dose-response analysis found an increasing likelihood of LBW and SGA with increasing frequency of prenatal cannabis use by the pregnant individual. Sensitivity analyses further supported an increased likelihood of LBW and SGA although associations with other outcomes did not reach significance. In utero cannabis exposure was associated with an increased likelihood of LBW, SGA, preterm birth, and NICU admission. Clinicians should counsel individuals who are pregnant or considering pregnancy about the potential adverse neonatal health outcomes associated with prenatal cannabis use.
Authors: Avalos, Lyndsay A;Adams, Sara R;Alexeeff, Stacey E;Oberman, Nina R;Does, Monique B;Ansley, Deborah;Goler, Nancy;Padon, Alisa A;Silver, Lynn D;Young-Wolff, Kelly C
Am J Obstet Gynecol. 2023 Nov 18.
Weight loss, stability and low weight gain during pregnancy among individuals with obesity: associations with adverse perinatal outcomes: an observational study
The safety of weight loss and low weight gain during pregnancy remains unclear. To determine how different patterns of gestational weight gain (GWG), including weight loss, stability and low GWG relate to perinatal outcomes by prepregnancy obesity class. The study population included 29,408 singleton livebirths among pregnant people with obesity from Kaiser Permanente Northern California (2008-2013). Clinically measured gestational weight gain was grouped into meaningful categories [Adequate (reference, met 2009 National Academy of Medicine (NAM) Guidelines (5-9.1 kg)), Excessive (>9.1 kg), Low (1-4.9 kg), Stable (+/-1 kg), Weight Loss (>1 kg)] or gestational weight gain z-score quintiles. Modified Poisson regression was used to estimate risk of adverse outcomes, stratified by obesity class. Electronic health record data were used to define outcomes, including Caesarean delivery, preterm birth, admission to the NICU, small and large for gestational age infants. Prevalence of weight stability and weight loss was 3.8% and 3.4%, respectively. Compared to those who gained within NAM, increased risk of small-for-gestational age was observed among those with weight loss among obesity class I (RR: 1.57, 95% CI: 1.12, 2.19), obesity class II (RR: 2.18, 95% CI: 1.52, 3.13) and obesity class III (RR: 1.72, 95% CI: 1.21, 2.45). Weight loss was associated with a decreased risk of Caesarean delivery among obesity class III, compared to NAM. Weight loss during pregnancy is associated with increased risk of small for gestational age among all obesity classes, but not other adverse perinatal outcomes, and may reduce risk of Caesarean delivery. Low weight gain and weight stability are not associated with risk of adverse outcomes among those with class III obesity. GWG guidelines may need to vary by obesity class.
Authors: Widen, Elizabeth M;Nichols, Amy R;Harper, Lorie M;Cahill, Alison G;Davis, Jaimie;Foster, Saralyn F;Rickman, Rachel;Xu, Fei;Hedderson, Monique
Am J Perinatol. 2023 Nov 15.
Development and psychometric validation of the Pandemic-Related Traumatic Stress Scale for children and adults
To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Authors: Blackwell, Courtney K;Avalos, Lyndsay A;Margolis, Amy E;et al.
Psychol Assess. 2023 Nov;35(11):1054-1067.
Effectiveness of COVID-19 vaccination during pregnancy by circulating viral variant
SARS-CoV-2 infection in pregnancy can result in a spectrum of asymptomatic to critical COVID-19 outcomes, including hospitalization, admission to the intensive care unit, or death. This study aimed to investigate the effectiveness of messenger RNA COVID-19 vaccination during pregnancy against both hospitalization and infection, stratified by different variant circulations and by time since the last vaccine dose. This was a retrospective cohort study among pregnant persons who were members of Kaiser Permanente Northern California and delivered between December 15, 2020, and September 30, 2022. Pregnant persons who received any vaccine dose before the pregnancy onset date were excluded. The primary outcome was hospitalization for COVID-19, and the secondary outcome was polymerase chain reaction-confirmed SARS-CoV-2 infection. Exposure was receipt of a messenger RNA vaccine during pregnancy. Poisson regression was used to estimate the risk ratio of hospitalization by comparing vaccinated pregnant persons with unvaccinated pregnant persons adjusted for sociodemographic factors and calendar time. Cox regression was used to estimate the hazard ratio of infection by comparing vaccinated pregnant persons with unvaccinated pregnant persons. Vaccine effectiveness was estimated as 1 minus the rate ratio or the hazard ratio multiplied by 100. Vaccine effectiveness was estimated overall and by variant periods (before Delta, Delta, Omicron, and subvariants). Of 57,688 pregnant persons, 16,153 (28%) received at least 1 dose of a messenger RNA COVID-19 vaccine during pregnancy; moreover, 4404 pregnant persons tested positive for SARS-CoV-2 infection, and 108 pregnant persons were hospitalized during pregnancy. Overall, 2-dose vaccine effectiveness against hospitalization was 91% within <150 days of vaccination and 48% >150 days after vaccination. The 2-dose vaccine effectiveness within <150 days after vaccination was 100% during the original virus strain and Delta variant periods of the virus; vaccine effectiveness was 51% during the Omicron period. Of the hospitalization cases, 97% of pregnant persons were unvaccinated. During hospitalization, none of the vaccinated pregnant persons required ventilation or were admitted to the intensive care unit. Moreover, 2-dose vaccine effectiveness against infection was 54% within <150 days after vaccination and 26% ≥150 days after vaccination. Messenger RNA COVID-19 vaccination during pregnancy was effective against hospitalization for COVID-19 and SARS-CoV-2 infection. COVID-19 was mild among pregnant persons who were vaccinated compared with those who were unvaccinated. Thus, all pregnant persons should be strongly encouraged to receive messenger RNA COVID-19 vaccines to prevent severe disease.
Authors: Zerbo, Ousseny;Ray, G Thomas;Fireman, Bruce;Layefsky, Evan;Goddard, Kristin;Ross, Pat;Greenberg, Mara;Klein, Nicola P
AJOG Glob Rep. 2023 Nov;3(4):100264. Epub 2023-08-25.
Neighborhood Disadvantage, Race and Ethnicity, and Postpartum Depression
Postpartum depression (PPD) is a debilitating condition with higher rates among Black individuals. Increasingly, neighborhood disadvantage is being recognized as a contributor to poor health and may be associated with adverse postpartum mental health; however, associations between neighborhood disadvantage, race and ethnicity, and PPD have not been examined. To investigate the association between neighborhood disadvantage and PPD and evaluate the extent to which these associations may differ by race and ethnicity. This population-based cross-sectional study included 122 995 postpartum Kaiser Permanente Northern California members 15 years or older with a live birth between October 7, 2012, and May 31, 2017, and an address in the electronic health record. Analyses were conducted from June 1, 2022, through June 30, 2023. Neighborhood disadvantage defined using quartiles of the Neighborhood Deprivation Index (NDI), a validated census-based socioeconomic status measure; self-reported race and ethnicity ascertained from Kaiser Permanente Northern California electronic health records. Multivariable Poisson regression was conducted to assess associations between neighborhood disadvantage, race and ethnicity, and a diagnosis of PPD. Of 122 995 included postpartum individuals, 17 554 (14.3%) were younger than 25 years, 29 933 (24.3%) were Asian, 8125 (6.6%) were Black, 31 968 (26.0%) were Hispanic, 47 527 (38.6%) were White, 5442 (4.4%) were of other race and ethnicity, and 15 436 (12.6%) had PPD. Higher neighborhood disadvantage and race and ethnicity were associated with PPD after covariate adjustment. Compared with White individuals, Black individuals were more likely to have PPD (adjusted relative risk [ARR], 1.30; 95% CI, 1.24-1.37), whereas Asian (ARR, 0.48; 95% CI, 0.46-0.50), and Hispanic (ARR, 0.92; 95% CI, 0.89-0.96) individuals and those identified as having other race and ethnicity (ARR, 95% CI, 0.90; 0.85-0.98) were less likely to have PPD. Associations between NDI and PPD differed by race and ethnicity (likelihood ratio test for interaction, χ212 = 41.36; P < .001). Among Black individuals, the risk of PPD was the greatest overall and increased with neighborhood disadvantage in a dose-response manner (quartile [Q] 2 ARR, 1.39 [95% CI, 1.13-1.71]; Q3 ARR, 1.50 [95% CI, 1.23-1.83]; Q4 ARR, 1.60 [95% CI, 1.32-1.93]; Cochrane-Armitage test for trend, P < .001). Neighborhood disadvantage was associated with PPD among Asian (Q2 ARR, 1.17 [95% CI, 1.04-1.31]; Q3 ARR, 1.20 [95% CI, 1.06-1.35]) and White (Q3 ARR, 1.14 [95% CI, 1.07-1.21]; Q4 ARR, 1.17 [95% CI, 1.09-1.26]) individuals and those of other race and ethnicity (Q3 ARR, 1.34 [95% CI, 1.09-1.63]; Q4 ARR, 1.28 [95% CI, 1.03-1.58]), but the magnitude of risk was lower. Neighborhood disadvantage was not associated with PPD among Hispanic individuals (eg, Q2 ARR, 1.04 [95% CI, 0.94-1.14]; Q3 ARR, 1.00 [95% CI, 0.91-1.10]; Q4 ARR, 0.98 [95% CI, 0.90-1.08]). In this cross-sectional study of postpartum individuals, residing in more disadvantaged neighborhoods was associated with PPD, except among Hispanic individuals. Neighborhood disadvantage may be associated with racial and ethnic differences in postpartum mental health. Geographic targeting of mental health interventions may decrease postpartum mental health inequities.
Authors: Onyewuenyi, Ticara L;Peterman, Kelli;Zaritsky, Eve;Ritterman Weintraub, Miranda L;Pettway, Bria L;Quesenberry, Charles P;Nance, Nerissa;Surmava, Ann-Marie;Avalos, Lyndsay A
JAMA Netw Open. 2023 Nov 01;6(11):e2342398. Epub 2023-11-01.
Opportunities for Examining Child Health Impacts of Early-Life Nutrition in the ECHO Program: Maternal and Child Dietary Intake Data from Pregnancy to Adolescence
Longitudinal measures of diet spanning pregnancy through adolescence are needed from a large, diverse sample to advance research on the effect of early-life nutrition on child health. The Environmental influences on Child Health Outcomes (ECHO) Program, which includes 69 cohorts, >33,000 pregnancies, and >31,000 children in its first 7-y cycle, provides such data, now publicly available. This study aimed to describe dietary intake data available in the ECHO Program as of 31 August, 2022 (end of year 6 of Cycle 1) from pregnancy through adolescence, including estimated sample sizes, and to highlight the potential for future analyses of nutrition and child health. We identified and categorized ECHO Program dietary intake data, by assessment method, participant (pregnant person or child), and life stage of data collection. We calculated the number of maternal-child dyads with dietary data and the number of participants with repeated measures. We identified diet-related variables derived from raw dietary intake data and nutrient biomarkers measured from biospecimens. Overall, 66 cohorts (26,941 pregnancies, 27,103 children, including 22,712 dyads) across 34 US states/territories provided dietary intake data. Dietary intake assessments included 24-h recalls (1548 pregnancies and 1457 children), food frequency questionnaires (4902 and 4117), dietary screeners (8816 and 23,626), and dietary supplement use questionnaires (24,798 and 26,513). Repeated measures were available for ∼70%, ∼30%, and ∼15% of participants with 24-h recalls, food frequency questionnaires, and dietary screeners, respectively. The available diet-related variables describe nutrient and food intake, diet patterns, and breastfeeding practices. Overall, 17% of participants with dietary intake data had measured nutrient biomarkers. ECHO cohorts have collected longitudinal dietary intake data spanning pregnancy through adolescence from a geographically, socioeconomically, and ethnically diverse US sample. As data collection continues in Cycle 2, these data present an opportunity to advance the field of nutrition and child health.
Authors: Bragg, Megan G;Hedderson, Monique M;Zhu, Yeyi;program collaborators for Environmental influences on Child Health Outcomes,;et al.
Curr Dev Nutr. 2023 Nov;7(11):102019. Epub 2023-10-23.
Independent Impact of Eat, Sleep, Console Assessment on Neonatal Opioid Withdrawal Syndrome
Compared with the Finnegan Neonatal Abstinence Scoring System (FNASS), the Eat, Sleep, Console (ESC) approach reduces pharmacotherapy and length of stay (LOS) for neonatal opioid withdrawal syndrome (NOWS) infants. The independent outcome contribution of ESC is unknown as the approach combines ESC assessment with additional management changes. Our objective was to evaluate ESC assessment’s independent impact on outcomes compared with FNASS. We conducted a retrospective cohort study of in utero opioid-exposed infants ≥35 weeks gestation managed with FNASS versus ESC. Outcomes included pharmacotherapy initiation, LOS, length of pharmacotherapy, and emergency department visit/readmissions. Among 151 FNASS and 100 ESC managed infants, pharmacotherapy initiation (P = .47), LOS for all infants (P = .49), and LOS for pharmacologically treated infants (P = .68) were similar. Length of pharmacotherapy did not differ (P = .84). Emergency department evaluation/NOWS readmission was equally rare (P = .65). Using equivalent models of care, comparison of ESC and FNASS assessment tools showed no difference in NOWS outcomes.
Authors: Chyi, Lisa J;Li, Sherian;Lee, Catherine;Walsh, Eileen M;Kuzniewicz, Michael W
Clin Pediatr (Phila). 2023 Oct 05:99228231204448.
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
Authors: Tobias, Deirdre K;Zhu, Yeyi;Franks, Paul W;et al.
Nat Med. 2023 Oct;29(10):2438-2457. Epub 2023-10-05.
Association between maternal prenatal cannabis use and missed child preventive care visits in an integrated health care delivery system in Northern California
The periodicity of well-child visits recommended by the American Academy of Pediatrics emphasizes the importance of continuity of care in health management. Exposure to cannabis in utero has been associated with adverse development, and adherence to well-child visits is critical for earlier detection and intervention. To assess whether maternal prenatal cannabis use was associated with missed well-child visits in the first three years after birth we conducted a longitudinal cohort study in Kaiser Permanente Northern California of pregnant individuals and their children born between January 1, 2011 and December 31, 2018. Maternal prenatal cannabis use was defined as any self-reported cannabis use since becoming pregnant and/or a positive urine toxicology test for cannabis during pregnancy. Well-child visits were defined as an encounter for a well-child visit or physical exam and categorized into seven time periods from birth to 36 months. Modified Poisson regression models were conducted. Of the 168,589 eligible pregnancies, 3.4% screened positive for maternal prenatal cannabis use. Compared to no use, maternal prenatal cannabis use was associated with more missed well-child visits at every time period; (missed 12-month visit: adjusted relative risk (aRR): 1.43, 95%CI: 1.32-1.54; missed 3-year visit: aRR: 1.15, 95%CI: 1.11-1.20). Maternal prenatal cannabis use was also associated with missing two or more well-child visits through 36 months of age (35.8% among cannabis users vs. 23.0% among non-users, Χ2p < .001). Educating pregnant individuals who use cannabis on the importance of well-child visits may benefit children's health and development.
Authors: Avalos, Lyndsay A;Oberman, Nina;Alexeeff, Stacey E;Croen, Lisa A;Adams, Sara R;Davignon, Meghan;Young-Wolff, Kelly C
Prev Med. 2023 Oct;175:107716. Epub 2023-09-28.
Accounting for Nulliparity in the Prediction of Hypoxic-Ischemic Encephalopathy Using Cardiotocography
Nulliparous pregnancies, those where the mother has not previously given birth, are associated with longer labors and hence expose the fetus to more contractions and other adverse intrapartum conditions such as chorioamnionitis. The objective of the present study was to test if accounting for nulliparity could improve the detection of fetuses at increased risk of developing hypoxic-ischemic encephalopathy (HIE). During labor, clinicians assess the fetal heart rate and uterine pressure signals to identify fetuses at risk of developing HIE. In this study, we performed random forest classification using fetal heart rate and uterine pressure features from 40,831 births, including 374 that developed HIE. We analyzed a two-path classification approach that analyzed separately the fetuses from nulliparous and multiparous mothers, and a one-path classification approach that included the clinical variable for nulliparity as a classification feature. We compared these two approaches to a one-path classifier that had no information about the parity of the mothers. We also compared our results to the rate of Caesarean deliveries in each group, which is used clinically to interrupt the progression towards HIE. All the classifiers detected more fetuses that developed HIE than the observed Caesarean rate, but accounting for nulliparity did not improve performance.
Authors: Vargas-Calixto, Johann;Wu, Yvonne W;Kuzniewicz, Michael;Cornet, Marie-Coralie;Forquer, Heather;Gerstley, Lawrence;Hamilton, Emily;Warrick, Philip A;Kearney, Robert E
IEEE EMBS Int Conf Biomed Health Inform. 2023 Oct;2023. Epub 2023-11-14.
PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort
Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.
Authors: Peterson, Alicia K;Zhu, Yeyi;Fuller, Sophia;Feng, Juanran;Alexeeff, Stacey;Mitro, Susanna D;Kannan, Kurunthachalam;Robinson, Morgan;Padula, Amy;Ferrara, Assiamira
BMC Pregnancy Childbirth. 2023 Sep 13;23(1):657. Epub 2023-09-13.
Individual and neighborhood factors associated with being unvaccinated against COVID-19 among pregnant persons
We investigated whether unvaccinated pregnant persons cluster geographically and determined factors associated with being unvaccinated using spatial and multivariate logistic regression analyses. Pregnant persons with deliveries from December 15, 2020, through September 30, 2022, at Kaiser Permanente Northern California were included. Of the 85,852 pregnant persons in the study, 46.6% were unvaccinated before and during pregnancy. Spatial analysis identified 5 clusters with high prevalence of unvaccinated pregnant persons. Within these clusters, the proportion of unvaccinated varied from 53% to 62% versus 39% outside the clusters. In covariate-adjusted analyses, residence in a cluster increased the odds of being unvaccinated by 1.64 (95% confidence interval (CI): 1.59,1.69). The odds of being unvaccinated increased among those aged 16-24 years (odds ratio [OR] = 2.69, CI: 2.55, 2.83), aged 25-34 years (OR = 1.59, CI: 1.54, 1.64) compared with age ≥ 35 years, black race (OR = 1.45, CI:1.37, 1.54), and subsidized insurance (OR = 1.32, CI: 1.26, 1.38). The odds of being unvaccinated also increased for pregnant persons living in neighborhoods where the proportion of adults with high school education or less was greater than 20%. Geographic clustering of unvaccinated pregnant persons suggests a need for population-specific-interventions to increase vaccine coverage.
Authors: Zerbo, Ousseny;Ray, G Thomas;Fireman, Bruce;Layefsky, Evan;Goddard, Kristin;Ross, Pat;Greenberg, Mara;Klein, Nicola P
Hum Vaccin Immunother. 2023 Aug 01;19(2):2256042.
Updates to the Autism Intervention Research Network on Physical Health (AIR-P) Research Agenda
Autistic individuals, now representing one in 36 individuals in the U.S., experience disproportionate physical health challenges relative to non-autistic individuals. The Health Resources and Services Administration’s (HRSA) Autism Intervention Research Network on Physical Health (AIR-P) is an interdisciplinary, multi-center Research Network that aims to increase the health, well-being, and quality of life of autistic individuals. The current paper builds on the initial AIR-P Research Agenda (proposed in Year 1) and provides an updated vision for the Network. Updates to the Research Agenda were made via the administration of a Qualtrics survey, and disseminated widely to all AIR-P entities, including the Research Node Leaders, Steering Committee, Autistic Researcher Review Board, and collaborating academic and non-academic entities. Network members were tasked with evaluating the Year 1 Research Agenda and proposing additional priorities. Within each Research Node, all Year 1 priorities were endorsed as continued priorities for research on autism and physical health. Specific topics, including co-occurring conditions and self-determination, advocacy, and decision-making, were particularly endorsed. Opportunities for exploratory studies and intervention research were identified across Research Nodes. Qualitative responses providing feedback on additional research priorities were collected. The updated AIR-P Research Agenda represents an important step toward enacting large-scale health promotion efforts for autistic individuals across the lifespan. This updated agenda builds on efforts to catalyze autism research in historically underrepresented topic areas while adopting a neurodiversity-oriented approach to health promotion.
Authors: Hotez, Emily;Croen, Lisa A;Kuo, Alice;et al.
Cureus. 2023 Aug;15(8):e44388. Epub 2023-08-30.
Prenatal Weight Change Trajectories and Perinatal Outcomes among Twin Gestations
Despite an increase in twin pregnancies in recent decades, the Institute of Medicine twin weight gain recommendations remain provisional and provide no guidance for the pattern or timing of weight change. We sought to characterize gestational weight change trajectory patterns and examine associations with birth outcomes in a cohort of twin pregnancies. Prenatal and delivery records were examined for 320 twin pregnancies from a maternal-fetal medicine practice in Austin, TX 2011-2019. Prenatal weights for those with >1 measured weight in the first trimester and ≥3 prenatal weights were included in analyses. Trajectories were estimated to 32 weeks (mean delivery: 33.7 ± 3.3 weeks) using flexible latent class mixed models with low-rank thin-plate splines. Associations between trajectory classes and infant outcomes were analyzed using multivariable Poisson or linear regression. Weight change from prepregnancy to delivery was 15.4 ± 6.3 kg for people with an underweight body mass index, 15.4 ± 5.8 kg for healthy weight, 14.7 ± 6.9 kg for overweight, and 12.5 ± 6.4 kg for obesity. Three trajectory classes were identified: low (Class 1), moderate (Class 2), or high gain (Class 3). Class 1 (24.7%) maintained weight for 15 weeks and then gained an estimated 6.6 kg at 32 weeks. Class 2 (60.9%) exhibited steady gain with 13.5 kg predicted total gain, and Class 3 (14.4%) showed rapid gain across pregnancy with 21.3 kg predicted gain. Compared to Class 1, Class 3 was associated with higher birth weight z-score (β = 0.63, 95% confidence interval [CI]: 0.31,0.96), increased risk for large for gestational age (IRR = 5.60, 95% CI: 1.59, 19.67), and birth <32 weeks (IRR = 2.44, 95%CI: 1.10, 5.4) that was attenuated in sensitivity analyses. Class 2 was associated with moderately elevated birth weight z-score (β = 0.24, 95%CI: 0.00, 0.48, p = 0.050). Gestational weight change followed a low, moderate, or high trajectory; both moderate and high gain patterns were associated with increased infant size outcomes. Optimal patterns of weight change that balance risk during the prenatal, perinatal, and neonatal periods require further investigation, particularly in high-risk twin pregnancies. · A majority gained weight below IOM twin recommendations.. · Three patterns of GWC across pregnancy were identified.. · Moderate or high GWC was associated with infant size..
Authors: Nichols, Amy R;Haeri, Sina;Rudine, Anthony;Burns, Natalie;Rathouz, Paul J;Hedderson, Monique M;Abrams, Steven A;Foster, Saralyn F;Rickman, Rachel;McDonnold, Mollie;Widen, Elizabeth M
Am J Perinatol. 2023 Jul 11.
Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort
Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a “high” exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.
Authors: Martenies, Sheena E;Cowell, Whitney;Program Collaborators for Environmental Influences on Child Health Outcomes,;et al.
Int J Environ Res Public Health. 2023 Jul 10;20(14). Epub 2023-07-10.
Timely Detection of Infants at Risk of Intrapartum Acidosis and Hypoxic-Ischemic Encephalopathy Using Cardiotocography
This work aims to improve the intrapartum detection of fetuses with an increased risk of developing fetal acidosis or hypoxic-ischemic encephalopathy (HIE) using fetal heart rate (FHR) and uterine pressure (UP) signals. Our study population comprised 40,831 term births divided into 3 classes based on umbilical cord or early neonatal blood gas assessments: 374 with verified HIE, 3,047 with acidosis but no encephalopathy and 37,410 healthy babies with normal gases. We developed an intervention recommendation system based on a random forest classifier. The classifier was trained using classical and novel features extracted electronically from 20-minute epochs of FHR and UP. Then, using the predictions of the classifier on each epoch, we designed a decision rule to determine when to recommended intervention. Compared to the Caesarean rates in each study group, our system identified an additional 5.68% of babies who developed HIE (54.55% vs 60.23%, p < 0.01) with a specific alert threshold. Importantly, about 75% of these recommendations were made more than 200 minutes before birth. In the acidosis group, the system identified an additional 17.44% (37.15% vs 54.59%, p < 0.01) and about 2/3 of these recommendations were made more than 200 minutes before birth. Compared to the Caesarean rate in the healthy group, the associated false positive rate was increased by 1.07% (38.80% vs 39.87%, p<0.01).Clinical Relevance- This method recommended intervention in more babies affected by acidosis or HIE, than the intervention rate observed in practice and most often did so 200 minutes before delivery. This was early enough to expect that interventions would have clinical benefit and reduce the rate of HIE. Given the high burden associated with HIE, this would justify the marginal increase in the normal Cesarean rate.
Authors: Vargas-Calixto, Johann;Wu, Yvonne;Kuzniewicz, Michael;Cornet, Marie-Coralie;Forquer, Heather;Gerstley, Lawrence;Hamilton, Emily;Warrick, Philip A;Kearney, Robert E
Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-5.
Novel approaches to examining weight changes in pregnancies affected by obesity
Current gestational weight change (GWC) recommendations for obese individuals were established with limited evidence of the pattern and timing of weight change across pregnancy. Similarly, the recommendation of 5-9 kg does not differentiate by the severity of obesity. We sought to describe GWC trajectory classes by obesity grade and associated infant outcomes among a large, diverse cohort. The study population included 22,355 individuals with singleton pregnancies, obesity (BMI ≥30.0 kg/m2), and normal glucose tolerance who delivered at Kaiser Permanente Northern California between 2008 and 2013. Obesity grade-specific GWC trajectories were modeled at 38 wk using flexible latent class mixed modeling (package lcmm) in R. Multivariable Poisson or linear regression models estimated the associations between the GWC trajectory class and infant outcomes (size-for-gestational age and preterm birth) by obesity grade. Five GWC trajectory classes were identified for each obesity grade, each with a distinct pattern of weight change before 15 wk (including loss, stability, and gain) followed by weight gain thereafter (low, moderate, and high). Two classes with high overall gain were associated with an increased risk for large for gestational age (LGA) in obesity grade 1 (IRR = 1.27; 95% CI: 1.10, 1.46; IRR = 1.47; 95% CI: 1.24, 1.74). Both high (IRR = 2.02; 95% CI: 1.61, 2.52; IRR = 1.98; 95% CI: 1.52, 2.58) and 2 moderate-gain classes (IRR = 1.40; 95% CI 1.14, 1.71; IRR = 1.51; 95% CI: 1.20, 1.90) were associated with LGA in grade 2, and only early loss/late moderate-gain class 3 (IRR = 1.30; 95% CI: 1.04, 1.62) was associated in grade 3. This class was also associated with preterm birth in grade 2. No associations were detected between GWC and small for gestational age (SGA). Among the pregnancies affected by obesity, GWC was not linear or uniform. Different patterns of high gain were associated with an increased risk for LGA with the greatest magnitude in obesity grade 2, whereas GWC patterns were not associated with SGA.
Authors: Nichols, Amy R; Burns, Natalie; Xu, Fei; Foster, Saralyn F; Rickman, Rachel; Hedderson, Monique M; Widen, Elizabeth M
Am J Clin Nutr. 2023 May;117(5):1026-1034. Epub 2023-03-05.
Prenatal exposure to per- and polyfluoroalkyl substances and childhood autism-related outcomes
Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes. We included 10 cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) program (n = 1,429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex. Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adjusted β [95% confidence interval (CI)] = 1.5 [-0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adjusted β [95% highest posterior density interval] = 0.7 [-1.4, 3.0]). We did not observe consistent evidence of sex differences. Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes.
Authors: Ames, Jennifer L; Avalos, Lyndsay A; Croen, Lisa A; Ferrara, Assiamira; Hedderson, Monique M; Zhu, Yeyi; program collaborators for Environmental influences on Child Health Outcomes,; et al.
Epidemiology. 2023 May 01;34(3):450-459. Epub 2023-04-03.
Prepregnancy Body Mass Index and Risk of Childhood Asthma
Growing evidence suggests that maternal obesity may affect the intrauterine environment and increase a child’s risk of developing asthma. We aim to investigate the relationship between prepregnancy obesity and childhood asthma risk. Cohorts of children enrolled in Kaiser Permanente Northern California integrated healthcare system were followed from birth (2005-2014) to age 4 (n = 104,467), 6 (n = 63,084), or 8 (n = 31,006) using electronic medical records. Child’s asthma was defined using ICD codes and asthma-related prescription medication dispensing. Risk ratios (RR) and 95% confidence intervals (95% CIs) for child’s asthma were estimated using Poisson regression with robust error variance for (1) prepregnancy BMI categories (underweight [<18.5], normal [18.5-24.9], overweight [25-29.9], obese 1 [30-34.9], and obese 2/3 [≥35]) and (2) continuous prepregnancy BMI modeled using cubic splines with knots at BMI category boundaries. Models were adjusted for maternal age, education, race, asthma, allergies, smoking, gestational weight gain, child's birth year, parity, infant sex, gestational age, and child's BMI. Relative to normal BMI, RRs (95%CIs) for asthma at ages 4, 6, and 8 were 0.91 (0.75, 1.11), 0.95 (0.78, 1.16), and 0.97 (0.75, 1.27) for underweight, 1.06 (0.99, 1.14), 1.08 (1.01, 1.16), and 1.03 (0.94, 1.14) for overweight, 1.09 (1.00, 1.19), 1.12 (1.03, 1.23), 1.03 (0.91, 1.17) for obese 1, and 1.10 (0.99, 1.21), 1.13 (1.02, 1.25), 1.14 (0.99, 1.31) for obese 2/3. When continuous prepregnancy BMI was modeled with splines, child's asthma risk generally increased linearly with increasing prepregnancy BMI. Higher prepregnancy BMI is associated with modestly increased childhood asthma risk.
Authors: Rosenquist, Natalie A; Richards, Megan; Ferber, Jeannette R; Li, De-Kun; Ryu, So Young; Burkin, Heather; Strickland, Matthew J; Darrow, Lyndsey A
Allergy. 2023 May;78(5):1234-1244. Epub 2022-12-11.
Opportunities for Inclusion and Engagement in the Transition of Autistic Youth from Pediatric to Adult Healthcare: A Qualitative Study
Transitioning autistic youth from pediatric to adult healthcare requires coordination of multiple stakeholders, including youth, caregivers, and pediatric and adult care providers, whose interests at times overlap but often differ. To understand barriers and facilitators to inclusive transition experiences, we conducted thematic analysis of interviews with 39 stakeholders from the same large, integrated healthcare system. We identified three major themes: (1) Navigating the healthcare transition without guidance, (2) Health consequences of a passive healthcare transition, and (3) Strategies for inclusion and continuous engagement. Facilitators included gradual transition planning, a warm handoff between providers, and support of shared healthcare decision-making. Providers also sought clinical tools and logistical supports such as care coordinators and longer transition-specific visit types to enhance patient-centered care.
Authors: Ames, Jennifer L; Mahajan, Arjun; Davignon, Meghan N; Massolo, Maria L; Croen, Lisa A
J Autism Dev Disord. 2023 May;53(5):1850-1861. Epub 2022-03-09.
The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women’s study
In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.
Authors: Appiah, Duke; Hedderson, Monique M; Kim, Catherine; Sidney, Stephen; Sternfeld, Barbara; Quesenberry, Charles P; Wellons, Melissa F; Gunderson, Erica P
Diabetes Res Clin Pract. 2023 Apr;198:110593. Epub 2023-03-02.
NICU Versus Mother/Baby Unit Admission for Low-Acuity Infants Born at 35 Weeks’ Gestation
To estimate the effect of NICU admission of low-acuity infants born at 35 weeks’ gestation versus care in a mother/baby unit, on inpatient and outpatient medical outcomes. This retrospective cohort study included 5929 low-acuity infants born at 350/7 to 356/7 weeks’ gestation at 13 Kaiser Permanente Northern California hospitals with level II or level III NICUs between January 1, 2011, and December 31, 2021. Exclusion criteria included congenital anomalies and early respiratory support or antibiotics. We used multivariable regression and regression discontinuity analyses to control for confounding variables. Infants admitted to the NICU within 2 hours of birth (n = 862, 14.5%) had a 58 hour adjusted (98-hour unadjusted) longer length of stay. NICU admission was associated with an increased probability of a length of stay ≥96 hours (67% vs 21%; adjusted odds ratio [aOR], 4.94; 95% confidence interval [CI], 3.96-6.16). Regression discontinuity results suggested a similar (57 hour) increase in length of stay. Readmission risk, primarily for jaundice, was lower for those admitted to the NICU (3% vs 6%; aOR, 0.43; 95% CI, 0.27-0.69). Infants admitted to the NICU were slightly less likely to be receiving exclusive breast milk at 6-month follow-up (15% vs 25%; aOR, 0.73; 95% CI, 0.55-0.97; adjusted marginal risk difference -5%). Admitting low-acuity infants born at 35 weeks’ gestation to the NICU was associated with decreased readmission, but with longer length of stay and decreased exclusive breast milk feeding at 6 months. Routine NICU admission may be unnecessary for low-acuity infants born at 35 weeks’ gestation.
Authors: Wickremasinghe, Andrea C; Kuzniewicz, Michael W; Walsh, Eileen M; Li, Sherian; Newman, Thomas B
Pediatrics. 2023 Apr 01;151(4).
Changes in Body Mass Index Among School-Aged Youths Following Implementation of the Healthy, Hunger-Free Kids Act of 2010
The prevalence of obesity among youths 2 to 19 years of age in the US from 2017 to 2018 was 19.3%; previous studies suggested that school lunch consumption was associated with increased obesity. The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) strengthened nutritional standards of school-based meals. To evaluate the association between the HHFKA and youth body mass index (BMI). This cohort study was conducted using data from the Environmental Influences on Child Health Outcomes program, a nationwide consortium of child cohort studies, between January 2005 and March 2020. Cohorts in the US of youths aged 5 to 18 years with reported height and weight measurements were included. Full implementation of the HHFKA. The main outcome was annual BMI z-score (BMIz) trends before (January 2005 to August 2016) and after (September 2016 to March 2020) implementation of the HHFKA, adjusted for self-reported race, ethnicity, maternal education, and cohort group. An interrupted time-series analysis design was used to fit generalized estimating equation regression models. A total of 14 121 school-aged youths (7237 [51.3%] male; mean [SD] age at first measurement, 8.8 [3.6] years) contributing 26 205 BMI measurements were included in the study. Overall, a significant decrease was observed in the annual BMIz in the period following implementation of the HHFKA compared with prior to implementation (-0.041; 95% CI, -0.066 to -0.016). In interaction models to evaluate subgroup associations, similar trends were observed among youths 12 to 18 years of age (-0.045; 95% CI, -0.071 to -0.018) and among youths living in households with a lower annual income (-0.038; 95% CI, -0.063 to -0.013). In this cohort study, HHFKA implementation was associated with a significant decrease in BMIz among school-aged youths in the US. The findings suggest that school meal programs represent a key opportunity for interventions to combat the childhood obesity epidemic given the high rates of program participation and the proportion of total calories consumed through school-based meals.
Authors: Chandran, Aruna; Ferrara, Assiamira; Hedderson, Monique; Knapp, Emily; et al.
JAMA Pediatr. 2023 Apr 01;177(4):401-409.
In utero metabolomic signatures of refined grains intake and risk of gestational diabetes: A metabolome-wide association study
Epidemiologic evidence has linked refined grain intake to a higher risk of gestational diabetes (GDM), but the biological underpinnings remain unclear. We aimed to identify and validate refined grain-related metabolomic biomarkers for GDM risk. In a metabolome-wide association study of 91 cases with GDM and 180 matched controls without GDM (discovery set) nested in the prospective Pregnancy Environment and Lifestyle Study (PETALS), refined grain intake during preconception and early pregnancy and serum untargeted metabolomics were assessed at gestational weeks 10-13. We identified refined grain-related metabolites using multivariable linear regression and examined their prospective associations with GDM risk using conditional logistic regression. We further examined the predictivity of refined grain-related metabolites selected by least absolute shrinkage and selection operator regression in the discovery set and validation set (a random PETALS subsample of 38 individuals with and 336 without GDM). Among 821 annotated serum (87.4% fasting) metabolites, 42 were associated with refined grain intake, of which 17 (70.6% in glycerolipids, glycerophospholipids, and sphingolipids clusters) were associated with subsequent GDM risk (all false discovery rate-adjusted P values <0.05). Adding 7 of 17 metabolites to a conventional risk factor-based prediction model increased the C-statistic for GDM risk in the discovery set from 0.71 (95% CI: 0.64, 0.77) to 0.77 (95% CI: 0.71, 0.83) and in the validation set from 0.77 (95% CI: 0.69, 0.86) to 0.81 (95% CI: 0.74, 0.89), both with P-for-difference <0.05. Clusters of glycerolipids, glycerophospholipids, and sphingolipids may be implicated in the association between refined grain intake and GDM risk, as demonstrated by the significant associations of these metabolites with both refined grains and GDM risk and the incremental predictive value of these metabolites for GDM risk beyond the conventional risk factors. These findings provide evidence on the potential biological underpinnings linking refined grain intake to the risk of GDM and help identify novel disease-related dietary biomarkers to inform diet-related preventive strategies for GDM.
Authors: Chehab, Rana F; Ferrara, Assiamira; Zheng, Siwen; Barupal, Dinesh K; Ngo, Amanda L; Chen, Liwei; Fiehn, Oliver; Zhu, Yeyi
Am J Clin Nutr. 2023 Apr;117(4):731-740. Epub 2023-02-11.
Incidence Rates of Medically Attended COVID-19 in Infants Less Than 6 Months of Age
Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants.
Authors: Griffin, Isabel; Li, De-Kun; Munoz, Flor M; et al.
Pediatr Infect Dis J. 2023 Apr 01;42(4):315-320. Epub 2023-01-05.
Prenatal Antidepressant Exposures and Autism Spectrum Disorder or Traits: A Retrospective, Multi-Cohort Study
Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.
Authors: Brennan, Patricia A; Croen, Lisa A; Avalos, Lyndsay A; Paneth, Nigel; et al.
Res Child Adolesc Psychopathol. 2023 Apr;51(4):513-527. Epub 2022-11-22.
Racial-Ethnic Differences in Treatment Initiation for New Diagnoses of Perinatal Depression
The adverse consequences of untreated perinatal depression highlight the need to identify populations to target in order to increase treatment rates. The authors sought to evaluate treatment initiation for a new diagnosis of depression during pregnancy or postpartum and to describe racial-ethnic differences in initiation and type (psychotherapy, antidepressants) of treatment in a large health care system with universal perinatal depression screening. This retrospective cohort study included women who delivered a live birth in the Kaiser Permanente Northern California system between October 2012 and May 2017. Black, Latina, Asian, and White women ages ≥15 years were eligible. New depression diagnoses were defined by using ICD-9 and ICD-10 codes from electronic health records. Treatment initiation was defined as receiving at least one antidepressant medication dispensation or psychotherapy visit up to 90 days after the diagnosis. Modified Poisson regression was used to estimate the risk for initiating treatment and the type of treatment initiated. In total, 13,637 women with a new depression diagnosis (prenatal: N=7,041, 51.6%; postpartum: N=6,596, 48.4%) were identified. Of the pregnant women, 31.4% initiated treatment, and of the postpartum women, 73.1% initiated treatment. Latina and Asian women were less likely than White women to initiate treatment postpartum. During pregnancy and postpartum, non-White women were more likely to initiate psychotherapy. White women were more likely to initiate antidepressant medication during pregnancy and postpartum or a combination of antidepressant medication and psychotherapy during the postpartum period. Research is warranted to identify patient-, provider-, and system-level barriers that contribute to racial-ethnic disparities in perinatal mental health care.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Iturralde, Esti; Badon, Sylvia E; Quesenberry, Charles P; Sterling, Stacy; Li, De-Kun; Flanagan, Tracy
Psychiatr Serv. 2023 Apr 01;74(4):341-348. Epub 2022-10-13.
Incidence Rates of Childhood Asthma with Recurrent Exacerbations in the U.S. Environmental influences on Child Health Outcomes (ECHO) Program
Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. We hypothesized that IRs for ARE would vary by time, geography, age, race and ethnicity, irrespective of parental asthma history. We leveraged data from 17246 children born after 1990 enrolled in 59 U.S. and one Puerto Rican cohort in the Environmental Influences on Child Health Outcomes consortium to estimate IRs for AREs. The overall crude IR for ARE was 6.07/1000 person-years (95% confidence intervals (CI) 5.63, 6.51) and was highest for children age 2-4 years, for Hispanic and non-Hispanic Black children and for those with a parental history of asthma. ARE IRs were higher for 2-4 year olds in each race and ethnicity category and for both sexes. Multi-variable analysis confirmed higher adjusted ARE IRs (aIRR) for children born 2000-2009 compared to 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR=15.36; CI 12.09, 2.99), and for males versus females (aIRR=1.34; CI 1.16, 1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR=2.51; CI 2.10, 2.99 and aIRR=2.04; CI 1.22, 3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than the West (p<0.01 for each comparison). Children with a parental history of asthma had rates nearly three times higher than those without such history (aIRR=2.90; CI 2.43-3.46). Factors associated with time, geography, age, race and ethnicity, sex and parental history appear to influence the inception of ARE among children and adolescents.
Authors: Miller, Rachel L; Ferrara, Assiamira; program collaborators for Environmental influences on Child Health Outcomes,; et al.
J Allergy Clin Immunol. 2023 Mar 25.
The Environmental influences on Child Health Outcomes (ECHO)-wide Cohort
The Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children’s health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-wide Cohort data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in five main outcome areas: pre-, peri-, and post-natal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include place- (e.g., air pollution, neighborhood socioeconomic status), family- (e.g., parental mental health), and individual-level (e.g., diet, genomics) factors.
Authors: Knapp, Emily A; Croen, Lisa; Ferrara, Assiamira; Environmental Influences On Child Health Outcomes, On Behalf Of Program Collaborators For; et al.
Am J Epidemiol. 2023 Mar 24.
Modifying the social responsiveness scale for adaptive administration
The social responsiveness scale (SRS) is frequently used to quantify the autism-related phenotype and is gaining use in health outcomes research. However, it has a high respondent burden (65 items) for large-scale studies. Further, most evaluations of it have focused on the school-age form, not the preschool form. More validity evidence of shortened forms is necessary in the general population to support the broader health outcomes context of use. We evaluated the psychometrics of the SRS in 7030 individuals from multiple predominantly neurotypical samples in order to shorten it based on non-autistic sample metrics. Analyses included item factor analysis, differential item functioning (DIF), and multiple-group item response theory (IRT) to place the SRS items on a comparable scale, which was then simulated via computer adaptive testing (CAT) administration. The SRS was broadly unidimensional with few methodological residual dependencies. On average, males had more autistic characteristics than females, and preschoolers had fewer characteristics than school-age children. The final IRT calibration included 45 items equated across forms, and each form had 11 with significant wording discrepancies and 9 items with near-identical wording that exhibited form-related DIF. The CAT simulation suggested a median of 14 items was sufficient to reach a reliable score, demonstrating its feasibility across the range of impairments. IRT allows practitioners the ability to get highly reliable scores with fewer items than the full-length SRS. This supports the future application of the SRS in a computer adaptive testing mode in both neurotypical and ASD samples.
Authors: Kaat, Aaron J; Croen, Lisa A; Constantino, John; Newshaffer, Craig J; Lyall, Kristen
Qual Life Res. 2023 Mar 21.
A framework for measuring the cost to families of caring for children’s health: the design, methodology, and study population of the r-Kids study
All families experience financial and time costs related to caring for their children’s health. Understanding the economic burden faced by families of children with chronic health conditions (CHC) is crucial for designing effective policies to support families. In this prospective study we used electronic health records to identify children between 3 and 17 years old with autism spectrum disorder (ASD), asthma, or neither (control) from three Kaiser Permanente regions and several community health centers in the OCHIN network. We oversampled children from racial and ethnic minority groups. Parent/guardian respondents completed surveys three times, approximately four months apart. The surveys included the Family Economic Impact Inventory (measuring financial, time, and employment costs of caring for a child’s health), and standardized measures of children’s quality of life, behavioral problems, and symptom severity for children with ASD or asthma. We also assessed parenting stress and parent physical and mental health. All materials were provided in English and Spanish. Of the 1,461 families that enrolled (564 ASD, 468 asthma, 429 control), children were predominantly male (79%), with a mean age of 9.0 years, and racially and ethnically diverse (43% non-Hispanic white; 22% Hispanic; 35% Asian, Black, Native Hawaiian, or another race/ethnicity). The majority of survey respondents were female (86%), had a college degree (62%), and were married/partnered (79%). ASD group respondents were less likely to be employed (73%) than those in the asthma or control groups (both 80%; p = .023). Only 32% of the control group reported a household income ≤ $4,000/month compared with 41% of asthma and 38% of ASD families (p = .006). Utilizing a novel measure assessing family economic burden, we successfully collected survey responses from a large and diverse sample of families. Drawing upon the conceptual framework, survey measures, and self-report data described herein we will conduct future analyses to examine the economic burdens related to CHC and the incremental differences in these burdens between health groups. This information will help policy makers to design more equitable health and social policies that could reduce the burden on families.
Authors: Bulkley, Joanna E; Croen, Lisa A; Lynch, Frances L; et al.
BMC Pediatr. 2023 Mar 20;23(1):128. Epub 2023-03-20.
Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study
Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years). Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status. Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe). KPNC health plan members with moderate or severe AD (2007-2018). Malignancy IRs and 95% CIs per 1000 person-years were calculated. 7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma. This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations.
Authors: Hedderson, Monique M;Asgari, Maryam M;Xu, Fei;Quesenberry, Charles P;Sridhar, Sneha;Geier, Jamie;Lemeshow, Adina R
BMJ Open. 2023 Mar 10;13(3):e071172. Epub 2023-03-10.
Impact of sedentary behavior and emotional support on prenatal psychological distress and birth outcomes during the COVID-19 pandemic
Abstract. Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.
Authors: Hipwell, Alison E; Ferrera, Assiamira; program collaborators for Environmental influences on Child Health Outcomes,; et al.
Psychol Med. 2023 Mar 08:1-14.
Using Peer Support to Prevent Diabetes: Results of a Pragmatic RCT
High-contact structured diabetes prevention programs are effective in lowering weight and HbA1cs, yet their intensity level can create barriers to participation. Peer support programs improve clinical outcomes among adults with Type 2 diabetes, but their effectiveness in diabetes prevention is unknown. This study examined whether a low-intensity peer support program improved outcomes more than enhanced usual care in a diverse population with prediabetes. The intervention was tested in a pragmatic 2-arm RCT. Participants were adults with prediabetes at 3 healthcare centers. Participants randomized to the enhanced usual care arm received educational materials. Participants in the Using Peer Support to Aid in Prevention and Treatment in Prediabetes arm were matched with a peer supporter: another patient who had made healthy lifestyle changes and was trained in autonomy-supportive action planning. Peer supporters were instructed to provide weekly telephone support to their peers on specific action steps toward behavioral goals for 6 months, then monthly support for 6 months. Changes in primary outcomes of weight and HbA1c and secondary outcomes of enrollment in formal diabetes prevention programs, self-reported diet, physical activity, health-specific social support, self-efficacy, motivation, and activation at 6 and 12 months were examined. Data collection occurred from October 2018 to March 2022, with analyses completed in September 2022. Among 355 randomized patients, in intention-to-treat analyses, there were no between-group differences in HbA1c or weight changes at 6 and 12 months. Using Peer Support to Aid in Prevention and Treatment in Prediabetes participants were more likely to enroll in structured programs at 6 (AOR=2.45, p=0.009) and 12 (AOR=2.21, p=0.016) months and to report eating whole grains at 6 (4.49, p=0.026) and 12 (4.22, p=0.034) months. They reported greater improvements in perceived social support for diabetes prevention behaviors at 6 (6.39, p<0.001) and 12 (5.48, p<0.001) months, with no differences in other measures. A stand-alone, low-intensity peer support program improved social support and participation in formal diabetes prevention programs but not weight or HbA1c. It will be important to examine whether peer support could effectively complement higher-intensity, structured diabetes prevention programs. This trial is registered at ClinicalTrials.gov, NCT03689530. Full protocol available at https://clinicaltrials.gov/ct2/show/NCT03689530.
Authors: Heisler, Michele; Dyer, Wendy T; Finertie, Holly; Stoll, Shelley C; Wiley, Deanne; Turner, Cassie D; Sedgwick, Tali; Kullgren, Jeffrey; Richardson, Caroline R; Hedderson, Monique; Schmittdiel, Julie A
Am J Prev Med. 2023 Mar 08.
Associations between antidepressant use patterns during pregnancy and birth outcomes among periconception antidepressant users
Little is known about antidepressant medication use patterns during pregnancy among periconception (before and immediately following conception) users. Additionally, the associations between these patterns and birth outcomes is unclear, after taking into account underlying depression severity. This study describes patterns of antidepressant use among periconception users and examines associations between usage patterns and birth outcomes. This retrospective cohort study included pregnant Kaiser Permanente Northern California (KPNC) members with a live birth between 2014 and 2017 and an antidepressant medication fill that overlapped the 8th week of pregnancy. Outcomes were preterm birth and neonatal intensive care unit (NICU) admission. Data were extracted from KPNC’s electronic health records. Modified Poisson regression was conducted. Of the 3637 pregnancies meeting inclusion criteria, 33% (n = 1204) continued antidepressant use throughout the pregnancy (refilled throughout pregnancy), 47% (n = 1721) discontinued use (no refills), and 20% (n = 712) stopped and reinitiated use (refill after 30+ day gap in supply). Women who continued use had 1.86 (95% confidence interval (CI) 1.53, 2.27) times the risk of preterm birth and 1.76 (95% CI: 1.42, 2.19) times the risk of NICU admission, compared to women who discontinued use during pregnancy. Similarly, women with continued use had 1.66 (95% CI: 1.27, 2.18) times the risk of preterm birth and 1.85 (95% CI: 1.39, 2.46) times the risk of NICU admission, compared to women who stopped and reinitiated use. This relationship held when examining continuous exposure; the relationship between continuous exposure and preterm delivery was stronger in later trimesters. Periconception antidepressant users who continue use during pregnancy, particularly into the second and third trimesters, may be at higher risk of adverse birth outcomes. This evidence should be considered alongside the risks associated with depression relapse.
Authors: Nance, Nerissa; Badon, Sylvia E; Ridout, Kathryn; Ahern, Jennifer; Li, De-Kun; Quesenberry, Charles; Avalos, Lyndsay A
Pharmacotherapy. 2023 Mar 05.
Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program
Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of β=-0.15 [95% confidence interval (CI): -0.27, -0.03], β=-0.14 (95% CI: -0.28, -0.002), β=-0.22 (95% CI: -0.23, -0.10), β=-0.06 (95% CI: -0.18, 0.06), and β=-0.25 (95% CI: -0.37, -0.14), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [-0.28; 95% highest posterior density (HPD): -0.44, -0.14] and decreased odds of large-for-gestational-age (OR=0.49; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.
Authors: Padula, Amy M; Ferrara, Assiamira; Zhu, Yeyi; program collaborators for Environmental influences on Child Health Outcomes,; et al.
Environ Health Perspect. 2023 Mar;131(3):37006. Epub 2023-03-15.
Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group
To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching. We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed. We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60-0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66-0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48-0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28-1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery. Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.
Authors: Boller, Marie J; Xu, Fei; Lee, Catherine; Sridhar, Sneha; Greenberg, Mara B; Hedderson, Monique M
Obstet Gynecol. 2023 Mar 01;141(3):583-591. Epub 2023-02-02.
Metabolomic biomarkers of the mediterranean diet in pregnant individuals: A prospective study
Metabolomic profiling is a systematic approach to identifying biomarkers for dietary patterns. Yet, metabolomic markers for dietary patterns in pregnant individuals have not been investigated. The aim of this study was to identify plasma metabolomic markers and metabolite panels that are associated with the Mediterranean diet in pregnant individuals. This is a prospective study of 186 pregnant individuals who had both dietary intake and metabolomic profiles measured from the Fetal Growth Studies-Singletons cohort. Dietary intakes during the peri-conception/1st trimester and the second trimester were accessed at 8-13 and 16-22 weeks of gestation, respectively. Adherence to the Mediterranean diet was measured by the alternate Mediterranean Diet (aMED) score. Fasting plasma samples were collected at 16-22 weeks and untargeted metabolomics profiling was performed using the mass spectrometry-based platforms. Metabolites individually or jointly associated with aMED scores were identified using linear regression and least absolute shrinkage and selection operator (LASSO) regression models with adjustment for potential confounders, respectively. Among 459 annotated metabolites, 64 and 41 were individually associated with the aMED scores of the diet during the peri-conception/1st trimester and during the second trimester, respectively. Fourteen metabolites were associated with the Mediterranean diet in both time windows. Most Mediterranean diet-related metabolites were lipids (e.g., acylcarnitine, cholesteryl esters (CEs), linoleic acid, long-chain triglycerides (TGs), and phosphatidylcholines (PCs), amino acids, and sugar alcohols. LASSO regressions also identified a 10 metabolite-panel that were jointly associated with aMED score of the diet during the peri-conception/1st trimester (AUC: 0.74; 95% CI: 0.57, 0.91) and a 3 metabolites-panel in the 2nd trimester (AUC: 0.68; 95% CI: 0.50, 0.86). We identified plasma metabolomic markers for the Mediterranean diet among pregnant individuals. Some of them have also been reported in previous studies among non-pregnant populations, whereas others are novel. The results from our study warrant replication in pregnant individuals by future studies. This study was registered at ClinicalTrials.gov.
Authors: Chen, Liwei; Zhu, Yeyi; Zhang, Cuilin; et al.
Clin Nutr. 2023 Mar;42(3):384-393. Epub 2023-01-14.
Intergenerational transmission of the effects of maternal exposure to childhood maltreatment in the USA: a retrospective cohort study
Childhood maltreatment is associated with adverse health outcomes and this risk can be transmitted to the next generation. We aimed to investigate the association between exposure to maternal childhood maltreatment and common childhood physical and mental health problems, neurodevelopmental disorders, and related comorbidity patterns in offspring. We conducted a retrospective cohort study using data from the Environmental influences on Child Health Outcomes (ECHO) Program, which was launched to investigate the influence of early life exposures on child health and development in 69 cohorts across the USA. Eligible mother-child dyads were those with available data on maternal childhood maltreatment exposure and at least one child health outcome measure (autism spectrum disorder, attention-deficit hyperactivity disorder [ADHD], internalising problems, obesity, allergy, and asthma diagnoses). Maternal history of childhood maltreatment was obtained retrospectively from the Adverse Childhood Experiences or Life Stressor Checklist questionnaires. We derived the prevalence of the specified child health outcome measures in offspring across childhood and adolescence by harmonising caregiver reports and other relevant sources (such as medical records) across cohorts. Child internalising symptoms were assessed using the Child Behavior Checklist. Associations between maternal childhood maltreatment and childhood health outcomes were measured using a series of mixed-effects logistic regression models. Covariates included child sex (male or female), race, and ethnicity; maternal and paternal age; maternal education; combined annual household income; maternal diagnosis of depression, asthma, ADHD, allergy, or autism spectrum disorder; and maternal obesity. Two latent class analyses were conducted: to characterise patterns of comorbidity of child health outcomes; and to characterise patterns of co-occurrence of childhood maltreatment subtypes. We then investigated the association between latent class membership and maternal childhood maltreatment and child health outcomes, respectively. Our sample included 4337 mother-child dyads from 21 longitudinal cohorts (with data collection initiated between 1999 and 2016). Of 3954 mothers in the study, 1742 (44%) had experienced exposure to abuse or neglect during their childhood. After adjustment for confounding, mothers who experienced childhood maltreatment were more likely to have children with internalising problems in the clinical range (odds ratio [OR] 2·70 [95% CI 1·95-3·72], p<0·0001), autism spectrum disorder (1·70 [1·13-2·55], p=0·01), ADHD (2·09 [1·63-2·67], p<0·0001), and asthma (1·54 [1·34-1·77], p<0·0001). In female offspring, maternal childhood maltreatment was associated with a higher prevalence of obesity (1·69 [1·17-2·44], p=0·005). Children of mothers exposed to childhood maltreatment were more likely to exhibit a diagnostic pattern characterised by higher risk for multimorbidity. Exposure to multiple forms of maltreatment across all subtypes of maternal childhood maltreatment was associated with the highest risk increases for most offspring health outcomes, suggesting a dose-response relationship. Our findings suggest that maternal childhood maltreatment experiences can be a risk factor for disease susceptibility in offspring across a variety of outcomes and emphasise the need for policies focusing on breaking the intergenerational transmission of adversity. Environmental influences on Child Health Outcomes Program, Office of the Director, National Institutes of Health.
Authors: Moog, Nora K; Ferrara, Assiamira; ECHO collaborators,; et al.
Lancet Public Health. 2023 Mar;8(3):e226-e237.
The impact of autism spectrum disorder on parent employment: Results from the r-Kids study
Parents of children with autism spectrum disorder (ASD) and other chronic health conditions often face exceptional caregiving demands that can lead to challenges related to maintaining and succeeding in employment. Detailed information on the specific ways in which these health conditions impact parent employment could aid in designing equitable, effective policies to support families. The r-Kids study used electronic health records to identify three groups of children: those with ASD, asthma, or neither condition (control), from several health care systems. We oversampled racial and ethnic minorities and matched the asthma and control groups to the age and sex distribution of the ASD group. Parents completed three online surveys over the course of a year to measure annual employment outcomes. Surveys included the Family Economic Impact Inventory (measuring employment impacts) and measures of quality of life and symptom severity. All materials were provided in English and Spanish. The study enrolled 1461 families (564 ASD, 468 asthma, 429 control). Youth were 3-16.5 years old and predominantly male (79%). The sample was diverse (43% non-Hispanic White; 35% non-Hispanic Asian, Black, Native Hawaiian, or Other; and 21% Hispanic ethnicity). Parents of children with ASD were significantly less likely to be employed than parents of youth with asthma and control combined (OR: 14.2, p < 0.001), and were more likely to have other difficulties with employment and productivity while at work. Public and employer policies to help mitigate these impacts could aid families in managing care for youth with ASD.
Authors: Lynch, Frances L; Bulkley, Joanna E; Varga, Alexandra; Crawford, Phillip; Croen, Lisa A; Daida, Yihe G; Fombonne, Eric; Hatch, Brigit; Massolo, Maria; Dickerson, John F
Autism Res. 2023 Mar;16(3):642-652. Epub 2022-12-22.
Accuracy of diagnostic codes for prenatal opioid exposure and neonatal opioid withdrawal syndrome
Determine the accuracy of diagnostic codes in identifying Prenatal Opioid Exposure (POE) and Neonatal Opioid Withdrawal Syndrome (NOWS). A cross-sectional study of 374,222 mother-infant dyads with delivery from 01/01/2010 to 12/31/2019. We ascertained maternal diagnostic codes for opioid use during pregnancy and infant diagnostic codes for drug exposure and withdrawal. We assessed sensitivity and positive predictive value (PPV) for POE and NOWS, defined using laboratory, pharmacy, and clinical data. Maternal codes had low sensitivity (36.4%) and PPV (34.7%) for POE. Infant codes for drug exposure were neither sensitive for POE (14%) nor NOWS (31.6%) and had low PPV. Codes for newborn withdrawal had low sensitivity (31.6%) for detecting NOWS, but high PPV (85%). Sensitivity improved (95.1%) for NOWS requiring pharmacologic treatment. Diagnostic codes identify POE and NOWS poorly. Improved case identification would include pharmacy and laboratory results, and clearly defined criteria for evidence of withdrawal.
Authors: Kuzniewicz, Michael W; Campbell, Cynthia I; Li, Sherian; Walsh, Eileen M; Croen, Lisa A; Comer, Sandra D; Pimentel, Samuel D; Hedderson, Monique; Sun, Lena S
J Perinatol. 2023 Mar;43(3):293-299. Epub 2022-09-21.
Maternal and neonatal outcomes associated with treating hypertension in pregnancy at different thresholds
In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk. The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy. This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small-for-gestational-age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre-pregnancy body mass index) analyses were also conducted. In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: -0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. Initiation of antihypertensive medication at mild-to-moderate BP thresholds (140-155/90-105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence.
Authors: Avalos, Lyndsay A; Neugebauer, Romain S; Nance, Nerissa; Badon, Sylvia E; Cheetham, T Craig; Easterling, Thomas R; Reynolds, Kristi; Idu, Abisola; Bider-Canfield, Zoe; Holt, Victoria L; Dublin, Sascha
Pharmacotherapy. 2023 Feb 13.
Perinatal Outcomes During vs. Prior to the COVID-19 Pandemic and the Role of Maternal Depression and Perceived Stress: A Report from the ECHO Program
We sought to evaluate the impact of the COVID-19 pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic. Data dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program (N=2983) were used to compare birth outcomes before and during the pandemic (n= 2355), and a partially overlapping sample (n=1490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic’s effect on birth outcomes. Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic (B=-0.33 weeks, p=0.025), and depression was significantly associated with shortened gestation (B=-0.02 weeks, p=0.015) after adjustment. Birth weights were similar (B=-28.14 g, p=0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic (B=0.15 z-score units, p=0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of COVID-19 on their life. In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth as well as distress about changes in prenatal care early in the pandemic.
Authors: McKee, Kimberly S; Ferrara, Assiamira; Comstock, Sarah S; et al.
Am J Perinatol. 2023 Feb 13.
SARS-CoV-2 testing and detection during peripartum hospitalizations among a multi-center cohort of pregnant persons, March 2020-February 2021
Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03-1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [site 2]). Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.
Authors: Delahoy, Miranda J; Li, De Kun; Greenberg, Mara; Naleway, Allison L; et al.
Clin Infect Dis. 2023 Feb 08;76(3):e51-e59.
Dietary Quality Indices in Early Pregnancy and Rate of Gestational Weight Gain among a Prospective Multi-Racial and Ethnic Cohort
Meeting the Institute of Medicine (IOM) gestational weight gain (GWG) guidelines is associated with a reduced risk of adverse perinatal outcomes. Overall diet quality comprehensively assesses dietary components and accounts for interactions between them. While GWG is influenced by maternal diet, its association with overall diet quality-measured by various dietary quality indices-is not well-defined. We prospectively estimated the relationship between four established dietary quality indices and the risk of GWG rate above (excessive) or below (inadequate) IOM guidelines in a multi-racial and ethnic cohort of 2914 pregnant people from the Pregnancy Environment and Lifestyle Study (2014-2019). We assessed diet quality using the Healthy Eating Index 2010 (HEI-2010), alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and Empirical Dietary Inflammatory Index (EDIP). Following the first trimester, 56% of the cohort had excessive GWG, and 14% had inadequate GWG. Poor diet quality (below the 75th percentile), measured by HEI-2010, was associated with a higher risk of excessive GWG in the second and third trimesters [RR = 1.03 (1.00, 1.06)]. Effect modification of this relationship by race and ethnicity and pre-pregnancy BMI was assessed. We found poor diet quality to be associated with elevated risk of excessive GWG among Black participants [RR = 1.14 (1.02, 1.28)] and White participants [RR 1.07 (1.01, 1.12)]. This was also the case for participants with pre-pregnancy BMI < 25.0 [RR 1.05 (1.00, 1.10)]. These results suggest that diet quality measured by the HEI-2010 is associated with excessive GWG, and the associations appear to be stronger among pregnant people without overweight or obesity and pregnant people who identify as Black or White race and ethnicity.
Authors: Liu, Emily F; Zhu, Yeyi; Ferrara, Assiamira; Hedderson, Monique M
Nutrients. 2023 Feb 06;15(4). Epub 2023-02-06.
Association of the COVID-19 Pandemic With Unstable and/or Unsafe Living Situations and Intimate Partner Violence Among Pregnant Individuals
The social, behavioral, and economic consequences of the COVID-19 pandemic may be associated with unstable and/or unsafe living situations and intimate partner violence (IPV) among pregnant individuals. To investigate trends in unstable and/or unsafe living situations and IPV among pregnant individuals prior to and during the COVID-19 pandemic. A cross-sectional population-based interrupted time-series analysis was conducted among Kaiser Permanente Northern California members who were pregnant and screened for unstable and/or unsafe living situation and IPV as part of standard prenatal care between January 1, 2019, and December 31, 2020. COVID-19 pandemic (prepandemic period: January 1, 2019, to March 31, 2020; during pandemic period: April 1 to December 31, 2020). The 2 outcomes were unstable and/or unsafe living situations and IPV. Data were extracted from electronic health records. Interrupted time-series models were fit and adjusted for age and race and ethnicity. The study sample included 77 310 pregnancies (74 663 individuals); 27.4% of the individuals were Asian or Pacific Islander, 6.5% were Black, 29.0% were Hispanic, 32.3% were non-Hispanic White, and 4.8% were other/unknown/multiracial, with a mean (SD) age of 30.9 (5.3) years. Across the 24-month study period there was an increasing trend in the standardized rate of unsafe and/or unstable living situations (2.2%; rate ratio [RR], 1.022; 95% CI, 1.016-1.029 per month) and IPV (4.9%; RR, 1.049; 95% CI, 1.021-1.078 per month). The ITS model indicated a 38% increase (RR, 1.38; 95% CI, 1.13-1.69) in the first month of the pandemic for unsafe and/or unstable living situation, with a return to the overall trend afterward for the study period. For IPV, the interrupted time-series model suggested an increase of 101% (RR, 2.01; 95% CI, 1.20-3.37) in the first 2 months of the pandemic. This cross-sectional study noted an overall increase in unstable and/or unsafe living situations and IPV over the 24-month period, with a temporary increase associated with the COVID-19 pandemic. It may be useful for emergency response plans to include IPV safeguards for future pandemics. These findings suggest the need for prenatal screening for unsafe and/or unstable living situations and IPV coupled with referral to appropriate support services and preventive interventions.
Authors: Avalos, Lyndsay A; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique B; Watson, Carey; Young-Wolff, Kelly C
JAMA Netw Open. 2023 Feb 01;6(2):e230172. Epub 2023-02-01.
Trends in Screen Time Use Among Children During the COVID-19 Pandemic, July 2019 Through August 2021
The COVID-19 pandemic led to widespread lockdowns and school closures that may have affected screen time among children. Although restrictions were strongest early in the pandemic, it is unclear how screen time changed as the pandemic progressed. To evaluate change in children’s screen time from before the pandemic to during the pandemic, from July 2019 through August 2021. This is a longitudinal cohort study with repeated measures of screen time collected before the pandemic and during 2 pandemic periods. Children aged 4 to 12 years and their parent were enrolled in 3 pediatric cohorts across 3 states in the US participating in the Environmental Influences of Child Health Outcomes (ECHO) Program. Data analysis was performed from November 2021 to July 2022. COVID-19 pandemic period: prepandemic (July 2019 to March 2020), pandemic period 1 (December 2020 to April 2021), and pandemic period 2 (May 2021 to August 2021). The primary outcomes were total, educational (not including remote school), and recreational screen time assessed via the ECHO Child Media Use questionnaire. Linear mixed-effects models were used for screen time adjusted for child’s age, number of siblings, sex, race, ethnicity, and maternal education. The cohort included 228 children (prepandemic mean [SD] age, 7.0 [2.7] years; 100 female [43.9%]) with screen time measured during the prepandemic period and at least once during the pandemic period. Prepandemic mean (SD) total screen time was 4.4 (3.9) hours per day and increased 1.75 hours per day (95% CI, 1.18-2.31 hours per day) in the first pandemic period and 1.11 hours per day (95% CI, 0.49-1.72 hours per day) in the second pandemic period, in adjusted models. Prepandemic mean (SD) recreational screen time was 4.0 (3.5) hours per day and increased 0.89 hours per day (95% CI, 0.39-1.39 hours per day) in the first pandemic period and 0.70 hours per day (95% CI, 0.16-1.25 hours per day) in the second pandemic period. Prepandemic mean (SD) educational screen time was 0.5 (1.2) hours per day (median [IQR], 0.0 [0.0-0.4] hours per day) and increased 0.93 hours per day (95% CI, 0.67-1.19 hours per day) in the first pandemic period and 0.46 hours per day (95% CI, 0.18-0.74 hours per day) in the second pandemic period. These findings suggest that screen time among children increased during the COVID-19 pandemic and remained elevated even after many public health precautions were lifted. The long-term association of increased screen time during the COVID-19 pandemic with children’s health needs to be determined.
Authors: Hedderson, Monique M; Zhu, Yeyi; Ferrara, Assiamira; Environmental Influences on Child Health Outcomes Program,; et al.
JAMA Netw Open. 2023 Feb 01;6(2):e2256157. Epub 2023-02-01.
Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder
Examine bidirectional associations between daytime napping and nighttime sleep among pregnant individuals with insomnia disorder. We used baseline data from a randomized controlled trial of insomnia treatment during pregnancy (n = 116). Participants in their second or third trimester of pregnancy self-reported daytime napping and nighttime sleep parameters using a sleep diary and wore an Actiwatch-2 during the same 7-day period. Linear regression models, accounting for intraindividual correlation, were used to estimate associations between daytime napping and nighttime sleep parameters (duration, efficiency, quality, awakenings). Models were also stratified by trimester of pregnancy. Sixty-three percent of participants reported napping on at least 1 day. Among participants in the second trimester (65%), napping 15-59 minutes was associated with 6.3% greater self-reported sleep efficiency (95% confidence interval: 2.3, 10.2) and 0.5 units greater self-reported sleep quality (95% confidence interval: 0.0, 0.9) that night; napping 60+ minutes was associated with 0.6 hours shorter actigraphy-measured sleep duration (95% confidence interval: -1.0, -0.2). Napping was not associated with nighttime sleep overall or during the third trimester. Nighttime sleep parameters were not associated with napping duration the following day. Among pregnant individuals with insomnia in the second trimester, short napping duration was associated with higher self-reported sleep efficiency and quality; long napping duration was associated with shorter actigraphy-measured sleep duration. Additional research is needed to examine the interaction between nap duration and nap timing. In the future, these results may lead to more nuanced recommendations for daytime napping among pregnant individuals with insomnia disorder. Registry: ClinicalTrials.gov; Name: Treatment for Insomnia during Pregnancy; URL: https://clinicaltrials.gov/ct2/show/NCT01846585; Identifier: NCT01846585. Badon SE, Dietch R, Simpson N, Lyell DJ, Manber R. Daytime napping and nighttime sleep in pregnant individuals with insomnia disorder. J Clin Sleep Med. 2023;19(2):371-377.
Authors: Badon, Sylvia E; Dietch, Jessica R; Simpson, Norah; Lyell, Deirdre J; Manber, Rachel
J Clin Sleep Med. 2023 Feb 01;19(2):371-377.
Association of cannabis use during pregnancy with severe acute respiratory syndrome coronavirus 2 infection: a retrospective cohort study
Cannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy. This is a retrospective cohort study. The study was conducted in California, USA. A total of 58?114 pregnancies (with outcomes from 5 March 2020 to 30 September 2021) among 57?287 unique pregnant women aged 14-54?years who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (KPNC) (a health-care system) and had not tested positive for COVID-19 prior to pregnancy onset. We utilized data from the KPNC electronic health record. Cannabis use status (current, recently quit and non-user) was based on universal screenings during prenatal care (including urine toxicology testing and self-reported use on a self-administered questionnaire). SARS-CoV-2 infection [based on polymerase chain reaction (PCR) tests] was estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined differences in (a) SARS-CoV-2 testing rates and (b) SARS-CoV-2 infection rates among those tested. We observed 348?810 person-months of follow-up time in our cohort with 41?064 SARS-CoV-2 PCR tests and 6% (n?=?2414) of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection [adjusted hazard ratio (aHR)?=?0.60, 95% confidence interval (CI)?=?0.49-0.74 than non-use. Those who had recently quit did not differ from non-cannabis users in infection rates (aHR?=?0.96, 95% CI?=?0.86-1.08). Sensitivity analyses among patients who received a SARS-CoV-2 test also found lower odds of infection associated with current versus no cannabis use (aOR?=?0.76, CI?=?0.61-0.93). Current cannabis use appears to be associated with a reduced risk of SARS-CoV-2 infection among pregnant individuals.
Authors: Young-Wolff, Kelly C; Ray, G Thomas; Alexeeff, Stacey E; Benowitz, Neal; Adams, Sara R; Does, Monique B; Goler, Nancy; Ansley, Deborah; Conway, Amy; Avalos, Lyndsay A
Addiction. 2023 Feb;118(2):317-326. Epub 2022-10-12.
Impact of the COVID-19 pandemic on children’s sleep habits: an ECHO study
Sleep in childhood is affected by behavioral, environmental, and parental factors. We propose that these factors were altered during the COVID-19 pandemic. This study investigates sleep habit changes during the pandemic in 528 children 4-12 years old in the US, leveraging data from the Environmental Influences on Child Health Outcomes (ECHO) Program. Data collection occurred in July 2019-March 2020 (pre-pandemic) and two pandemic periods: December 2020-April 2021 and May-August 2021. Qualitative interviews were performed in 38 participants. We found no changes in sleep duration, but a shift to later sleep midpoint during the pandemic periods. There was an increase in latency at the first pandemic collection period but no increase in the frequency of bedtime resistance, and a reduced frequency of naps during the pandemic. Qualitative interviews revealed that parents prioritized routines to maintain sleep duration but were more flexible regarding timing. Children from racial/ethnic minoritized communities slept less at night, had later sleep midpoint, and napped more frequently across all collection periods, warranting in-depth investigation to examine and address root causes. The COVID-19 pandemic significantly impacted children sleep, but parental knowledge of the importance of sleep might have played a significant protective role. During the COVID-19 pandemic, US children changed their sleep habits, going to bed and waking up later, but their sleep duration did not change. Sleep latency was longer. Parental knowledge of sleep importance might have played a protective role. Regardless of data collection periods, children from racial/ethnic minoritized communities slept less and went to bed later. This is one of the first study on this topic in the US, including prospective pre-pandemic qualitative and quantitative data on sleep habits. Our findings highlight the pandemic long-term impact on childhood sleep. Results warrants further investigations on implications for overall childhood health.
Authors: Lucchini, Maristella; Ferrara, Assiamira; Hedderson, Monique; Environmental influences on Child Health Outcomes,; et al.
Pediatr Res. 2023 Feb;93(3):586-594. Epub 2022-10-04.
Placental Histopathologic Findings of a Large Cohort of Patients With SARS-CoV-2 Infection During Pregnancy
Pregnant individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at a higher risk for adverse pregnancy outcomes. Previous small cohort studies have shown increased frequency of placental lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, and inflammation among patients with SARS-CoV-2, without controlling for cardiometabolic risk factors among many such patients. We aimed to evaluate whether SARS-CoV-2 infection during pregnancy is independently associated with placental abnormalities when controlling for risk factors that could affect placental histopathology. Retrospective cohort study of placentas from singleton pregnancies in Kaiser Permanente Northern California from March to December 2020. Pathologic findings were compared among those with confirmed cases of SARS-CoV-2 during pregnancy and those without. We examined the association between SARS-CoV-2 infection and categorical placental pathologies, controlling for maternal age, gestational age, prepregnancy body mass index, gestational hypertension, preeclampsia/eclampsia, preexisting diabetes, history of thrombosis, and stillbirth. A total of 2,989 singleton gestation placentas were analyzed, 416 (13%) from pregnancies with SARS-CoV-2 infection and 2,573 (86%) from those without infection. Among placentas from pregnancies with SARS-CoV-2, 54.8% had evidence of inflammation, 27.1% maternal malperfusion abnormality, 20.7% massive perivillous fibrin or chronic villitis, 17.3% villous capillary abnormality, and 15.1% fetal malperfusion. After controlling for risks factors and stratifying interval time between SARS-CoV-2 infection and delivery, no association was found between placental abnormalities and SARS-CoV-2 infection during pregnancy. SARS-CoV-2 infection was not associated with an increased risk of placentally mediated adverse outcomes during pregnancy, compared with placentas sent for other indications, in this large diverse cohort.
Authors: Lin, Ruby; Forquer, Heather; Cviko-Pajt, Aida; Schauer, Galen M; Abellar, Rosanna G; Hedderson, Monique; Kuzniewicz, Michael W; Greenberg, Mara B
Int J Gynecol Pathol. 2023 Jan 25.
Ambient air pollutants are associated with morning serum cortisol in overweight and obese Latino youth in Los Angeles.
BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis dysfunction has been associated with a variety of mental health and cardio-metabolic disorders. While causal models of HPA-axis dysregulation have been largely focused on either pre-existing health conditions or psychosocial stress factors, recent evidence suggests a possible role for central nervous system activation via air pollutants, such as nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM). Therefore, in an observational study of Latino youth, we investigated if monthly ambient NO2, O3, and PM with aerodynamic diameter
Authors: Toledo-Corral, C M; Alderete, T L; Herting, M M; Habre, R; Peterson, A K; Lurmann, F; Goran, M I; Weigensberg, M J; Gilliland, F D
Environ Health. 2021 Apr 8;20(1):39. doi: 10.1186/s12940-021-00713-2.
Prenatal Maternal Cortisol Levels and Infant Birth Weight in a Predominately Low-Income Hispanic Cohort.
Infant birth weight influences numerous health outcomes throughout the life course including childhood obesity and metabolic morbidities. Maternal experience of stress, both before and during pregnancy, has been hypothesized to influence fetal growth and birth outcomes. However, these associations currently are not fully understood, due to conflicting results in the published literature. Salivary cortisol is often used as a biological biomarker to assess the diurnal pattern of the hypothalamic-pituitary-adrenal axis (HPA-axis) functioning. Cortisol metrics include both the total cortisol concentration secreted during waking hours, reflected by the area under the curve (AUC), and cortisol dynamics, which include the diurnal cortisol slope (DCS) and the cortisol awakening response (CAR). This study examined the association of these cortisol metrics measured during the third trimester of pregnancy and infant birth weight among 240 mother-infant dyads participating in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort study, which is predominately comprised of Hispanic low-income women. There were no significant associations with the maternal biological stress response and infant birth weight in this study. More research is needed in larger studies to better understand how the biological stress response influences birth weight in populations facing health disparities.
Authors: Peterson, Alicia K; Toledo-Corral, Claudia M.; Chavez, Thomas A; Naya, Christine H; Johnson, Mark; Eckel, Sandrah P; Lerner, Deborah; Grubbs, Brendan H; Farzan, Shohreh F; Dunton, Genevieve F; Bastain, Theresa M; Breton, Carrie V
Int J Environ Res Public Health. 2020 Sep 21;17(18). pii: ijerph17186896. doi: 10.3390/ijerph17186896.
Third trimester cortisol is positively associated with gestational weight gain in pregnant women with class one obesity.
BACKGROUND/OBJECTIVE: Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. SUBJECTS/METHODS: The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. RESULTS: There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). CONCLUSIONS: Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.
Authors: Naya, Christine H; Toledo-Corral, Claudia M; Chavez, Thomas; Lerner, Deborah; Lurvey, Nathana; Eckel, Sandrah P; Peterson, Alicia K; Grubbs, Brendan H; Dunton, Genevieve F; Breton, Carrie V; Bastain, Theresa M
Int J Obes (Lond). 2022 Feb;46(2):366-373. doi: 10.1038/s41366-021-01009-8. Epub 2021 Oct 30.
Effects of COVID-19 Financial and Social Hardships on Infants’ and Toddlers’ Development in the ECHO Program
The financial hardships and social isolation experienced during the COVID-19 pandemic have been found to adversely affect children’s developmental outcomes. While many studies thus far have focused on school-aged children and the pandemic-related impacts on their academic skills and behavior problems, relatively less is known about pandemic hardships and associations with children’s development during their early years. Using a racially and economically diverse sample, we examined whether hardships experienced during the pandemic were associated with children’s development with a particular focus on communication and socioemotional development. Participants from eight cohorts of the Environmental influences on Child Health Outcomes program provided data on pandemic-related financial and social hardships as well as child developmental outcomes. Financial hardship was defined as at least one parent experiencing job loss or change, and social hardship was defined as families’ quarantining from household members or extended family and friends. The development of children under 4 was assessed longitudinally, before and during the pandemic (N = 684), using the Ages and Stages Questionnaire (ASQ). The Generalized Estimating Equations, which accounted for within-child correlation, were used for analysis. Families from minority backgrounds and low socioeconomic status disproportionately experienced pandemic-related hardships. Male children had higher odds of experiencing negative changes in communication and personal social skills from pre- to during-pandemic visits (ORs ranged between 2.24 and 3.03 in analysis with binary ASQ outcomes and ranged from -0.34-0.36 in analyses with ASQ z-scores, ps = 0.000). Pandemic-related hardships in the social and financial areas did not explain within-individual changes in children’s developmental outcomes. Negative developmental changes from pre- to during-pandemic were found in boys, yet we did not find any associations between increased experience of pandemic-related hardships and children’s development. E how pandemic hardships affect development using a larger sample size and with longer follow-up is warranted.
Authors: Nozadi, Sara S; Croen, Lisa A; Ferrara, Assiamira; Lewis, Johnnye L; et al.
Int J Environ Res Public Health. 2023 Jan 05;20(2). Epub 2023-01-05.
Indoor and outdoor air pollution and couple fecundability: a systematic review
Air pollution is both a sensory blight and a threat to human health. Inhaled environmental pollutants can be naturally occurring or human-made, and include traffic-related air pollution (TRAP), ozone, particulate matter (PM) and volatile organic compounds, among other substances, including those from secondhand smoking. Studies of air pollution on reproductive and endocrine systems have reported associations of TRAP, secondhand smoke (SHS), organic solvents and biomass fueled-cooking with adverse birth outcomes. While some evidence suggests that air pollution contributes to infertility, the extant literature is mixed, and varying effects of pollutants have been reported. Although some reviews have studied the association between common outdoor air pollutants and time to pregnancy (TTP), there are no comprehensive reviews that also include exposure to indoor inhaled pollutants, such as airborne occupational toxicants and SHS. The current systematic review summarizes the strength of evidence for associations of outdoor air pollution, SHS and indoor inhaled air pollution with couple fecundability and identifies gaps and limitations in the literature to inform policy decisions and future research. We performed an electronic search of six databases for original research articles in English published since 1990 on TTP or fecundability and a number of chemicals in the context of air pollution, inhalation and aerosolization. Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of both air pollution and fecundability studies. The search returned 5200 articles, 4994 of which were excluded at the level of title and abstract screening. After full-text screening, 35 papers remained for data extraction and synthesis. An additional 3 papers were identified independently that fit criteria, and 5 papers involving multiple routes of exposure were removed, yielding 33 articles from 28 studies for analysis. There were 8 papers that examined outdoor air quality, while 6 papers examined SHS exposure and 19 papers examined indoor air quality. The results indicated an association between outdoor air pollution and reduced fecundability, including TRAP and specifically nitrogen oxides and PM with a diameter of ?2.5?�m, as well as exposure to SHS and formaldehyde. However, exposure windows differed greatly between studies as did the method of exposure assessment. There was little evidence that exposure to volatile solvents is associated with reduced fecundability. The evidence suggests that exposure to outdoor air pollutants, SHS and some occupational inhaled pollutants may reduce fecundability. Future studies of SHS should use indoor air monitors and biomarkers to improve exposure assessment. Air monitors that capture real-time exposure can provide valuable insight about the role of indoor air pollution and are helpful in assessing the short-term acute effects of pollutants on TTP.
Authors: Siegel, Eva L; Zhu, Yeyi; Kahn, Linda G; et al.
Hum Reprod Update. 2023 Jan 05;29(1):45-70.
Pregnancy post-bariatric surgery: Improved outcomes with telephonic nutritional management program
Pregnancies post-bariatric surgery are increasingly common. It is important to understand how to manage prenatal care in this high-risk population to optimize perinatal outcomes. To determine among pregnancies post-bariatric surgery whether participation in a telephonic nutritional management program was associated with improved perinatal outcomes and nutritional adequacy. Retrospective cohort study of pregnancies post-bariatric surgery from 2012 to 2018. Participation in a telephonic management program with nutritional counseling, monitoring and nutritional supplement adjustment. Modified Poisson Regression estimated the relative risk using propensity score methods to account for baseline differences between the patients who participated in the program and patients who did not. 1575 pregnancies occurred post-bariatric surgery, of which 1142 (72.5 % of pregnancies) participated in the telephonic nutritional management program. Participants in the program were less likely than non-participants to have a preterm birth (aRR 0.48, 95 % CI 0.35-0.67), preeclampsia (aRR 0.43, 95 % CI (0.27-0.69)), gestational hypertension (aRR 0.62, 95 % CI 0.41-0.93), and to have neonates admitted to a Level 2 or 3 (aRR 0.61, 95 % CI0.39-0.94; aRR 0.66, 95 % CI 0.45-0.97, respectively), after adjusting for the propensity score to account for baseline differences. Risk of cesarean delivery, gestational weight gain, glucose intolerance and birthweight did not differ by participation. Among 593 pregnancies with nutritional labs available, participants in the telephonic program were less likely to have nutritional inadequacy in late pregnancy (aRR 0.91, 95 % CI 0.88-0.94). Participation in a telephonic nutritional management program post-bariatric surgery was associated with improved perinatal outcomes and nutritional adequacy.
Authors: Hedderson, Monique M; Boller, Marie; Xu, Fei; Lee, Catherine; Sridhar, Sneha; Greenberg, Mara
Obes Res Clin Pract. 2023 Mar-Apr;17(2):144-150. Epub 2023-03-10.
Prenatal Opioid Exposure and Neurodevelopmental Outcomes
The opioid epidemic in the United States has resulted in a significant increase in opioid use disorder among pregnant women and a concomitant increase in the incidence of neonatal opioid withdrawal syndrome. The long-term consequences of prenatal opioid exposure on neurodevelopmental outcomes are not fully understood. Animal studies indicate increased neuronal apoptosis and decreased neuronal proliferation and myelination with opioid exposure in-utero. Meta-analyses of human studies suggest decreased cognition and psychomotor performance in infancy and deficits in cognition and language in preschool. However, current studies have primarily focused on heroin or methadone exposure and have been limited by small sample size, inadequate comparison groups, and the inability to account for additional risk factors and exposures such as polysubstance abuse, poor prenatal care, neonatal withdrawal and treatment with opioids, and unsupportive home environment. Future studies should aim to better understand the potential impact of these confounding factors on the neurodevelopmental trajectory of exposed infants. This review discusses the up-to-date literature, current gaps in knowledge, and considerations for future studies in the arena of prenatal opioid exposure and neurodevelopmental outcomes.
Authors: Lee, Jennifer J; Saraiya, Neeta; Kuzniewicz, Michael W
J Neurosurg Anesthesiol. 2023 Jan 01;35(1):142-146. Epub 2022-12-06.
Perinatal Anesthesia Exposure and Autism Spectrum Disorders
Epidural analgesia is frequently used during labor among pregnant people in the United States. Different factors have been associated with the development of autism spectrum disorder in the epidemiological literature: maternal health, infectious and pharmacological etiologies, social factors, and environmental exposures. Current data indicates no clear association between the use of epidural labor analgesia and the development of autism spectrum disorder in the offspring. This review presents the public health perspective on the postulated association between perinatal anesthesia exposure and autism spectrum disorders.
Authors: Houck, Philipp; Naus, Claire; Croen, Lisa; Sun, Lena S
J Neurosurg Anesthesiol. 2023 Jan 01;35(1):127-129. Epub 2022-12-06.
Method for Activity Sleep Harmonization (MASH): a novel method for harmonizing data from two wearable devices to estimate 24-h sleep-wake cycles
Daily 24-h sleep-wake cycles have important implications for health, however researcher preferences in choice and location of wearable devices for behavior measurement can make 24-h cycles difficult to estimate. Further, missing data due to device malfunction, improper initialization, and/or the participant forgetting to wear one or both devices can complicate construction of daily behavioral compositions. The Method for Activity Sleep Harmonization (MASH) is a process that harmonizes data from two different devices using data from women who concurrently wore hip (waking) and wrist (sleep) devices for ≥ 4 days. MASH was developed using data from 1285 older community-dwelling women (ages: 60-72 years) who concurrently wore a hip-worn ActiGraph GT3X + accelerometer (waking activity) and a wrist-worn Actiwatch 2 device (sleep) for ≥ 4 days (N = 10,123 days) at the same time. MASH is a two-tiered process using (1) scored sleep data (from Actiwatch) or (2) one-dimensional convolutional neural networks (1D CNN) to create predicted wake intervals, reconcile sleep and activity data disagreement, and create day-level night-day-night pairings. MASH chooses between two different 1D CNN models based on data availability (ActiGraph + Actiwatch or ActiGraph-only). MASH was evaluated using Receiver Operating Characteristic (ROC) and Precision-Recall curves and sleep-wake intervals are compared before (pre-harmonization) and after MASH application. MASH 1D CNNs had excellent performance (ActiGraph + Actiwatch ROC-AUC = 0.991 and ActiGraph-only ROC-AUC = 0.983). After exclusions (partial wear [n = 1285], missing sleep data proceeding activity data [n = 269], and < 60 min sleep [n = 9]), 8560 days were used to show the utility of MASH. Of the 8560 days, 46.0% had ≥ 1-min disagreement between the devices or used the 1D CNN for sleep estimates. The MASH waking intervals were corrected (median minutes [IQR]: -27.0 [-115.0, 8.0]) relative to their pre-harmonization estimates. Most correction (-18.0 [-93.0, 2.0] minutes) was due to reducing sedentary behavior. The other waking behaviors were reduced a median (IQR) of -1.0 (-4.0, 1.0) minutes. Implementing MASH to harmonize concurrently worn hip and wrist devices can minimizes data loss and correct for disagreement between devices, ultimately improving accuracy of 24-h compositions necessary for time-use epidemiology.
Authors: Dooley, Erin E;Badon, Sylvia E;Sternfeld, Barbara;Gabriel, Kelley Pettee;et al.
J Act Sedentary Sleep Behav. 2023;2. Epub 2023-04-05.
Association of maternal education, neighborhood deprivation, and racial segregation with gestational age at birth by maternal race/ethnicity and United States Census region in the ECHO cohorts
In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region. We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression. After adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master’s degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category. In this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.
Authors: Dunlop, Anne L;Avalos, Lyndsay A;Ferrara, Assiamira;Hedderson, Monique M;McGrath, Monica;et al.
Front Public Health. 2023;11:1165089. Epub 2023-11-30.
Changes in COVID-19 Vaccine Intent Among a Diverse Population of Older Adults, June 2021-February 2022
Introduction COVID-19 vaccination rates remain suboptimal in the United States. Clinicians and policymakers need to better understand how likely vaccine-hesitant individuals are to ultimately accept vaccination and what is associated with such changes. This study’s aims were to 1) describe changes between vaccine intentions and actual uptake from June 2021 through February 2022, and 2) identify modifiable factors associated with vaccine uptake among those with initial hesitancy. Methods This cohort study included a stratified random sample of adults aged 65 years and older in an integrated health care system. The survey, conducted June through August 2021, elicited intent and perceptions regarding COVID-19 vaccination. Subsequent vaccine uptake through February 2022 was analyzed using electronic health records. Results Of 1195 individuals surveyed, 66% responded; 213 reported not yet having received a COVID-19 vaccine and were further analyzed. At baseline, most individuals said they would definitely not (42%) or probably not (5%) get the COVID-19 vaccine or were not sure (26%). During follow-up, 61 individuals (29%) were vaccinated, including 19% of those who initially said they would definitely not be vaccinated. Among vaccine-hesitant individuals, the rate of vaccination was highest for those who initially considered COVID-19 less dangerous than the vaccine (46%) or named short-term side effects (36%) as their most important concern. Conclusions COVID-19 vaccine intent among older adults was malleable during the pandemic’s second year, even among those who initially said they would definitely not be vaccinated. Vaccine uptake could be enhanced by increasing awareness of COVID-19 risks and by addressing vaccine side effects.
Authors: Durojaiye, Cimone; Prausnitz, Stephanie; Elkin, Eric P; Escobar, Patricia; Finn, Lucy; Chen, Yi-Fen Irene; Lieu, Tracy A
Perm J. 2022 Dec 19;26(4):78-84. Epub 2022-10-31.
Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes – a prospective study
Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003). Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.
Authors: Yang, Jiaxi; Zhu, Yeyi; Zhang, Cuilin; et al.
Am J Clin Nutr. 2022 Dec 19;116(6):1693-1703.
Physical activity and individual plasma phospholipid saturated fatty acids in pregnancy, a longitudinal study among a multiracial/multiethnic cohort in the United States
Circulating individual SFAs in pregnant females are critical for maternal and fetal health. However, research on identifying their modifiable factors is limited. We aimed to examine the associations of total physical activity (PA) and types of PA with circulating individual SFAs during pregnancy in a multiracial/multiethnic cohort of pregnant females in the United States. The study included participants in a nested case-control study (n = 321) from the Eunice Kennedy Shriver NICHD Fetal Growth Studies-Singleton Cohort. Sampling weights were applied, so the results represented the entire Fetal Growth Cohort. Plasma phospholipid SFAs were measured at 4 visits [10-14 (visit 1), 15-26 (visit 2), 23-31 (visit 3), and 33-39 (visit 4) weeks of gestation] throughout pregnancy. PA of the previous year at visit 1 and since the previous visit at the subsequent visits was assessed using the validated Pregnancy PA Questionnaire. Time-specific and longitudinal associations were examined using multivariable linear and generalized estimating equation models. Total PA (metabolic equivalent of task-h/wk) was positively associated with circulating heptadecanoic acid (17:0) at visit 1 (β × 103: 0.07; 95% CI: 0.02, 0.11) and pentadecanoic acid (15:0) at visit 3 (β × 103: 0.09; 95% CI: 0.03, 0.14) independent of sociodemographic, reproductive, pregnancy, and dietary factors. Across the 4 visits, the positive associations with total PA were consistent for pentadecanoic acid (β × 103: 0.06; 95% CI: 0.02, 0.10) and heptadecanoic acid (β × 103: 0.10; 95% CI: 0.06, 0.14). Out of the 4 PA types (i.e., sports/exercise, household/caregiving, transportation, and occupational PA) considered, the magnitude of positive associations was the largest for sports/exercise PA. Our findings suggest that maternal PA is positively associated with circulating pentadecanoic and heptadecanoic acids. The findings warrant confirmation by future studies.This trial was registered at clinicaltrials.gov as NCT00912132.
Authors: Liu, Xinyue; Zhu, Yeyi; Zhang, Cuilin; et al.
Am J Clin Nutr. 2022 Dec 19;116(6):1729-1737.
Examining shortened versions of the Social Responsiveness Scale for use in autism spectrum disorder prediction and as a quantitative trait measure: Results from a validation study of 3-5 year old children
The Social Responsiveness Scale (SRS) is a 65-item measure yielding a continuous score capturing autism-related traits. Scores based on SRS item subsets have been analytically examined but administration of shortened versions has not been evaluated prospectively. The goal of this study was to compare psychometric properties of two shortened versions of the SRS to the full 65-item SRS, in young children from both a clinical and general population setting. Study participants (aged 3-5 years) were drawn from the AJ Drexel Autism Institute clinic (n = 154) and Kaiser Permanente Northern California (n = 201) and block randomized to receive either the 16-item short SRS, a newly developed computer adaptive testing-SRS, or the published full-length SRS. Total scores across the three SRS administration methods were scaled to facilitate comparisons. Scores were plotted to assess distributional properties, while Receiver Operating Characteristic analysis was used to estimate Area Under the Curve (AUC) and address predictive ability. Overall, distributional properties of the three administration methods were highly comparable, with shortened measures demonstrating similar ability to capture the range of the distribution and case non-case separation as the full SRS. In addition, AUC values were high (0.91-0.97) and comparable across the administration methods, though there was evidence of difference in predictive ability across measures for females (AUC for full SRS = 0.99 vs. 0.84 for short). Within individual comparisons of short versus full scores (available only for participants at the general population site) suggested underestimation of actual full SRS scores with the CAT-SRS. Our findings broadly support the construct validity and performance of shortened SRS versions examined here, though the full measure may be needed to more accurately assess traits consistent with ASD diagnosis in females. This work suggests opportunities for collection of ASD-related phenotype in settings where participant burden or feasibility considerations may have otherwise prohibited such measurement.
Authors: Lyall, Kristen; Croen, Lisa A; program collaborators for Environmental influences on Child Health Outcomes,; et al.
JCPP Adv. 2022 Dec;2(4):e12106. Epub 2022-10-05.
Racial/Ethnic Differences in Psychiatric and Medical Diagnoses Among Autistic Adults
Racial/ethnic disparities in access to diagnostic services are pervasive for autistic children. However, a few studies have examined racial/ethnic health disparities among autistic adults, who commonly experience higher rates of health conditions than non-autistic adults. We aimed at examining the intersection of autism and race/ethnicity in association with psychiatric and medical diagnoses. The study population included adult members of Kaiser Permanente Northern California enrolled from 2008 to 2012. We ascertained 1507 adults who had an autism diagnosis documented in their electronic medical records. We sampled a matched control group of adults without an autism diagnosis (N = 15,070) at a 10:1 ratio. Our sample was 46% White, 17% Hispanic, 16% Asian, 7% Black, and 14% other race/ethnicity. We compared health diagnoses (a) between autistic and non-autistic adults within strata of race/ethnicity and (b) across race/ethnicity within strata of autistic and non-autistic adults. Lastly, we examined the interaction between autism and race/ethnicity on both multiplicative and additive scales. Autistic adults were more likely to be diagnosed with most medical and psychiatric conditions compared with their non-autistic counterparts of the same race/ethnicity. Among autistic adults, Black, Hispanic, and Asian adults were less likely to be diagnosed with psychiatric conditions and Black and Hispanic autistic adults were more likely to be diagnosed with obesity than their White counterparts. In interaction models, we found that adults who were Black and autistic were disproportionately less likely to be diagnosed with psychiatric conditions and autoimmune disease and more likely to be diagnosed with hypertension than expected. Health vulnerabilities may be compounded at the intersection of autism and race/ethnicity. Future research should continue to apply an intersectional lens toward understanding and addressing these disparities. Our findings likely underestimate the health disparities that exist in uninsured autistic adults and those living in other parts of the United States. Very few studies have looked at how the combination of a person’s autistic and racial/ethnic identities affects their health in adulthood. Dual experiences of ableism and structural racism may have a larger negative effect on the health of autistic people of color than either one experience alone. It is important to identify potential health disparities so that they can be addressed. We wanted to understand whether autistic adults of color were more likely to be diagnosed with medical and psychiatric conditions than non-autistic and/or White peers. We studied a diverse group of 1507 autistic adults and 15,070 non-autistic adults who all received health care from the same large, health plan in California. We examined electronic health records to determine whether diagnoses of health conditions differed by autism status and race/ethnicity. We then looked at whether autistic people of color were disproportionately diagnosed with these conditions compared with other groups. Within every racial/ethnic group, autistic adults were more likely than non-autistic adults to be diagnosed with most medical and psychiatric conditions. Among the autistic group, Black, Hispanic, and Asian adults were less likely to be diagnosed with psychiatric conditions compared with White adults. We saw similar differences in psychiatric diagnoses by race/ethnicity among non-autistic adults. Further, the diagnostic patterns among adults who were autistic and Black suggested that this group may experience unique difficulties receiving mental health and autoimmune diagnoses. They also may be at a higher risk of hypertension. Previous studies have found racial/ethnic disparities in both mental health and access to health care among autistic children. This study suggests that racial/ethnic disparities, especially in mental health care, may also exist among autistic adults. As a broad social label, race/ethnicity does not tell us much about people’s lived experiences. Future studies should replace race/ethnicity with more useful measures of our social environment, including economic opportunity and experiences of structural racism. In addition, health records may imperfectly represent the actual occurrence of health conditions. For example, we cannot tell from this study whether autistic people of color actually experience fewer psychiatric problems, are less likely to visit the doctor, or are more likely to have their problems missed by doctors. Lastly, because our findings are from an insured population, we have likely underestimated the health disparities that exist among autistic adults who do not have consistent insurance coverage or health care access. We hope this study highlights the need for greater attention to the unique health risks at the intersection of autism and race/ethnicity in adults. Through more research and advocacy, we can increase awareness and understanding of these potential health disparities. This will lead to changes that promote more equal access to health care and greater well-being among autistic people of color.
Authors: Ames, Jennifer L; Morgan, Elizabeth H; Onaiwu, Morénike Giwa; Qian, Yinge; Massolo, Maria L; Croen, Lisa A
Autism Adulthood. 2022 Dec 01;4(4):290-305. Epub 2022-12-13.
Associations of Neighborhood Opportunity and Social Vulnerability With Trajectories of Childhood Body Mass Index and Obesity Among US Children
Physical and social neighborhood attributes may have implications for children’s growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied. To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence. This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022. Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years). BMI (calculated as weight in kilograms divided by length [if aged <2 years] or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (<20th percentile), low (20th percentile to <40th percentile), moderate (40th percentile to <60th percentile), high (60th percentile to <80th percentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI). Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages. In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children.
Authors: Aris, Izzuddin M; Ferrara, Assiamira; Zhu, Yeyi; Program Collaborators for Environmental Influences on Child Health Outcomes,; et al.
JAMA Netw Open. 2022 Dec 01;5(12):e2247957. Epub 2022-12-01.
COVID-19 Pandemic Experiences and Symptoms of Pandemic-Associated Traumatic Stress Among Mothers in the US
The primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown. To identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms. This multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022. The primary exposures were pandemic-associated changes in mothers’ health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators. The primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure. The study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences-one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster. In this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.
Authors: Bastain, Theresa M; Avalos, Lyndsay A; Environmental Influences on Child Health Outcomes Program Collaborators,; et al.
JAMA Netw Open. 2022 Dec 01;5(12):e2247330. Epub 2022-12-01.
Changes in 24-Hour Movement Behaviors From Early to Late Pregnancy in Individuals With Prepregnancy Overweight or Obesity
Understanding how sleep, sedentary behavior (SED), and physical activity (PA) (24-h movement profile) changes across pregnancy in individuals with prepregnancy overweight or obesity and how parity (previous births) impacts these changes can help inform interventions. In 155 participants, movement was measured using wrist-worn accelerometers, and sleep was self-reported in early (8-15 wk) and late (29-38 wk) pregnancy. The 24-hour movement profiles were analyzed using compositional analyses. Nulliparous participants (no previous births) spent 33.95%, 38.14%, 25.32%, and 2.58% of the 24-hour day in early pregnancy in sleep, SED, light-intensity PA, and moderate/vigorous-intensity PA, respectively. Multiparous participants (≥1 previous birth) spent 2.50 percentage points less in SED (mean log-ratio difference = -0.068; 95% confidence interval [CI], -0.129 to -0.009) and 2.73 percentage points more in light-intensity PA (mean log-ratio difference = 0.102; 95% CI, 0.035 to 0.180). From early to late pregnancy, participants decreased the proportion of the 24-hour day spent asleep by 1.67 percentage points (mean log-ratio difference = -0.050; 95% CI, -0.092 to -0.011) and increased light-intensity PA by 1.56 percentage points (mean log-ratio difference = 0.057; 95% CI, 0.003 to 0.108), with no change in other behaviors. Nulliparous and multiparous individuals with prepregnancy overweight or obesity both had high levels of SED, with no change across pregnancy, and may require interventions to reduce SED.
Authors: Badon, Sylvia E; Ferrara, Assiamira; Gabriel, Kelley Pettee; Avalos, Lyndsay A; Hedderson, Monique M
J Phys Act Health. 2022 Dec 01;19(12):842-846. Epub 2022-11-12.
Fibroids and vitamin D: another piece of the puzzle
Authors: Mitro, Susanna D; Waetjen, L Elaine; Hedderson, Monique M
Fertil Steril. 2022 Dec;118(6):1137-1138. Epub 2022-11-04.
Plasma Phospholipids Monounsaturated Fatty Acids and Gestational Diabetes Mellitus: a Longitudinal Study in the NICHD Fetal Growth Studies-Singleton Cohort
Fatty acids (FAs) have been implicated in the development of gestational diabetes mellitus (GDM), but the role of monounsaturated FAs (MUFAs) remains understudied. We investigated the associations of plasma phospholipid MUFAs in early to mid-pregnancy with cardiometabolic biomarkers and GDM risk. From the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (2009-2013), we identified 107 women with GDM according to Carpenter and Coustan criteria and 214 control participants without GDM matched (2:1) on age, race/ethnicity, and gestational week (GW) of blood collection. MUFAs were measured at 10-14, 15-26, 23-31, and 33-39 GWs by gas chromatography mass spectrometry. We found that the concentration of total 18:1 MUFAs was significantly lower among women with GDM than those without GDM at 15-26 GWs. Each SD increment in the level of total 18:1 MUFAs was associated with a 40% lower risk of GDM at 15-26 GWs. Moreover, each SD increment in vaccenic acid (18:1n-7) levels at 10-14 and 15-26 GWs were associated with a 36% and 45% lower risk of GDM, respectively. Our extensive assessments of MUFAs advance our understanding of the unique associations of FA composition with GDM risk, suggesting the potentially beneficial role of MUFAs in GDM pathophysiology.
Authors: Tsoi, Kit Ying; Zhu, Yeyi; Wu, Jing; Sun, Qi; Hinkle, Stefanie N; Li, Ling-Jun; Chen, Zhen; Weir, Natalie L; Tsai, Michael Y; Ma, Ronald Cw; Zhang, Cuilin
Diabetes. 2022 Dec 01;71(12):2707-2715.
The effect of the COVID-19 pandemic on prenatal cannabis use by pre-conception depression and anxiety status
Authors: Avalos, Lyndsay A; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique; Ansley, Deborah; Tucker, Lue-Yen; Conway, Amy; Ettenger, Allison; Goler, Nancy; Young-Wolff, Kelly C
J Affect Disord Rep. 2022 Dec;10:100432. Epub 2022-11-11.
Associations between accelerated parental biologic age, autism spectrum disorder, social traits, and developmental and cognitive outcomes in their children
Parental age is a known risk factor for autism spectrum disorder (ASD), however, studies to identify the biologic changes underpinning this association are limited. In recent years, “epigenetic clock” algorithms have been developed to estimate biologic age and to evaluate how the epigenetic aging impacts health and disease. In this study, we examined the relationship between parental epigenetic aging and their child’s prospective risk of ASD and autism related quantitative traits in the Early Autism Risk Longitudinal Investigation study. Estimates of epigenetic age were computed using three robust clock algorithms and DNA methylation measures from the Infinium HumanMethylation450k platform for maternal blood and paternal blood specimens collected during pregnancy. Epigenetic age acceleration was defined as the residual of regressing chronological age on epigenetic age while accounting for cell type proportions. Multinomial logistic regression and linear regression models were completed adjusting for potential confounders for both maternal epigenetic age acceleration (n = 163) and paternal epigenetic age acceleration (n = 80). We found accelerated epigenetic aging in mothers estimated by Hannum’s clock was significantly associated with lower cognitive ability and function in offspring at 12 months, as measured by Mullen Scales of Early Learning scores (β = -1.66, 95% CI: -3.28, -0.04 for a one-unit increase). We also observed a marginal association between accelerated maternal epigenetic aging by Horvath’s clock and increased odds of ASD in offspring at 36 months of age (aOR = 1.12, 95% CI: 0.99, 1.26). By contrast, fathers accelerated aging was marginally associated with decreased ASD risk in their offspring (aOR = 0.83, 95% CI: 0.68, 1.01). Our findings suggest epigenetic aging could play a role in parental age risks on child brain development.
Authors: Song, Ashley Y; Croen, Lisa A; Ladd-Acosta, Christine; et al.
Autism Res. 2022 Dec;15(12):2359-2370. Epub 2022-10-03.
Urinary Phenols in Early to Mid-Pregnancy and Risk of Gestational Diabetes: A Longitudinal Study in a Multiracial Cohort
Environmental phenols are ubiquitous endocrine disruptors and putatively diabetogenic. However, data during pregnancy are scant. We investigated the prospective associations between pregnancy phenol concentrations and gestational diabetes mellitus (GDM) risk. In a nested matched case-control study of 111 individuals with GDM and 222 individuals without GDM within the prospective PETALS cohort, urinary bisphenol A (BPA), BPA substitutes (bisphenol F and bisphenol S [BPS]), benzophenone-3, and triclosan were quantified during the first and second trimesters. Cumulative concentrations across the two times were calculated using the area under the curve (AUC). Multivariable conditional logistic regression examined the association of individual phenols with GDM risk. We conducted mixture analysis using Bayesian kernel machine regression. We a priori examined effect modification by Asian/Pacific Islander (A/PI) race/ethnicity resulting from the case-control matching and highest GDM prevalence among A/PIs. Overall, first-trimester urinary BPS was positively associated with increased risk of GDM (adjusted odds ratio comparing highest vs. lowest tertile [aORT3 vs. T1] 2.12 [95% CI 1.00-4.50]). We identified associations among non-A/Ps, who had higher phenol concentrations than A/PIs. Among non-A/PIs, first-trimester BPA, BPS, and triclosan were positively associated with GDM risk (aORT3 vs. T1 2.91 [95% CI 1.05-8.02], 4.60 [1.55-13.70], and 2.88 [1.11-7.45], respectively). Triclosan in the second trimester and AUC were positively associated with GDM risk among non-A/PIs (P < 0.05). In mixture analysis, triclosan was significantly associated with GDM risk. Urinary BPS among all and BPA, BPS, and triclosan among non-A/PIs were associated with GDM risk. Pregnant individuals should be aware of these phenols' potential adverse health effects.
Authors: Zhu, Yeyi; Hedderson, Monique M; Calafat, Antonia M; Alexeeff, Stacey E; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
Diabetes. 2022 Dec 01;71(12):2539-2551.
The clinical burden of extremely preterm birth in a large medical records database in the United States: complications, medication use, and healthcare resource utilization
Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28?weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system. The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3?years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22?weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (?1?year, >1?year and ?2?years, and >2?years and ?3?years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits. A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3?years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3?years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition. The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3?years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term.
Authors: Siffel, Csaba; Hirst, Andrew K; Sarda, Sujata P; Chen, Hong; Ferber, Jeannette; Kuzniewicz, Michael W; Li, De-Kun
J Matern Fetal Neonatal Med. 2022 Dec;35(26):10271-10278. Epub 2022-09-28.
Efficacious lifestyle interventions for appropriate gestational weight gain in women with overweight or obesity set in the health care system: a scoping review
Purpose: Health care systems offer opportunities to scale up interventions for appropriate gestational weight gain (GWG); however, GWG interventions in the health care setting remain largely unavailable to women with overweight or obesity. To inform the translation of efficacious lifestyle interventions to health care delivery systems, this scoping review aimed to systematically identify randomized controlled trials for appropriate GWG in women with overweight or obesity that were set in a health care system.Methods: A scoping review allows for the systematic synthesis of knowledge on an exploratory research question aimed at mapping key concepts (e.g. time, location, source, and evidence) and gaps in a specific area of study. The Colquhoun et al. (2014) framework to conducting scoping reviews was used to develop the research question, identify relevant studies, select studies, extract data, and synthesize data. Specifically, two reviewers searched publication databases for English-language articles published from January 2009 to May 2020 using specific keywords/MeSH terms.Results: Eight peer-reviewed journal articles were identified; six trials were based in Europe and two in the U.S. Only four included lifestyle interventions that were efficacious in reducing GWG. Three trials with efficacious interventions were among women with obesity only and encouraged them to gain at or below the lower limit for total GWG (i.e. ≤5 kg) of the Institute of Medicine (IOM) guidelines. The fourth was among women with overweight or obesity and encouraged women to gain within the IOM guidelines with a telehealth behavioral intervention. Efficacious interventions were initiated in the first half of pregnancy and included frequent contact delivered through multiple modalities (i.e. in-person visits, telephone calls, text messages, email) by trained intervention staff (i.e. dietitian, lifestyle coach, and/or physiotherapist). Only one efficacious intervention trial briefly mentioned theoretical components for health promotion (e.g. self-monitoring); likewise, only one included cost-effectiveness analyses.Conclusions: This review systematically identified randomized controlled trials of efficacious lifestyle interventions (i.e. consisting of diet and physical activity components) for appropriate GWG in women with overweight or obesity that were set in the health care system and delivered by non-clinicians. Translation efforts could draw upon aspects of the efficacious lifestyle interventions described in this review. Future studies should examine theory-based telehealth interventions and cost-effectiveness.
Authors: Barroso, Cristina S; Yockey, Andrew; Degon, Emoni; Gautam Poudel, Pragya; Brown, Susan D; Hedderson, Monique M; Moreno-Hunt, Carey; Ehrlich, Samantha F
J Matern Fetal Neonatal Med. 2022 Dec;35(25):6411-6424. Epub 2021-05-25.
Antepartum and intrapartum stillbirth rates across gestation: a cross-sectional study using the revised foetal death reporting system in the U.S
There is a renewed call to address preventable foetal deaths in high-income countries, especially where progress has been slow. The Centers for Disease Control and Prevention released publicly, for the first time, the initiating cause and estimated timing of foetal deaths in 2014. The objective of this study is to describe risk and characteristics of antepartum versus intrapartum stillbirths in the U.S., and frequency of pathological examination to determine cause. We conducted a cross-sectional study of singleton births (24-43 weeks) using 2014 U.S. Fetal Death and Natality data available from the National Center for Health Statistics. The primary outcome was timing of death (antepartum (n = 6200), intrapartum (n = 453), and unknown (n = 5403)). Risk factors of interest included maternal sociodemographic, behavioural, medical and obstetric factors, along with foetal sex. We estimated gestational week-specific stillbirth hazard, risk factors for intrapartum versus antepartum stillbirth using multivariable log-binomial regression models, conditional probabilities of intrapartum and antepartum stillbirth at each gestational week, and frequency of pathological examination by timing of death. The gestational age-specific stillbirth hazard was approximately 2 per 10,000 foetus-weeks among preterm gestations and > 3 per 10,000 foetus-weeks among term gestations. Both antepartum and intrapartum stillbirth risk increased in late-term and post-term gestations. The risk of intrapartum versus antepartum stillbirth was higher among those without a prior live birth, relative to those with at least one prior live birth (RR 1.32; 95% CI 1.08-1.61) and those with gestational hypertension, relative to those with no report of gestational hypertension (RR 1.47; 95% CI 1.09-1.96), and lower among Black, relative to white, individuals (RR 0.70; 95% CI 0.55-0.89). Pathological examination was not performed/planned in 25% of known antepartum stillbirths and 29% of known intrapartum stillbirths. These findings suggest greater stillbirth risk in the late-term and post-term periods. Primiparous mothers had greater risk of intrapartum than antepartum still birth, suggesting the need for intrapartum interventions for primiparous mothers in this phase of pregnancy to prevent some intrapartum foetal deaths. Efforts are needed to improve understanding, prevention and investigation of foetal deaths as well as improve stillbirth data quality and completeness in the United States.
Authors: Ncube, Collette N; McCormick, Sarah M; Badon, Sylvia E; Riley, Taylor; Souter, Vivienne L
BMC Pregnancy Childbirth. 2022 Nov 29;22(1):885. Epub 2022-11-29.
Association between Quality of Maternal Prenatal Food Source and Preparation and Breastfeeding Duration in the Environmental Influences on Child Health Outcome (ECHO) Program
This study examined the relationship between maternal food source and preparation during pregnancy and the duration of breastfeeding among 751 mother-child dyads in the United States. The data collected from the Environmental influences on Child Health Outcomes (ECHO) Program included twelve cohorts of mothers (age ≥ 18) who delivered infant(s). Three categories of maternal food source and preparation including, High, Moderate, or Low Food Source Quality were derived from the mother report. The mean duration of breastfeeding differed strongly across the three categories. The High Food Source Quality group breastfed an average of 41 weeks, while shorter durations were observed for the Moderate (26 weeks) and Low (16 weeks) Food Source Quality groups. Cox proportional hazards models were used to estimate the relative hazard of time to breastfeeding cessation for each participant characteristic. The full model adjusted for clustering/cohort effect for all participant characteristics, while the final model adjusted for the subset of characteristics identified from variable reduction modeling. The hazard of breastfeeding cessation for those in the High Food Source Quality group was 24% less than the Moderate group (RH = 0.76; 95% CI, 0.63-0.92). Pregnant women in the High Food Source Quality group breastfed longer than the Moderate and Low groups. We encourage more detailed studies in the future to examine this relationship longitudinally.
Authors: Zimmerman, Emily; Zhu, Yeyi; On Behalf Of Program Collaborators For Environmental Influences On Child Health Outcomes,; et al.
Nutrients. 2022 Nov 21;14(22). Epub 2022-11-21.
Association of serum folate levels during pregnancy and prenatal depression
To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control’s Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR]?=?1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Caan, Bette; Sujan, Ayesha C; Uriu-Adams, Janet Y; Li, De-Kun; Quesenberry, Charles P; Hedderson, Monique M
J Matern Fetal Neonatal Med. 2023 Dec;36(1):1-4. Epub 2022-11-17.
Medically Attended Influenza During Pregnancy in the 2019-2020 and 2020-2021 Influenza Seasons
Influenza testing and case-confirmation rates in pregnant populations have not been reported during the coronavirus disease 2019 (COVID-19) pandemic. Using electronic medical record data from a cohort of nearly 20,000 pregnancies in the United States, this retrospective cohort study examines the frequency of acute respiratory or febrile illness encounters, influenza testing, and influenza positivity during the 2020-2021 influenza season, which occurred during the COVID-19 pandemic, compared with the 2019-2020 influenza season, which largely did not. The ratios of influenza tests to acute respiratory or febrile illness visits were similar in the 2019-2020 and 2020-2021 influenza seasons (approximately 1:8 and 1:9, respectively) but were low and varied by study site. Although influenza testing in pregnant patients continued in the 2020-2021 season, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulation was widespread in the United States, no cases of influenza were identified in our study cohort.
Authors: Irving, Stephanie A; Li, De-Kun; Naleway, Allison L; et al.
Obstet Gynecol. 2022 11 01;140(5):874-877. Epub 2022-10-05.
Geographic Accessibility of Retail Cannabis in Northern California and Prenatal Cannabis Use During the COVID-19 Pandemic
Prenatal cannabis use is associated with health risks for mothers and their children. Prior research suggests that rates of prenatal cannabis use in Northern California increased during the COVID-19 pandemic, but it is unknown whether increases varied with the local cannabis retail and policy environment. To test whether pandemic-related increases in prenatal cannabis use were greater among pregnant individuals with greater retail availability of cannabis around their homes or among those living in jurisdictions that allowed storefront retailers. A cross-sectional, population-based time series study used data from pregnancies in the Kaiser Permanente Northern California health care system screened for cannabis use before (January 1, 2019, to March 31, 2020) and during (April 1 to December 31, 2020) the early COVID-19 pandemic. Proximity to the nearest retailer and number of retailers within a 15-minute drive from one’s home and local cannabis storefront retailer policy (banned vs permitted) were calculated. Interrupted time series models were fit using multiplicative and additive Poisson regression, adjusting for age and race and ethnicity. The COVID-19 pandemic. Prenatal cannabis use based on universal urine toxicology tests conducted during early pregnancy at entrance to prenatal care. The sample (n = 99 127 pregnancies) included 26.2% Asian or Pacific Islander, 6.8% Black, 27.6% Hispanic, 34.4% non-Hispanic White, and 4.9% other, unknown, or multiracial individuals, with a mean (SD) age of 30.8 (5.3) years. Prenatal cannabis use before (6.8%) and during (8.2%) the pandemic was associated with closer proximity to a retailer, greater retailer density, and residing in a jurisdiction that permitted vs banned retailers. There was a greater absolute increase in cannabis use from before to during the pandemic among those within a 10-minute drive (<10 minutes: adjusted rate difference [aRD], 0.93 cases/100 patients; 95% CI, 0.56-1.29 cases/100 patients; ≥10 minutes: aRD, 0.40 cases/100 patients; 95% CI, 0.12-0.68 cases/100 patients; interaction P = .02). Otherwise, relative and absolute rates increased similarly across categories of cannabis retailer proximity/density and local policy (interaction P > .05). Prenatal cannabis use was more common among individuals living in areas with greater retail availability of cannabis. Although relative rates increased similarly during the pandemic regardless of local cannabis retail and policy environment, there was a larger absolute increase associated with living closer to a storefront cannabis retailer. Continued monitoring of local cannabis policy, the retail environment, and prenatal cannabis use is needed.
Authors: Young-Wolff, Kelly C; Alexeeff, Stacey E; Campbell, Cynthia I; Avalos, Lyndsay A; et al.
JAMA Netw Open. 2022 Nov 01;5(11):e2244086. Epub 2022-11-01.
Time to positivity of blood cultures in neonatal late-onset bacteraemia
To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours. Retrospective cohort study. 16 birth centres in two healthcare systems. Infants with positive blood cultures obtained >72 hours after birth. The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours. Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia. Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.
Authors: Mukhopadhyay, Sagori; Briker, Sara M; Flannery, Dustin D; Dhudasia, Miren B; Coggins, Sarah A; Woodford, Emily; Walsh, Eileen M; Li, Sherian; Puopolo, Karen M; Kuzniewicz, Michael W
Arch Dis Child Fetal Neonatal Ed. 2022 Nov;107(6):583-588. Epub 2022-03-10.
Peri-Pregnancy Cannabis Use and Autism Spectrum Disorder in the Offspring: Findings from the Study to Explore Early Development
The association of autism spectrum disorder (ASD) with self-reported maternal cannabis use from 3 months pre-conception to delivery (“peri-pregnancy”) was assessed in children aged 30-68 months, born 2003 to 2011. Children with ASD (N = 1428) were compared to children with other developmental delays/disorders (DD, N = 1198) and population controls (POP, N = 1628). Peri-pregnancy cannabis use was reported for 5.2% of ASD, 3.2% of DD and 4.4% of POP children. Adjusted odds of peri-pregnancy cannabis use did not differ significantly between ASD cases and DD or POP controls. Results were similar for any use during pregnancy. However, given potential risks suggested by underlying neurobiology and animal models, further studies in more recent cohorts, in which cannabis use and perception may have changed, are needed.
Authors: DiGuiseppi, Carolyn; Daniels, Julie L; Robinson Rosenberg, Cordelia; et al.
J Autism Dev Disord. 2022 Nov;52(11):5064-5071. Epub 2021-11-12.
Patterns of Substance Use During Early Pregnancy and Associations With Behavioral Health Characteristics
The aims of the study are to identify patterns of early pregnancy substance use and to examine how these patterns relate to behavioral health conditions measured in early pregnancy. We conducted a retrospective observational study (N= 265,274 pregnancies) screened for alcohol, cannabis, nicotine, pharmaceutical opioids, and stimulants during the first trimester via self-report and urine toxicology tests in Kaiser Permanente Northern California from January 1, 2012, to December 31, 2019. To identify patterns of prenatal substance use, we conducted latent class analysis. We then calculated the prevalence of depression, anxiety, intimate partner violence, and family drug use history for each prenatal substance use group and compared the prevalences by estimating prevalence ratios using modified Poisson regression, adjusting for sociodemographic characteristics. We identified the following 4 latent groups with different patterns of substance use: (a) predominantly alcohol and no other substances (9.30%), (b) predominantly cannabis and no other substances (4.88%), (c) predominantly nicotine and some pharmaceutical opioids (1.09%), and (d) high-polysubstance (alcohol, cannabis, nicotine, and stimulants; 0.36%); these pregnancies were compared with (e) no prenatal substance use (84.37%). The prevalence of all behavioral health conditions was elevated in all prenatal substance use groups compared with the no substance use group. Furthermore, the prevalence of depressive and anxiety disorders, intimate partner violence and family drug use history were greater in the high-polysubstance cluster than the alcohol and cannabis clusters. Results highlight the importance of screening and interventions for all types of substance use during early pregnancy and suggest a particularly high need to prioritize targeting early interventions to pregnant and reproductive age individuals with polysubstance use.
Authors: Sujan, Ayesha C; Alexeeff, Stacey E; Slama, Natalie; Avalos, Lyndsay A; Adams, Sara R; Conway, Amy; Ansley, Deborah; Young-Wolff, Kelly C
J Addict Med. 2022 Oct 18.
Reconciling Between Medication Orders and Medication Fills for Lupus in Pregnancy
Most studies consider either medications ordered or filled, but not both. Medication underuse based on filling data cannot necessarily be ascribed to patient nonadherence. Using both data sources, we quantified primary medication adherence in a cohort of prevalent systemic lupus erythematosus (SLE) pregnancies. We identified 419 pregnancies in Kaiser Permanente Northern California in patients with prevalent SLE from 2011 to 2020. We calculated the number of physician-initiated orders or pharmacy-initiated reorders during pregnancy and a comparable 9-month window the year before (prepregnancy) and the proportion of orders ever filled and filled within 30 days for hydroxychloroquine (HCQ), azathioprine, and corticosteroids. For pregnancies without an order or reorder, we identified the proportion with previous prescription fills overlapping into the respective study period. New orders for lupus medications were usually filled. HCQ was prescribed most often (45.8% pregnancies) and usually filled (89.7% in prepregnancy, 93.2% during pregnancy). The majority filled within 30 days (80.5% prepregnancy, 83.3% pregnancy). Some pregnancies without new HCQ orders had continuous refills from prior orders; 53% of 2011-2015 pregnancies either had a new order or fill coverage from a previous period, compared to 63.2% of pregnancies delivering in 2016-2019. Corticosteroid fill frequencies were 90.6% in prepregnancy and 83.6% during pregnancy. Fewer patients used azathioprine; however, most new orders were filled (94.3% prepregnancy, 91.7% pregnancy). For azathioprine and corticosteroids, fill rates were modestly higher in prepregnancy compared to pregnancy. We observed that patients have high adherence to filling new orders for lupus medications, such as HCQ and azathioprine, in pregnancy.
Authors: Simard, Julia F; Liu, Emily F; Chakravarty, Eliza; Rector, Amadeia; Cantu, Miranda; Kuo, Daniel Z; Shaw, Gary M; Druzin, Maurice; Weisman, Michael H; Hedderson, Monique M
ACR Open Rheumatol. 2022 Oct 17.
Gestational diabetes mellitus, prenatal maternal depression, and risk for postpartum depression: an Environmental influences on Child Health Outcomes (ECHO) Study
Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. Participants in the current analysis included 5,822 women from the National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.
Authors: Shuffrey, Lauren C; Hedderson, Monique M; Zhu, Yeyi; program collaborators for Environmental influences on Child Health Outcomes,; et al.
BMC Pregnancy Childbirth. 2022 Oct 08;22(1):758. Epub 2022-10-08.
Development and validation of prediction models for gestational diabetes treatment modality using supervised machine learning: a population-based cohort study
Gestational diabetes (GDM) is prevalent and benefits from timely and effective treatment, given the short window to impact glycemic control. Clinicians face major barriers to choosing effectively among treatment modalities [medical nutrition therapy (MNT) with or without pharmacologic treatment (antidiabetic oral agents and/or insulin)]. We investigated whether clinical data at varied stages of pregnancy can predict GDM treatment modality. Among a population-based cohort of 30,474 pregnancies with GDM delivered at Kaiser Permanente Northern California in 2007-2017, we selected those in 2007-2016 as the discovery set and 2017 as the temporal/future validation set. Potential predictors were extracted from electronic health records at different timepoints (levels 1-4): (1) 1-year preconception to the last menstrual period, (2) the last menstrual period to GDM diagnosis, (3) at GDM diagnosis, and (4) 1 week after GDM diagnosis. We compared transparent and ensemble machine learning prediction methods, including least absolute shrinkage and selection operator (LASSO) regression and super learner, containing classification and regression tree, LASSO regression, random forest, and extreme gradient boosting algorithms, to predict risks for pharmacologic treatment beyond MNT. The super learner using levels 1-4 predictors had higher predictability [tenfold cross-validated C-statistic in discovery/validation set: 0.934 (95% CI: 0.931-0.936)/0.815 (0.800-0.829)], compared to levels 1, 1-2, and 1-3 (discovery/validation set C-statistic: 0.683-0.869/0.634-0.754). A simpler, more interpretable model, including timing of GDM diagnosis, diagnostic fasting glucose value, and the status and frequency of glycemic control at fasting during one-week post diagnosis, was developed using tenfold cross-validated logistic regression based on super learner-selected predictors. This model compared to the super learner had only a modest reduction in predictability [discovery/validation set C-statistic: 0.825 (0.820-0.830)/0.798 (95% CI: 0.783-0.813)]. Clinical data demonstrated reasonably high predictability for GDM treatment modality at the time of GDM diagnosis and high predictability at 1-week post GDM diagnosis. These population-based, clinically oriented models may support algorithm-based risk-stratification for treatment modality, inform timely treatment, and catalyze more effective management of GDM.
Authors: Liao, Lauren D; Ferrara, Assiamira; Greenberg, Mara B; Ngo, Amanda L; Feng, Juanran; Zhang, Zhenhua; Bradshaw, Patrick T; Hubbard, Alan E; Zhu, Yeyi
BMC Med. 2022 09 15;20(1):307. Epub 2022-09-15.
Strategies Facilitating Video Visit Implementation by a Medical Group Serving a Diverse Population
IntroductionVideo visits have created new opportunities to enhance access to care, but limited information exists on strategies medical groups can employ to facilitate video visit use by higher-risk patients. Our objective was to identify generalizable strategies to facilitate successful delivery of video visits by systems serving highly diverse patient populations. MethodsThe authors conducted a qualitative study of physicians and staff members in a large group practice with 4.5 million patients with diverse race and ethnicity and socioeconomic status. Semi-structured interviews were conducted between January 2021 and April 2021, with key informants identified via purposive and snowball sampling. Video-recorded interviews were transcribed and analyzed using thematic analysis to identify major themes and subthemes. ResultsThe 42 key informants included regional and medical center leaders, primary care physicians, service managers, and medical assistants. Participants described clinical leadership in technology and multidisciplinary collaboration as crucial to sustained video care adoption. Strategies to facilitate real-time learning included local innovation, rapid communication channels, and psychological safety. The organization offered broad access to frequently updated data reports to help managers and practitioners understand processes, measure performance, and share best practices. Medical assistants and physicians developed new approaches to empathize, tailor interactions with patients, and overcome psychological and technical barriers to connecting via video. ConclusionsKey strategies for sustained video care adoption included clinical leadership articulating its purpose, multidisciplinary collaboration, local innovation, effective data use, empathy, and personalized care. These findings provide a model for how health care systems can foster robust adoption of technologies to serve diverse populations.
Authors: Lieu, Tracy A; Altschuler, Andrea; Hsueh, Loretta; Warton, E Margaret; Levan, Christine; Dixon, Matthew; San, Karen; Awsare, Sameer; Chen, Yi-Fen Irene; Lee, Edward R; Reed, Mary E
Perm J. 2022 Sep 14;26(3):20-29. Epub 2022-07-20.
Racial/ethnic disparities in subjective sleep duration, sleep quality, and sleep disturbances during pregnancy: an ECHO study
In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants’ self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: β = -0.55 [-0.80,-0.31]; T3: β = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: β = 1.92 [1.09,2.75]; T3: β = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: β = 0.22 [0.00004,0.44]; T2: β = 0.61 [0.47,0.76]; T3: β = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: β = -0.5 [-1.0,-0.12]; T3: β = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.
Authors: Lucchini, Maristella; Wright, Rosalind J; Environmental influences on Child Health Outcomes; et al.
Sleep. 2022 Sep 08;45(9).
Glycemic Control Trajectories and Risk of Perinatal Complications Among Individuals With Gestational Diabetes
Glycemic control is the cornerstone of gestational diabetes management. Glycemic control trajectories account for differences in longitudinal patterns throughout pregnancy; however, studies on glycemic control trajectories are scarce. To examine whether glycemic control trajectories from gestational diabetes diagnosis to delivery were associated with differential risk of perinatal complications. This population-based cohort study included individuals with gestational diabetes with longitudinal electronic health record data from preconception to delivery who received prenatal care at Kaiser Permanente Northern California (KPNC) and were enrolled in KPNC’s telemedicine-based gestational diabetes care program between January 2007 and December 2017. Data analysis was conducted from September 2021 to January 2022. Glycemic control trajectories were derived using latent class modeling based on the American Diabetes Association’s recommended self-monitoring of blood glucose measurements. Optimal glycemic control was defined as at least 80% of all measurements meeting the targets at KPNC clinical settings. Multivariable Poisson regression models were used to estimate the associations of glycemic control trajectories with cesarean delivery, preterm birth, shoulder dystocia, large- and small-for-gestational-age, and neonatal intensive care unit admission and stay of 7 days or longer. Among a total of 26 774 individuals (mean [SD] age, 32.9 [5.0] years; 11 196 Asian or Pacific Islander individuals [41.8%], 1083 Black individuals [4.0%], 7500 Hispanic individuals [28.0%], and 6049 White individuals [22.6%]), 4 glycemic control trajectories were identified: stably optimal (10 528 individuals [39.3%]), rapidly improving to optimal (9151 individuals [34.2%]), slowly improving to near-optimal (4161 individuals [15.5%]), and slowly improving to suboptimal (2934 individuals [11.0%]). In multivariable models with the rapidly improving to optimal trajectory group as the reference group, glycemic control trajectories were associated with perinatal complications with a gradient across stably optimal to slowly improving to suboptimal. For individuals in the stably optimal trajectory group, there were lower risks of cesarean delivery (adjusted relative risk [aRR], 0.93 [95% CI, 0.89-0.96]), shoulder dystocia (aRR, 0.75 [95% CI, 0.61-0.92]), large-for-gestational age (aRR, 0.74 [95% CI, 0.69-0.80]), and neonatal intensive care unit admission (aRR, 0.90 [95% CI, 0.83-0.97]), while for patients in the slowly improving to suboptimal glycemic control trajectory group, risks were higher for cesarean delivery (aRR, 1.18 [95% CI, 1.12-1.24]; (P for trend < .001), shoulder dystocia (aRR, 1.41 [95% CI, 1.12-1.78]; P for trend < .001), large-for-gestational-age (aRR, 1.42 [95% CI, 1.31-1.53]; P for trend < .001), and neonatal intensive care unit admission (aRR, 1.33 [95% CI, 1.20-1.47]; P for trend < .001). The risk of small-for-gestational-age was higher in patients in the stably optimal group (aRR, 1.10 [95% CI, 1.02-1.20]) and lower in the slowly improving to suboptimal group (aRR, 0.63 [95% CI, 0.53-0.75]). These findings suggest that slowly improving to near-optimal and slowly improving to suboptimal glycemic control trajectories were associated with increased risk of perinatal complications. Future interventions should help individuals achieve glycemic control early after gestational diabetes diagnosis and throughout pregnancy to decrease the risk of perinatal complications.
Authors: Chehab, Rana F; Ferrara, Assiamira; Greenberg, Mara B; Ngo, Amanda L; Feng, Juanran; Zhu, Yeyi
JAMA Netw Open. 2022 Sep 01;5(9):e2233955. Epub 2022-09-01.
Predicting the Need for Phototherapy After Discharge: Update for 2022 Phototherapy Guidelines
Authors: Kuzniewicz, Michael W; Li, Sherian Xu; McCulloch, Charles E; Newman, Thomas B
Pediatrics. 2022 09 01;150(3).
Changes in BMI During the COVID-19 Pandemic
Experts hypothesized increased weight gain in children associated with the coronavirus disease 2019 (COVID-19) pandemic. Our objective was to evaluate whether the rate of change of child body mass index (BMI) increased during the COVID-19 pandemic compared with prepandemic years. The study population of 1996 children ages 2 to 19 years with at least 1 BMI measure before and during the COVID-19 pandemic was drawn from 38 pediatric cohorts across the United States participating in the Environmental Influences on Child Health Outcomes-wide cohort study. We modeled change in BMI using linear mixed models, adjusting for age, sex, race, ethnicity, maternal education, income, baseline BMI category, and type of BMI measure. Data collection and analysis were approved by the local institutional review board of each institution or by the central Environmental Influences on Child Health Outcomes institutional review board. BMI increased during the COVID-19 pandemic compared with previous years (0.24 higher annual gain in BMI during the pandemic compared with previous years, 95% confidence interval 0.02 to 0.45). Children with BMI in the obese range compared with the healthy weight range were at higher risk for excess BMI gain during the pandemic, whereas children in higher-income households were at decreased risk of BMI gain. One effect of the COVID-19 pandemic is an increase in annual BMI gain during the COVID-19 pandemic compared with the 3 previous years among children in our national cohort. This increased risk among US children may worsen a critical threat to public health and health equity.
Authors: Knapp, Emily A; Hedderson, Monique; Bekelman, Traci A; Chandran, Aruna; et al.
Pediatrics. 2022 09 01;150(3).
Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability
Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) cross the placenta, access the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in the exposed offspring. We previously reported maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1, and YBOX) and that reactivity to nine specific combinations of these proteins (MAR ASD patterns) was predictive of ASD risk. The aim of the current study was to validate the previously identified MAR ASD patterns (CRMP1 + GDA, CRMP1 + CRMP2, NSE + STIP1, CRMP2 + STIP1, LDHA + YBOX, LDHB + YBOX, GDA + YBOX, STIP1 + YBOX, and CRMP1 + STIP1) and their accuracy in predicting ASD risk in a prospective cohort employing maternal samples collected prior to parturition. We used prenatal plasma from mothers of autistic children with or without co-occurring intellectual disability (ASD = 540), intellectual disability without autism (ID = 184) and general population controls (GP = 420) collected by the Early Markers for Autism (EMA) study. We found reactivity to one or more of the nine previously identified MAR ASD patterns in 10% of the ASD group compared with 4% of the ID group and 1% of the GP controls (ASD vs GP: Odds Ratio (OR) = 7.81, 95% Confidence Interval (CI) 3.32 to 22.43; ASD vs ID: OR = 2.77, 95% CI (1.19-7.47)) demonstrating that the MAR ASD patterns are strongly associated with the ASD group and could be used to assess ASD risk prior to symptom onset. The pattern most strongly associated with ASD was CRMP1 + CRMP2 and increased the odds for an ASD diagnosis 16-fold (3.32 to >999.99). In addition, we found that several of these specific MAR ASD patterns were strongly associated with ASD with intellectual disability (ASD + ID) and others associated with ASD without ID (ASD-no ID). Prenatal screening for these MAR patterns may lead to earlier identification of ASD and facilitate access to the appropriate early intervention services based on each child’s needs.
Authors: Ramirez-Celis, Alexandra; Croen, Lisa A; Yoshida, Cathleen K; Alexeeff, Stacey E; Schauer, Joseph; Yolken, Robert H; Ashwood, Paul; Van de Water, Judy
Mol Psychiatry. 2022 Sep;27(9):3760-3767. Epub 2022-05-26.
Ovarian Cystadenomas: Growth Rate and Reliability of Imaging Measurements
To evaluate the growth rate of benign ovarian cystadenomas and the degree of variability in ultrasound measurements. Two independent retrospective cohorts of women found to have benign cystadenomas at surgery were identified. To assess growth rate, ultrasounds on women in a community-based health system were reviewed and the growth rate was determined based on the maximum reported size dimension using a mixed effect model. To assess measurement variability, two radiologists independently measured presurgical adnexal imaging findings for women in a tertiary care referral setting. Interobserver, intra-observer, and intermodality (cine clip versus still images) variability in measurements was determined using correlation coefficients (CC) and Bland-Altman analysis, with the proportion of measurements varying by more than 1 cm calculated. For growth rate assessment, 405 women with 1412 ultrasound examinations were identified. The median growth rate was 0.65 cm/year with mucinous cystadenomas growing faster at 0.83 cm/year compared to 0.51 cm/year for serous cystadenomas (median test P < .0001). To evaluate measurement variability, 75 women were identified with 176 ultrasound studies. The within-subject standard deviations for ultrasound measurements were 0.74 cm for cine clip images and 0.41 cm for static images, with 11% of measurements overall differing by more than 1 cm. Cystadenomas grow on average 0.65 cm/year, which is similar in magnitude to the inherent error observed in measurement on ultrasound, suggesting that repeat ultrasound at intervals of longer than a year will often be needed to accurately assess growth if a cyst represents a benign cystadenoma.
Authors: Suh-Burgmann, Elizabeth; Nakhaei, Masoud; Gupta, Sonia; Brook, Alexander; Hecht, Jonathan; Hung, Yun-Yi; Levine, Deborah
J Ultrasound Med. 2022 Sep;41(9):2157-2167. Epub 2021-11-30.
Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy
Studies in newborns with mild neonatal encephalopathy (mNE) demonstrated normal outcomes, but recent literature suggests otherwise. This retrospective cohort study examined inborn infants between 2014 and 2017. Biochemical and clinical characteristics determined the presence of NE and an encephalopathy score categorized infants as Definite or Possible mNE. An Unexposed control group consisted of newborns not meeting the inclusion criteria. Long-term outcomes assessed included cerebral palsy, seizures, developmental disorder, and motor and speech delay. The association of mNE with seizure disorder by 3 years of age was assessed with logistic regression and developmental disorders with Cox proportional hazards models. Of the 156,501 births, we identified 130 with Definite mNE and 445 with Possible mNE (0.8 and 2.8 per 1000 births, respectively). Both groups had significantly higher rates of any developmental disorder and motor and speech delay when compared to the Unexposed (p < 0.05, except for p = 0.07 for motor delay in the Possible NE group). The Definite mNE group had higher rates of developmental disorder and motor and speech delay when compared to the Unexposed with hazard ratios (95% CI) 2.0 (1.2-3.2), 3.7 (1.5-8.8), and 2.1 (1.3-3.5), respectively. An estimate of short- and long-term consequences of mNE suggests that there may be a higher risk of adverse outcome. Infants with mild NE are at significant risk for adverse short- and long-term outcomes. The risk of having an abnormal long-term outcome at 3 years of age were doubled in the mild NE group compared to the Unexposed group. Randomized clinical trials are needed as neuroprotective strategies may mitigate these.
Authors: Akula, Vishnu-Priya; Sriram, Achyuth; Xu, Sherian; Walsh, Eileen; Van Meurs, Krisa; Cranshaw, Matthew; Kuzniwiecz, Michael
Pediatr Res. 2022 Aug 23.
Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts
Prenatal vitamin use is recommended before and during pregnancies for normal fetal development. Prenatal vitamins do not have a standard formulation, but many contain calcium, folic acid, iodine, iron, omega-3 fatty acids, zinc, and vitamins A, B6, B12, and D, and usually they contain higher concentrations of folic acid and iron than regular multivitamins in the US Nutrient levels can impact epigenetic factors such as DNA methylation, but relationships between maternal prenatal vitamin use and DNA methylation have been relatively understudied. We examined use of prenatal vitamins in the first month of pregnancy in relation to cord blood and placenta DNA methylation in two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk Learning Early Signs (MARBLES) studies. In placenta, prenatal vitamin intake was marginally associated with -0.52% (95% CI -1.04, 0.01) lower mean array-wide DNA methylation in EARLI, and associated with -0.60% (-1.08, -0.13) lower mean array-wide DNA methylation in MARBLES. There was little consistency in the associations between prenatal vitamin intake and single DNA methylation site effect estimates across cohorts and tissues, with only a few overlapping sites with correlated effect estimates. However, the single DNA methylation sites with p-value < 0.01 (EARLI cord nCpGs = 4068, EARLI placenta nCpGs = 3647, MARBLES cord nCpGs = 4068, MARBLES placenta nCpGs = 9563) were consistently enriched in neuronal developmental pathways. Together, our findings suggest that prenatal vitamin intake in the first month of pregnancy may be related to lower placental global DNA methylation and related to DNA methylation in brain-related pathways in both placenta and cord blood.
Authors: Dou, John F; Hertz-Picciotto, Irva; Bakulski, Kelly M; et al.
Epigenetics Chromatin. 2022 Aug 02;15(1):28. Epub 2022-08-02.
In-utero cannabis exposure and long-term psychiatric and neurodevelopmental outcomes: The limitations of existing literature and recommendations for future research
Given increases in cannabis use in pregnancy and animal model research showing effects of in-utero cannabis exposure, high-quality information on long-term consequences of in-utero cannabis exposure in humans is needed. While reviews have summarized findings from observational studies with humans, reviews have not focused on limitations of these studies and recommendations for future research. Therefore, we critically reviewed observational research on in-utero cannabis exposure and psychiatric and neurodevelopmental outcomes measured at or after age 3 and provided recommendations for future research. We used Web of Science, Google Scholar, and work cited from relevant identified publications to identify 46 papers to include in our review. Our review includes two main sections. The first section highlights the extensive limitations of the existing research, which include small and nongeneralizable samples, reliance on self-reported data, lack of detail on timing and amount of exposure, inclusion of older exposure data only, not accounting for important confounders, inclusion of potential mediators as covariates, not including outcome severity measures, and not assessing for offspring sex differences. The second section provides recommendations for future research regarding exposure and outcome measures, sample selection, confounder adjustment, and other methodological considerations. For example, with regard to exposure definition, we recommend that studies quantify the amount of cannabis exposure, evaluate the influence of timing of exposure, and incorporate biological measures (e.g., urine toxicology measures). Given that high-quality information on long-term consequences of in-utero cannabis exposure in humans does not yet exit, it is crucial for future research to address the limitations we have identified.
Authors: Sujan, Ayesha C; Young-Wolff, Kelly C; Avalos, Lyndsay A
Birth Defects Res. 2022 08 01;114(13):689-713. Epub 2022-06-16.
The clinical burden of extremely preterm birth in a large medical records database in the United States: Mortality and survival associated with selected complications
Preterm birth is a leading cause of infant mortality, particularly for those born extremely prematurely (EP; <28 weeks' gestational age [GA]). Survivors are predisposed to complications such as bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). To examine the epidemiology, complications, and mortality/survival among EP infants. Retrospective analysis of electronic medical records from the Kaiser Permanente Northern California database. EP infants live-born between 22 and <28 weeks' GA from 1997 to 2016. Cumulative all-cause mortality/survival were analyzed and stratified by GA (22 to <24, 24 to <26, 26 to <28 weeks), complications (BPD/CLD, IVH, ROP), and birth period (1997 to 2003, 2004 to 2009, 2010 to 2016). Cox proportional hazard models were constructed to assess the mortality risk associated with BPD/CLD or IVH. 2154 EP infants were identified; of these, 916 deaths were recorded. Mortality was highest during the first 3 months (41.7 % cumulative mortality), and few were reported after 2 years (42.5 % cumulative mortality). Mortality decreased with higher GA and over more recent birth periods. BPD/CLD and IVH grade 3/4 were associated with increased mortality risk versus no complications (adjusted hazard ratios 1.41 and 1.78, respectively). The risk of mortality is high during the first few months of life for EP infants, and is even higher for those with BPD and IVH. Despite an overall trend toward increased survival for EP infants, strategies targeting survival of EP infants with these complications are needed.
Authors: Siffel, Csaba; Hirst, Andrew K; Sarda, Sujata P; Kuzniewicz, Michael W; Li, De-Kun
Early Hum Dev. 2022 08;171:105613. Epub 2022-06-22.
Predictive Metabolomic Markers in Early to Mid-Pregnancy for Gestational Diabetes: A Prospective Test and Validation Study
Gestational diabetes mellitus (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (GDM n = 91 and non-GDM n = 180; discovery set), a random PETALS subsample (GDM n = 42 and non-GDM n = 372; validation set 1), and a case-control sample within the GLOW trial (GDM n = 35 and non-GDM n = 70; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined associations between metabolites and GDM. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10-13 and 16-19 for GDM. Purinone metabolites at GW 10-13 and 16-19 and amino acids, amino alcohols, hexoses, indoles, and pyrimidine metabolites at GW 16-19 were positively associated with GDM risk (false discovery rate <0.05). A 17-metabolite panel at GW 10-13 outperformed the model using conventional risk factors, including fasting glycemia (area under the curve: discovery 0.871 vs. 0.742, validation 1 0.869 vs. 0.731, and validation 2 0.972 vs. 0.742; P < 0.01). Similar results were observed with a 13-metabolite panel at GW 17-19. Dysmetabolism is present early in pregnancy among individuals progressing to GDM. Multimetabolite panels in early pregnancy can predict GDM risk beyond conventional risk factors.
Authors: Zhu, Yeyi; Barupal, Dinesh K; Ngo, Amanda L; Quesenberry, Charles P; Feng, Juanran; Fiehn, Oliver; Ferrara, Assiamira
Diabetes. 2022 08 01;71(8):1807-1817.
Health Behavior Changes during the COVID-19 Pandemic: A Longitudinal Analysis among Children
This longitudinal study compared children’s health behaviors before the COVID-19 pandemic versus during the pandemic. This analysis examined the association between individual-level characteristics and health behavior change. Four prospective cohort studies in the Environmental influences on Child Health Outcomes (ECHO) Program contributed data. Children aged 4-12 years and their caregivers were recruited in California, Colorado, North Dakota, and New Hampshire. Dietary intake, physical activity, screen time, and sleep duration were assessed with questionnaires pre-pandemic and during the pandemic. The final sample included 347 children: 47% female and 62% non-Hispanic White. Compared with pre-pandemic, weekday screen time duration was higher during the pandemic (3.0 vs. 4.5 h, p < 0.001). Unadjusted increases in screen time duration differed by race and ethnicity: 1.3 h/day for non-Hispanic White children, 2.3 h/day for Hispanic children, and 5.3 h/day for non-Hispanic Black children. Overall, no changes occurred in sugar-sweetened beverage (SSB) intake (p = 0.26), discretionary food intake (p = 0.93), and physical activity (p = 0.15). Sleep duration increased by 30 min among children who did not meet sleep recommendations pre-pandemic. Child sex and maternal education level were not associated with health behavior change. The pandemic may have exacerbated disparities in some health behaviors. Families may need support to re-establish healthy routines.
Authors: Bekelman, Traci A; Friesen, Kaylyn; Hockett, Christine W; Program Collaborators for Environmental influences on Child Health Outcomes (ECHO),; et al.
Int J Environ Res Public Health. 2022 Jul 28;19(15). Epub 2022-07-28.
Cardiometabolic Pregnancy Complications in Association with Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO
Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.
Authors: Lyall, Kristen; Avalos, Lyndsay A; Croen, Lisa A; Ferrara, Assiamira; Environmental Influences On Child Health Outcomes, On Behalf Of Program Collaborators For; et al.
Am J Epidemiol. 2022 Jul 23;191(8):1407-1419.
Sociodemographic Variation in Children’s Health Behaviors During the COVID-19 Pandemic
Background: Societal changes during the COVID-19 pandemic may affect children’s health behaviors and exacerbate disparities. This study aimed to describe children’s health behaviors during the COVID-19 pandemic, how they vary by sociodemographic characteristics, and the extent to which parent coping strategies mitigate the impact of pandemic-related financial strain on these behaviors. Methods: This study used pooled data from 50 cohorts in the Environmental influences on Child Health Outcomes Program. Children or parent proxies reported sociodemographic characteristics, health behaviors, and parent coping strategies. Results: Of 3315 children aged 3-17 years, 49% were female and 57% were non-Hispanic white. Children of parents who reported food access as a source of stress were 35% less likely to engage in a higher level of physical activity. Children of parents who changed their work schedule to care for their children had 82 fewer min/day of screen time and 13 more min/day of sleep compared with children of parents who maintained their schedule. Parents changing their work schedule were also associated with a 31% lower odds of the child consuming sugar-sweetened beverages. Conclusions: Parents experiencing pandemic-related financial strain may need additional support to promote healthy behaviors. Understanding how changes in parent work schedules support shorter screen time and longer sleep duration can inform future interventions.
Authors: Bekelman, Traci A; Ferrara, Assiamira; Hedderson, Monique M; program collaborators for Environmental influences on Child Health Outcomes (ECHO),; et al.
Child Obes. 2022 Jul 19.
Reach, acceptability, and perceived success of a telehealth diabetes prevention program among racially and ethnically diverse patients with gestational diabetes: the GEM cluster-randomized trial
Patients with gestational diabetes mellitus and from racial/ethnic minority groups face disproportionate risk for type 2 diabetes. Lifestyle interventions, if accessible and acceptable to diverse patients, could advance diabetes prevention and mitigate racial/ethnic disparities. Here we describe overall and race/ethnicity-specific reach, acceptability, and perceived success from an effective telehealth diabetes prevention lifestyle program for patients with gestational diabetes mellitus, implemented in the Gestational Diabetes Effects on Moms (GEM) cluster-randomized controlled trial. GEM tested a program of 13 telephone sessions and behavior change techniques (BCTs, e.g., goal setting) in a healthcare system. We evaluated participation (completing ≥1 session), acceptability of BCTs, and perceived success reaching program goals. Among 1,087 patients (75.2% from minority groups), 50.3% participated. Participation rates were 61.7% among Black, 56.4% among Hispanic, 55.6% among multiracial/other, 53.0% among White, and 43.7% among Asian/Pacific Islander patients. Evaluation survey respondents (n = 433/547; 79.2%) largely rated BCTs as very helpful (range 40.9%-58.4%) or moderately helpful (27.3%-34.9%). Respondents from minority groups largely rated goal setting for weight management as very or moderately helpful, with fewer minority respondents rating it as only a little/not at all helpful than White respondents (p = .02). Black and White respondents reported more limited success reaching a healthy weight than Asian/Pacific Islander, Hispanic, and multiracial/other women (p = .005). A telehealth diabetes prevention lifestyle program demonstrated reach and acceptability across racial/ethnic groups. While perceived success can be improved among Black and White participants, such programs could promote access to preventive care and help mitigate disparities in diabetes risk.
Authors: Brown, Susan D; Hedderson, Monique M; Gordon, Nancy; Albright, Cheryl L; Tsai, Ai-Lin; Quesenberry, Charles P; Ferrara, Assiamira
Transl Behav Med. 2022 Jul 18;12(7):793-799.
Coping strategies for COVID-19 pandemic-related stress and mental health during pregnancy
Increased stress has likely contributed to the observed high prevalence of depression and anxiety in pregnant individuals during the COVID-19 pandemic. The objective of this study was to assess the prevalence of coping strategies for COVID-19 pandemic-related stress and associations of these coping strategies with depression and anxiety symptoms during pregnancy. 8320 members of Kaiser Permanente Northern California who were pregnant between June 22, 2020 and May 10, 2021 completed an online survey including questions about coping strategies since the start of the COVID-19 pandemic and current depression and anxiety symptoms. We used weighted regression to estimate prevalence ratios for moderate/severe depression and anxiety symptom severity associated with coping strategies. The most common coping strategies for COVID-19 pandemic-related stress were talking with friends and family (77%), outdoor physical activity (54%), and increasing screen time activities (52%). Exercising using online programs or videos, outdoor physical activity, talking with friends and family, and engaging in more family activities were associated with 29% to 38% lower prevalence of moderate/severe depression symptom severity and 16% to 34% lower prevalence of moderate/severe anxiety symptom severity. We are unable to rule out reverse temporality as an explanation for the observed results because of the cross-sectional design; depression or anxiety symptom severity may influence use of specific coping strategies. Our results suggest that physical activity and connecting with others are coping strategies for COVID-19 pandemic-related stress that may be associated with better mental health in pregnant individuals.
Authors: Badon, Sylvia E; Croen, Lisa A; Ferrara, Assiamira; Ames, Jennifer L; Hedderson, Monique M; Young-Wolff, Kelly C; Zhu, Yeyi; Avalos, Lyndsay A
J Affect Disord. 2022 Jul 15;309:309-313. Epub 2022-04-28.
Multi-Chain Semi-Markov Analysis of Intrapartum Cardiotocography
Visual assessment of the evolution of fetal heart rate (FHR) and uterine pressure (UP) patterns is the standard of care in the intrapartum period. Unfortunately, this assessment has high levels of intra- and inter-observer variability. This study processed and analyzed FHR and UP patterns using computerized pattern recognition tools. The goal was to evaluate differences in FHR and UP patterns between fetuses with normal outcomes and those who developed hypoxic-ischemic encephalopathy (HIE). For this purpose, we modeled the sequence of FHR patterns and uterine contractions using Multi-Chain Semi-Markov models (MCSMMs). These models estimate the probability of transitioning between FHR or UP patterns and the dwell time of each pattern. Our results showed that in comparison to the control group, the HIE group had: (1) more frequent uterine contractions during the last 12 hours before birth; (2) more frequent FHR decelerations during the last 12 hours before birth; (3) longer decelerations during the last eight hours before birth; and (4) shorter baseline durations during the last five hours before birth. These results demonstrate that the fetuses in the HIE group were subject to a more stressful environment than those in the normal group. Clinical Relevance- Our results revealed statistically significant differences in FHR/UP patterns between the normal and HIE groups in the hours before birth. This indicates that features derived using MCSMMs may be useful in a machine learning framework to detect infants at increased risk of developing HIE allowing preventive interventions.
Authors: Vargas-Calixto, Johann; Wu, Yvonne; Kuzniewicz, Michael; Cornet, Marie-Coralie; Forquer, Heather; Gerstley, Lawrence; Hamilton, Emily; Warrick, Philip A; Kearney, Robert E
Annu Int Conf IEEE Eng Med Biol Soc. 2022 Jul;2022:1948-1952.
Associations between combined exposure to environmental hazards and social stressors at the neighborhood level and individual perinatal outcomes in the ECHO-wide cohort
Limited studies examine how prenatal environmental and social exposures jointly impact perinatal health. Here we investigated relationships between a neighborhood-level combined exposure (CE) index assessed during pregnancy and perinatal outcomes, including birthweight, gestational age, and preterm birth. Across all participants, higher CE index scores were associated with small decreases in birthweight and gestational age. We also observed effect modification by race; infants born to Black pregnant people had a greater risk of preterm birth for higher CE values compared to White infants. Overall, our results suggest that neighborhood social and environmental exposures have a small but measurable joint effect on neonatal indicators of health.
Authors: Martenies, Sheena E; Croen, Lisa A; program collaborators for Environmental influences on Child Health Outcomes,; et al.
Health Place. 2022 07;76:102858. Epub 2022-07-21.
Association Between Prenatal Cannabis Use and Psychotropic Medication Use in Pregnant Patients With Depression and Anxiety
This cross-sectional study examined associations between prenatal cannabis use and prescribed psychotropic medication use among pregnant patients with depression or anxiety in a large, integrated healthcare system. Study patients had a confirmed pregnancy and a depressive or anxiety disorder defined by International Classification of Diseases codes between 2012 and 2018 at Kaiser Permanente Northern California. Patients were screened for prenatal substance use via a self-reported questionnaire and urine toxicology test as part of standard prenatal care. Generalized estimating equation models tested for associations between prenatal cannabis use and any dispensation of antidepressants, benzodiazepines, and hypnotics during gestation. Models were stratified by diagnosis (depression or anxiety) and depression symptom severity. This study included 35,047 pregnancies (32,278 patients; 17.6% aged <25 years, 48.1% non-Hispanic White). Adjusting for patient age, income, race/ethnicity, and depression symptom severity, the 12.6% of patients who screened positive for prenatal cannabis use demonstrated higher odds of prenatal benzodiazepine (adjusted odds ratios [aOR] = 1.40; 95% confidence interval [CI] = 1.20-1.62) and hypnotic (aOR = 1.28; 95% CI = 1.11-1.48), but not antidepressants (aOR = 1.05, 95% CI = 0.96-1.14) use. This pattern persisted when diagnostic groups were examined separately. The odds of prenatal benzodiazepine and hypnotic use associated with prenatal cannabis use were higher among pregnancies with severe depression symptom severity (31.8% of the sample). Among pregnant patients with depression or anxiety, prenatal cannabis use was associated with higher odds of prenatal benzodiazepine and hypnotic use. As patients may be using cannabis to address depression and anxiety, prescribers should remain vigilant for under- or untreated psychiatric symptoms among pregnant patients and provide evidence-based treatments.
Authors: Hirschtritt, Matthew E; Avalos, Lyndsay A; Sarovar, Varada; Ridout, Kathryn K; Goler, Nancy C; Ansley, Deborah R; Satre, Derek D; Young-Wolff, Kelly C
J Addict Med. 2022 Jul-Aug 01;16(4):e269-e273. Epub 2022-01-22.
Maternal Dietary Patterns during Pregnancy and Child Autism-Related Traits: Results from Two US Cohorts
We examined the relationship between maternal intake of established dietary patterns and child autism-related outcomes in two prospective cohorts in the United States. Participants were drawn from the Early Autism Risk Longitudinal Investigation (EARLI, n = 154) and the Nurses’ Health Study II (NHSII, n = 727). Dietary information was collected via food frequency questionnaires (FFQs) and used to calculate the empirical dietary inflammatory pattern (EDIP), Alternative Healthy Eating Index (AHEI), Western and Prudent dietary patterns, and the alternative Mediterranean Diet (aMED) score. Primary analyses examined associations with continuous autism-related traits as measured by the Social Responsiveness Scale (SRS), and secondary analyses with autism spectrum disorder (ASD) diagnosis. We used crude and multivariable quantile regression fixed at the 50th percentile to examine associations between quartiles of dietary patterns and SRS scores, and logistic regression to examine associations with ASD diagnosis. There was suggestion of a positive association with the Western diet (Q4 vs. Q1, ß = 11.19, 95% CI: 3.30, 19.90) in EARLI, though the association was attenuated with adjustment for total energy intake, and no clear associations were observed with other dietary patterns and ASD diagnosis or SRS scores. Further work is needed to better understand the role of maternal dietary patterns in ASD and related outcomes.
Authors: Vecchione, Rachel; Wang, Siwen; Rando, Juliette; Chavarro, Jorge E; Croen, Lisa A; Fallin, M Daniele; Hertz-Picciotto, Irva; Newschaffer, Craig J; Schmidt, Rebecca J; Lyall, Kristen
Nutrients. 2022 Jun 30;14(13). Epub 2022-06-30.
Placental morphology in association with autism-related traits in the EARLI study
In prior work we observed differences in morphology features in placentas from an autism-enriched cohort as compared to those from a general population sample. Here we sought to examine whether these differences associate with ASD-related outcomes in the child. Participants (n = 101) were drawn from the Early Autism Risk Longitudinal Investigation (EARLI), a cohort following younger siblings of children with autism spectrum disorder (ASD). ASD-related outcomes, including the Social Responsiveness Scale (SRS), Mullen Scales of Early Learning (MSEL) Early Learning Composite, and ASD diagnosis, were assessed at age 3. Crude and adjusted linear regression was used to examine associations between placental morphological features (parametrized continuously and in quartiles) and SRS and MSEL scores; comparisons by ASD case status were explored as secondary analyses due to the small number of cases (n = 20). In adjusted analyses, we observed a modest positive association between umbilical cord eccentricity, defined as the ratio of the maximum:minimum radius from the cord insertion point, and SRS scores (Beta = 1.68, 95%CI = 0.45, 2.9). Positive associations were also suggested between placental maximum thickness and cord centrality and SRS scores, though these were estimated with little precision. Associations between other placental morphological features and outcomes were not observed. Our analyses suggested a potential association between umbilical cord features and ASD-related traits, of interest as non-central cord insertion may reflect reduced placenta efficiency. Future studies with larger sample sizes are needed to further examine these and other placental features in association with ASD-related outcomes.
Authors: Zhong, Caichen; Croen, Lisa A; Lyall, Kristen; et al.
BMC Pregnancy Childbirth. 2022 Jun 28;22(1):525. Epub 2022-06-28.
Impaired fasting glucose in pregnancy: improved perinatal outcomes with active glycemic management
To assess the association between active glycemic management and large for gestational age (LGA) neonates and cesarean delivery (CD) among pregnant women with impaired fasting glucose (IFG). Retrospective cohort study using electronic health record data of women with IFG who delivered at Kaiser Permanente Northern California from 2012-2017. IFG was defined as isolated fasting glucose ≥95 mg/dL. Women with gestational diabetes (GDM) or in whom GDM could not be ruled out were excluded. Baseline and treatment characteristics, and pregnancy outcomes were compared among women with IFG who participated in telephonic home glucose monitoring and glycemic management through a centralized standardized program (participants) with those who did not participate (non-participants). The relative risks (RR) of perinatal complications associated with participation versus non-participation were estimated with Poisson regression models. We identified 1,584 women meeting inclusion criteria, of whom 1,151 (72.7%) were participants and 433 (27.3%) were non-participants. There were no differences between groups in baseline characteristics or comorbidities, except for higher mean levels of fasting glucose (FG) at the time of IFG diagnosis in participants than in non-participants (98.9 mg/dL vs 98.0 mg/dL, p=0.01). Participants received hypoglycemic medications more frequently than non-participants (68.2% vs 0.9%, p<0.01). The rate of LGA was significantly lower in participants compared with non-participants (19.1% vs 25.0%, p=0.01). After adjusting for age, race/ethnicity, education, body mass index, and level of FG impairment, the RR for LGA for participants compared with non-participants was 0.68, 95% CI: 0.55-0.84. The risk of cesarean delivery did not differ significantly by participation status, in unadjusted or adjusted analyses. Active standardized glycemic management was associated with a decreased risk of LGA for women with IFG. This finding supports an active glycemic management strategy for patients with IFG during pregnancy to reduce the risk of LGA, similar to GDM management.
Authors: Berglin, Mendy; Anderson, Meredith; Ritterman Weintraub, Miranda; Navalta, Stephanie; Hedderson, Monique; Ferrara, Assiamira; Greenberg, Mara
Am J Perinatol. 2022 Jun 24.
A Web-Based mHealth Intervention With Telephone Support to Increase Physical Activity Among Pregnant Patients With Overweight or Obesity: Feasibility Randomized Controlled Trial
Pregnant patients with overweight or obesity are at high risk for perinatal complications. Excess gestational weight gain (GWG) further exacerbates this risk. Mobile health (mHealth) lifestyle interventions that leverage technology to facilitate self-monitoring and provide just-in-time feedback may motivate behavior change to reduce excess GWG, reduce intervention costs, and increase scalability by improving access. This study aimed to test the acceptability and feasibility of a pilot mHealth lifestyle intervention for pregnant patients with overweight or obesity to promote moderate intensity physical activity (PA), encourage guideline-concordant GWG, and inform the design of a larger pragmatic cluster randomized controlled trial. We conducted a mixed methods acceptability and feasibility randomized controlled trial among pregnant patients with a prepregnancy BMI of 25 to 40 kg/m2. Patients with singletons at 8 to 15 weeks of gestation who were aged ≥21 years and had Wi-Fi access were recruited via email from 2 clinics within Kaiser Permanente Northern California and randomized to receive usual prenatal care or an mHealth lifestyle intervention. Participants in the intervention arm received wireless scales, access to an intervention website, activity trackers to receive automated feedback on weight gain and activity goals, and monthly calls from a lifestyle coach. Surveys and focus groups with intervention participants assessed intervention satisfaction and ways to improve the intervention. PA outcomes were self-assessed using the Pregnancy Physical Activity Questionnaire, and GWG was assessed using electronic health record data for both arms. Overall, 33 patients were randomly assigned to the intervention arm, and 35 patients were randomly assigned to the usual care arm. All participants in the intervention arm weighed themselves at least once a week, compared with 20% (7/35) of the participants in the usual care arm. Participants in the intervention arm wore the activity tracker 6.4 days per week and weighed themselves 5.3 times per week, and 88% (29/33) of them rated the program “good to excellent.” Focus groups found that participants desired more nutrition-related support to help them manage GWG and would have preferred an app instead of a website. Participants in the intervention arm had a 23.46 metabolic equivalent of task hours greater change in total PA per week and a 247.2-minute greater change in moderate intensity PA per week in unadjusted models, but these effects were attenuated in adjusted models (change in total PA: 15.55 metabolic equivalent of task hours per week; change in moderate intensity PA: 199.6 minutes per week). We found no difference in total GWG (mean difference 1.14 kg) compared with usual care. The pilot mHealth lifestyle intervention was feasible, highly acceptable, and promoted self-monitoring. Refined interventions are needed to effectively affect PA and GWG among pregnant patients with overweight or obesity. ClinicalTrials.gov NCT03936283; https://clinicaltrials.gov/ct2/show/NCT03936283.
Authors: Thomas, Tainayah; Xu, Fei; Sridhar, Sneha; Sedgwick, Tali; Nkemere, Linda; Badon, Sylvia E; Quesenberry, Charles; Ferrara, Assiamira; Mandel, Sarah; Brown, Susan D; Hedderson, Monique
JMIR Form Res. 2022 Jun 22;6(6):e33929. Epub 2022-06-22.
Examining associations between prenatal biomarkers of oxidative stress and ASD-related outcomes using quantile regression
We examined associations between prenatal oxidative stress (OS) and child autism-related outcomes. Women with an autistic child were followed through a subsequent pregnancy and that younger sibling’s childhood. Associations between glutathione (GSH), glutathione disulfide (GSSG), 8-oxo-deoxyguanine (8-OHdG), and nitrotyrosine and younger sibling Social Responsiveness Scale (SRS) scores were examined using quantile regression. Increasing GSH:GSSG (suggesting decreasing OS) was associated with minor increases in SRS scores (50th percentile β: 1.78, 95% CI: 0.67, 3.06); no other associations were observed. Results from this cohort with increased risk for autism do not support a strong relationship between OS in late pregnancy and autism-related outcomes. Results may be specific to those with enriched autism risk; future work should consider other timepoints and biomarkers.
Authors: Carey, Meghan E; Croen, Lisa A; Lyall, Kristen; et al.
J Autism Dev Disord. 2022 Jun 09.
Associations between antenatal corticosteroid exposure and neurodevelopment in infants
It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may significantly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised. This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age. In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, third edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions. Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone-exposed and 483 were prednisone-exposed. Dexamethasone was prescribed most often in late pregnancy while prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08-2.18; P=.017). For medication-specific exposure, those exposed versus not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10-2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary significantly between preterm and term infants, singletons and twins, or assisted-reproductive-technology- and spontaneously conceived infants (all P >.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy. In this cohort study, antenatal corticosteroid, particularly dexamethasone exposure, was significantly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.
Authors: Tao, Shiyao; Zhu, Yeyi; CNBC Study Group,; et al.
Am J Obstet Gynecol. 2022 Jun 03.
Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA
Clinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA). Within the context of Gestational Diabetes’ Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974). Overall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67)). Guideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care.
Authors: Brown, Susan D; Hedderson, Monique M; Zhu, Yeyi; Tsai, Ai-Lin; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
BMJ Open Diabetes Res Care. 2022 06;10(3).
Effect of Electronic and Mail Outreach From Primary Care Physicians for COVID-19 Vaccination of Black and Latino Older Adults: A Randomized Clinical Trial
COVID-19 morbidity is highest in Black and Latino older adults. These racial and ethnic groups initially had lower vaccination uptake than others, and rates in Black adults continue to lag. To evaluate the effect of outreach via electronic secure messages and mailings from primary care physicians (PCPs) on COVID-19 vaccination uptake among Black and Latino older adults and to compare the effects of culturally tailored and standard PCP messages. This randomized clinical trial was conducted from March 29 to May 20, 2021, with follow-up surveys through July 31, 2021. Latino and Black individuals aged 65 years and older from 4 Kaiser Permanente Northern California (KPNC) service areas were included. Data were analyzed from May 27, 2021, to September 28, 2021. Individuals who had not received COVID-19 vaccination after previous outreach were randomized to electronic secure message and/or mail outreach from their PCP, similar outreach with additional culturally tailored content, or usual care. Outreach groups were sent a secure message or letter in their PCP’s name, followed by a postcard to those still unvaccinated after 4 weeks. The primary outcome was time to receipt of COVID-19 vaccination during the 8 weeks after initial study outreach. KPNC data were supplemented with state data from external sources. Intervention effects were evaluated via proportional hazards regression. Of 8287 included individuals (mean [SD] age, 72.6 [7.0] years; 4665 [56.3%] women), 2434 (29.4%) were Black, 3782 (45.6%) were Latino and preferred English-language communications, and 2071 (25.0%) were Latino and preferred Spanish-language communications; 2847 participants (34.4%) had a neighborhood deprivation index at the 75th percentile or higher. A total of 2767 participants were randomized to culturally tailored PCP outreach, 2747 participants were randomized to standard PCP outreach, and 2773 participants were randomized to usual care. Culturally tailored PCP outreach led to higher COVID-19 vaccination rates during follow-up compared with usual care (664 participants [24.0%] vs 603 participants [21.7%]; adjusted hazard ratio (aHR), 1.22; 95% CI, 1.09-1.37), as did standard PCP outreach (635 participants [23.1%]; aHR, 1.17; 95% CI, 1.04-1.31). Individuals who were Black (aHR, 1.19; 95% CI, 1.06-1.33), had high neighborhood deprivation (aHR, 1.17; 95% CI, 1.03-1.33), and had medium to high comorbidity scores (aHR, 1.19; 95% CI, 1.09-1.31) were more likely to be vaccinated during follow-up. This randomized clinical trial found that PCP outreach using electronic and mailed messages increased COVID-19 vaccination rates among Black and Latino older adults. ClinicalTrials.gov Identifier: NCT05096026.
Authors: Lieu, Tracy A; Klein, Nicola P; Quesenberry, Charles P; Chen, Yi-Fen Irene; et al.
JAMA Netw Open. 2022 Jun 01;5(6):e2217004. Epub 2022-06-01.
Association of Medical Assistant-Supported Virtual Rooming With Successful Video Visit Connections
Authors: Lieu, Tracy A; Warton, E Margaret; Levan, Christine; San, Karen; Hsueh, Loretta; Awsare, Sameer; Reed, Mary E
JAMA Intern Med. 2022 06 01;182(6):680-682.
What do we know about in-utero antidepressant exposure, and are these medications safe to use during pregnancy?
Authors: Sujan, Ayesha C
Acta Psychiatr Scand. 2022 06;145(6):541-543. Epub 2022-04-20.
Perspectives on Postpartum Diabetes Screening among Patients with Gestational Diabetes in an Integrated Healthcare System
Authors: Glaser, Katherine; Ferrara, Assiamira; Ritchie, Jenna L; Tsai, Ai-Lin; Greenberg, Mara; Quesenberry, Charles P; Brown, Susan D
Am J Obstet Gynecol. 2022 06;226(6):857-859.e1. Epub 2022-02-12.
The Association of Prenatal Vitamins and Folic Acid Supplement Intake with Odds of Autism Spectrum Disorder in a High-Risk Sibling Cohort, the Early Autism Risk Longitudinal Investigation (EARLI)
We examined maternal prenatal vitamin use or supplemental folic acid intake during month one of pregnancy for association with autism spectrum disorder (ASD) in the Early Autism Risk Longitudinal Investigation, an enriched-risk pregnancy cohort. Total folic acid intake was calculated from monthly prenatal vitamins, multivitamins, and other supplement reports. Clinical assessments through age 3 years classified children as ASD (n = 38) or non-ASD (n = 153). In pregnancy month one, prenatal vitamin use (59.7%) was not significantly associated with odds of ASD (OR = 0.70, 95%CI 0.32, 1.53). Sample size was limited and residual confounding was possible. Given the estimated effect sizes in this and previous work, prenatal vitamin intake during early pregnancy could be a clinically useful preventative measure for ASD.
Authors: Brieger, Katharine K; Bakulski, Kelly M; Pearce, Celeste L; Baylin, Ana; Dou, John F; Feinberg, Jason I; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Fallin, M Daniele; Schmidt, Rebecca J
J Autism Dev Disord. 2022 Jun;52(6):2801-2811. Epub 2021-06-10.
Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children
To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy. We used Swedish register-based data to examine associations between maternal-reported use of selective-serotonin reuptake inhibitor (SSRI) and selective serotonin-norepinephrine reuptake inhibitors (SNRI) in pregnancy and diagnosis of neonatal seizures and/or epilepsy in over 1.2 million children. To account for systematic differences between exposed and unexposed children we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression and anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, co-morbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy). Compared with all other children, children of women that reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR]=1.41, 95% confidence interval [CI]=1.03-1.94; hazard ratio [HR]=1.21, 95% CI=1.03-1.43 respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR=1.30, 95% CI=0.94-1.79; HR = 1.13, 95% CI = 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR = 1.10, 95% CI = 0.79-1.53; HR = 0.96, 95% CI = 0.81-1.14). The present study found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children’s risk for neonatal seizures or epilepsy. This study provides Class II evidence that exposure to SSRI/SNRI’s in the first trimester of pregnancy is not associated with an increased incidence of neo-natal seizures/epilepsy.
Authors: Wiggs, Kelsey Kathleen; Sujan, Ayehsa C; Rickert, Martin E; Quinn, Patrick D; Larsson, Henrik; Lichtenstein, Paul; D'Onofrio, Brian M; Oberg, A Sara
Neurology. 2022 May 11.
The Effect of Readmission for Phototherapy on Early Breast Milk Feeding
To estimate the effect of readmission for inpatient phototherapy on parent-reported exclusive and any breast milk feeding at 2-month well-child visits. We performed a retrospective cohort study using electronic health record data. From births at 16 Kaiser Permanente Northern California hospitals (2013-2017), we identified a cohort of infants ≥35 weeks’ gestation with outpatient total serum bilirubin levels ranging from 1 mg/dL below to 2.9 mg/dL above the American Academy of Pediatrics phototherapy threshold at <15 days of age. We compared breast milk feeding at 2-month well-child visits among those readmitted and not readmitted to the hospital for phototherapy, adjusting for bilirubin and other confounding variables. Approximately one-quarter (26.5%) of the cohort (n = 7729) were readmitted for phototherapy. Almost half (48.5%) of the infants who were not readmitted for phototherapy received exclusively breast milk at the 2-month visit compared with slightly fewer infants who were readmitted (42.9%). In both groups of infants, most (82.2% not readmitted and 81.2% readmitted) received any breast milk. Readmission for phototherapy was associated with a lower adjusted risk of exclusive breast milk feeding (adjusted risk ratio 0.90; 95% confidence interval [CI], 0.84 to 0.96), corresponding to a marginal absolute reduction in exclusive breast milk feeding of 5.0% (95% CI, -7.9% to -2.1%). It was not associated with a reduction in any breast milk feeding (adjusted risk ratio, 1.00; 95% CI, 0.97 to 1.02). Infants readmitted for phototherapy were more likely to receive any formula, but no less likely to receive any breast milk at 2-month well-child visits.
Authors: Digitale, Jean C; Chang, Pearl W; Li, Sherian X; Kuzniewicz, Michael W; Newman, Thomas B
Hosp Pediatr. 2022 05 01;12(5):e146-e153.
Prenatal exposure to pesticide residues in the diet in association with child autism-related traits: Results from the EARLI study
Prior work has suggested associations between prenatal exposure to several classes of pesticides and child autism spectrum disorder (ASD). We examined a previously developed pesticide residue burden score (PRBS) and intake of high pesticide residue foods in association with ASD-related traits. Participants were drawn from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 256), a cohort following mothers who previously had a child with ASD through a subsequent pregnancy and that child’s development. ASD-related traits were captured according to total Social Responsiveness Scale (SRS) scores at age 3 (mean raw total SRS score = 35.8). Dietary intake was assessed through a food frequency questionnaire collected during pregnancy. We also incorporated organic intake and fatty foods in modified versions of the PRBS. Associations between high-residue fruit and vegetable intake, the overall PRBS and modified versions of it, and SRS scores were assessed using multivariable linear regression. Overall, we did not observe associations between pesticide residues in foods and ASD-related outcomes, and modified versions of the PRBS yielded similar findings. However, reductions in ASD-related traits were observed with higher overall fruit and vegetable intake (adjusted estimates for Q4 vs. Q1: β -12.76, 95%CI -27.8, 2.3). Thus, findings from this high familial probability cohort did not suggest relationships between pesticide residues in the diet according to the PRBS and ASD-related traits. Beneficial effects of fruit and vegetable intake may influence these relationships. Future work should consider fruit and vegetable intake in association with ASD-related outcomes. LAY SUMMARY: Diet is the main source of exposure to most pesticides in use today. In this study, we examined the relationship between pesticide exposure from residues in the diet during pregnancy and child autism-related traits. We found that these pesticide residues from the diet were not related to child autism-related outcomes at age three. However, higher prenatal fruit and vegetable intake was associated with reductions in child autism-related traits.
Authors: Joyce, Emily E; Chavarro, Jorge E; Rando, Juliette; Song, Ashley Y; Croen, Lisa A; Fallin, M Daniele; Hertz-Picciotto, Irva; Schmidt, Rebecca J; Volk, Heather; Newschaffer, Craig J; Lyall, Kristen
Autism Res. 2022 05;15(5):957-970. Epub 2022-03-08.
Contribution of Maternal Cardiometabolic Risk Factors to Racial-Ethnicity Disparities in Preterm Birth Subtypes
There are recognized racial-ethnic disparities in preterm birth and in maternal cardiometabolic risk factors likely linked to systemic racism. However, it is unclear the extent to which cardiometabolic risk factors contribute to the higher rates of preterm birth among minoritized populations. This study aimed to evaluate racial-ethnic disparities in preterm birth subtypes and the role of maternal cardiometabolic risk factors as mediators of the association between maternal race-ethnicity and preterm birth subtypes. This was a retrospective cohort study of 295,210 singleton live births from 2011 to 2018. Preterm birth subtypes were defined as medically indicated and spontaneous preterm birth. Poisson regression with robust standard errors were used to provide estimates of the relative risks and 95% confidence intervals for preterm birth subtypes. Causal mediation analysis used logistic regression models to estimate the natural direct and natural indirect (mediated) effects of maternal cardiometabolic risk factors. Compared with White individuals, Black, Asian, and Hispanic individuals were at increased risk for having both medically indicated preterm birth (1.45, 1.30-1.61; 1.21, 1.12-1.31; and 1.13, 1.05-1.22, respectively) (risk ratios, 95% confidence intervals, respectively) and spontaneous preterm birth (1.20, 1.08-1.34; 1.34, 1.26-1.43; and 1.16, (1.08-1.23), independent of established risk factors. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs White in separate analyses) and preterm birth subtypes varied by race-ethnicity. Hypertensive disorders mediated 30.1% of the association between Black race-ethnicity and medically indicated preterm birth, but it did not mediate the association for other racial-ethnic groups or for spontaneous preterm birth. Any glucose disorder in pregnancy was a mediator of medically indicated preterm birth and spontaneous preterm birth for Asian (65.8% and 13.9%, respectively) and Hispanic (17.3% and 11.9%) race-ethnicity but not for Black race-ethnicity. Overweight or obesity mediated the association between race-ethnicity and medically indicated preterm birth (15.5% among Black individuals and 25.1% among Hispanic individuals) and spontaneous preterm birth (10.7% among Hispanic individuals) but was not a mediator among Asian individuals. Black, Asian, and Hispanic individuals are at increased risk for preterm birth. Maternal cardiometabolic risk factors partially mediate the associations between race-ethnicity and preterm birth subtypes but the extent varies by race-ethnicity. These findings suggest that strategies that improve and diminish differences in cardiometabolic health between race-ethnicity populations may diminish disparities in preterm birth.
Authors: Hedderson, Monique M; Xu, Fei; Dayo, Olumayowa M; Liu, Emily; Sridhar, Sneha; Lee, Catherine; Greenberg, Mara
Am J Obstet Gynecol MFM. 2022 05;4(3):100608. Epub 2022-03-04.
Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy
Additional research from population-based studies is needed to inform the treatment of SARS-CoV-2 infection during pregnancy and to provide health risk information to pregnant individuals. To assess the risk of perinatal complications associated with SARS-CoV-2 infection and to describe factors associated with hospitalizations. This population-based cohort study included 43 886 pregnant individuals with longitudinal electronic health record data from preconception to delivery who delivered at Kaiser Permanente Northern California between March 1, 2020, and March 16, 2021. Individuals with diagnostic codes for COVID-19 that did not have a confirmatory polymerase chain reaction test for SARS-CoV-2 were excluded. SARS-CoV-2 infection detected by polymerase chain reaction test (from 30 days before conception to 7 days after delivery) as a time varying exposure. Severe maternal morbidity including 21 conditions (eg, acute myocardial infarction, acute renal failure, acute respiratory distress syndrome, and sepsis) that occurred at any time during pregnancy or delivery; preterm birth; pregnancy hypertensive disorders; gestational diabetes; venous thromboembolism (VTE); stillbirth; cesarean delivery; and newborn birth weight and respiratory conditions. Standardized mean differences between individuals with and without SARS-CoV-2 were calculated. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for the association between SARS-CoV-2 infection and perinatal complications and hospitalization and to consider the timing of SARS-CoV-2 infection relative to outcomes. In this study of 43 886 pregnant individuals (mean [SD] age, 30.7 [5.2] years), individuals with a SARS-CoV-2 infection (1332 [3.0%]) were more likely to be younger, Hispanic, multiparous individuals with a higher neighborhood deprivation index and obesity or chronic hypertension. After adjusting for demographic characteristics, comorbidities, and smoking status, individuals with SARS-CoV-2 infection had higher risk for severe maternal morbidity (HR, 2.45; 95% CI, 1.91-3.13), preterm birth (<37 weeks; HR, 2.08; 95% CI, 1.75-2.47), and VTE (HR, 3.08; 95% CI, 1.09-8.74) than individuals without SARS-CoV-2. SARS-CoV-2 infection was also associated with increased risk of medically indicated preterm birth (HR, 2.56; 95% CI, 2.06-3.19); spontaneous preterm birth (HR, 1.61; 95% CI, 1.22-2.13); and early (HR, 2.52; 95% CI, 1.49-4.24), moderate (HR, 2.18; 95% CI, 1.25-3.80), and late (HR, 1.95; 95% CI, 1.61-2.37) preterm birth. Among individuals with SARS-CoV-2 infection, 76 (5.7%) had a hospitalization; pregestational diabetes (HR, 7.03; 95% CI, 2.22-22.2) and Asian or Pacific Islander (HR, 2.33; 95% CI, 1.06-5.11) and Black (HR, 3.14; 95% CI, 1.24-7.93) race and ethnicity were associated with an increased risk of hospitalization. In this cohort study, SARS-CoV-2 infection was associated with increased risk of severe maternal morbidity, preterm birth, and VTE. The study findings inform clinicians and patients about the risk of perinatal complications associated with SARS-CoV-2 infection in pregnancy and support vaccination of pregnant individuals and those planning conception.
Authors: Ferrara, Assiamira; Hedderson, Monique M; Zhu, Yeyi; Avalos, Lyndsay A; Kuzniewicz, Michael W; Myers, Laura C; Ngo, Amanda L; Gunderson, Erica P; Ritchie, Jenna L; Quesenberry, Charles P; Greenberg, Mara
JAMA Intern Med. 2022 05 01;182(5):503-512.
The Autism Intervention Research Network on Physical Health (AIR-P) Research Agenda
In the United States, autistic individuals experience disproportionate physical and mental health challenges relative to non-autistic individuals, including higher rates of co-occurring and chronic conditions and lower physical, social, and psychological health-related quality of life. The Autism Intervention Research Network on Physical Health (AIR-P) is an interdisciplinary, multicenter research network for scientific collaboration and infrastructure that aims to increase the life expectancy and quality of life for autistic individuals, with a focus on underserved or vulnerable populations. The current paper describes the development of the AIR-P Research Agenda. Development of the research agenda involved an iterative and collaborative process between the AIR-P Advisory Board, Steering Committee, and Autistic Researcher Review Board. The methodology consisted of 3 phases: (1) ideation and design, (2) literature review and synthesis; and (3) network engagement. Six core research priorities related to the health of autistic individuals were identified: (1) primary care services and quality, (2) community-based lifestyle interventions, (3) health systems and services, (4) gender, sexuality, and reproductive health, (5) neurology, and (6) genetics. Specific topics within each of these priorities were identified. Four cross-cutting research priorities were also identified: (1) neurodiversity-oriented care, (2) facilitating developmental transitions, (3) methodologically rigorous intervention studies, and (4) addressing health disparities. The AIR-P Research Agenda represents an important step forward for enacting large-scale health-promotion efforts for autistic individuals across the lifespan. This agenda will catalyze autism research in historically underrepresented topic areas while adopting a neurodiversity-oriented approach to health-promotion.
Authors: Kuo AA; Croen LA; Kogan MD; et al.
Pediatrics. 2022 Apr 01;149(Suppl 4).
The Autism Intervention Research Network on Physical Health (AIR-P) Charter
Authors: Kuo, Alice A; Croen, Lisa A; Kogan, Michael D; et al.
Pediatrics. 2022 Apr 01;149(Suppl 4).
Improving the Sexual and Reproductive Health and Health Care of Autistic People
Authors: Graham Holmes L; Ames JL; Massolo ML; Nunez DM; Croen LA
Pediatrics. 2022 Apr 01;149(Suppl 4).
Youth Well-being During the COVID-19 Pandemic
The family stress model proposes economic hardship results in caregiver distress and relational problems, which negatively impact youth outcomes. We extend this model to evaluate the impact of coronavirus disease 2019 pandemic-related family hardships on caregiver and youth stress, and, in turn, youth’s psychological well-being. We also investigate how social supports moderate this relationship. We used 2 samples of cross-sectional survey data collected between May 2020 and May 2021: children aged 2 to 12 years (n = 977) and adolescents aged 11 to 17 years (n = 669). Variables included pandemic-related family hardships, stress, social support, and youth life satisfaction. Data were analyzed using structural equation modeling. Experiencing more pandemic-related family hardships was associated with increased caregiver and youth stress (b = 0.04 to 0.21, SE = 0.01-0.02) and, in turn, decreased youth life satisfaction (b = -0.36 to -0.38, SE = 0.04-0.07). Social connectedness (b^ = 0.11-0.17, SE = 0.04) and family engagement (b^ = 0.12-0.18, SE = 0.05-0.06) had direct positive associations with life satisfaction; for children aged 2 to 12 years, greater family engagement was associated with decreased effect of child stress on life satisfaction (b^ = 0.15, SE = 0.05). For adolescents, females had higher levels of stress compared with males (b^ = 0.40, SE = 0.6), and having anxiety and/or depression was associated with decreased life satisfaction (b^ = -0.24, SE = 0.11). Caregivers and youth who experienced more coronavirus disease 2019 pandemic hardships had higher levels of stress, particularly adolescent females. Although stress negatively impacted life satisfaction across all ages, family engagement was a protective factor for children aged 2 to 12 years, whereas having anxiety and/or depression was a risk factor for adolescents. For all youth, however, being more socially connected and engaged with family promoted life satisfaction.
Authors: Blackwell, Courtney K; Deoni, Sean; Fry, Rebecca C; Wright, Rosalind J; et al.
Pediatrics. 2022 04 01;149(4).
Emotional and Behavioral Problems in Youth with Autism: High Prevalence and Impact on Functioning
Emotional and behavioral problems (EBPs) may co-occur with autism spectrum disorder (ASD) and impair children’s functioning beyond autism symptomatology. We compared the prevalence of EBPs in youths with or without ASD and evaluated their unique contribution to impairment in ASD. We surveyed 1267 children (79.4% boys, mean age: 9.2 years, range: 3-17) recruited at 3 sites in Kaiser Permanente and OCHIN primary care clinical networks, with confirmed International Classification of Diseases-10th ed. diagnosis of ASD (N = 564), asthma (N = 468), or neither (N = 429). Children from the 2 comparison groups were age-matched and sex-matched to the ASD group. EBPs and impairment were measured by the Strengths and Difficulties Questionnaire and autism symptomatology by the Social Responsiveness Scale in the ASD group only. EBPs and impairment mean scores were significantly (p < 0.001) higher in participants with ASD compared with children from the 2 comparison groups, across sexes and age groups, with no significant difference between the asthma and control groups. Among children with ASD, both EBPs and autistic symptoms were significantly correlated with impairment (r = 0.64 and r = 0.65, respectively) and explained a significant proportion of impairment variance (R2 = 0.525; p < 0.001) in multiple linear regression. In the relative importance analysis, EBPs and autistic symptoms explained comparable proportions of impairment variance (46% and 52%, respectively) with no significant difference between their relative weights (mean difference: 0.03; 95% confidence interval: -0.049 to 0.114). Among youth with ASD, high levels of EBPs impair daily functioning as much as autistic symptoms. Systematic detection and management of EBPs may improve functioning and outcomes in youth with ASD.
Authors: Fombonne, Eric; Croen, Lisa A; Bulkley, Joanna E; Varga, Alexandra M; Daida, Yihe G; Hatch, Brigit A; Dickerson, John F; Lynch, Frances L
J Dev Behav Pediatr. 2022 04 01;43(3):140-148. Epub 2021-10-21.
Intrapartum antibiotics and childhood asthma and allergic rhinitis: a retrospective cohort study
This study aimed to evaluate the association between intrapartum antibiotics (IABX) and asthma and allergic rhinitis among children by ages 6, 8 and 10 years. Retrospective cohort. Data were collected though Kaiser Permanente Northern California’s (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital between 1997 and 2012 and stayed enrolled through age 6. Modified Poisson regressions with robust error variances were used to estimate risk ratios for IABX and each outcome at each follow-up age during two separate time periods: 1997-2004 (n = 91 739) and 2005-2012 (n = 108 314). Asthma and allergic rhinitis by ages 6, 8 and 10. The proportion of women receiving IABX increased drastically over the study period (from 4% in 1997 to 49% in 2011), while the incidence of asthma (8%) and allergic rhinitis (6%) stayed relatively stable. In adjusted models, risk ratios for the association between IABX and asthma and allergic rhinitis were largely compatible with the null, with some slightly elevated risk ratios observed. For births from 1997 to 2004, risk ratios for asthma were 1.08 (95% CI 1.00-1.17) at age 6, 1.05 (95% CI 0.97-1.15) at age 8, and 1.08 (95% CI 0.99-1.18) at age 10. For births from 2005 to 2012, risk ratios were 1.00 (95% CI 0.95-1.04) at age 6, 1.07 (95% CI 1.01-1.12) at age 8, and 1.11 (95% CI 1.03-1.20) at age 10. Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk. Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk.
Authors: Richards, M; Ferber, J; Swor, E; Frescholtz, T; Li, D-K; Darrow, L A
BJOG. 2022 Apr;129(5):722-730. Epub 2021-11-08.
Associations between infant growth and pubertal onset timing in a multiethnic prospective cohort of girls
Early puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche), pubic hair development (pubarche), and menarche in girls. A prospective cohort of girls born at a Kaiser Permanente Northern California medical facility in 2005-11 was used. Weight-for-age z-scores were calculated at birth and 24 months. Difference in z-scores greater than 0.67 represent rapid “catch-up” growth, less than -0.67 represent delayed “catch-down” growth, and between -0.67 and 0.67 represent “normal” growth. Pubertal onset was measured using clinician-assessed sexual maturity ratings (SMRs) and defined as the age at transition from SMR 1 to SMR 2 + for both thelarche and pubarche. SMR data was collected through June 2020. Menarche was analyzed as a secondary outcome. Weibull and modified Poisson regression models were used. Models were adjusted for potential confounders. There were 15,196 girls included in the study. Approximately 30.2% experienced catch-up growth, 25.8% experienced catch-down growth, and 44% had normal growth. Girls with catch-up growth had increased risk of earlier thelarche (hazard ratio = 1.26, 95% confidence interval (CI): 1.18, 1.35), pubarche (1.38, 95% CI: 1.28, 1.48), and menarche (< 12y, relative risk = 1.52, 95% CI: 1.36, 1.69) compared to those with normal growth, after adjusting for covariates. These associations were partially mediated by childhood body mass index. Catch-down growth was associated with later pubertal onset. Girls who experience infant catch-up growth have higher risk of earlier pubertal development compared to girls with normal growth and the associations are partially explained by childhood obesity. This information may help clinicians to monitor girls who are at high risk of developing earlier.
Authors: Aghaee, Sara; Quesenberry, Charles P; Deardorff, Julianna; Kushi, Lawrence H; Greenspan, Louise C; Ferrara, Assiamira; Kubo, Ai
BMC Pediatr. 2022 Mar 31;22(1):171. Epub 2022-03-31.
A retrospective, observational study on medication for opioid use disorder during pregnancy and risk for neonatal abstinence syndrome
The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS). In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine. Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant. Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS. Medications for opioid use disorder (MOUD), such as buprenorphine and methadone, are effective in reducing the significant harms associated with untreated opioid use disorder (OUD) in nonpregnant and pregnant adults. While previous research clearly documents that the risks of MOUD in pregnancy are less than the risks of untreated OUD in pregnancy, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of methadone and buprenorphine. In a clinical sample of infants born to women with OUD, we showed that buprenorphine-exposed infants were at significantly reduced risk for neonatal abstinence syndrome compared with methadone-exposed infants. Our study adds to the growing body of evidence supporting the use of buprenorphine over methadone for the treatment of OUD among pregnant women.
Authors: Sujan, Ayesha; Cleary, Emma; Douglas, Edie; Aujla, Rubin; Boyars, Lisa; Smith, Claire; Guille, Constance
Fam Pract. 2022 03 24;39(2):311-315.
Association of Glyburide and Subcutaneous Insulin With Perinatal Complications Among Women With Gestational Diabetes
Nearly 30% of individuals with gestational diabetes (GDM) do not achieve glycemic control with lifestyle modification alone and require medication treatment. Oral agents, such as glyburide, have several advantages over insulin for the treatment of GDM, including greater patient acceptance; however, the effectiveness of glyburide for the treatment of GDM remains controversial. To compare the perinatal and neonatal outcomes associated with glyburide vs insulin using causal inference methods in a clinical setting with information on glycemic control. The population-based cohort study included patients with GDM who required medication treatment from 2007 to 2017 in Kaiser Permanente Northern California. Machine learning and rigorous casual inference methods with time-varying exposures were used to evaluate associations of exposure to glyburide vs insulin with perinatal outcomes. Data analysis was conducted from March 2018 to July 2017. Time-varying exposure to glyburide vs insulin during pregnancy. Outcomes evaluated separately included neonatal hypoglycemia, jaundice, shoulder dystocia, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, size-for-gestational age, and cesarean delivery. Inverse probability weighting (IPW) estimation was used to separately compare perinatal outcomes between those initiating glyburide and insulin. This approach was combined with Super Learning for propensity score estimation to account for both baseline and time-dependent confounding in both per-protocol (primary) and intention-to-treat (secondary) analyses to evaluate sustained exposure to the same therapy. From 2007 to 2017, 11 321 patients with GDM (mean [SD] age, 32.9 [4.9] years) initiated glyburide or insulin during pregnancy. In multivariate models, the risk of neonatal respiratory distress was 2.03 (95% CI, 0.13-3.92) per 100 births lower and the risk of NICU admission was 3.32 (95% CI, 0.20-6.45) per 100 births lower after continuous exposure to glyburide compared with insulin. There were no statistically significant differences in glyburide vs insulin initiation in risk for neonatal hypoglycemia (0.85 [95% CI, -1.17 to 2.86] per 100 births), jaundice (0.02 [95% CI, -1.46 to 1.51] per 100 births), shoulder dystocia (-1.05 [95% CI, -2.71 to 0.62] per 100 births), or large-for-gestational age categories (-2.75 [95% CI, -6.31 to 0.80] per 100 births). Using data from a clinical setting and contemporary causal inference methods, our findings do not provide evidence of a difference in the outcomes examined between patients with GDM initiating glyburide compared with those initiating insulin.
Authors: Hedderson, Monique M; Badon, Sylvia E; Pimentel, Noel; Xu, Fei; Regenstein, Anne; Ferrara, Assiamira; Neugebauer, Romain
JAMA Netw Open. 2022 03 01;5(3):e225026. Epub 2022-03-01.
Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts
Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child’s risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results.
Authors: Hertz-Picciotto, Irva; Dabelea, Dana; program collaborators for Environmental influences on Child Health Outcomes (ECHO),; et al.
Autism Res. 2022 03;15(3):551-569. Epub 2022-02-24.
Closing Evidence Gaps in Clinical Prevention: A Report From the National Academies of Sciences, Engineering, and Medicine
Authors: Lieu, Tracy A; Wojtowicz, Alexis; Stratton, Kathleen
JAMA. 2022 03 01;327(9):815-816.
Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)
The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate q-value <0.1), near the genes CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead-associated sites were enriched (FDR q-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR q-value <0.1), one of which was near the gene ARID2. Manganese-associated sites were enriched for cellular metabolism pathways (FDR q-value<0.1). Effect estimates for DNA methylation sites associated (p < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.
Authors: Aung, Max T; Croen, Lisa A; Fallin, M Daniele; et al.
Epigenetics. 2022 03;17(3):253-268. Epub 2021-04-02.
Prenatal Cannabis Use Before and During the COVID-19 Pandemic-Reply
Authors: Young-Wolff, Kelly C; Ansley, Deborah; Avalos, Lyndsay A
JAMA. 2022 02 08;327(6):587-588.
Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes
Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women’s Health Study (2012-2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996-2002), we assessed associations of cumulative lactation duration (none, <6 months, 6-12 months, ≥12-24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9-16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0-6, 6-12, 12-24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9-16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.
Authors: Wander, Pandora L; Zhu, Yeyi; Zhang, Cuilin; et al.
Nutrients. 2022 Feb 03;14(3). Epub 2022-02-03.
Longitudinal Associations of Plasma Phospholipid Fatty Acids in Pregnancy with Neonatal Anthropometry: Results from the NICHD Fetal Growth Studies-Singleton Cohort
Despite increasing interest in the health effects of polyunsaturated FAs (PUFAs), their roles in fetal and neonatal growth remain understudied. Within the NICHD Fetal Growth Studies-Singleton Cohort, we prospectively investigated the associations of individual and subclasses of plasma phospholipid PUFAs at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39 with neonatal anthropometric measures as surrogates for fetal growth among 107 women with gestational diabetes mellitus (GDM) and 214 non-GDM controls. Multivariable weighted linear regression models estimated the associations between plasma phospholipid PUFAs and neonatal anthropometric measures. Adjusted beta coefficients for phospholipid docosahexaenoic acid (DHA) per standard deviation (SD) increase at GW 23-31 in association with birthweight z-score, neonatal length, and neonatal fat mass were 0.25 (95% CI: 0.08-0.41), 0.57 (0.11-1.03) cm, and 54.99 (23.57-86.42) g, respectively; all false discovery rates (FDRs) < 0.05. Estimated Δ5-desaturase activity per SD increase at GW 33-39 but not at other time points was positively associated with birthweight z-score: 0.29 (95% CI: 0.08-0.33); neonatal length: 0.61 (0.29-0.94) cm; and neonatal fat mass: 32.59 (8.21-56.96) g; all FDRs < 0.05. Longitudinal analysis showed consistent results. Our findings suggest that mid-to-late pregnancy presented as critical windows for primarily diet-derived DHA and Δ5-desaturase activity in relation to neonatal anthropometric measures.
Authors: Wang E; Zhu Y; Chehab RF; Wu J; Hinkle SN; Weir NL; Bremer AA; Yang J; Chen Z; Tsai MY; Zhang C
Nutrients. 2022 Jan 29;14(3). Epub 2022-01-29.
Respiratory Viral Infections and Infection Prevention Practices among Women with Acute Respiratory Illness during Delivery Hospitalizations during the 2019-2020 Influenza Season
We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. Peripartum respiratory infections may be underrecognized.
Authors: Dawood, Fatimah S; Li, De-Kun; Campbell, Angela P; et al.
J Infect Dis. 2022 01 05;225(1):50-54.
Identifying hypertensive disorders of pregnancy, a comparison of two epidemiologic definitions
Studies of hypertension in pregnancy that use electronic health care data generally identify hypertension using hospital diagnosis codes alone. We sought to compare results from this approach to an approach that included diagnosis codes, antihypertensive medications and blood pressure (BP) values. We conducted a retrospective cohort study of 1,45,739 pregnancies from 2009 to 2014 within an integrated healthcare system. Hypertensive pregnancies were identified using the “BP-Inclusive Definition” if at least one of three criteria were met: (1) two elevated outpatient BPs, (2) antihypertensive medication fill plus an outpatient hypertension diagnosis, or (3) hospital discharge diagnosis for preeclampsia or eclampsia. The “Traditional Definition” considered only delivery hospitalization discharge diagnoses. Outcome event analyses compared rates of preterm delivery and small for gestational age (SGA) between the two definitions. The BP-Inclusive Definition identified 14,225 (9.8%) hypertensive pregnancies while the Traditional Definition identified 13,637 (9.4%); 10,809 women met both definitions. Preterm delivery occurred in 20.9% of BP-Inclusive Definition pregnancies, 21.8% of Traditional Definition pregnancies and 6.6% of non-hypertensive pregnancies; for SGA the numbers were 15.6, 16.3, and 8.6%, respectively (p < 0.001 for all events compared to non-hypertensive pregnancies). Analyses in women meeting only one hypertension definition (21-24% of positive cases) found much lower rates of both preterm delivery and SGA. Prevalence of hypertension in pregnancy was similar between the two study definitions. However, a substantial number of women met only one of the study definitions. Women who met only one of the hypertension definitions had much lower rates of adverse neonatal events than women meeting both definitions.
Authors: Cheetham, T Craig; Avalos, Lyndsay A; Neugebauer, Romain S; Dublin, Sascha; et al.
Front Cardiovasc Med. 2022;9:1006104. Epub 2022-11-23.
Maternal and neonatal outcomes of antihypertensive treatment in pregnancy: A retrospective cohort study
To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. Retrospective cohort study. Kaiser Permanente, a large healthcare system in the United States. Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension. We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.
Authors: Dublin, Sascha; Avalos, Lyndsay A; Neugebauer, Romain S; Badon, Sylvia E; Shortreed, Susan M; et al.
PLoS One. 2022;17(5):e0268284. Epub 2022-05-16.
A longitudinal study on associations of moderate-to-vigorous physical activity with plasma monounsaturated fatty acids in pregnancy
Physical activity (PA) during pregnancy influences women and offspring’s health via fatty acids metabolism. However, studies on associations of PA with plasma monounsaturated fatty acids (MUFAs) across pregnancy are sparse. Thus, our study aimed to examine associations of PA with individual plasma phospholipid MUFAs throughout pregnancy in a prospective and longitudinal study in the United States (US). The study included 318 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons cohort. PA was measured four times: PA reported at 10-14 gestational weeks (GWs) representing PA in the past year, and at 15-26 GWs, 23-31 GWs, and 33-39 GWs representing PA since the last visit. Plasma phospholipid MUFAs were measured at the same four visits as the measurement of PA. Associations between moderate-to-vigorous PA (MVPA) and the total MUFAs and seven individual plasma phospholipid MUFAs (i.e., palmitoleic acid, 18:1n6-9 trans, 18:1n6c, cis-vaccenic acid, oleic acid, eicosenoic acid, and nervonic acid) were assessed at each visit using multivariable linear regression models adjusting for confounders. MVPA (hours/week) reported at 15-26 GWs representing MVPA since the last visit was positively associated with total MUFAs (% of total fatty acids) [adjusted β*102 (standard error (SE)*102) = 10.41 (3.19), P = 0.001] at 15-26 GWs. For individual MUFAs, MVPA reported at 15-26 GWs representing MVPA since the last visit was positively associated with oleic acid [adjusted β*102 (SE*102) = 8.56 (2.65), P = 0.001] and eicosenoic acid [adjusted β*102 (SE*102) = 0.55 (0.20), P = 0.01] at 15-26 GWs. MVPA reported at 23-31 GWs representing MVPA since the last visit was positively associated with palmitoleic acid [adjusted β*102 (SE*102) = 2.24 (0.64), P = 0.001] at 23-31 GWs. MVPA reported at 10-14 GWs and 33-39 GWs was not associated with total or individual MUFAs. We found novel positive associations of MVPA with individual MUFAs, such as oleic acid, eicosenoic acid, and palmitoleic acid, during middle-to-late pregnancy. These findings suggest that MVPA represents a potentially modifiable factor for plasma individual MUFA levels during pregnancy.
Authors: Xia, Tong; Chen, Liwei; Fei, Zhe; Liu, Xinyue; Dai, Jin; Hinkle, Stefanie N; Zhu, Yeyi; Wu, Jing; Weir, Natalie L; Tsai, Michael Y; Zhang, Cuilin
Front Nutr. 2022;9:983418. Epub 2022-10-24.
Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study
Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1-3.2), 2.0 (1.5-2.5), 1.6 (1.2-2.1), and 0.7 (0.5-1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians.
Authors: Hedderson, Monique M; Asgari, Maryam M; Xu, Fei; Quesenberry, Charles P; Sridhar, Sneha; Geier, Jamie; Lemeshow, Adina R
PLoS One. 2022;17(11):e0277469. Epub 2022-11-17.
Prenatal Exposure to Ambient Air Pollution and Epigenetic Aging at Birth in Newborns
In utero air pollution exposure has been associated with adverse birth outcomes, yet effects of air pollutants on regulatory mechanisms in fetal growth and critical windows of vulnerability during pregnancy are not well understood. There is evidence that epigenetic alterations may contribute to these effects. DNA methylation (DNAm) based age estimators have been developed and studied extensively with health outcomes in recent years. Growing literature suggests environmental factors, such as air pollution and smoking, can influence epigenetic aging. However, little is known about the effect of prenatal air pollution exposure on epigenetic aging. In this study, we leveraged existing data on prenatal air pollution exposure and cord blood DNAm from 332 mother-child pairs in the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), two pregnancy cohorts enrolling women who had a previous child diagnosed with autism spectrum disorder, to assess the relationship of prenatal exposure to air pollution and epigenetic aging at birth. DNAm age was computed using existing epigenetic clock algorithms for cord blood tissue-Knight and Bohlin. Epigenetic age acceleration was defined as the residual of regressing chronological gestational age on DNAm age, accounting for cell type proportions. Multivariable linear regression models and distributed lag models (DLMs), adjusting for child sex, maternal race/ethnicity, study sites, year of birth, maternal education, were completed. In the single-pollutant analysis, we observed exposure to PM2.5, PM10, and O3 during preconception period and pregnancy period were associated with decelerated epigenetic aging at birth. For example, pregnancy average PM10 exposure (per 10 unit increase) was associated with epigenetic age deceleration at birth (weeks) for both Knight and Bohlin clocks (β = -0.62, 95% CI: -1.17, -0.06; β = -0.32, 95% CI: -0.63, -0.01, respectively). Weekly DLMs revealed that increasing PM2.5 during the first trimester and second trimester were associated with decelerated epigenetic aging and that increasing PM10 during the preconception period was associated with decelerated epigenetic aging, using the Bohlin clock estimate. Prenatal ambient air pollution exposure, particularly in early and mid-pregnancy, was associated with decelerated epigenetic aging at birth.
Authors: Song, Ashley Y; Feinberg, Jason I; Bakulski, Kelly M; Croen, Lisa A; Fallin, M Daniele; Newschaffer, Craig J; Hertz-Picciotto, Irva; Schmidt, Rebecca J; Ladd-Acosta, Christine; Volk, Heather E
Front Genet. 2022;13:929416. Epub 2022-06-28.
Associations of COVID-19-Related Health, Healthcare and Economic Factors With Prenatal Depression and Anxiety
Objective: This study evaluated whether COVID-19 pandemic-related health, healthcare and economic factors during pregnancy are associated with prenatal depression and anxiety. Methods: We conducted a cross-sectional study of 6,628 pregnant members of Kaiser Permanente Northern California who responded to a survey between 22 June and 30 September 2020. The survey included questions about depression (Patient Health Questionnaire) and anxiety (Generalized Anxiety Disorder) symptoms and COVID-19-related health and healthcare (e.g., had COVID-19) and economic (e.g., food insecurity) factors. Results: Over one third of individuals reported depression (25% mild, 8% moderate, 3% severe) or anxiety (22% mild, 8% moderate, 5% severe) symptoms. In multivariable analyses, COVID-19 during pregnancy, employment with greater risk of COVID-19, distress over changes in prenatal care, job loss, changes in childcare and food insecurity were associated with greater odds of prenatal depression or anxiety. Conclusion: Findings suggest the COVID-19 pandemic may have severe mental health repercussions for pregnant individuals. Support services for pregnant individuals experiencing these COVID-19-related factors and monitoring of those who had moderate/severe prenatal depression and anxiety symptoms during the COVID-19 pandemic is warranted.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Badon, Sylvia E; Young-Wolff, Kelly; Ames, Jennifer; Zhu, Yeyi; Hedderson, Monique M; Ferrara, Assiamira; Zerbo, Ousseny; Greenberg, Mara; Croen, Lisa A
Int J Public Health. 2022;67:1604433. Epub 2022-05-04.
Contributions of COVID-19 Pandemic-Related Stressors to Racial and Ethnic Disparities in Mental Health During Pregnancy
This study aimed to identify racial and ethnic disparities in prenatal mental health and identify COVID-19 pandemic-related health/healthcare and economic contributors to these disparities, using an established framework for disparity investigation. This cross-sectional study includes 10,930 pregnant people at Kaiser Permanente Northern California who completed an online survey between June 22, 2020 and April 28, 2021 on COVID-19 pandemic-related health/healthcare and economic stressors, depression, and anxiety. Self-reported race and ethnicity were extracted from electronic health records. Weighted analyses were used to evaluate the association between racial and ethnic category and prenatal depression and anxiety; the prevalence of each stressor by race and ethnicity; and the relationship between each stressor and prenatal depression and anxiety in each racial and ethnic category. The sample was 22% Asian, 3% Black, 20% Hispanic, 5% Other/Multiracial/Unknown, and 49% White. Compared to White people, Black and Hispanic people had a higher prevalence of prenatal depression (aPR: 1.85, 95% CI: 1.45, 2.35 and aPR: 1.17, 95% CI: 1.00, 1.37, respectively) and anxiety (aPR: 1.71, 95% CI: 1.34, 2.18 and aPR: 1.10, 95% CI: 0.94, 1.29, respectively). Compared to White people, Black and Hispanic people had a higher prevalence of moderate/severe distress due to changes in prenatal care (24 vs. 34 and 31%), and food insecurity (9 vs. 31 and 24%). Among Black and Hispanic people, distress due to changes in prenatal care was associated with a greater prevalence of prenatal depression (aPR: 2.27, 95% CI: 1.41, 3.64 and aPR: 2.76, 95% CI: 2.12, 3.58, respectively) and prenatal anxiety (aPR: 3.00, 95% CI: 1.85, 4.84 and aPR: 2.82, 95% CI: 2.15, 3.71, respectively). Additionally, among Hispanic people, high-risk employment and food insecurity were associated with a greater prevalence of prenatal depression and anxiety. This study identified racial and ethnic disparities in mental health for pregnant Black and Hispanic people. Distress due to prenatal care changes contributed to the observed disparities in prenatal depression and anxiety for Black and Hispanic people and food insecurity additionally contributed to the observed disparities for Hispanic people. Addressing distress due to changes to prenatal care and food insecurity specifically in Black and Hispanic people may help reduce the high burden of poor mental health and reduce observed disparities in these communities.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Zhu, Yeyi; Croen, Lisa A; Young-Wolff, Kelly C; Zerbo, Ousseny; Hedderson, Monique M; Ferrara, Assiamira; Ames, Jennifer L; Badon, Sylvia E
Front Psychiatry. 2022;13:837659. Epub 2022-03-14.
Considering Toxic Chemicals in the Etiology of Autism
Authors: Volk, Heather E; Ames, Jennifer L; Chen, Aimin; Fallin, M Daniele; Hertz-Picciotto, Irva; Halladay, Alycia; Hirtz, Deborah; Lavin, Arthur; Ritz, Beate; Zoeller, Tom; Swanson, Maureen
Pediatrics. 2022 01 01;149(1).
A Nation-Wide Swedish Cohort Study on Early Maternal Age at First Childbirth and Risk for Offspring Deaths, Accidents, and Suicide Attempts
In a sample of over one million Swedish first-born offspring, we examined associations between early maternal age at first childbirth (MAFC; i.e., < 20 and 20-24 vs 25-29 years) and offspring non-accidental deaths, accidental deaths, deaths by suicide, non-fatal accidents, and suicide attempts. We included year of birth and several maternal and paternal characteristics as covariates and conducted maternal cousin comparisons to adjust for unmeasured confounding. Early MAFC (e.g., teenage childbearing) was associated with all outcomes, with the most pronounced risk elevation for accidental deaths [Hazard Ratio (HR) < 20 2.50, 95% confidence interval (CI) 2.23, 2.80], suicides (HR < 20 2.08, 95% CI 1.79, 2.41), and suicide attempts (HR < 20 2.85, 95% CI 2.71, 3.00). Adjusting for covariates and comparing cousins greatly attenuated associations (e.g., accidental deaths HR < 20 1.61, 95% CI 1.22, 2.11; suicides HR < 20 1.01, 95% CI 0.69, 1.47; and suicide attempts HR < 20 1.35, 95% CI 1.19, 1.52). A similar pattern emerged for non-accidental deaths and non-fatal accidents. Therefore, results indicated maternal background factors may be largely responsible for observed associations.
Authors: Sujan, Ayesha C; O'Reilly, Lauren M; Rickert, Martin E; Larsson, Henrik; Lichtenstein, Paul; Oberg, A Sara; D'Onofrio, Brian M
Behav Genet. 2022 01;52(1):38-47. Epub 2021-11-11.
The Role of Childhood Asthma in Obesity Development: A Nationwide U.S. Multi-cohort Study
Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.
Authors: Stratakis, Nikos; Ferrara, Assiamira; Zhu, Yeyi; program collaborators for Environmental influences on Child Health Outcomes,; et al.
Epidemiology. 2022 01 01;33(1):131-140.
Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort
As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10-14, 15-26, 23-31, and 33-39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5-DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (-475 g; 95% CI, -942, -6.79), birthweight z score (-0.39, -0.71, -0.06), and birth length (-1.38 cm, -2.49, -0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.
Authors: Song, Yiqing; Zhu, Yeyi; Zhang, Cuilin; et al.
Metabolites. 2021 Dec 17;11(12). Epub 2021-12-17.
Are you what you eat? Through the lens of prepregnancy plant-based diets and risk of gestational diabetes
Authors: Zhu, Yeyi
Am J Clin Nutr. 2021 12 01;114(6):1892-1893.
Regional and sociodemographic differences in average BMI among US children in the ECHO program
The aim of this study was to describe the association of individual-level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region. This study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex-specific BMI z scores were the outcome. The final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non-Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β = -0.12, 95% CI: -0.19 to -0.05) and West (β = -0.12, 95% CI: -0.20 to -0.04). Compared with non-Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β = 0.09, 95% CI: 0.05 to 0.14) and lower in the South (β = -0.12, 95% CI: -0.16 to -0.08) and West (β = -0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight. Region of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI-related disparities among children.
Authors: Bekelman, Traci A; Ferrara, Assiamira; Program collaborators for Environmental influences on Child Health Outcomes (ECHO),; et al.
Obesity (Silver Spring). 2021 12;29(12):2089-2099. Epub 2021-08-31.
Tooth biomarkers to characterize the temporal dynamics of the fetal and early-life exposome
Teeth have unique histology that make this biomatrix a time-capsule for retrospective exposure analysis of fetal and early life. However, most analytic methods require pulverizing the whole tooth, which eliminates exposure timing information. Further, the range of chemicals and endogenous exposures that can be measured in teeth has yet to be fully characterized. We performed untargeted metabolomics on micro-dissected layers from naturally shed deciduous teeth. Using four liquid-chromatography high-resolution mass spectrometry analytical modes, we profiled small molecules (<1000 Da) from prenatal and postnatal tooth fractions. In addition, we employed linear regression on the tooth fraction pairs from 31 children to identify metabolites that discriminate between prenatal and postnatal exposures. Of over 10,000 features measured in teeth dentin, 390 unique compounds were annotated from 62 chemical classes. The class with the largest number of compounds was carboxylic acids and their derivatives (36%). Of the annotated exogenous metabolites (phthalates, parabens, perfluoroalkyl compounds, and cotinine) and endogenous metabolites (fatty acids, steroids, carnitines, amino acids, and others), 91 are linked to 256 health conditions through published literature. Differential analysis revealed 267 metabolites significantly different between the prenatal and the postnatal tooth fractions (adj. p-value < 0.05, Bonferroni correction), and 21 metabolites exclusive to the prenatal fraction. The prenatal and early postnatal exposome revealed from dental biomarkers represents a broad range of endogenous and exogenous metabolites for a comprehensive characterization in environmental health research. Most importantly, this technology provides a direct window into fetal exposures that is not possible by maternal biomarkers. Indeed, we identified several metabolites exclusively in the prenatal fraction, suggesting unique fetal exposures that are markedly different to postnatal exposures. Expansion of databases that include tooth matrix metabolites will strengthen biological interpretation and shed light on exposures during gestation and early life that may be causally linked with later health conditions.
Authors: Yu, Miao; Croen, Lisa; Petrick, Lauren M; et al.
Environ Int. 2021 12;157:106849. Epub 2021-09-02.
Changes of Plasma Phospholipid Fatty Acids Profiles in Pregnancy in Relation to the Diagnosis and Treatment of Gestational Diabetes Mellitus
Plasma phospholipid fatty acids (FAs) in early and mid-pregnancy have been prospectively related to gestational diabetes mellitus (GDM) risk. Yet, changes of FAs following GDM diagnosis and treatment and their implications for glucose metabolism and control remain understudied. From the Eunice Kennedy Shriver National Institute Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2802 pregnant women, we ascertained 85 GDM cases using the Carpenter and Coustan criteria and 85 non-GDM controls after exclusion. Using plasma collected before (23-31 weeks) and after GDM diagnosis (33-39 weeks), we quantified 25 saturated, poly- and monounsaturated FAs levels. We estimated the fold change of FAs before and after GDM diagnosis, using multiple linear mixed models adjusting for confounders. Eight FAs showed significant fold changes from the baseline values (23-31 weeks) among GDM cases as compared to women without GDM. Five FAs showed reduced fold changes [myristic acid (14:0): β: -0.22 (95% CI: -0.30, -0.14), palmitic acid (16:0): β: -0.02 (95% CI: -0.04, -0.01), cis-palmitoleic acid (16:1n7): β: -0.15 (95% CI: -0.24, -0.05), alpha-linolenic acid (18:3n3): β: -0.19 (95% CI: -0.31, -0.07], and dihomo-gamma-linoleic acid (20:3n6): β:-0.16; 95% CI: -0.21, -0.11)], whereas 3 showed increases [heptadecanoic acid (17:0): β: 0.17 (95% CI: 0.11, 0.22), cis-vaccenic acid (18:1n7): β: 0.06 (95% CI: 0.03, 0.10), and arachidonic acid (20:4n6): β: 0.10 (95% CI: 0.06, 0.13)]. Our study identified 8 FAs with unique patterns of change before and after GDM diagnosis that differed significantly between women with and without GDM. Our findings may shed light on the role of FA metabolism in the pathophysiology and disease management and progression of GDM. NCT00912132.
Authors: Li, Lingjun; Zhu, Yeyi; Wu, Jing; Hinkle, Stefanie N; Tobias, Deirdre K; Ma, Ronald C W; Weir, Natalie L; Tsai, Michael Y; Zhang, Cuilin
Clin Chem. 2021 Nov 26;67(12):1660-1675.
Disparities in Risks of Inadequate and Excessive Intake of Micronutrients during Pregnancy
Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes. The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI. Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups. Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients). Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.
Authors: Sauder, Katherine A; Avalos, Lyndsay A; Zhu, Yeyi; Breton, Carrie V; Program Collaborators for Environmental influences on Child Health Outcomes (ECHO),; et al.
J Nutr. 2021 11 02;151(11):3555-3569.
Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic
Authors: Young-Wolff, Kelly C; Ray, G Thomas; Alexeeff, Stacey E; Adams, Sara R; Does, Monique B; Ansley, Deborah; Avalos, Lyndsay A
JAMA. 2021 11 02;326(17):1745-1747.
Update on Phototherapy and Childhood Cancer in a Northern California Cohort
We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. This cohort study included 139 100 children born at ≥35 weeks’ gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.
Authors: Digitale, Jean C; Kim, Mi-Ok; Kuzniewicz, Michael W; Newman, Thomas B
Pediatrics. 2021 11;148(5). Epub 2021-10-29.
Prevalence of prescription opioid use during pregnancy in 8 U.S. health plans during 2001-2014
To estimate prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014. We conducted a cohort study of singleton live birth deliveries. Maternal characteristics were ascertained from health plan and/or birth certificate data and opioids dispensed during pregnancy from health plan pharmacy records. Prevalence of prescription opioid use during pregnancy was calculated for any use, cumulative days of use, and number of dispensings. We examined prevalence of prescription opioid use during pregnancy in each health plan. Tennessee Medicaid had appreciably greater prevalence of use compared to the seven other health plans. Thus, results for the two groups were reported separately. In the seven health plans (n = 587 093 deliveries), prevalence of use during pregnancy was relatively stable at 9%-11% throughout 2001-2014. In Tennessee Medicaid (n = 256 724 deliveries), prevalence increased from 29% in 2001 to a peak of 36%-37% in 2004-2010, and then declined to 28% in 2014. Use for ≥30 days during pregnancy was stable at 1% in the seven health plans and increased from 2% to 7% in Tennessee Medicaid during 2001-2014. Receipt of ≥5 opioid dispensings during pregnancy increased in the seven health plans (0.3%-0.6%) and Tennessee Medicaid (3%-5%) during 2001-2014. During 2001-2014, prescription opioid use during pregnancy was more common in Tennessee Medicaid (peak prevalence in late 2000s) compared to the seven health plans (relatively stable prevalence). Although a small percentage of women had opioid use during pregnancy for ≥30 days or ≥ 5 dispensings, they represent thousands of women during 2001-2014.
Authors: Pocobelli, Gaia; Li, De-Kun; Boudreau, Denise M; et al.
Pharmacoepidemiol Drug Saf. 2021 11;30(11):1541-1550. Epub 2021-07-07.
The effect of hospital phototherapy on early breastmilk feeding
The effect of phototherapy on breastmilk feeding is unclear. To estimate the effect of inpatient phototherapy on breastmilk feeding at 2-month well-child visits. We performed a retrospective cohort study using electronic health record data. From births at 16 Kaiser Permanente Northern California hospitals (2013-2017), we identified a cohort of infants ≥ 35 weeks’ gestation with total serum bilirubin levels close to the American Academy of Pediatrics 2004 phototherapy threshold during their birth hospitalisation. We compared self-reported breastmilk feeding at 2-month well-child visits among those who had and had not received birth hospitalisation phototherapy, adjusting for bilirubin levels and other confounding variables. We used multiple imputation (K = 200) to address missing data. Approximately a quarter of infants in the cohort (24.5%) received phototherapy during their birth hospitalisation. At the 2-month visit, exclusive breastmilk feeding was less common (RR 0.91, 95% interval [CI] 0.88, 0.95) among those who received phototherapy (41.3%) than those who did not (45.2%). However, no association remained after adjusting for potential confounders (RR 0.99, 95% CI 0.95, 1.04; average treatment effect on the treated [ATET] -0.2%, 95% CI -2.0%, 1.5%). In contrast, any breastmilk feeding was similar between infants who did (76.8%) and did not get phototherapy (77.9%). After adjusting for confounders, phototherapy had a slightly positive association with any breastmilk feeding at 2 months (RR 1.02, 95% CI 1.00, 1.04). Among infants who received phototherapy, the proportion being fed any breastmilk at the 2-month visit was an estimated 1.6 percentage points higher than it would have been if they had not received phototherapy (ATET 1.6%, 95% CI 0.1%, 3.1%). Multiple imputation results were similar. Birth hospitalisation phototherapy can be delivered in a way that does not adversely affect breastmilk feeding at 2 months.
Authors: Digitale, Jean C; Chang, Pearl W; Li, Sherian X; Kuzniewicz, Michael W; Newman, Thomas B
Paediatr Perinat Epidemiol. 2021 11;35(6):717-725. Epub 2021-06-29.
Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development
Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management.
Authors: Reynolds, Ann M; Croen, Lisa A; Levy, Susan E; et al.
J Autism Dev Disord. 2021 Nov;51(11):3806-3817. Epub 2021-01-04.
Maternal Proinflammatory Adipokines Throughout Pregnancy and Neonatal Size and Body Composition: A Prospective Study
Increased maternal adiposity and inflammation have impacts on fetal growth. The purpose of this prospective study was to investigate the associations of 3 proinflammatory adipokines in pregnancy with neonatal anthropometry. In a sample of 321 US pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (NCT00912132), plasma IL-6, fatty acid binding protein-4 (FABP4), and chemerin were measured in plasma samples collected at 10-14, 15-26, 23-31, and 33-39 weeks of gestation. Generalized linear models were used to estimate associations of adipokines with neonatal weight, thigh, and crown-heel length, and skinfolds at birth. Models adjusted for age, race/ethnicity, education, nulliparity, prepregnancy BMI, and weeks of gestation at blood collection. At each time point, higher IL-6 was associated with lower neonatal birthweight and thigh length. At 15-26 weeks of gestation, a 1 SD pg/mL increase in IL-6 was associated with -84.46 g lower neonatal birthweight (95% CI: -150.70, -18.22), -0.17 cm shorter thigh length (95% CI: -0.27, -0.07), -0.43 cm shorter crown-heel length (95% CI: -0.75, -0.10), and -0.75 mm smaller sum of skinfolds (95% CI: -1.19, -0.31), with similar associations at 23-31 and 33-39 weeks of gestation. There were no associations of FABP4 and chemerin with neonatal anthropometry. Starting as early as 15 weeks of gestation, higher maternal IL-6 concentrations in pregnancy were associated with lower neonatal birthweight, thigh and crown-heel length, and skinfolds. These data provide insight into the relevance of maternal inflammatory markers with neonatal anthropometry.
Authors: Francis, Ellen C; Li, Mengying; Hinkle, Stefanie N; Chen, Jinbo; Wu, Jing; Zhu, Yeyi; Cao, Haiming; Tsai, Michael Y; Chen, Liwei; Zhang, Cuilin
Curr Dev Nutr. 2021 Oct;5(10):nzab113. Epub 2021-09-07.
Methods-Motivational Interviewing Approach for Enhanced Retention and Attendance
Suboptimal and differential participant engagement in randomized trials-including retention at primary outcome assessments and attendance at intervention sessions-undermines rigor, internal validity, and trial conclusions. First, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009-2013, n=194]; Get Social [2016-2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014-2018, n=389]). Using a pre-post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported. After adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics. The Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats. All 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232).
Authors: Jake-Schoffman, Danielle E; Brown, Susan D; Ferrara, Assiamira; Hedderson, Monique M; Kiernan, Michaela; et al.
Am J Prev Med. 2021 10;61(4):606-617.
Ultrasound characteristics of early stage high-grade serous ovarian cancer
Survival from ovarian cancer is strongly dependent on the stage at diagnosis. Therefore, when confronted with a woman with an isolated adnexal mass, clinicians worry about missing the opportunity to detect cancer at an early stage. High-grade serous ovarian cancers account for 80% of ovarian cancer deaths, largely because of their tendency to be diagnosed at a late stage. Among adnexal masses, large size and the presence of solid areas on ultrasound examination have been found to be associated with cancer, but it is unclear whether these characteristics identify early-stage cases. This study aimed to evaluate the ultrasound findings associated with clinically detected early-stage high-grade serous ovarian cancer. This was a retrospective cohort study of women diagnosed with stage I or II high-grade serous ovarian or fallopian tube cancer measuring at least 1 cm at pathology from 2007 to 2017. Preoperative ultrasound examinations were independently reviewed by 3 radiologists. Adnexal masses were scored for size and volume; overall appearance; presence, thickness, and vascularity of septations; morphology and vascularity of other solid components; and degree of ascites. Characteristics were compared between masses of <5 cm and larger masses and between stage I and stage II cases. Interobserver variability was assessed. Among 111 women identified, 4 had bilateral ovarian involvement, for a total of 115 adnexal masses characterized by ultrasound examination. The mean age at diagnosis was 61.8 years (range, 42-91 years). The median mass size was 9.6 cm (range, 2.2-23.6 cm) with 87% of cases having a mass size of ≥5 cm. A mixed cystic and solid appearance was most common (77.4%), but a completely solid appearance was more frequently seen for tumors of <5 cm compared with larger tumors (26.7% vs 13.0%). Solid components other than septations were seen in 97.4% of cases. The characteristics of stage I and II cases were similar other than ascites, which was more commonly seen in stage II cases (18.0% vs 3.1%, respectively). Interobserver concordance was high for size and volume measurements (correlation coefficients, 0.96-0.99), with moderate agreement observed across the other ultrasound characteristics (Fleiss kappa, 0.45-0.58). In this community-based cohort, early-stage high-grade serous cancers rarely presented as masses of <5 cm or masses without solid components other than septations. Our findings provide additional support for the observation of small masses without solid areas on ultrasound examination.
Authors: Suh-Burgmann, Elizabeth; Brasic, Natasha; Jha, Priyanka; Hung, Yun-Yi; Goldstein, Ruth B
Am J Obstet Gynecol. 2021 10;225(4):409.e1-409.e8. Epub 2021-05-13.
Associations of household food insufficiency with childhood depression and anxiety: a nationwide cross-sectional study in the USA
Household food insufficiency (HFIS) is a major public health threat to children. Children may be particularly vulnerable to HFIS as a psychological stressor due to their rapid growth and accelerated behavioural and cognitive states, whereas data focusing on HFIS and childhood mental disorders are as-yet sparse. We aimed to examine the associations of HFIS with depression and anxiety in US children. Cross-sectional study. The 2016-2018 National Survey of Children’s Health, a nationally-representative study. Primary caregivers of 102 341 children in the USA. Physician diagnosed depression and anxiety were assessed by questionnaires administered to primary caregivers of 102 341 children. Multivariable logistic regression models estimated adjusted OR (aOR) for current depression or anxiety associated with HFIS measured through a validated single-item instrument. Among children aged 3-17 years, 3.2% and 7.4% had parent-reported physician-diagnosed current depression and anxiety, respectively. Compared with children without HFIS, children with HFIS had approximately twofold higher weighted prevalence of anxiety or depression. After adjusting for covariates, children with versus without HFIS had a 1.53-fold (95% CI 1.15 to 2.03) and 1.48-fold (95% CI 1.20 to 1.82) increased odds of current depression and anxiety, respectively. Associations were slightly more pronounced among girls (aOR (95% CI): depression 1.69 (1.16 to 2.48); anxiety 1.78 (1.33 to 2.38)) than boys (1.42 (0.98 to 2.08); 1.32 (1.00 to 1.73); both P-for-interaction <0.01). The associations did not vary by children's age or race/ethnicity. HFIS was independently associated with depression and anxiety among US children. Girls presented slightly greater vulnerability to HFIS in terms of impaired mental health. Children identified as food-insufficient may warrant mental health assessment and possible intervention. Assessment of HFIS among children with impaired mental health is also warranted. Our findings also highlight the importance of promptly addressing HFIS with referral to appropriate resources and inform its potential to alleviate childhood mental health issues.
Authors: Zheng, Siwen; Ngo, Amanda L; Forman, Michele R; Barcellos, Anna L; Liao, Lauren; Ferrara, Assiamira; Zhu, Yeyi
BMJ Open. 2021 09 07;11(9):e054263. Epub 2021-09-07.
Longitudinal Plasma Metabolomics Profile in Pregnancy-A Study in an Ethnically Diverse U.S. Pregnancy Cohort
Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n = 214 women at 10-14 and 15-26 weeks, 107 at 26-31 weeks, and 103 at 33-39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.
Authors: Mitro, Susanna D; Zhu, Yeyi; Zhang, Cuilin; et al.
Nutrients. 2021 Sep 01;13(9). Epub 2021-09-01.
Association of Habitual Alcohol Consumption With Long-term Risk of Type 2 Diabetes Among Women With a History of Gestational Diabetes
Women with gestational diabetes are at high risk for type 2 diabetes. Identifying modifiable dietary and lifestyle factors, such as alcohol intake, that can be useful in delaying or preventing progression to overt type 2 diabetes is of particular interest. To evaluate the association between alcohol consumption and risk for type 2 diabetes among women with a history of gestational diabetes. This cohort study included women from the Nurses’ Health Study II cohort who reported a history of gestational diabetes and were followed up from January 1, 1991, to December 31, 2017, as part of the Diabetes & Women’s Health Study. Data analysis was performed from 2020 to 2021. Dietary intakes, including alcohol, were assessed every 4 years using validated food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association of alcohol intake with risk for incident type 2 diabetes after a pregnancy during which gestational diabetes was diagnosed. A total of 4740 women were included in the study; the mean (SD) age at baseline was 38.2 (5.0) years, and the median follow-up time was 24 years (interquartile range, 18-28 years), resulting in 78 328 person-years of follow-up. During this period, 897 incident cases of type 2 diabetes were reported. After adjustment for major dietary and lifestyle factors, compared with women who did not consume any alcohol, only alcohol consumption of 5.0 to 14.9 g/d was associated with decreased risk for incident type 2 diabetes (HR, 0.45; 95% CI, 0.33-0.61); there was no association of alcohol consumption of 0.1 to 4.9 g/d or 15.0 g/d or more (maximum, 74.2 g/d) with risk of type 2 diabetes (0.1 to 4.9 g/d: HR, 0.87 [95% CI, 0.73-1.03]; ≥15.0 g/d: HR, 0.62 [95% CI, 0.37-1.04]). After additional adjustment for body mass index, women who reported alcohol consumption of 5.0 to 14.9 g/d had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59; 95% CI, 0.42-0.81); consumption of 0.1 to 4.9 g/d and consumption of 15.0 g/d or more were still not associated with risk of type 2 diabetes, but the results were attenuated (0.1-4.9 g/d: HR, 1.02 [95% CI, 0.85-1.23]; ≥15.0 g/d: HR, 0.75 [95% CI, 0.42-1.33]). In this cohort study, among women with a history of gestational diabetes, usual alcohol intake of 5.0 to 14.9 g/d (approximately 0.5-1 drinks per day) was associated with a lower risk for type 2 diabetes. These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes.
Authors: Hinkle, Stefanie N; Zhu, Yeyi; Zhang, Cuilin; et al.
JAMA Netw Open. 2021 09 01;4(9):e2124669. Epub 2021-09-01.
Steps per Day and All-Cause Mortality in Middle-aged Adults in the Coronary Artery Risk Development in Young Adults Study
Steps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality. To estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women. This prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021. Daily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more. All-cause mortality. A total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality. This cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.
Authors: Paluch, Amanda E; Gabriel, Kelley Pettee; Fulton, Janet E; Lewis, Cora E; Schreiner, Pamela J; Sternfeld, Barbara; Sidney, Stephen; Siddique, Juned; Whitaker, Kara M; Carnethon, Mercedes R
JAMA Netw Open. 2021 09 01;4(9):e2124516. Epub 2021-09-01.
Maternal prepregnancy weight and gestational weight gain in association with autism and developmental disorders in offspring
Maternal prepregnancy BMI and gestational weight gain (GWG) are examined in relation to autism spectrum disorder (ASD) and other developmental disorders (DD) in offspring in a multisite case-control study. Maternal prepregnancy BMI, obtained from medical records or self-report, was categorized as underweight, normal weight, overweight, obesity Class 1, or obesity Class 2/3. GWG was standardized for gestational age (GWG z score), and the rate (pounds/week) was categorized per adherence with clinical recommendations. Logistic regression models, adjusting for demographic factors, were used to assess associations with ASD (n = 1,159) and DD (n = 1,617), versus control children (n = 1,633). Maternal obesity Class 2/3 was associated with ASD (adjusted odds ratio [AOR] = 1.87, 95% CI: 1.40-2.51) and DD (AOR = 1.61, 95% CI: 1.22-2.13). GWG z score was not associated with DD (AOR = 1.14, 95% CI: 0.95-1.36), but the GWG z score highest tertile was associated with higher odds of ASD, particularly among male children (AOR = 1.47, 95% CI: 1.15-1.88). Results indicate that maternal prepregnancy severe obesity increases risk of ASD and DD in children and suggest high gestational-age-adjusted GWG is a risk factor for ASD in male children. Because maternal BMI and GWG are routinely measured and potentially modifiable, these findings could inform early interventions for high-risk mother-child dyads.
Authors: Matias, Susana L; Pearl, Michelle; Lyall, Kristen; Croen, Lisa A; Kral, Tanja V E; Fallin, Daniele; Lee, Li-Ching; Bradley, Chyrise B; Schieve, Laura A; Windham, Gayle C
Obesity (Silver Spring). 2021 09;29(9):1554-1564. Epub 2021-08-04.
Use of Complete Blood Cell Count Components to Screen for Hereditary Spherocytosis in Neonates
The neonatal hereditary spherocytosis (HS) index, defined as the mean corpuscular hemoglobin concentration divided by the mean corpuscular volume, has been proposed as a screening tool for HS in neonates. In a population of mostly white infants, an HS Index >0.36 was 97% sensitive and >99% specific. We evaluated the utility of the HS Index among a more racially and ethnically diverse population and determined if its discrimination varies with total serum bilirubin (TSB) levels. Infants born at ≥35 weeks’ gestation at 15 Kaiser Permanente Northern California hospitals from 1995 to 2015 were eligible (N = 670 272). Erythrocyte indices from the first complete blood count drawn at ≤7 days and TSB levels drawn at ≤30 days were obtained. Diagnoses of HS were confirmed via chart review. HS was confirmed in 79 infants, 1.2 per 10 000. HS was more common among infants of white and “other” race or ethnicity and among those with higher peak TSB levels. The area under the receiver operating characteristic curve for the HS Index was 0.84 (95% confidence interval 0.78-0.90). Likelihood ratios ranged from 10.1 for an HS Index ≥0.380 to 0.1 for an HS Index <0.310. Dichotomized at 0.36, the HS Index was 56% sensitive and 93% specific. Discrimination of the HS Index appeared best among infants with TSB levels <10 mg/dL. The HS Index, when obtained from a CBC drawn within the first week after birth, had only modest ability to alter the probability of HS.
Authors: Weiss, Nicole M; Kuzniewicz, Michael W; Shimano, Kristin A; Walsh, Eileen M; Newman, Thomas B
Pediatrics. 2021 09;148(3). Epub 2021-08-10.
Longitudinal bidirectional associations of physical activity and depressive symptoms: The CARDIA study
Depression affects many aspects of health and may be attenuated through increases in physical activity. While bidirectional associations between physical activity (PA) and depressive symptoms have been examined, few studies have examined these associations using both self-reported and accelerometer-estimated measures. Using data from Years 20 (2005-06, age 38-50) and 30 of the Coronary Artery Risk Development in Young Adults (CARDIA) study (N = 2,871), the bidirectional associations between moderate to vigorous intensity physical activity (MVPA) and depressive symptoms were examined using a cross-lagged panel model. Differences in the observed associations by physical activity assessment method were also examined. An inverse bidirectional association between self-reported MVPA and depressive symptoms was found. In subsequent analyses stratified by intensity category, higher levels of vigorous intensity physical activity at baseline, but not moderate intensity physical activity were associated with lower levels of depressive symptoms at the 10-year follow-up (ϕ = -0.04, p < 0.01; ϕ = -0.03, p = 0.15, respectively). A 10-year increase in self-reported MVPA was associated with a 10-year decrease in depressive symptoms. No associations were observed between accelerometer MVPA estimates and depressive symptoms. These findings may support the notion that each assessment method captures related, but also unique, aspects of physical activity behavior. When possible, future studies should explore measures of association by each physical activity assessment method to gain a better understanding of the complex relationship between physical activity and health.
Authors: Zhang, Dong; Pettee Gabriel, Kelley; Sidney, Stephen; Sternfeld, Barbara; Jacobs, David; Whitaker, Kara M
Prev Med Rep. 2021 Sep;23:101489. Epub 2021-07-12.
Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes
It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. Two cohorts were analysed including 771 diabetic participants, 30-70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20-45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management.
Authors: Gu, Yong; Ferrara, Assiamira; Action LADA consortium and the Diabetes in Young Adults (DiYA) Study Group,; et al.
Diabetologia. 2021 09;64(9):2052-2060. Epub 2021-07-16.
Associations of accelerometer-determined sedentary behavior and physical activity with physical performance outcomes by race/ethnicity in older women
To determine the cross-sectional associations of accelerometer-measured time spent in physical activity intensity categories (sedentary, low and high light intensity, or moderate to vigorous intensity physical activity (MVPA) with physical performance outcomes [stair climb ascent, 40 foot walk test, and short physical performance battery (SPPB)] in older women and examine differences by race/ethnicity. Data were from 1,256 Study of Women’s Health Across the Nation (SWAN) participants [aged 64.9 (2.7) years at Visit 15 (2015-16); 54.1% non-White]. Three sets of adjusted multivariable linear or logistic regression models were built to test the study objectives using the backward elimination approach to identify relevant covariates. In the full analytic sample, a 10 min increment in MVPA was related to faster performance on the stair climb [β = -0.023 (95% CI: -0.04, -0.005) seconds] and 40 foot walk test [β = -0.066 (95% CI: -0.133, -0.038) seconds], and a 9% lower odds [OR: 0.91; 95% CI: 0.87, 0.96; p = 0.004] of limitations based on the SPPB. Statistically significant differences by race/ethnicity were found for the stair climb ascent time as MVPA was associated with better performance for White, Chinese, and Japanese participants while high light intensity physical activity, but not MVPA, was deemed beneficial in Black women. Findings from the isotemporal substitution models were consistent. Findings further support the importance of MVPA on physical performance outcomes in older women. Further research is needed to examine the complex associations between physical (in)activity and physical performance outcomes by race/ethnicity to provide more targeted recommendations.
Authors: Pettee Gabriel, Kelley; Karvonen-Gutierrez, Carrie A; Colvin, Alicia B; Ylitalo, Kelly R; Whitaker, Kara M; Lange-Maia, Brittney S; Lucas, Alexander R; Dugan, Sheila A; Derby, Carol; Cauley, Jane A; Sternfeld, Barbara
Prev Med Rep. 2021 Sep;23:101408. Epub 2021-05-19.
Lifestyle-related education and counseling resource utilization and cardiovascular biomarkers in midlife women with low physical activity
Health plan-based resources are promising avenues for decreasing cardiovascular disease risk. This study examined associations of lifestyle-related resource utilization within a healthcare delivery system and cardiovascular biomarkers among midlife women with low physical activity. Midlife women (45-55 years old) with <10 min/week of reported physical activity at a primary care visit within a large integrated healthcare delivery system in Northern California in 2015 (n = 55,393) were identified. Within this cohort, subsequent lifestyle-related health education and individual coaching resource utilization, and the next recorded physical activity, weight, systolic blood pressure, plasma glucose, HDL and LDL cholesterol measures up to 2 years after the index primary care visit were identified from electronic health records. We used a multilevel linear model to estimate associations. About 3% (n = 1587) of our cohort had ≥1 lifestyle-related resource encounter; 0.3% (n = 178) had ≥ 4 encounters. Participation in ≥4 lifestyle-related resource encounters (compared to none) was associated with 51 more minutes/week of physical activity (95% CI: 33,69) at the next clinical measurement in all women, 6.2 kg lower weight (95% CI: -7.0,-5.5) at the next measurement in women with obesity, and 8-10 mg/dL lower plasma glucose (95% CI: -30,14 and -23,2, respectively) at the next measurement in women with diabetes or prediabetes. Our results support the sustained utilization of health plan-based lifestyle-related resources for improving physical activity, weight, and plasma glucose in high-risk midlife women. Given the observed low utilization, health system-wide efforts may be warranted to increase utilization of lifestyle-related resources in this population.
Authors: Badon, Sylvia E; Nance, Nerissa; Fogelberg, Renee; Quesenberry, Charles; Hedderson, Monique M; Avalos, Lyndsay A
Prev Med Rep. 2021 Sep;23:101401. Epub 2021-05-17.
Cardiovascular risk and functional burden at midlife: Prospective associations of isotemporal reallocations of accelerometer-measured physical activity and sedentary time in the CARDIA study
Cardiovascular risk and functional burden, or the accumulation of cardiovascular risk factors coupled with functional decline, may be an important risk state analogy to multimorbidity. We investigated prospective associations of sedentary time (ST), light intensity physical activity (LPA), and moderate to vigorous intensity physical activity (MVPA) with cardiovascular risk and functional burden at midlife. Participants were 1648 adults (mean ± SD age = 45 ± 4 years, 61% female, 39% Black) from Coronary Artery Risk Development in Young Adults (CARDIA) who wore accelerometers in 2005-2006 and 2015-2016. Cardiovascular risk and functional burden was defined as ≥2 cardiovascular risk factors (untreated/uncontrolled hypertension and hypercholesterolemia, type 2 diabetes, reduced kidney function) and/or functional decline conditions (reduced physical functioning and depressive symptoms). Prospective logistic regression models tested single activity, partition, and isotemporal substitution associations of accelerometer-measured ST, LPA, and MVPA with cardiovascular risk and functional burden 10 years later. In isotemporal models of baseline activity, reallocating 24 min of ST to MVPA was associated with 15% lower odds of cardiovascular risk and functional burden (OR: 0.85; CI: 0.75, 0.96). Reallocating 24 min of LPA to MVPA was associated with a 14% lower odds of cardiovascular risk and functional burden (OR: 0.86; CI: 0.75, 0.99). In longitudinal isotemporal models, similar beneficial associations were observed when 10-year increases in MVPA replaced time in ST or LPA. Findings suggest that maintaining an MVPA dose reflecting daily physical activity recommendations in early midlife is associated with lower odds of cardiovascular risk and functional burden later in midlife.
Authors: Full, Kelsie M; Whitaker, Kara M; Pettee Gabriel, Kelley; Lewis, Cora E; Sternfeld, Barbara; Sidney, Stephen; Reis, Jared P; Jacobs, David R; Gibbs, Bethany Barone; Schreiner, Pamela J
Prev Med. 2021 09;150:106626. Epub 2021-05-19.
Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders
This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring. We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy. Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD. Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.
Authors: Ames, Jennifer L; Croen, Lisa A; et al.
Biol Psychiatry. 2021 08 15;90(4):253-262. Epub 2021-04-14.
Associations between longitudinal trajectories of insomnia symptoms and sleep duration with objective physical function in postmenopausal women: the Study of Women’s Health Across the Nation
Examine the association between trajectories of self-reported insomnia symptoms and sleep duration over 13 years with objective physical function. We utilized data from 1,627 Study of Women’s Health Across the Nation participants, aged 61.9 ± 2.7 years at the end of the 13-year follow-up. Latent class growth models identified trajectories of insomnia symptoms (trouble falling asleep, frequent night-time awakenings, and/or early morning awakening) and sleep duration over 13 years. Physical function tests were performed at the end of the 13-year period: 40-ft walk, 4-m walk, repeated chair stand, grip strength, and balance. Multivariable regression analyses examined each physical function measure according to the insomnia symptom or sleep duration trajectory group. Five insomnia symptom trajectories and two sleep duration trajectories were identified. Women with a consistently high likelihood of insomnia symptoms and women with a decreased likelihood of insomnia symptoms (i.e. improving) had slower gait speed (3.5% slower 40-ft walk [consistently high], 3.7% slower 4-m walk [improving]; each p ≤ .05) than those with a consistently low likelihood of insomnia symptoms. In contrast, women with a steep increase in the likelihood of insomnia symptoms over time and women with persistent insufficient sleep duration had lower odds of having a balance problem (odds ratio [OR] = 0.36 and OR = 0.61, respectively; each p < .02) compared to those with a consistently low likelihood of insomnia symptoms and those with persistent sufficient sleep duration, respectively. These results suggest that women's sleep during midlife has important implications for maintaining physical function during the transition into older adulthood.
Authors: Kline, Christopher E; Colvin, Alicia B; Pettee Gabriel, Kelley; Karvonen-Gutierrez, Carrie A; Cauley, Jane A; Hall, Martica H; Matthews, Karen A; Ruppert, Kristine M; Neal-Perry, Genevieve S; Strotmeyer, Elsa S; Sternfeld, Barbara
Sleep. 2021 08 13;44(8).
Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study
Preterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown. We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk. This prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery <37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score <75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors. One hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs. A healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.
Authors: Zhu, Yeyi; Hedderson, Monique M; Brown, Susan D; Badon, Sylvia E; Feng, Juanran; Quesenberry, Charles P; Ferrara, Assiamira
Am J Clin Nutr. 2021 08 02;114(2):813-821.
A longitudinal study of plasma acylcarnitines throughout pregnancy and associations with risk of gestational diabetes mellitus
Prospective and longitudinal data on the association between acylcarnitines and gestational diabetes (GDM) are lacking. This study aims to prospectively investigate 28 acylcarnitines in relation to subsequent GDM risk. Within the NICHD Fetal Growth Studies-Singleton Cohort, plasma levels of acylcarnitines and cardiometabolic biomarkers were measured at gestational week (GW) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases and 214 controls. At GW 10-14, per standard deviation (SD) increased level of C14:1-OH was associated with a 55% increased risk of GDM after adjusting for major risk factors for GDM [OR (95% CI): 1.55 (1.05-2.29)]. At GW 15-26, C4, C8:1 and C16:1-OH were associated with an increased risk of GDM [OR (95% CI) for per SD increase: 1.42 (1.01-2.00), 1.41 (1.02-1.96), and 1.77 (1.10-2.84), respectively]. Whereas increased C10 and C18 were related to lower risk of GDM [OR (95% CI) for per SD increase: 0.74 (0.55-1.00), and 0.69 (0.49-0.97), respectively]. Moreover, we observed correlations of individual acylcarnitine with multiple clinical markers implicated in glucose homeostasis and cardiometabolic function among non-GDM women. Our results demonstrate that several plasma acylcarnitine species are differentially associated with GDM risk by chain length. Future studies are warranted to investigate the distinct roles of individual acylcarnitine in glucose homeostasis in pregnancy.
Authors: Lin, Yuan; Wu, Jing; Zhu, Yeyi; Hinkle, Stefanie N; Rawal, Shristi; Liang, Liming; Weir, Natalie L; Tsai, Michael Y; Zhang, Cuilin
Clin Nutr. 2021 08;40(8):4863-4870. Epub 2021-07-10.
Cardiovascular risk and midlife cognitive decline in the Study of Women’s Health Across the Nation
Cardiovascular risk factors in midlife have been linked to late life risk for Alzheimer’s disease and related dementias (ADRD). The relation of vascular risk factors on cognitive decline within midlife has been less studied. Using data from the Study of Women’s Health Across the Nation, we examined associations of midlife hypertension, elevated lipid levels, diabetes, fasting glucose, central adiposity, and Framingham heart age with rates of cognitive decline in women who completed multiple cognitive assessments of processing speed, and working and verbal memory during midlife. Diabetes, elevated fasting glucose, central obesity, and heart age greater than chronological age were associated with rate of decline in processing speed during midlife. Vascular risk factors were not related to rate of decline in working or verbal memory. Midlife may be a critical period for intervening on cardiovascular risk factors to prevent or delay later life cognitive impairment and ADRD.
Authors: Derby, Carol A; Hutchins, Franya; Greendale, Gail A; Matthews, Karen A; Sternfeld, Barbara; Everson-Rose, Susan A; Kazlauskaite, Rasa; Whitmer, Rachel A; Brooks, Maria M
Alzheimers Dement. 2021 08;17(8):1342-1352. Epub 2021-03-12.
Relative-Intensity Physical Activity and Its Association With Cardiometabolic Disease
Authors: Siddique, Juned; Welch, Whitney A; Aaby, David; Sternfeld, Barbara; Pettee Gabriel, Kelley; Carnethon, Mercedes R; Rana, Jamal S; Sidney, Stephen
J Am Heart Assoc. 2021 07 20;10(14):e019174. Epub 2021-07-14.
Engagement in perinatal depression treatment: a qualitative study of barriers across and within racial/ethnic groups
To better understand previously observed racial/ethnic disparities in perinatal depression treatment rates we examined care engagement factors across and within race/ethnicity. Obstetric patients and women’s health clinician experts from a large healthcare system participated in this qualitative study. We conducted focus groups with 30 pregnant or postpartum women of Asian, Black, Latina, and White race/ethnicity with positive depression screens. Nine clinician experts in perinatal depression (obstetric, mental health, and primary care providers) were interviewed. A semi-structured format elicited treatment barriers, cultural factors, and helpful strategies. Discussion transcripts were coded using a general inductive approach with themes mapped to the Capability-Opportunity-Motivation-Behavior (COM-B) theoretical framework. Treatment barriers included social stigma, difficulties recognizing one’s own depression, low understanding of treatment options, and lack of time for treatment. Distinct factors emerged for non-White women including culturally specific messages discouraging treatment, low social support, trauma history, and difficulty taking time off from work for treatment. Clinician factors included knowledge and skill handling perinatal depression, cultural competencies, and language barriers. Participants recommended better integration of mental health treatment with obstetric care, greater treatment convenience (e.g., telemedicine), and programmatic attention to cultural factors and social determinants of health. Women from diverse backgrounds with perinatal depression encounter individual-level, social, and clinician-related barriers to treatment engagement, necessitating care strategies that reduce stigma, offer convenience, and attend to cultural and economic factors. Our findings suggest the importance of intervention and policy approaches effecting change at multiple levels to increase perinatal depression treatment engagement.
Authors: Iturralde, Esti; Hsiao, Crystal A; Nkemere, Linda; Kubo, Ai; Sterling, Stacy A; Flanagan, Tracy; Avalos, Lyndsay A
BMC Pregnancy Childbirth. 2021 Jul 16;21(1):512. Epub 2021-07-16.
Perceived Barriers and Motivators for Physical Activity in Women With Perinatal Depression
Physical activity (PA) can help reduce depression symptom severity in women with perinatal depression. However, PA is low, and barriers and motivators for PA among women with perinatal depression are not well understood. An ethnically diverse sample of women with perinatal depression was identified using a universal perinatal depression screening program. The authors conducted 8 focus groups (4 in pregnant women [n = 15] and 4 in postpartum women [n = 20]). Depression symptoms were measured using the Patient Health Questionnaire-8 at recruitment. Focus groups were analyzed using an inductive approach. Pregnant participants were 27 weeks gestation, and postpartum participants were 11.5 months postpartum, on average. Depression symptoms were moderately severe (mean Patient Health Questionnaire-8 score: 16). Women identified practical barriers and motivators for PA common to perinatal women (physical health, parental responsibilities, PA tracking tools, and environmental factors) and described emotional and social factors influencing PA. Motivators included using PA to improve mood, relieve stress, boost self-image, and spend time with others. Bad mood, fear of social judgment, and feeling discouraged made it difficult to be active. PA interventions in women with perinatal depression should include components addressing emotional and social barriers to PA in addition to addressing additional common practical barriers to PA.
Authors: Badon, Sylvia E; Iturralde, Esti; Nkemere, Linda; Nance, Nerissa; Avalos, Lyndsay A
J Phys Act Health. 2021 07 01;18(7):801-810. Epub 2021-05-12.
Mediating Effects of Cardiometabolic Risk Factors on the Association Between Maternal Race-Ethnicity and Cesarean Delivery Among Low-Risk Women
Background: While racial-ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to which potentially modifiable maternal cardiometabolic risk factors (obesity, maternal hyperglycemia and hypertensive disorders) underlie these disparities. We examined race-ethnicity and risk of NTSV cesarean deliveries and whether the associations were mediated by maternal cardiometabolic risk factors. Materials and Methods: A cohort study of 62,048 NTSV deliveries in Kaiser Permanente Northern California. The outcome was cesarean delivery. Results: Black, Asian, and Hispanic women were at increased risk of having a NTSV cesarean delivery compared with White women (relative risks and 95% confidence intervals: 1.37 [1.28-1.45]; 1.11 [1.07-1.16]; 1.12 [1.07-1.16], respectively), independent of established risk factors and prenatal care utilization. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs. White, in separate analyses) and NTSV cesarean delivery varied by race-ethnicity. Maternal overweight/obesity (body mass index ≥25.0) mediated the association between Black and Hispanic race-ethnicity and NTSV cesarean delivery (21.1% [15.8-26.4] and 24.7% [14.6-34.8, respectively), but not for Asian race. Maternal hyperglycemia (gestational diabetes mellitus or preexisting diabetes) mediated the association between Asian and Hispanic race and NTSV cesarean delivery (18.5% [9.8-27.2] and 9.8% [5.0-14.7], respectively), but not for Black race. Hypertensive disorders mediated 3.2% (0.70-5.8) of the association between Black race and cesarean delivery, but not for other race-ethnicities. Conclusion: Black, Asian, and Hispanic women are at increased risk for NTSV cesarean deliveries. Maternal cardiometabolic risk factors only partially mediate the associations between race-ethnicity and NSTV cesarean deliveries.
Authors: Hedderson, Monique M; Xu, Fei; Liu, Emily; Sridhar, Sneha B; Quesenberry, Charles P; Flanagan, Tracy A
J Womens Health (Larchmt). 2021 07;30(7):1028-1037. Epub 2021-02-11.
Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research
Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item “short” to 65-item “full” SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.
Authors: Lyall, Kristen; Croen, Lisa A; program collaborators for Environmental influences on Child Health Outcomes,; et al.
J Autism Dev Disord. 2021 Jul;51(7):2241-2253.
Exploring the evidence for epigenetic regulation of environmental influences on child health across generations
Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. One putative mechanism for these environmental health effects is via altered epigenetic regulation. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications.
Authors: Breton, Carrie V; Fry, Rebecca; Fry, Rebecca; et al.
Commun Biol. 2021 06 22;4(1):769. Epub 2021-06-22.
Pharmacists’ knowledge, perspectives, and experiences with mifepristone dispensing for medication abortion
The U.S. Food and Drug Administration (FDA) restricts dispensing of mifepristone for medication abortion to certified health care providers at clinical facilities, thus prohibiting pharmacist dispensing. Allowing mifepristone dispensing by pharmacists could improve access to medication abortion. To assess the feasibility of pharmacists dispensing mifepristone to patients who have undergone evaluation for eligibility and counseling for medication abortion by a clinician. Before providing a study training on medication abortion, we administered baseline surveys to pharmacists who participated in a multisite mifepristone-dispensing intervention. The survey assessed medication abortion knowledge-using a 15-item score-and perceptions about the benefits and challenges of the model. We administered follow-up surveys in the study’s final month that also assessed the pharmacists’ satisfaction and experiences with mifepristone dispensing. To investigate the association of the study intervention with the pharmacists’ knowledge, perceptions, and experiences dispensing mifepristone, we conducted multivariable linear regression analyses using generalized estimating equation models, accounting for clustering by individual. Among the 72 pharmacists invited from 6 pharmacies, 47 (65%) completed the baseline surveys, and 56 (78%) received training. At the study’s end (mean 18 months later), 43 of the 56 pharmacists who received training (77%) completed the follow-up surveys. At follow-up, 36 (83%) respondents were very or somewhat satisfied with mifepristone dispensing, and 24 (56%) reported experiencing no challenges dispensing mifepristone. Four (6%) of the 72 pharmacists invited objected to participating in mifepristone dispensing. In regression analyses, average knowledge scores, perceived ease of implementation, and level of support for the pharmacist-dispensing model were higher at follow-up (P < 0.001). Most pharmacists were willing to be trained, dispensed mifepristone with few challenges when given the opportunity, were satisfied with the model, and had higher knowledge levels at follow-up. Our findings support removal of FDA's restriction on pharmacist dispensing of mifepristone.
Authors: Kaller S; Raine-Bennett TR; Grossman D; et al.
J Am Pharm Assoc (2003). 2021 Jun 18.
Genetic and Epigenetic Variations of HPV52 in Cervical Precancer
The goal of this study was to identify human papillomavirus (HPV) type 52 genetic and epigenetic changes associated with high-grade cervical precancer and cancer. Patients were selected from the HPV Persistence and Progression (PaP) cohort, a cervical cancer screening program at Kaiser Permanente Northern California (KPNC). We performed a nested case-control study of 89 HPV52-positive women, including 50 cases with predominantly cervical intraepithelial neoplasia grade 3 (CIN3) and 39 controls without evidence of abnormalities. We conducted methylation analyses using Illumina sequencing and viral whole genome Sanger sequencing. Of the 24 CpG sites examined, increased methylation at CpG site 5615 in HPV52 L1 region was the most significantly associated with CIN3, with a difference in median methylation of 17.9% (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 1.9-11.8) and an area under the curve of 0.73 (AUC; 95% CI = 0.62-0.83). Complete genomic sequencing of HPV52 isolates revealed associations between SNPs present in sublineage C2 and a higher risk of CIN3, with ORs ranging from 2.8 to 3.3. This study identified genetic and epigenetic HPV52 variants associated with high risk for cervical precancer, improving the potential for early diagnosis of cervical neoplasia caused by HPV52.
Authors: Bee KJ; Gradissimo A; Chen Z; Harari A; Schiffman M; Raine-Bennett T; Castle PE; Clarke M; Wentzensen N; Burk RD
Int J Mol Sci. 2021 Jun 16;22(12). Epub 2021-06-16.
Bidirectional associations of accelerometer-derived physical activity and stationary behavior with self-reported mental and physical health during midlife
Moderate-to-vigorous intensity physical activity (MVPA) is associated with favorable self-rated mental and physical health. Conversely, poor self-rated health in these domains could precede unfavorable shifts in activity. We evaluated bidirectional associations of accelerometer-estimated time spent in stationary behavior (SB), light intensity physical activity (LPA), and MVPA with self-rated health over 10 years in in the CARDIA longitudinal cohort study. Participants (n = 894, age: 45.1 ± 3.5; 63% female; 38% black) with valid accelerometry wear and self-rated health at baseline (2005-6) and 10-year follow-up (2015-6) were included. Accelerometry data were harmonized between exams and measured mean total activity and duration (min/day) in SB, LPA, and MVPA; duration (min/day) in long-bout and short-bout SB (≥30 min vs. < 30 min) and MVPA (≥10 min vs. < 10 min) were also quantified. The Short-Form 12 Questionnaire measured both a mental component score (MCS) and physical component score (PCS) of self-rated health (points). Multivariable linear regression associated baseline accelerometry variables with 10-year changes in MCS and PCS. Similar models associated baseline MCS and PCS with 10-year changes in accelerometry measures. Over 10-years, average (SD) MCS increased 1.05 (9.07) points, PCS decreased by 1.54 (7.30) points, and activity shifted toward greater SB and less mean total activity, LPA, and MVPA (all p < 0.001). Only baseline short-bout MVPA was associated with greater 10-year increases in MCS (+ 0.92 points, p = 0.021), while baseline mean total activity, MVPA, and long-bout MVPA were associated with greater 10-year changes in PCS (+ 0.53 to + 1.47 points, all p < 0.005). In the reverse direction, higher baseline MCS and PCS were associated with favorable 10-year changes in mean total activity (+ 9.75 cpm, p = 0.040, and + 15.66 cpm, p < 0.001, respectively) and other accelerometry measures; for example, higher baseline MCS was associated with - 13.57 min/day of long-bout SB (p < 0.001) and higher baseline PCS was associated with + 2.83 min/day of MVPA (p < 0.001) in fully adjusted models. The presence of bidirectional associations between SB and activity with self-rated health suggests that individuals with low overall activity levels and poor self-rated health are at high risk for further declines and supports intervention programming that aims to dually increase activity levels and improve self-rated health.
Authors: Barone Gibbs, Bethany; Sternfeld, Barbara; Whitaker, Kara M; Brach, Jennifer S; Hergenroeder, Andrea L; Jacobs, David R; Reis, Jared P; Sidney, Stephen; White, Daniel; Pettee Gabriel, Kelley
Int J Behav Nutr Phys Act. 2021 06 06;18(1):74. Epub 2021-06-06.
A prognostic information system for real-time personalized care: Lessons for embedded researchers
Embedded researchers could play a central role in developing tools to personalize care using electronic medical records (EMRs). However, few studies have described the steps involved in developing such tools, or evaluated the key factors in success and failure. This case study describes how we used an EMR-derived data warehouse to develop a prototype informatics tool to help oncologists counsel patients with pancreatic cancer about their prognosis. The tool generated real-time prognostic information based on tumor type and stage, age, comorbidity status and lab tests. Our multidisciplinary team included embedded researchers, application developers, user experience experts, and an oncologist leader.This prototype succeeded in establishing proof of principle, but did not reach adoption into actual practice. In pilot testing, oncologists succeeded in generating prognostic information in real time. A few found it helpful in patient encounters, but all identified critical areas for further development before implementation. Generalizable lessons included the need to (1) include a wide range of potential use cases and stakeholders when selecting use cases for such tools; (2) develop talking points for clinicians to explain results from predictive tools to patients; (3) develop ways to reduce lag time between events and data availability; and (4) keep the options presented in the user interface very simple. This case demonstrates that embedded researchers can lead collaborations using EMR-derived data to create systems for real-time personalized patient counseling, and highlights challenges that such teams can anticipate.
Authors: Lieu, Tracy A; Neugebauer, Romain; Van Den Eeden, Stephen K; Baer, David M; et al.
Healthc (Amst). 2021 Jun;8 Suppl 1:100486. Epub 2021-06-23.
Bidirectional associations of accelerometer measured sedentary behavior and physical activity with knee pain, stiffness, and physical function: The CARDIA study
The objective was to examine bidirectional associations of accelerometer estimated sedentary time and physical activity with reported knee symptoms. Participants were 2,034 adults (mean age 45.3 ± 3.6 years, 58.7% female) from CARDIA. Generalized estimating equations for logistic regression and linear mixed regression models examined associations of accelerometer estimated sedentary time, light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA) at baseline (2005-06) with knee discomfort, pain, stiffness, and physical function (yes/no and continuous scores from short-form WOMAC function scale) at the 5- and 10-year follow-up exams. Linear regression models examined associations between knee symptoms at the 5-year follow-up with accelerometer estimates at the 10-year follow-up. Models were adjusted for confounders; individuals with comorbidities were excluded in sensitivity analyses. A 30 min/day increment in sedentary time at baseline was associated with lower odds of knee symptoms at the 5- and 10-year follow-up (OR: 0.95, 95% CI range: 0.92-0.98), while LPA and MVPA were associated with greater odds of knee symptoms (LPA OR range: 1.04-1.05, 95% CI range: 1.01-1.09; MVPA OR range: 1.17-1.19, 95% CI range: 1.06-1.32). Report of knee symptoms at the 5-year follow-up was associated with 13.52-17.51 (95% CI range: -29.90, -0.56) fewer minutes/day of sedentary time and 14.58-17.51 (95% CI range: 2.48, 29.38) more minutes/day of LPA at the 10-year follow-up, compared to those reporting no symptoms. Many associations were no longer statistically significant when excluding individuals with comorbidities. Findings support a bidirectional association of accelerometer estimated sedentary time and physical activity with knee symptoms across midlife.
Authors: Whitaker, Kara M; Pettee Gabriel, Kelley; Laddu, Deepika; White, Daniel K; Sidney, Stephen; Sternfeld, Barbara; Lewis, Cora E; Jacobs, David R
Prev Med Rep. 2021 Jun;22:101348. Epub 2021-03-09.
Design of the Association of Uterine Perforation and Expulsion of IUD (APEX-IUD) Study: A Multisite Retrospective Cohort Study
Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.
Authors: Anthony, Mary S; Getahun, Darios; Asiimwe, Alex; et al.
Am J Obstet Gynecol. 2021 06;224(6):599.e1-599.e18. Epub 2021-01-15.
Predicting the Need for Phototherapy After Discharge
Bilirubin screening before discharge is performed to identify neonates at risk for future hyperbilirubinemia. The American Academy of Pediatrics recommends using a graph of bilirubin levels by age (the Bhutani Nomogram) to guide follow-up and a different graph to determine phototherapy recommendations. Our objective was to evaluate predictive models that incorporate the difference between the last total serum bilirubin (TSB) before discharge and the American Academy of Pediatrics phototherapy threshold (Δ-TSB) to predict a postdischarge TSB above the phototherapy threshold by using a single graph. We studied 148 162 infants born at ≥35 weeks’ gestation at 11 Kaiser Permanente Northern California facilities from 2012 to 2017 whose TSB did not exceed phototherapy levels and who did not receive phototherapy during the birth hospitalization. We compared 3 logistic models (Δ-TSB; Δ-TSB-Plus, which included additional variables; and the Bhutani Nomogram) by using the area under the receiver operating characteristic curve (AUC) in a 20% validation subset. A total of 2623 infants (1.8%) exceeded the phototherapy threshold postdischarge. The predicted probability of exceeding the phototherapy threshold after discharge ranged from 56% for a predischarge Δ-TSB 0 to 1 mg/dL below the threshold to 0.008% for Δ-TSB >7 mg/dL below the threshold. Discrimination was better for the Δ-TSB model (AUC 0.93) and the Δ-TSB-Plus model (AUC 0.95) than for the Bhutani Nomogram (AUC 0.88). The use of Δ-TSB models had excellent ability to predict postdischarge TSB above phototherapy thresholds and may be simpler to use than the Bhutani Nomogram.
Authors: Kuzniewicz, Michael W; Park, Jina; Niki, Hamid; Walsh, Eileen M; McCulloch, Charles E; Newman, Thomas B
Pediatrics. 2021 05;147(5).
DISCARDED MEDICATIONS IN VIALS ARE A SYMPTOM OF OUR HEALTH CARE SYSTEM: A CALL TO ACTION
DISCLOSURES: No funding was received for the writing of this letter. All authors were members of the National Academies study committee to which this letter refers, with Shortliffe as the chair. All committee members who contributed to the report were themselves vetted for potential conflicts of interest, as is described in the recently published version of the report. Lieu is an employee of Kaiser Permanente and the content does not represent the official views of Kaiser Permanente. The other authors have nothing to disclose.
Authors: Watanabe, Jonathan H; Lieu, Tracy; Shortliffe, Edward H
J Manag Care Spec Pharm. 2021 May;27(5):689-690.
Evaluation of sex differences in preschool children with and without autism spectrum disorder enrolled in the study to explore early development
Research in school-aged children, adolescents, and adults with autism spectrum disorder (ASD) has found sex-based differences in behavioral, developmental, and diagnostic outcomes. These findings have not been consistently replicated in preschool-aged children. We examined sex-based differences in a large sample of 2-5-year-old children with ASD symptoms in a multi-site community-based study. Based on a comprehensive evaluation, children were classified as having ASD (n = 1480, 81.55 % male) or subthreshold ASD characteristics (n = 593, 70.15 % male). Outcomes were behavior problems, developmental abilities, performance on ASD screening and diagnostic tests, and parent-reported developmental conditions diagnosed before study enrollment. We found no statistically significant sex differences in behavioral functioning, developmental functioning, performance on an ASD screening test, and developmental conditions diagnosed before study enrollment among children with ASD or subthreshold ASD characteristics. Males in both study groups had more parent reported restricted interests and repetitive behaviors than females, but these differences were small in magnitude and not clinically meaningful. Preschool males and females who showed risk for ASD were more similar than different in the outcomes assessed in our study. Future research could examine sex-based differences in ASD phenotypes as children age.
Authors: Wiggins, Lisa D; Croen, Lisa; Schieve, Laura; et al.
Res Dev Disabil. 2021 May;112:103897. Epub 2021-02-17.
Prenatal Air Pollution Exposure and Neurodevelopment: A Review and Blueprint for a Harmonized Approach within ECHO
Air pollution exposure is ubiquitous with demonstrated effects on morbidity and mortality. A growing literature suggests that prenatal air pollution exposure impacts neurodevelopment. We posit that the Environmental influences on Child Health Outcomes (ECHO) program will provide unique opportunities to fill critical knowledge gaps given the wide spatial and temporal variability of ECHO participants. We briefly describe current methods for air pollution exposure assessment, summarize existing studies of air pollution and neurodevelopment, and synthesize this information as a basis for recommendations, or a blueprint, for evaluating air pollution effects on neurodevelopmental outcomes in ECHO. We review peer-reviewed literature on prenatal air pollution exposure and neurodevelopmental outcomes, including autism spectrum disorder, attention deficit hyperactivity disorder, intelligence, general cognition, mood, and imaging measures. ECHO meta-data were compiled and evaluated to assess frequency of neurodevelopmental assessments and prenatal and infancy residential address locations. Cohort recruitment locations and enrollment years were summarized to examine potential spatial and temporal variation present in ECHO. While the literature provides compelling evidence that prenatal air pollution affects neurodevelopment, limitations in spatial and temporal exposure variation exist for current published studies. As >90% of the ECHO cohorts have collected a prenatal or infancy address, application of advanced geographic information systems-based models for common air pollutant exposures may be ideal to address limitations of published research. In ECHO we have the opportunity to pioneer unifying exposure assessment and evaluate effects across multiple periods of development and neurodevelopmental outcomes, setting the standard for evaluation of prenatal air pollution exposures with the goal of improving children’s health.
Authors: Volk, Heather E; Eskenazi, Brenda; Environmental influences on Child Health Outcomes,; et al.
Environ Res. 2021 05;196:110320. Epub 2020-10-22.
Physician Stress During Electronic Health Record Inbox Work: In Situ Measurement With Wearable Sensors
Increased work through electronic health record (EHR) messaging is frequently cited as a factor of physician burnout. However, studies to date have relied on anecdotal or self-reported measures, which limit the ability to match EHR use patterns with continuous stress patterns throughout the day. The aim of this study is to collect EHR use and physiologic stress data through unobtrusive means that provide objective and continuous measures, cluster distinct patterns of EHR inbox work, identify physicians’ daily physiologic stress patterns, and evaluate the association between EHR inbox work patterns and physician physiologic stress. Physicians were recruited from 5 medical centers. Participants (N=47) were given wrist-worn devices (Garmin Vivosmart 3) with heart rate sensors to wear for 7 days. The devices measured physiological stress throughout the day based on heart rate variability (HRV). Perceived stress was also measured with self-reports through experience sampling and a one-time survey. From the EHR system logs, the time attributed to different activities was quantified. By using a clustering algorithm, distinct inbox work patterns were identified and their associated stress measures were compared. The effects of EHR use on physician stress were examined using a generalized linear mixed effects model. Physicians spent an average of 1.08 hours doing EHR inbox work out of an average total EHR time of 3.5 hours. Patient messages accounted for most of the inbox work time (mean 37%, SD 11%). A total of 3 patterns of inbox work emerged: inbox work mostly outside work hours, inbox work mostly during work hours, and inbox work extending after hours that were mostly contiguous to work hours. Across these 3 groups, physiologic stress patterns showed 3 periods in which stress increased: in the first hour of work, early in the afternoon, and in the evening. Physicians in group 1 had the longest average stress duration during work hours (80 out of 243 min of valid HRV data; P=.02), as measured by physiological sensors. Inbox work duration, the rate of EHR window switching (moving from one screen to another), the proportion of inbox work done outside of work hours, inbox work batching, and the day of the week were each independently associated with daily stress duration (marginal R2=15%). Individual-level random effects were significant and explained most of the variation in stress (conditional R2=98%). This study is among the first to demonstrate associations between electronic inbox work and physiological stress. We identified 3 potentially modifiable factors associated with stress: EHR window switching, inbox work duration, and inbox work outside work hours. Organizations seeking to reduce physician stress may consider system-based changes to reduce EHR window switching or inbox work duration or the incorporation of inbox management time into work hours.
Authors: Akbar F; Mark G; Prausnitz S; Warton EM; East JA; Moeller MF; Reed ME; Lieu TA
JMIR Med Inform. 2021 Apr 28;9(4):e24014. Epub 2021-04-28.
Physicians’ electronic inbox work patterns and factors associated with high inbox work duration
Electronic health record systems are increasingly used to send messages to physicians, but research on physicians’ inbox use patterns is limited. This study’s aims were to (1) quantify the time primary care physicians (PCPs) spend managing inboxes; (2) describe daily patterns of inbox use; (3) investigate which types of messages consume the most time; and (4) identify factors associated with inbox work duration. We analyzed 1 month of electronic inbox data for 1275 PCPs in a large medical group and linked these data with physicians’ demographic data. PCPs spent an average of 52 minutes on inbox management on workdays, including 19 minutes (37%) outside work hours. Temporal patterns of electronic inbox use differed from other EHR functions such as charting. Patient-initiated messages (28%) and results (29%) accounted for the most inbox work time. PCPs with higher inbox work duration were more likely to be female (P < .001), have more patient encounters (P < .001), have older patients (P < .001), spend proportionally more time on patient messages (P < .001), and spend more time per message (P < .001). Compared with PCPs with the lowest duration of time on inbox work, PCPs with the highest duration had more message views per workday (200 vs 109; P < .001) and spent more time on the inbox outside work hours (30 minutes vs 9.7 minutes; P < .001). Electronic inbox work by PCPs requires roughly an hour per workday, much of which occurs outside scheduled work hours. Interventions to assist PCPs in handling patient-initiated messages and results may help alleviate inbox workload.
Authors: Akbar, Fatema; Mark, Gloria; Warton, E Margaret; Reed, Mary E; Prausnitz, Stephanie; East, Jeffrey A; Moeller, Mark F; Lieu, Tracy A
J Am Med Inform Assoc. 2021 04 23;28(5):923-930.
Development and psychometric testing of the AASPIRE Adult Autism Healthcare Provider Self-Efficacy Scale
The adult healthcare system is ill-prepared to provide high-quality care to autistic adults. Lack of provider training may contribute to the problem, but there are few previously tested survey instruments to guide provider training efforts. Our objective was to develop and test a measure of healthcare providers’ confidence (or “self-efficacy”) in providing healthcare to autistic adults and to use it to better understand their training needs. We used a community-based participatory research (CBPR) approach, in partnership with academic researchers, autistic adults, supporters, and healthcare providers, throughout the project. We developed a one-page questionnaire and surveyed 143 primary care providers from eight primary care clinics in Oregon and California, United States. Preliminary testing of the AASPIRE Adult Autism Healthcare Provider Self-Efficacy Scale suggests that the measure is reliable and valid. Using this scale, we found only a minority of providers reported high confidence in communicating with patients (25%); performing physical exams or procedures (43%); accurately diagnosing and treating other medical issues (40%); helping patients stay calm and comfortable during visits (38%); identifying accommodation needs (14%); and making necessary accommodations (16%). While providers need training across all aspects of care related to autism in adulthood, interventions should pay particular attention to helping providers communicate with patients, and identify and make necessary accommodations. Future research is needed to further validate this scale and to understand how to meet providers’ training needs most effectively.
Authors: Nicolaidis, Christina; Schnider, Gavin; Lee, Junghee; Raymaker, Dora M; Kapp, Steven K; Croen, Lisa A; Urbanowicz, Anna; Maslak, Joelle
Autism. 2021 04;25(3):767-773. Epub 2020-08-28.
Dual trajectories of physical activity and blood lipids in midlife women: The Study of Women’s Health Across the Nation
Physical activity (PA) has the potential to attenuate cardiovascular disease risk in midlife women through multiple pathways, including improving lipid profiles. Longitudinal patterns of PA and blood lipid levels have not been studied in midlife women. Our study identified trajectories of PA and blood lipids across midlife and characterized the associations between these trajectories. We evaluated 2,789 participants from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study with follow-up over the menopause transition. Women reported PA using the Kaiser Physical Activity Survey at seven study visits across 17 years of follow-up. Serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were measured at eight study visits across the same 17-year follow-up period. We used group-based trajectory models to characterize trajectories of PA and blood lipids over midlife and dual trajectory models to determine the association between PA and blood lipid trajectories adjusted for race/ethnicity, body mass index category, smoking, and lipid-lowering medication use. Women were 46 years old, on average, at study entry. Forty-nine percent were non-Hispanic white; 32 % were Black; 10 % were Japanese; and 9 % were Chinese. We identified four PA trajectories, three HDL cholesterol trajectories, four LDL cholesterol trajectories, and two triglyceride trajectories. The most frequently occurring trajectories were the consistently low PA trajectory (69 % of women), the low HDL cholesterol trajectory (43 % of women), the consistently moderate LDL cholesterol trajectory (45 % of women), and the consistently low triglycerides trajectory (90 % of women). In dual trajectory analyses, no clear associations were observed between PA trajectories and HDL cholesterol, LDL cholesterol, or triglycerides trajectories. The most frequently observed trajectories across midlife were characterized by low physical activity, low HDL cholesterol, moderate LDL cholesterol, and low triglycerides. Despite the absence of an association between long-term trajectories of PA and blood lipids in this study, a large body of evidence has established the importance of clinical and public health messaging and interventions targeted at midlife women to promote regular and sustained PA during midlife to achieve other cardiovascular and metabolic benefits.
Authors: Badon, Sylvia E; Gabriel, Kelley Pettee; Karvonen-Gutierrez, Carrie; Sternfeld, Barbara; Gold, Ellen B; Waetjen, L Elaine; Lee, Catherine; Avalos, Lyndsay A; El Khoudary, Samar R; Hedderson, Monique M
Maturitas. 2021 Apr;146:49-56. Epub 2021-02-06.
Household mold, pesticide use, and childhood asthma: A nationwide study in the U.S
To investigate the associations of household mold and pesticide use with risk of childhood asthma and examine the potential effect modification by child’s sex at a national level in the U.S. Nationally representative data were drawn from the cross-sectional 2017 and 2018 National Surveys of Children’s Health. Household mold and pesticide exposures during the past 12 months and physician-diagnosed childhood asthma were assessed by standard questionnaires administered to primary caregivers. Multivariable logistic regression models were used to calculate adjusted odds ratios (aOR) for current asthma, adjusting for child, caregiver, and household covariates. We also examined potential effect modification by child’s sex. Sampling weights accounted for the complex survey design. Among 41,423 U.S. children in 2017-2018, the weighted prevalence of current asthma was 10.8% in household mold-exposed children, compared with 7.2% in non-exposed children (P < 0.001). After adjusting for covariates including child's obesity, children with household mold exposure compared to those with no household mold exposure had a 1.41-fold (95% CI: 1.07, 1.87) higher odds of current asthma. Associations between household mold and current asthma were pronounced among boys (aOR 1.57; 95% CI: 1.03-2.38) but not girls (aOR 1.28; 0.90-1.83; P for interaction <0.001). No significant associations were observed between household pesticide use and current asthma, after adjusting for covariates. Our findings suggest that household mold is associated with current asthma among children, independent of other major risk factors including child's obesity status. Our findings may inform strategies targeting mitigation of household mold as an important indoor environment factor to address childhood asthma.
Authors: Xiao, Siyuan; Ngo, Amanda L; Mendola, Pauline; Bates, Michael N; Barcellos, Anna L; Ferrara, Assiamira; Zhu, Yeyi
Int J Hyg Environ Health. 2021 04;233:113694. Epub 2021-02-06.
Psychometric testing of a set of patient-reported instruments to assess healthcare interventions for autistic adults
Interventions to improve healthcare for autistic adults are greatly needed. To evaluate such interventions, researchers often use surveys to collect data from autistic adults (or sometimes, their supporters), but few survey measures have been tested for use with autistic adults. Our objective was to create and test a set of patient- or proxy-reported survey measures for use in studies that evaluate healthcare interventions. We used a community-based participatory research (CBPR) approach, in partnership with autistic adults, healthcare providers, and supporters. We worked together to create or adapt survey measures. Three survey measures focus on things that interventions may try to change directly: (1) how prepared patients are for visits; (2) how confident they feel in managing their health and healthcare; and (3) how well the healthcare system is making the accommodations patients feel they need. The other measures focus on the outcomes that interventions may hope to achieve: (4) improved patient-provider communication; (5) reduced barriers to care; and (6) reduced unmet healthcare needs. We then tested these measures in a survey of 244 autistic adults recruited from 12 primary care clinics in Oregon and California, USA (with 194 participating directly and 50 participating via a proxy reporter). Community partners made sure items were easy to understand and captured what was important about the underlying idea. We found the survey measures worked well in this sample. These measures may help researchers evaluate new healthcare interventions. Future research needs to assess whether interventions improve healthcare outcomes in autistic adults.
Authors: Nicolaidis, Christina; Zhen, Kelly Y; Lee, Junghee; Raymaker, Dora M; Kapp, Steven K; Croen, Lisa A; Urbanowicz, Anna; Maslak, Joelle; Scharer, Mirah
Autism. 2021 04;25(3):786-799. Epub 2020-10-25.
Healthcare service utilization and cost among transition-age youth with autism spectrum disorder and other special healthcare needs
Youth with autism spectrum disorder often have complex medical needs. Disruptions of healthcare during the transition from pediatric to adult healthcare may put youth with autism spectrum disorder at higher risk of medical emergencies and high medical costs. To understand healthcare utilization during the transition years, we conducted a study among transition-age youth (14-25 years old) receiving healthcare at Kaiser Permanente Northern California during 2014-2015. We examined differences in healthcare utilization and costs among youth with autism spectrum disorder (n = 4123), attention deficit and hyperactivity disorder (n = 20,6015), diabetes mellitus (n = 2156), and general population controls (n = 20,615). Analyses were also stratified by age and sex. Youth with autism spectrum disorder had the highest utilization of outpatient primary care, mental health, and psychotropic medications and the lowest utilization of obstetrics/gynecology and urgent care. Costs for youth with autism spectrum disorder were higher than those for attention deficit and hyperactivity disorder and general population peers and lower than for diabetes mellitus. Healthcare utilization patterns varied by age. Transition-age youth with autism spectrum disorder generally used healthcare at higher rates relative to attention deficit and hyperactivity disorder and general population peers but at similar or lower rates than diabetes mellitus peers, indicating this group’s complex combination of psychiatric and medical healthcare needs. The relatively high utilization of psychiatric services and low utilization of women’s health services in transition-age youth with autism spectrum disorder may have implications for long-term health and warrants additional research.
Authors: Ames JL; Massolo ML; Davignon MN; Qian Y; Croen LA
Autism. 2021 04;25(3):705-718. Epub 2020-06-25.
Transitioning youth with autism spectrum disorders and other special health care needs into adult primary care: A provider survey
The transition from pediatric to adult care is a critical inflection point for the long-term health of youth with autism spectrum disorders and other special health care needs. However, for many patients, their caregivers, and providers, the transition lacks coordination. This survey study demonstrates that pediatric and adult providers struggle to implement many components of transition best practices for youth with autism and other chronic conditions, highlighting the urgent need for enhanced medical coordination and additional transition training and resources.
Authors: Ames JL; Massolo ML; Davignon MN; Qian Y; Cerros HJ; Croen LA
Autism. 2021 04;25(3):731-743. Epub 2020-06-18.
Maternal health around pregnancy and autism risk: a diagnosis-wide, population-based study
Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring. This exploratory case-cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period). The analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92-3.90), p = 2.43 × 10-8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38-2.57), p = 7.06 × 10-5] and psychiatric [depressive disorder; HR = 2.11 (1.32-3.35), p = 1.70 × 10-3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54-0.71), p = 1.80 × 10-11]. Sixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.
Authors: Kodesh, Arad; Croen, Lisa; Janecka, Magdalena; et al.
Psychol Med. 2021 Mar 26:1-9.
A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California
The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.
Authors: Lyall, Kristen; Ames, Jennifer L; Croen, Lisa A; et al.
Mol Autism. 2021 03 18;12(1):24. Epub 2021-03-18.
mHealth Mindfulness Intervention for Women with Moderate-to-Moderately-Severe Antenatal Depressive Symptoms: a Pilot Study Within an Integrated Health Care System
Traditional mindfulness-based interventions have been shown to reduce depression symptoms in pregnant women, although in-person classes may pose significant accessibility barriers, particularly during the COVID-19 pandemic. Mobile technology offers greater convenience, but little is known regarding the efficacy of self-paced, mobile-delivered (mHealth) mindfulness interventions in this population. This study tested the feasibility and acceptability of offering such an intervention for pregnant women with moderate-to-moderately-severe depression symptoms. We conducted a single-arm trial within Kaiser Permanente Northern California (KPNC). Participants were identified through KPNC’s universal perinatal depression screening program. Eligible participants included English-speaking pregnant women (<28 weeks of gestation) with moderate-to-moderately-severe depressive symptoms without a regular (<3 times/week) mindfulness/meditation practice. Participants were asked to follow a self-paced, 6-week mindfulness meditation program using a mobile app, Headspace™, 10-20 min/day. Outcome measures included feasibility, acceptability, and patient-reported outcomes (e.g., depression symptoms). Of the 27 women enrolled, 20 (74%) completed the study. Over half (55%) of participants used the app ≥50% of the days during the 6-week intervention. Responses to the semi-structured interviews indicated that women appreciated the convenience of the intervention and the ability to engage without having to attend classes or arrange childcare. We observed significant improvements in pre-postintervention scores for depression symptoms, perceived stress, sleep disturbance, and mindfulness. Our study demonstrates the feasibility and acceptability of an mHealth mindfulness intervention for women with moderate-to-moderately-severe antenatal depression symptoms. The preliminary data further suggest that an efficacy trial is warranted.
Authors: Kubo, Ai; Aghaee, Sara; Kurtovich, Elaine M; Nkemere, Linda; Quesenberry, Charles P; McGinnis, MegAnn K; Avalos, Lyndsay A
Mindfulness (N Y). 2021 Mar 11:1-11.
Editorial Expression of Concern: Exposure to Magnetic Field Non-Ionizing Radiation and the Risk of Miscarriage: A Prospective Cohort Study
Authors: Li DK; Chen H; Ferber JR; Odouli R; Quesenberry C
Sci Rep. 2021 03 10;11(1):6021. Epub 2021-03-10.
Association of Cannabis Retailer Proximity and Density With Cannabis Use Among Pregnant Women in Northern California After Legalization of Cannabis for Recreational Use
Authors: Young-Wolff, Kelly C; Adams, Sara R; Padon, Alisa; Silver, Lynn D; Alexeeff, Stacey E; Van Den Eeden, Stephen K; Avalos, Lyndsay A
JAMA Netw Open. 2021 03 01;4(3):e210694. Epub 2021-03-01.
Plasma lipidomics profile in pregnancy and gestational diabetes risk: a prospective study in a multiracial/ethnic cohort
Disruption of lipid metabolism is implicated in gestational diabetes (GDM). However, prospective studies on lipidomics and GDM risk in race/ethnically diverse populations are sparse. Here, we aimed to (1) identify lipid networks in early pregnancy to mid-pregnancy that are associated with subsequent GDM risk and (2) examine the associations of lipid networks with glycemic biomarkers to understand the underlying mechanisms. This study included 107 GDM cases confirmed using the Carpenter and Coustan criteria and 214 non-GDM matched controls from the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, untargeted lipidomics data of 420 metabolites (328 annotated and 92 unannotated), and information on glycemic biomarkers in maternal plasma at visit 0 (10-14 weeks) and visit 1 (15-26 weeks). We constructed lipid networks using weighted correlation network analysis technique. We examined prospective associations of lipid networks and individual lipids with GDM risk using linear mixed effect models. Furthermore, we calculated Pearson’s partial correlation for GDM-related lipid networks and individual lipids with plasma glucose, insulin, C-peptide and glycated hemoglobin at both study visits. Lipid networks primarily characterized by elevated plasma diglycerides and short, saturated/low unsaturated triglycerides and lower plasma cholesteryl esters, sphingomyelins and phosphatidylcholines were associated with higher risk of developing GDM (false discovery rate (FDR) <0.05). Among individual lipids, 58 metabolites at visit 0 and 96 metabolites at visit 1 (40 metabolites at both time points) significantly differed between women who developed GDM and who did not (FDR <0.05). Furthermore, GDM-related lipid networks and individual lipids showed consistent correlations with maternal glycemic markers particularly in early pregnancy at visit 0. Plasma lipid metabolites in early pregnancy both individually and interactively in distinct networks were associated with subsequent GDM risk in race/ethnically diverse US women. Future research is warranted to assess lipid metabolites as etiologic markers of GDM.
Authors: Rahman, Mohammad L; Feng, Yen-Chen A; Fiehn, Oliver; Albert, Paul S; Tsai, Michael Y; Zhu, Yeyi; Wang, Xiaobin; Tekola-Ayele, Fasil; Liang, Liming; Zhang, Cuilin
BMJ Open Diabetes Res Care. 2021 03;9(1).
Gestational weight gain and adverse pregnancy outcomes by pre-pregnancy BMI category in women with chronic hypertension: A cohort study
It is important to understand relationships of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension, given their high baseline risk of adverse outcomes. We assessed associations of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension by pre-pregnancy body mass index categories. We identified 14,369 women with chronic hypertension using electronic health records from 3 integrated health care delivery systems (2005-2014). Gestational weight gain-for-gestational age charts were used to calculate gestational weight gain z-scores, which account for gestational age. Modified Poisson regression models using generalized estimating equations were used to calculate relative risks and 95% confidence intervals, adjusted for sociodemographic and medical characteristics. Preeclampsia, preterm delivery, cesarean delivery, neonatal intensive care unit admission, birthweight (extracted from the electronic health record). In women with normal weight or overweight, low gestational weight gain (z-score < -1) was associated with 27-28% greater risk of preterm delivery and 48-82% greater risk of small-for-gestational age birthweight, while high gestational weight gain (z-score > 1) was associated with 40-90% greater risk of preeclampsia and 59-113% greater risk of large-for-gestational age birthweight. In women with obesity, low gestational weight gain was associated with 27-54% lower risk of several adverse pregnancy outcomes, including preeclampsia and cesarean delivery. In women with chronic hypertension and normal weight or overweight, moderate gestational weight gain may confer the lowest risk of adverse outcomes. In women with chronic hypertension and obesity, low gestational weight gain may be necessary for the lowest risk of adverse pregnancy outcomes.
Authors: Badon, Sylvia E; Dublin, Sascha; Nance, Nerissa; Hedderson, Monique M; Neugebauer, Romain; Easterling, Thomas; Cheetham, T Craig; Chen, Lu; Holt, Victoria L; Avalos, Lyndsay A
Pregnancy Hypertens. 2021 Mar;23:27-33. Epub 2020-10-24.
Reinventing Pediatrics Through Video Care First
Authors: Lieu, Tracy A; Gizzi, Elio; Lee, Edward R
JAMA Pediatr. 2021 03 01;175(3):232-234.
Persistent organic pollutants and couple fecundability: a systematic review
Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research. We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants’ prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP. Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.
Authors: Kahn, Linda G; Harley, Kim G; Siegel, Eva L; Zhu, Yeyi; Factor-Litvak, Pam; Porucznik, Christina A; Klein-Fedyshin, Michele; Hipwell, Alison E; program collaborators for Environmental Influences on Child Health Outcomes Program,
Hum Reprod Update. 2021 02 19;27(2):339-366.
Prenatal Exposure to Mixtures of Phthalates, Parabens, and Other Phenols and Obesity in Five-Year-Olds in the CHAMACOS Cohort
Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.
Authors: Berger, Kimberly; Hyland, Carly; Ames, Jennifer L; Mora, Ana M; Huen, Karen; Eskenazi, Brenda; Holland, Nina; Harley, Kim G
Int J Environ Res Public Health. 2021 02 12;18(4). Epub 2021-02-12.
Bayesian Weighted Sums: A Flexible Approach to Estimate Summed Mixture Effects
Methods exist to study exposure mixtures, but each is distinct in the research question it aims to address. We propose a new approach focused on estimating both the summed effect and individual weights of one or multiple exposure mixtures: Bayesian Weighted Sums (BWS). We applied BWS to simulated and real datasets with correlated exposures. The analytic context in our real-world example is an estimation of the association between polybrominated diphenyl ether (PBDE) congeners (28, 47, 99, 100, and 153) and Autism Spectrum Disorder (ASD) diagnosis and Social Responsiveness Scores (SRS). Simulations demonstrate that BWS performs reliably. In adjusted models using Early Autism Risk Longitudinal Investigation (EARLI) data, the odds of ASD for a 1-unit increase in the weighted sum of PBDEs were 1.41 (95% highest posterior density 0.82, 2.50) times the odds of ASD for the unexposed and the change in z-score standardized SRS per 1 unit increase in the weighted sum of PBDEs is 0.15 (95% highest posterior density -0.08, 0.38). BWS provides a means of estimating the summed effect and weights for individual components of a mixture. This approach is distinct from other exposure mixture tools. BWS may be more flexible than existing approaches and can be specified to allow multiple exposure groups based on a priori knowledge from epidemiology or toxicology.
Authors: Hamra, Ghassan B; Maclehose, Richard F; Croen, Lisa; Kauffman, Elizabeth M; Newschaffer, Craig
Int J Environ Res Public Health. 2021 02 03;18(4). Epub 2021-02-03.
Longitudinal Associations of Midlife Accelerometer Determined Sedentary Behavior and Physical Activity With Cognitive Function: The CARDIA Study
Background To determine if accelerometer measured sedentary behavior (SED), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) in midlife is prospectively associated with cognitive function. Methods and Results Participants were 1970 adults enrolled in the CARDIA (Coronary Artery Risk Development in Young Adults) study who wore an accelerometer in 2005 to 2006 (ages 38-50 years) and had cognitive function assessments completed 5 and/or 10 years later. SED, LPA, and MVPA were measured by an ActiGraph 7164 accelerometer. Cognitive function tests included the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop Test. Compositional isotemporal substitution analysis examined associations of SED, LPA, and MVPA with repeated measures of the cognitive function standardized scores. In men, statistical reallocation of 30 minutes of LPA with 30 minutes of MVPA resulted in an estimated difference of SD 0.07 (95% CI, 0.01-0.14), SD 0.09 (95% CI, 0.02-0.17), and SD -0.11 (95% CI, -0.19 to -0.04) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating better performance. Associations were similar when reallocating time in SED with MVPA, but results were less robust. Reallocation of time in SED with LPA resulted in an estimated difference of SD -0.05 (95% CI, -0.06 to -0.03), SD -0.03 (95% CI, -0.05 to -0.01), and SD 0.05 (95% CI, 0.03- 0.07) in the Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and Stroop scores, respectively, indicating worse performance. Associations were largely nonsignificant among women. Conclusions Our findings support the idea that for men, higher-intensity activities (MVPA) may be necessary in midlife to observe beneficial associations with cognition.
Authors: Whitaker, Kara M; Zhang, Dong; Pettee Gabriel, Kelley; Ahrens, Monica; Sternfeld, Barbara; Sidney, Stephen; Jacobs, David R; Palta, Priya; Yaffe, Kristine
J Am Heart Assoc. 2021 02 02;10(3):e018350. Epub 2021-01-20.
Notice of Retraction and Replacement. Li et al. Association Between Maternal Exposure to Magnetic Field Nonionizing Radiation During Pregnancy and Risk of Attention-Deficit/Hyperactivity Disorder in Offspring in a Longitudinal Birth Cohort. JAMA Netw Open. 2020;3(3):e201417
Authors: Li DK
JAMA Netw Open. 2021 Feb 01;4(2):e2033605. Epub 2021-02-01.
Exercise During the First Trimester of Pregnancy and the Risks of Abnormal Screening and Gestational Diabetes Mellitus
To estimate the effects of exercise during the first trimester on the risks of abnormal screening and gestational diabetes mellitus (GDM). Data come from PETALS, a prospectively followed pregnancy cohort (n = 2,246, 79% minorities) receiving care at Kaiser Permanente Northern California. A Pregnancy Physical Activity Questionnaire was used to assess exercise. Glucose testing results for screening and diagnostic tests were obtained from electronic health records. Inverse probability of treatment weighting and targeted maximum likelihood with data-adaptive estimation (machine learning) of propensity scores and outcome regressions were used to obtain causal risk differences adjusted for potential confounders, including prepregnancy BMI, exercise before pregnancy, and gestational weight gain. Exercise was dichotomized at 1) the cohort’s 75th percentile for moderate- to vigorous-intensity exercise (≥13.2 MET-h per week or ≥264 min per week of moderate exercise), 2) current recommendations (≥7.5 MET-h per week or ≥150 min per week of moderate exercise), and 3) any vigorous exercise. Overall, 24.3% and 6.5% had abnormal screening and GDM, respectively. Exercise meeting or exceeding the 75th percentile decreased the risks of abnormal screening and GDM by 4.8 (95% CI 1.1, 8.5) and 2.1 (0.2, 4.1) fewer cases per 100, respectively, in adjusted analyses. Exercise reduces the risks of abnormal screening and GDM, but the amount needed to achieve these risk reductions is likely higher than current recommendations. Future interventions may consider promoting ≥38 min per day of moderate-intensity exercise to prevent GDM.
Authors: Ehrlich, Samantha F; Ferrara, Assiamira; Hedderson, Monique M; Feng, Juanran; Neugebauer, Romain
Diabetes Care. 2021 02;44(2):425-432. Epub 2020-12-21.
The Association Between Maternal Prenatal Fish Intake and Child Autism-Related Traits in the EARLI and HOME Studies
We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes.
Authors: Vecchione R; Croen LA; Lyall K; et al.
J Autism Dev Disord. 2021 Feb;51(2):487-500.
Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies
Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the ‘tails’ of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children’s ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3-8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.
Authors: Patti, Marisa A; Croen, Lisa A; Braun, Joseph M; et al.
Int J Environ Res Public Health. 2021 01 30;18(3). Epub 2021-01-30.
Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women’s Study
Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women’s Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05. Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.
Authors: Lin, Annie W; Sternfeld, Barbara; Lujan, Marla E; et al.
BMC Public Health. 2021 01 06;21(1):35. Epub 2021-01-06.
Evaluation of Attention Switching and Duration of Electronic Inbox Work Among Primary Care Physicians
Primary care physicians (PCPs) report multitasking during workdays while processing electronic inbox messages, but scant systematic information exists on attention switching and its correlates in the health care setting. To describe PCPs’ frequency of attention switching associated with electronic inbox work, identify potentially modifiable factors associated with attention switching and inbox work duration, and compare the relative association of attention switching and other factors with inbox work duration. This cross-sectional study of the work of 1275 PCPs in an integrated group serving 4.5 million patients used electronic health record (EHR) access logs from March 1 to 31, 2018, to evaluate PCPs’ frequency of attention switching. Statistical analysis was performed from October 15, 2018, to August 28, 2020. Attention switching was defined as switching between the electronic inbox, other EHR work, and non-EHR periods. Inbox work duration included minutes spent on electronic inbox message views and related EHR tasks. Multivariable models controlled for the exposures. The 1275 PCPs studied (721 women [56.5%]; mean [SD] age, 45.9 [8.5] years) had a mean (SD) of 9.0 (7.6) years of experience with the medical group and received a mean (SD) of 332.6 (148.3) (interquartile range, 252-418) new inbox messages weekly. On workdays, PCPs made a mean (SD) of 79.4 (21.8) attention switches associated with inbox work and did a mean (SD) 64.2 (18.7) minutes of inbox work over the course of 24 hours on workdays. In the model for attention switching, each additional patient secure message beyond the reference value was associated with 0.289 (95% CI, 0.217-0.362) additional switches, each additional results message was associated with 0.203 (95% CI, 0.127-0.278) additional switches, each additional request message was associated with 0.190 (95% CI, 0.124-0.257) additional switches, and each additional administrative message was associated with 0.262 (95% CI, 0.166-0.358) additional switches. Having a panel (a list of patients assigned to a primary care team) with more elderly patients (0.144 switches per percentage increase [95% CI, 0.009-0.278]) and higher inbox work duration (0.468 switches per additional minute of inbox work [95% CI, 0.411-0.524]) were also associated with higher attention switching involving the inbox. In the model for inbox work duration, each additional patient secure message beyond the reference value was associated with 0.151 (95% CI, 0.085-0.217) additional minutes, each additional results message was associated with 0.338 (95% CI, 0.272-0.404) additional minutes, each additional request message was associated with 0.101 (95% CI, 0.041-0.161) additional minutes, and each additional administrative message was associated with 0.179 (95% CI, 0.093-0.265) additional minutes. A higher percentage of the panel’s patients initiating messages (0.386 minutes per percentage increase [95% CI, 0.026-0.745]) and attention switches (0.373 minutes per switch [95% CI, 0.328-0.419]) were also associated with higher inbox work duration. In addition, working at a medical center where all PCPs had high inbox work duration was independently associated with high or low inbox work duration. This study suggests that PCPs make frequent attention switches during workdays while processing electronic inbox messages. Message quantity was associated with both attention switching and inbox work duration. Physician and patient panel characteristics had less association with attention switching and inbox work duration. Assisting PCPs with message quantity might help modulate both attention switching and inbox work duration.
Authors: Lieu, Tracy A; Warton, E Margaret; East, Jeffrey A; Moeller, Mark F; Prausnitz, Stephanie; Ballesca, Manuel; Mark, Gloria; Akbar, Fatema; Awsare, Sameer; Chen, Yi-Fen Irene; Reed, Mary E
JAMA Netw Open. 2021 01 04;4(1):e2031856. Epub 2021-01-04.
Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci. Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes. Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database. Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10-29, maternal blood early pregnancy P = 6.1 × 10-27, maternal blood late pregnancy P = 2.8 × 10-16, maternal placenta P = 5.6 × 10-15, fetal placenta P = 1.3 × 10-20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes. Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.
Authors: Bakulski, Kelly M; Croen, Lisa A; Fallin, Margaret D; et al.
Front Mol Neurosci. 2021;14:775390. Epub 2021-11-25.
Development and Validation of an Obstetric Comorbidity Risk Score for Clinical Use
Background: A comorbidity summary score may support early and systematic identification of women at high risk for adverse obstetric outcomes. The objective of this study was to conduct the initial development and validation of an obstetrics comorbidity risk score for automated implementation in the electronic health record (EHR) for clinical use. Methods: The score was developed and validated using EHR data for a retrospective cohort of pregnancies with delivery between 2010 and 2018 at Kaiser Permanente Northern California, an integrated health care system. The outcome used for model development consisted of adverse obstetric events from delivery hospitalization (e.g., eclampsia, hemorrhage, death). Candidate predictors included maternal age, parity, multiple gestation, and any maternal diagnoses assigned in health care encounters in the 12 months before admission for delivery. We used penalized regression for variable selection, logistic regression to fit the model, and internal validation for model evaluation. We also evaluated prenatal model performance at 18 weeks of pregnancy. Results: The development cohort (n = 227,405 pregnancies) had an outcome rate of 3.8% and the validation cohort (n = 41,683) had an outcome rate of 2.9%. Of 276 candidate predictors, 37 were included in the final model. The final model had a validation c-statistic of 0.72 (95% confidence interval [CI] 0.70-0.73). When evaluated at 18 weeks of pregnancy, discrimination was modestly diminished (c-statistic 0.68 [95% CI 0.67-0.70]). Conclusions: The obstetric comorbidity score demonstrated good discrimination for adverse obstetric outcomes. After additional appropriate validation, the score can be automated in the EHR to support early identification of high-risk women and assist efforts to ensure risk-appropriate maternal care.
Authors: Ruppel, Halley; Liu, Vincent X; Kipnis, Patricia; Hedderson, Monique M; Greenberg, Mara; Forquer, Heather; Lawson, Brian; Escobar, Gabriel J
Womens Health Rep (New Rochelle). 2021;2(1):507-515. Epub 2021-11-02.
COVID-19 prevalence, symptoms, and sociodemographic disparities in infection among insured pregnant women in Northern California
Research on COVID-19 during pregnancy has mainly focused on women hospitalized for COVID-19 or other reasons during their pregnancy. Little is known about COVID-19 in the general population of pregnant women. To describe the prevalence of COVID-19, symptoms, consequent healthcare use, and possible sources of COVID-19 exposure among a population-based sample of pregnant women residing in Northern California. We analyzed data from 19,458 members of Kaiser Permanente Northern California who were pregnant between January 2020 and April 2021 and responded to an online survey about COVID-19 testing, diagnosis, symptoms, and their experiences during the COVID-19 pandemic. Medical diagnosis of COVID-19 during pregnancy was defined separately by self-report and by documentation in electronic health records (EHR). We examined relationships of COVID-19 with sociodemographic factors, underlying comorbidities, and survey measures of COVID-19-like symptoms, consequent healthcare utilization, and possible COVID-19 exposures. Among 19,458 respondents, the crude prevalence of COVID-19 was 2.5% (n = 494) according to self-report and 1.4% (n = 276) according to EHR. After adjustment, the prevalence of self-reported COVID-19 was higher among women aged <25 years compared with women aged ≥35 years (prevalence ratio [PR], 1.75, 95% CI: 1.23, 2.49) and among Hispanic women compared with White women (PR, 1.91, 95% CI: 1.53, 2.37). Prevalence of self-reported COVID-19 was higher among women affected by personal or partner job loss during the pandemic (PR, 1.23, 95% CI: 1.02, 1.47) and among women living in areas of high vs. low neighborhood deprivation (PR, 1.74, 95% CI: 1.33, 2.27). We did not observe differences in self-reported COVID-19 between women with and without underlying comorbidities. Results were similar for EHR-documented COVID-19. Loss of smell or taste was a unique and common symptom reported among women with COVID-19 (42.3% in self-reported; 54.0% in EHR-documented). Among women with symptomatic COVID-19, approximately 2% were hospitalized, 71% had a telehealth visit, and 75% quarantined at home. Over a third of women with COVID-19 reported no known exposure to someone with COVID-19. Observed COVID-19 prevalence differences by sociodemographic and socioeconomic factors underscore social and health inequities among reproductive-aged women. Women with COVID-19 reported unique symptoms and low frequency of hospitalization. Many were not aware of an exposure to someone with COVID-19.
Authors: Ames, Jennifer L; Ferrara, Assiamira; Avalos, Lyndsay A; Badon, Sylvia E; Greenberg, Mara B; Hedderson, Monique M; Kuzniewicz, Michael W; Young-Wolff, Kelly C; Zerbo, Ousseny; Zhu, Yeyi; Croen, Lisa A; et al.
PLoS One. 2021;16(9):e0256891. Epub 2021-09-03.
Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts
Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate’s degree, vocational or technical training [reference category]; bachelor’s degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor’s degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor’s degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.
Authors: Dunlop, Anne L; Alvalos, Lyndsay; Hedderson, Monique M; program collaborators for Environmental Influences on Child Health Outcomes,; et al.
PLoS One. 2021;16(1):e0245064. Epub 2021-01-08.
Association between self-reported caffeine intake during pregnancy and social responsiveness scores in childhood: The EARLI and HOME studies
Maternal nutrition during gestation has been investigated for its role in child neurodevelopment. However, little is known about the potential impact of gestational caffeine exposure on child autistic behaviors. Here, we assess the relation between maternal caffeine intake during pregnancy and children’s behavioral traits related to Autism Spectrum Disorder (ASD). We harmonized data from two pregnancy cohorts, Early Autism Risk Longitudinal Investigation (EARLI) (n = 120), an enriched-risk cohort of mothers who previously had a child with ASD, from Pennsylvania, Maryland, and Northern California (2009-2012), and the Health Outcomes and Measures of the Environment (HOME) Study (n = 269), a general population cohort from Cincinnati, Ohio (2003-2006). Mothers self-reported caffeine intake twice during pregnancy. Caregivers reported child behavioral traits related to ASD using the Social Responsiveness Scale (SRS) when children were aged 3-8 years. Higher scores indicate more ASD-related behaviors. We estimated covariate-adjusted differences in continuous SRS T-scores per interquartile range increase in caffeine intake. Self-reported caffeine intake during pregnancy was positively associated with SRS T-scores among children in EARLI (β: 2.0; 95% CI -0.1, 4.0), but to a lesser extent in HOME (β: 0.6; 95% CI -0.5, 1.6). In HOME, pre-pregnancy body mass index (BMI) modified the association between caffeine intake and SRS T-scores, where more positive associations were observed among women with higher BMIs. Our findings suggest gestational caffeine intake may represent a marker of vulnerability to childhood ASD-related behaviors. Additional studies are warranted to extend these findings.
Authors: Patti, Marisa A; Braun, Joseph M; Braun, Joseph M; et al.
PLoS One. 2021;16(1):e0245079. Epub 2021-01-15.
Incidence and predictors of type 1 diabetes among younger adults aged 20-45 years: The diabetes in young adults (DiYA) study
To estimate incidence of type 1 diabetes (T1D) and to develop a T1D prediction model among young adults. Adults 20-45 years newly-diagnosed with diabetes in 2017 were identified within Kaiser Permanente’s healthcare systems in California and invited for diabetes autoantibody (DAA) testing. Multiple imputation was conducted to assign missing DAA status. The primary outcome for incidence rates (IR) and the prediction model was T1D defined by ≥1 positive DAA. Among 2,347,989 persons at risk, 7862 developed diabetes, 2063 had DAA measured, and 166 (8.0%) had ≥1 positive DAA. T1D IR (95% CI) per 100,000 person-years was 15.2 (10.2-20.1) for ages 20-29 and 38.2 (28.6-47.8) for ages 30-44 years. The age-standardized IRs were 32.5 (22.2-42.8) for men and 27.2 (21.0-34.5) for women. The age/sex-standardized IRs were 30.1 (23.5-36.8) overall; 41.4 (25.3-57.5) for Hispanics, 37.0 (11.6-62.4) for Blacks, 21.4 (14.3-28.6) for non-Hispanic Whites, and 19.4 (8.5-30.2) for Asians. Predictors of T1D among cases included female sex, younger age, lower BMI, insulin use and having T1D based on diagnostic codes. T1D may account for up to 8% of incident diabetes cases among young adults. Follow-up is needed to establish the clinical course of patients with one DAA at diagnosis.
Authors: Lawrence, Jean M; Quesenberry, Charles; Ferrara, Assiamira; et al.
Diabetes Res Clin Pract. 2021 Jan;171:108624. Epub 2020-12-15.
Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study
Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. EMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency’s Air Quality System data using the maternal residential address reported during the prenatal screening visit. Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring.
Authors: Volk, Heather E; Alexeeff, Stacey E; Croen, Lisa A; et al.
J Neurodev Disord. 2020 12 16;12(1):42. Epub 2020-12-16.
Prenatal Multivitamin Use and MTHFR Genotype Are Associated with Newborn Cord Blood DNA Methylation
Fetal development involves cellular differentiation and epigenetic changes-complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null -0.06% (95% CI: -0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.
Authors: Bakulski, Kelly M; Dou, John F; Feinberg, Jason I; Brieger, Katharine K; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Schmidt, Rebecca J; Fallin, M Daniele
Int J Environ Res Public Health. 2020 12 09;17(24). Epub 2020-12-09.
Rethinking ethical oversight in the era of the learning health system
Opportunities to advance science increasingly arise through investigations embedded within routine clinical practice in the form of learning health systems. Such activities challenge conventional approaches to research regulation that have not caught up with those opportunities, often imposing burdens generalized from riskier research. We analyze the rules and conventions in the US, demonstrating how even those rules are compatible with a much more flexible approach to participant risk, institutional oversight, participant consent, and disclosure for low-risk learning activities in all jurisdictions.
Authors: Asch, David A; Joffe, Steven; Bierer, Barbara E; Greene, Sarah M; Lieu, Tracy A; Platt, Jodyn E; Whicher, Danielle; Ahmed, Mahnoor; Platt, Richard
Healthc (Amst). 2020 Dec;8(4):100462. Epub 2020-08-25.
Maternal Vitamin D Levels During Pregnancy in Association With Autism Spectrum Disorders (ASD) or Intellectual Disability (ID) in Offspring; Exploring Non-linear Patterns and Demographic Sub-groups
Increasing vitamin D deficiency and evidence for vitamin D’s role in brain and immune function have recently led to studies of neurodevelopment; however, few are specific to autism spectrum disorder (ASD) and vitamin D in pregnancy, a likely susceptibility period. We examined this in a case-control study of 2000-2003 Southern Californian births; ASD and intellectual disability (ID) were identified through the Department of Developmental Services and controls from birth certificates (N = 534, 181, and 421, respectively, in this analysis). Total 25-Hydroxyvitamin D (25(OH)D) was measured in mid-pregnancy serum, categorized as deficient (<50 nmol/L), insufficient (50-74 nmol/L), or sufficient (≥75 nmol/L, referent category), and examined continuously (per 25 nmol/L). Crude and adjusted odds ratios (AORs) and 95% confidence intervals (95% CI) were calculated. Non-linearity was examined with cubic splines. AORs (95% CI) for ASD were 0.79 (0.49-1.3) for maternal deficiency (9.5%), 0.93 (0.68-1.3) for insufficiency (25.6%), and 0.95 (0.86, 1.05) for linear continuous 25(OH)D. Results were similarly null for ASD with or without ID, and ID only. Interactions were observed; non-Hispanic whites (NHW) (AOR = 0.82, 95% CI = 0.69-0.98) and males (AOR = 0.89, 95% CI = 0.80-0.99) had protective associations for ASD with continuous 25(OH)D. A positive association with ASD was observed in females (AOR = 1.40, 95% CI = 1.06-1.85). With splines, a non-linear inverted j-shaped pattern was seen overall (P = 0.009 for non-linearity), with the peak around 100 nmol/L; a non-linear pattern was not observed among NHW, females, nor for ID. Our findings from a large study of ASD and prenatal vitamin D levels indicate that further research is needed to investigate non-linear patterns and potentially vulnerable sub-groups. LAY SUMMARY: We studied whether mothers' vitamin D levels during pregnancy were related to their children having autism (or low IQ) later. Low vitamin D levels were not related to greater risk of autism or low IQ in children overall. With higher levels of mothers' vitamin D, risk of autism went down in boys, but went up in girls. Risk of autism also went down in children of non-Hispanic white mothers with higher vitamin D levels, but we did not find a relation in other race/ethnic groups.
Authors: Windham, Gayle C; Pearl, Michelle; Poon, Victor; Berger, Kimberly; Soriano, Jasmine W; Eyles, Darryl; Lyall, Kristen; Kharrazi, Martin; Croen, Lisa A
Autism Res. 2020 12;13(12):2216-2229. Epub 2020-11-02.
Antibiotic stewardship for early-onset sepsis
Antibiotics are administered to the vast majority of preterm newborns and to a substantial proportion of term infants in the hours after birth due to risk for early-onset sepsis. The approaches taken to determine which newborns should be evaluated for early-onset sepsis, and what type and duration of antibiotics are administered, are important elements of neonatal antibiotic stewardship. The use of multivariate prediction models for sepsis risk assessment among infants born ≥35 weeks’ gestation can safely reduce the use of empiric antibiotic therapy. Approaches incorporating serial physical examination may also contribute to decreasing empiric antibiotic exposure among such infants. Among infants born <35 weeks' gestation, delivery characteristics can be used to identify preterm infants at low enough risk of early infection that empiric therapies are not required. Data informing the epidemiology, microbiology and antibiotic susceptibility patterns of early-onset sepsis pathogens can be used to optimize antibiotic choice for empiric and targeted antibiotic therapy to ensure that effective therapies are administered, while decreasing the risks associated with broad-spectrum antibiotic exposure. Optimal use of blood culture and time to positivity data can also contribute to decreasing the risks associated with prolonged antibiotic administration in the face of sterile cultures.
Authors: Kuzniewicz, Michael W; Puopolo, Karen M
Semin Perinatol. 2020 Dec;44(8):151325. Epub 2020-10-12.
Impact of nulliparity, hypertensive disorders of pregnancy, and gestational diabetes on vasomotor symptoms in midlife women
To determine whether women with a history of nulliparity, hypertensive disorders of pregnancy (HDP), or gestational diabetes mellitus (GDM) have a higher odds of reporting vasomotor symptoms (VMS) at midlife. A longitudinal analysis was performed with 2,249 women with pregnancy history data in the Study of Women’s Health Across the Nation. Women were classified as nulliparous, no HDP/GDM, or a history of HDP/GDM. VMS (hot flashes, night sweats) were assessed separately at baseline and at each follow-up visit. VMS was recorded as any versus none; 0 , 1-5 , 6+ days in past 2 weeks. Pregnancy history was examined in relation to each VMS (hot flashes, night sweats) using generalized estimating equations adjusting for age (time-varying), site, race/ethnicity, education, financial strain, smoking, and body mass index. Models excluded women with hysterectomy/bilateral oophorectomy and observations with hormone therapy use. Women in the HDP/GDM group (n = 208, 9%) were more likely to be Black, financially strained, and overweight. Compared to women with no HDP/GDM, women with HDP/GDM had greater odds of reporting any hot flashes (OR:1.27; 95% CI:1.05-1.53). Nulliparous women had lower odds of any hot flashes (OR:0.64; 95% CI:0.51-0.80) and night sweats (OR:0.73; 95% CI:0.58-0.93) in age-adjusted models. Similar patterns were observed for frequency of hot flashes and night sweats; associations were attenuated to nonsignificance after adjusting for covariates. History of HDP/GDM may be associated with more VMS and nulliparity with fewer VMS, but not independently of sociodemographic factors. Our findings underscore the importance of social and economic disparities in both reproductive outcomes and VMS. VIDEO SUMMARY:: https://links.lww.com/MENO/A631. https://links.lww.com/MENO/A631.
Authors: Cortés, Yamnia I; Conant, Rhoda; Catov, Janet M; Matthews, Karen A; Crawford, Sybil L; Hedderson, Monique M; Thurston, Rebecca C
Menopause. 2020 12;27(12):1363-1370.
Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort
Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results. To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS. Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63). Limitations Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium. This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies.
Authors: Terloyeva, Dina; Croen, Lisa A; Snyder, Nathaniel W; et al.
Mol Autism. 2020 11 23;11(1):93. Epub 2020-11-23.
Plasma Phospholipid n-3/n-6 Polyunsaturated Fatty Acids and Desaturase Activities in Relation to Moderate-to-Vigorous Physical Activity through Pregnancy: A Longitudinal Study within the NICHD Fetal Growth Studies
Maternal plasma phospholipid polyunsaturated fatty acids (PUFAs) play critical roles in maternal health and fetal development. Beyond dietary factors, maternal moderate-to-vigorous physical activity (MVPA) has been linked to multiple health benefits for both the mother and offspring, but studies investigating the influence of maternal MVPA on maternal PUFA profile are scarce. The objective of present study was to examine the time-specific and prospective associations of MVPA with plasma PUFA profile among pregnant women. This study included 321 participants from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10-14, 15-26, 23-31, and 33-39 gestational weeks (GW)). Associations of maternal MVPA with individual plasma PUFAs and desaturase activity were examined using generalized linear models. Maternal MVPA was associated inversely with plasma phospholipid linoleic acid, gamma-linolenic acid, and Δ6-desaturase in late pregnancy (23-31 or 33-39 GW), independent of maternal age, race, education, parity, pre-pregnancy body mass index, and dietary factors. Findings from this longitudinal study indicate that maternal habitual MVPA may play a role on PUFAs metabolism, particular by alerting plasma n-6 subclass and desaturase activity in late pregnancy. These associations are novel and merit confirmation in future studies.
Authors: Chen, Liwei; Zhu, Yeyi; Zhang, Cuilin; et al.
Nutrients. 2020 Nov 19;12(11). Epub 2020-11-19.
A Mobile Health Mindfulness Intervention for Women With Moderate to Moderately Severe Postpartum Depressive Symptoms: Feasibility Study
Approximately 20% of women suffer from postpartum depression (PPD). Due to barriers such as limited access to care, half of the women with PPD do not receive treatment. Therefore, it is critical to identify effective and scalable interventions. Traditional mindfulness programs have been effective in reducing depressive symptoms, however access remains a barrier. A self-paced mobile health (mHealth) mindfulness program may fit the lifestyle of busy mothers who are unable to attend in-person classes. However, little is known regarding the feasibility or efficacy of mHealth mindfulness interventions in postpartum women with depressive symptoms. This study aims to assess the feasibility, acceptability, and preliminary efficacy of an mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms. We conducted a single-arm feasibility trial of an mHealth mindfulness intervention within Kaiser Permanente Northern California (KPNC), a large integrated health care system. Participants were identified through clinician referral and electronic health records via KPNC’s universal perinatal depression screening program and recruited by the study team. Inclusion criteria included the following: English-speaking, up to 6 months postpartum with a Patient Health Questionnaire (PHQ-8) score of 10 to 19, and no regular mindfulness/meditation practice. Participants were asked to use a mindfulness app, Headspace, 10 to 20 min/day for 6 weeks. Baseline and postintervention surveys captured data on patient-reported outcomes (depression and stress symptoms, sleep quality, and mindfulness). Semistructured interviews captured acceptability. Retention and adherence were used to assess feasibility. Of the 115 women who were contacted and met the eligibility criteria or declined participation before eligibility assessment, 27 (23%) were enrolled. In addition, 70% (19/27) completed the study. The mean age of participants was 31 years (SD 5.2), 30% (8/27) were non-Hispanic White, and, on average, participants were 12.3 weeks postpartum (SD 5.7). Of the women who completed the study, 100% (19/19) used the Headspace app at least once, and nearly half (9/19, 47%) used the app on ≥50% of the days during the 6-week intervention period. Of the 16 participants who completed the postintervention interview, 69% (11/16) reported that they were very or extremely satisfied with the app. Interviews indicated that women appreciated the variety of meditations and felt that the program led to reduced anxiety and improved sleep. Significant improvements in pre- and postintervention scores were observed for depressive symptoms (PHQ-8: -3.8, P=.004), perceived stress (10-item Perceived Stress Scale: -6.0, P=.005), and sleep quality (Pittsburgh Sleep Quality Index: -2.1, P=.02, indicating less sleep disturbance). Improvements in mindfulness were also significant (Five Facet Mindfulness Questionnaire-Short Form: 10.9, P=.01). An mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms is feasible and acceptable. An efficacy trial is warranted.
Authors: Avalos, Lyndsay A; Aghaee, Sara; Kurtovich, Elaine; Quesenberry, Charles; Nkemere, Linda; McGinnis, MegAnn K; Kubo, Ai
JMIR Ment Health. 2020 Nov 12;7(11):e17405. Epub 2020-11-12.
Translating Research on Diabetes and Obesity in Pregnancy Into Prevention: The 2019 Norbert Freinkel Award Lecture
Epidemiological studies on the intergenerational transmission of hyperglycemia and obesity via in utero exposure have established the scientific foundation for the vicious cycle of diabetes and obesity. The findings compel us to address an urgent public health question: how do we break this vicious cycle and implement upstream prevention strategies that are feasible for patients and health care delivery systems? To address this question, it is necessary to work across a continuum of translational research from basic science, epidemiology, and efficacy trials to pragmatic trials, which, along with evaluations of health programs, may lead to implementation of positive changes in clinical care. Three strategies for translating research on diabetes and obesity in pregnancy into prevention are discussed: 1) identifying diagnostic criteria of gestational diabetes mellitus (GDM) practicable in clinical settings to implement treatment and prevention, 2) examining trends in the prevalence of diabetes in pregnancy and related complications across racial/ethnic groups to plan prevention efforts, and 3) developing and evaluating scalable upstream diabetes and obesity prevention interventions. Upstream preventive interventions aimed at breaking the vicious cycle are discussed. Areas of future research needed to break the vicious cycle are identified. Evaluating the effectiveness of programs for the management of pregnancy hyperglycemia is necessary to reduce complications. Understanding racial/ethnic differences in the pathophysiology of GDM and its complications will be important for risk stratification. Pragmatic trials in real-world clinical settings for upstream prevention are needed to break the vicious cycle at the population level. Finally, leveraging basic science with intergenerational studies will inform targeted interventions.
Authors: Ferrara, Assiamira
Diabetes Care. 2020 11;43(11):2635-2642.
Validity of diagnosis and procedure codes for identifying neural tube defects in infants
The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database. This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported. The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants’ medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs. Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.
Authors: Cheetham, T Craig; Li, De-Kun; Boudreau, Denise M; et al.
Pharmacoepidemiol Drug Saf. 2020 11;29(11):1489-1493. Epub 2020-09-15.
Understanding Racial/Ethnic Disparities in Physical Performance in Mid-Life Women: Findings from SWAN (Study of Women’s Health Across the Nation)
Evaluate degree to which racial/ethnic differences in physical performance are mediated by sociodemographic, health, behavioral, and psychosocial factors. Physical performance was evaluated using a decile score derived from grip strength, timed 4 m walk, and timed repeat chair stand in 1,855 African American, Caucasian, Chinese, Hispanic, and Japanese women, mean age = 61.8 (SD = 2.7) in the Study of Women’s Health Across the Nation. Mediators included education, financial strain, comorbidities, pain, body mass index (BMI), physical activity, and perceived stress. Structural equation models provided estimates of the total difference in physical performance between Caucasians and each race/ethnic groups and differences due to direct effects of race/ethnicity and indirect effects through mediators. The mean decile score for Caucasian women was 16.9 (SD = 5.6), 1.8, 2.6, and 2.1 points higher than the model-estimated scores in African Americans, Hispanics and Chinese, respectively, and 1.3 points lower than the Japanese. Differences between Caucasians and the Chinese and Japanese were direct effects of race/ethnicity whereas in African Americans and Hispanics 75% or more of that disparity was through mediators, particularly education, financial strain, BMI, physical activity, and pain. Addressing issues of poverty, racial inequality, pain, and obesity could reduce some racial/ethnic disparity in functional limitations as women age.
Authors: Sternfeld B; Colvin A; Stewart A; Appelhans BM; Cauley JA; Dugan SA; El Khoudary SR; Greendale GA; Strotmeyer E; Karvonen-Gutierrez C
J Gerontol B Psychol Sci Soc Sci. 2020 10 16;75(9):1961-1971.
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes. We performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females. We identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development. At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.
Authors: Mordaunt, Charles E; Newschaffer, Craig J; LaSalle, Janine M; et al.
Genome Med. 2020 10 14;12(1):88. Epub 2020-10-14.
Gestational weight gain, birthweight and early-childhood obesity: between- and within-family comparisons
Associations of excessive gestational weight gain (GWG) with greater birthweight and childhood obesity may be confounded by shared familial environment or genetics. Sibling comparisons can minimize variation in these confounders because siblings grow up in similar environments and share the same genetic predisposition for weight gain. We identified 96 289 women with live births in 2008-2014 at Kaiser Permanente Northern California. Fifteen percent of women (N = 14 417) had at least two births during the study period for sibling analyses. We assessed associations of GWG according to the Institute of Medicine (IOM) recommendations with birthweight and obesity at age 3 years, using conventional analyses comparing outcomes between mothers and sibling analyses comparing outcomes within mothers, which control for stable within-family unmeasured confounders such as familial environment and genetics. We used generalized estimating-equations and fixed-effects models. In conventional analyses, GWG above the IOM recommendations was associated with 88% greater odds of large-for-gestational age birthweight [95% confidence interval (CI): 1.80, 1.97] and 30% greater odds of obesity at 3 years old (95% CI: 1.24, 1.37) compared with GWG within the IOM recommendations. In sibling analyses, GWG above the IOM recommendations was also associated with greater odds of large-for-gestational age [odds ratio (OR): 1.36; 95% CI: 1.20, 1.54], but was not associated with obesity at 3 years old (OR = 0.98; 95% CI: 0.84, 1.15). GWG likely has a direct impact on birthweight; however, shared environmental and lifestyle factors within families may play a larger role in determining early-childhood weight status and obesity risk than GWG.
Authors: Badon, Sylvia E; Quesenberry, Charles P; Xu, Fei; Avalos, Lyndsay A; Hedderson, Monique M
Int J Epidemiol. 2020 10 01;49(5):1682-1690.
Feasibility of Measuring Preferences for Chemotherapy Among Early-Stage Breast Cancer Survivors Using a Direct Rank Ordering Multicriteria Decision Analysis Versus a Time Trade-Off
Chemotherapy is increasingly a preference-based choice among women diagnosed with early-stage breast cancer. Multicriteria decision analysis (MCDA) is a promising but underutilized method to facilitate shared decision making. We explored the feasibility of conducting an MCDA using direct rank ordering versus a time trade-off (TTO) to assess chemotherapy choice in a large population-based sample. We surveyed 904 early-stage breast cancer survivors who were within 5 years of diagnosis and reported to the Western Washington State Cancer System and Kaiser Permanente Northern California registries. Direct rank ordering of 11 criteria and TTO surveys were conducted from September 2015 to July 2016; clinical data were obtained from registries or medical records. Multivariable regressions estimated post hoc associations between the MCDA, TTO, and self-reported chemotherapy receipt, considering covariates. Survivors ranged in age from 25 to 74 years and 73.9% had stage I tumors. The response rate for the rank ordering was 81.0%; TTO score was 94.2%. A one-standard deviation increase in the difference between the chemotherapy and no chemotherapy MCDA scores was associated with a 75.1% (95% confidence interval 43.9-109.7%; p < 0.001) increase in the adjusted odds of having received chemotherapy; no association was found between the TTO score and chemotherapy receipt. A rank-order-based MCDA was feasible and was associated with chemotherapy choice. Future research should consider developing and testing this MCDA for use in clinical encounters. Additional research is required to develop a TTO-based model and test its properties against a pragmatic MCDA to inform future shared decision-making tools.
Authors: Panattoni L; Phelps CE; Lieu TA; Alexeeff S; O'Neill S; Mandelblatt JS; Ramsey SD
Patient. 2020 10;13(5):557-566.
Cesarean Delivery and the Risk of Allergic Rhinitis in Children
Cesarean delivery (C-section) may influence the infant microbiome and affect immune system development and subsequent risk for allergic rhinitis (AR). To investigate the association between C-section and AR at ages 6, 8, and 10 years. Data were collected prospectively through Kaiser Permanente Northern Californias (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital and remained in the KPNC system for minimum 6 years (n = 117,768 age 6; n = 75,115 age 8; n = 40,332 age 10). Risk ratios (RR) for C-section and AR were estimated at each follow-up age and adjusted for important covariates, including intrapartum antibiotics, pre-pregnancy body mass index, maternal allergic morbidities, and breastfeeding. Subanalyses considered information on C-section indication, labor, and membrane rupture. After adjusting for confounders, we did not observe an association between C-section and AR at follow-up ages 6, 8, or 10 years (RR [CI]: 6 years, 0.98 [0.91, 1.04]; 8 years, 1.00 [0.95, 1.07]; 10 years, 1.03 [0.96, 1.10]). In stratified analyses, there was limited evidence that C-section increases the risk of AR in certain subgroups (eg, children of non-atopic mothers, second or higher birth order children), but most estimated risk ratios were consistent with no association. Estimated associations were unaffected by participant attrition, missing data, or intrapartum antibiotics. C-section delivery was not associated with AR at follow-up ages of 6, 8, or 10 years in a large contemporary US cohort.
Authors: Richards M; Ferber J; Li DK; Darrow LA
Ann Allergy Asthma Immunol. 2020 09;125(3):280-286.e5. Epub 2020-05-06.
Nut Consumption and Renal Function Among Women With a History of Gestational Diabetes
Nut intake has been associated with reduced cardiometabolic risk, but few studies have examined its association with renal function. We examined associations between nut intake and renal function among women with previous gestational diabetes mellitus (GDM), a population with an increased risk for renal dysfunction. This study included 607 women with a history of GDM who participated in the Diabetes & Women’s Health Study (2012-2014) follow-up clinical examination in Denmark. At the clinic, biospecimens were collected, and habitual intake of nuts (9 types) in the past year was assessed using a food frequency questionnaire. A total of 330 women free of major chronic diseases were included in the analysis. Total nut intake was classified as none (≤1 serving/month), monthly (2-3 servings/month), weekly (1-6 servings/week), and daily (≥1 serving/day). One serving was defined as 28 g. Renal function markers included estimated glomerular rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), calculated based on plasma creatinine (mg/dL), and urinary albumin (mg/L), and creatinine (mg/dL) measurements, respectively. We estimated percent differences with 95% confidence intervals for each outcome by nut intake, adjusted for current body mass index, age, physical activity, energy intake, alcohol consumption, and vegetables intake. We observed a nonlinear association between total nut intake and UACR with lowest UACR values among women with weekly intake. Compared to women with weekly intake (n = 222), the adjusted UACR values were higher by 86% [95% confidence interval: 15%, 202%], 24% [-1%, 54%], and 117% [22%, 288%] among women with no (n = 13), monthly (n = 86), and daily (n = 9) intake, respectively. Compared to weekly consumers, daily nut consumers also had 9% [0%, 19%] significantly higher eGFR values, but eGFR values were similar among women with no and monthly intake. Moderate nut consumption may be beneficial to kidney health among women with prior GDM.
Authors: Ajjarapu AS; Zhu Y; Zhang C; et al.
J Ren Nutr. 2020 09;30(5):415-422. Epub 2020-01-17.
Body mass index versus bioelectrical impedance analysis for classifying physical function impairment in a racially diverse cohort of midlife women: the Study of Women’s Health Across the Nation (SWAN)
Body composition strongly influences physical function in older adults. Bioelectrical impedance analysis (BIA) differentiates fat mass from skeletal muscle mass, and may be more useful than body mass index (BMI) for classifying women on their likelihood of physical function impairment. This study tested whether BIA-derived estimates of percentage body fat (%BF) and height-normalized skeletal muscle mass (skeletal muscle mass index; SMI) enhance classification of physical function impairment relative to BMI. Black, White, Chinese, and Japanese midlife women (N = 1482) in the Study of Women’s Health Across the Nation (SWAN) completed performance-based measures of physical function. BMI (kg/m2) was calculated. %BF and SMI were derived through BIA. Receiver-operating characteristic (ROC) curve analysis, conducted in the overall sample and stratified by racial group, evaluated optimal cutpoints of BMI, %BF, and SMI for classifying women on moderate-severe physical function impairment. In the overall sample, a BMI cutpoint of ≥ 30.1 kg/m2 correctly classified 71.1% of women on physical function impairment, and optimal cutpoints for %BF (≥ 43.4%) and SMI (≥ 8.1 kg/m2) correctly classified 69% and 62% of women, respectively. SMI did not meaningfully enhanced classification relative to BMI (change in area under the ROC curve = 0.002; net reclassification improvement = 0.021; integrated discrimination improvement = - 0.003). Optimal cutpoints for BMI, %BF, and SMI varied substantially across race. Among Black women, a %BF cutpoint of 43.9% performed somewhat better than BMI (change in area under the ROC curve = 0.017; sensitivity = 0.69, specificity = 0.64). Some race-specific BMI and %BF cutpoints have moderate utility for identifying impaired physical function among midlife women.
Authors: Appelhans BM; Lange-Maia BS; Pettee Gabriel K; Karvonen-Gutierrez C; Karavolos K; Dugan SA; Greendale GA; Avery EF; Sternfeld B; Janssen I; Kravitz HM
Aging Clin Exp Res. 2020 Sep;32(9):1739-1747. Epub 2019-10-04.
Study protocol: Using peer support to aid in prevention and treatment in prediabetes (UPSTART)
There is an urgent need to develop and evaluate effective and scalable interventions to prevent or delay the onset of type 2 diabetes mellitus (T2DM). In this randomized controlled pragmatic trial, 296 adults with prediabetes will be randomized to either a peer support arm or enhanced usual care. Participants in the peer support arm meet face-to-face initially with a trained peer coach who also is a patient at the same health center to receive information on locally available wellness and diabetes prevention programs, discuss behavioral goals related to diabetes prevention, and develop an action plan for the next week to meet their goals. Over six months, peer coaches call their assigned participants weekly to provide support for weekly action steps. In the final 6 months, coaches call participants at least once monthly. Participants in the enhanced usual care arm receive information on local resources and periodic updates on available diabetes prevention programs and resources. Changes in A1c, weight, waist circumference and other patient-centered outcomes and mediators and moderators of intervention effects will be assessed. At least 296 participants and approximately 75 peer supporters will be enrolled. Despite evidence that healthy lifestyle interventions can improve health behaviors and reduce risk for T2DM, engagement in recommended behavior change is low. This is especially true among racial and ethnic minority and low-income adults. Regular outreach and ongoing support from a peer coach may help participants to initiate and sustain healthy behavior changes to reduce their risk of diabetes. The ClinicalTrials.gov registration number is NCT03689530.
Authors: Heisler M; Adams A; Hedderson M; Schmittdiel JA; et al.
Contemp Clin Trials. 2020 08;95:106048. Epub 2020-06-01.
Adipokines in early and mid-pregnancy and subsequent risk of gestational diabetes: a longitudinal study in a multiracial cohort
Several adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a panel of adipokines in early and mid-pregnancy with GDM risk. Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n=2802), a panel of 10 adipokines (plasma fatty acid binding protein-4 (FABP4), chemerin, interleukin-6 (IL-6), leptin, soluble leptin receptor (sOB-R), adiponectin, omentin-1, vaspin, and retinol binding protein-4) were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used to estimate ORs of each adipokine and GDM, controlling for known GDM risk factors including pre-pregnancy body mass index. Throughout pregnancy changes in chemerin, sOB-R, adiponectin, and high-molecular-weight adiponectin (HMW-adiponectin) concentrations from 10-14 to 15-26 GWs were significantly different among GDM cases compared with non-GDM controls. In early and mid-pregnancy, FABP4, chemerin, IL-6 and leptin were positively associated with increased GDM risk. For instance, at 10-14 GWs, the OR comparing the highest versus lowest quartile (ORQ4-Q1) of FABP4 was 3.79 (95% CI 1.63 to 8.85). In contrast, in both early and mid-pregnancy adiponectin (eg, ORQ4-Q1 0.14 (0.05, 0.34) during 10-14 GWs) and sOB-R (ORQ4-Q1 0.23 (0.11, 0.50) during 10-14 GWs) were inversely related to GDM risk. At 10-14 GWs a model that included conventional GDM risk factors and FABP4, chemerin, sOB-R, and HMW-adiponectin improved the estimated prediction (area under the curve) from 0.71 (95% CI 0.66 to 0.77) to 0.77 (95% CI 0.72 to 0.82). A panel of understudied adipokines including FABP4, chemerin, and sOB-R may be implicated in the pathogenesis of GDM with significant associations detected approximately 10-18 weeks before typical GDM screening.
Authors: Francis, Ellen C; Zhu, Yeyi; Zhang, Cuilin; et al.
BMJ Open Diabetes Res Care. 2020 07;8(1).
Time to Positivity of Neonatal Blood Cultures for Early-onset Sepsis
In newborns at risk for early-onset sepsis, empiric antibiotics are often initiated while awaiting the results of blood cultures. The duration of empiric therapy can be guided by the time to positivity (TTP) of blood cultures. The objective of the study was to determine the TTP of neonatal blood cultures for early-onset sepsis and the factors which may impact TTP. Observational study of blood cultures growing pathogenic species obtained within 72 hours of birth from infants born at 23-42 weeks gestation, at 19 hospitals in Northern California, Boston, and Philadelphia. TTP was defined as the time from blood culture collection to the time organism growth was reported by the microbiology laboratory. A total of 594 blood cultures growing pathogenic bacteria were identified. Group B Streptococcus and Escherichia coli accounted for 74% of blood culture isolates. Median TTP was 21.0 hours (interquartile range, 17.1-25.3 hours). Blood cultures were identified as positive by 24 hours after they were obtained in 68% of cases; by 36 hours in 94% of cases; and by 48 hours in 97% of cases. Neither the administration of maternal intrapartum antibiotic prophylaxis, gestational age <35 weeks, nor blood culture system impacted median TTP. Pathogens are isolated by 36 hours after blood culture collection in 94% of neonatal early blood cultures, regardless of maternal antibiotic administration. TTP information can inform decisions regarding the duration of empiric neonatal antibiotic therapies.
Authors: Kuzniewicz MW; Mukhopadhyay S; Li S; Walsh EM; Puopolo KM
Pediatr Infect Dis J. 2020 07;39(7):634-640.
Cesarean Delivery and the Risk of Atopic Dermatitis in Children
Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. Maternal and child information was collected through Kaiser Permanente Northern California’s (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.
Authors: Richards M; Ferber J; Chen H; Swor E; Quesenberry CP; Li DK; Darrow LA
Clin Exp Allergy. 2020 07;50(7):805-814. Epub 2020-06-11.
Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications
Breast cancer risk has been extensively studied in women with genetic predisposition, i.e. BRCA1/2. Though there are guidelines for performing bilateral salpingo-oophorectomies in individuals with specific genetic risks, oophorectomies are also performed in many average-risk women. The risk of breast cancer in average risk women who undergo hysterectomy with bilateral salpingo-oophorectomy for benign indications is less clear. We aim to estimate breast cancer risk following hysterectomy with and without concomitant bilateral salpingo-oophorectomy for benign indications. From 2001 to 2015, women aged 18 and older from Kaiser Permanente Northern California who underwent hysterectomy alone and hysterectomy with bilateral salpingo-oophorectomy were identified using ICD-9 procedure and CPT codes. Women with a BRCA mutation and prior history of breast or gynecologic cancer were excluded. Descriptive and bivariate analyses were used to describe and compare demographic and clinical characteristics. Breast cancer incidence rates were calculated per 100,000 person-years. Survival analysis and Cox proportional hazard models were conducted to compare risk of developing breast cancer. Of 49,215 women who underwent hysterectomy, 19,826 had hysterectomy with bilateral salpingo-oophorectomy. Whites comprised 51.2%, Hispanics 20.3%, Blacks 12.7%, Asians 10.4%, and other/unknown 5.3% of the study population. The average age of women with hysterectomy only was 45.5 compared to 50.8 with hysterectomy with bilateral salpingo-oophorectomy. During the study period, 915 women were diagnosed with breast cancer. Age-specific breast cancer incidence rates were higher in women over 60 with oophorectomy compared with hysterectomy alone (471.2 [95% CI 386.2-556.2] vs. 463.0 [95% CI 349.6-576.5], respectively). After controlling for age, race, income, and Charlson comorbidity index, women with bilateral salpingo-oophorectomy had a 14% lower risk of breast cancer compared with women with hysterectomy only (HR=0.86, 95% CI 0.75-0.98). All-cause mortality was higher with oophorectomy versus hysterectomy only (64.4% vs. 35.6%, p
Authors: Chow S; Raine-Bennett T; Samant ND; Postlethwaite DA; Holzapfel M
Am J Obstet Gynecol. 2020 Jun 22.
Prenatal bisphenol A exposure, fetal thyroid hormones and neurobehavioral development in children at 2 and 4 years: A prospective cohort study
Findings about the association between prenatal Bisphenol A (BPA) exposure and neurobehavioral development in children are still inconsistent. In addition, whether fetal thyroid hormones (THs) mediate the reported association remains unclear. The present study aimed to examine the association between prenatal BPA exposure and risks of child behavioral problems at 2 and 4 years of age and whether the association could be explained by alteration of fetal THs as measured in cord plasma. Using the Shanghai-Minhang Birth Cohort Study (S-MBCS), BPA concentration was measured in maternal urine samples collected at 12-16 weeks of gestation. Children’s neurobehavioral development was assessed using the Child Behavior Checklist/1.5-5 (CBCL), at 2 and 4 years of age. Using generalized estimating equation (GEE) models, 745 mother-pairs were included to examine associations of BPA with CBCL scores, Using multiple linear regression models, 348 mother-pairs were included to evaluate the association between maternal BPA and THs in cord plasma. A mediation analysis was conducted to explore the potential mediating role of THs. After adjusting for potential confounders, prenatal BPA level was associated with increased risks of Emotionally Reactive problem, Anxious/Depressed problem, having Somatic Complaints, exhibiting Aggressive Behavior, and Internalizing and Externalizing Problems: compared to the lowest tertile, the risks in the highest tertile and middle tertile, ranged between 1.55-fold (95% CI: 1.09, 2.21) and 2.59-fold (95% CI: 1.52, 4.42). The association was more pronounced among boys. None of the associations reached statistical significance among girls. An inverse association between prenatal BPA and fetal TH level was also observed. However, the observed neurotoxic effects of prenatal BPA exposure did not appear to be mediated by THs levels. The current findings suggest that prenatal exposure to BPA may disrupt fetal THs levels and may induce long-lasting behavioral alterations, especially in boys.
Authors: Li F; Yang F; Li DK; Tian Y; Miao M; Zhang Y; Ji H; Yuan W; Liang H
Sci Total Environ. 2020 Jun 20;722:137887. Epub 2020-03-12.
Alternative Wear-time Estimation Methods Compared to Traditional Diary Logs for Wrist-Worn ActiGraph Accelerometers in Pregnant Women
This study sought to compare three sensor-based wear-time estimation methods to conventional diaries for ActiGraph wGT3X-BT accelerometers worn on the non-dominant wrist in early pregnancy. Pregnant women (n= 108) wore ActiGraph wGT3X-BT accelerometers for 7 days and recorded their device on and off times in a diary (criterion). Average daily wear-time estimates from the Troiano and Choi algorithms and the wGT3X-BT accelerometer wear sensor were compared against the diary. The Hibbing 2-regression model was used to estimate time spent in activity (during periods of device wear) for each method. Wear-time and time spent in activity were compared with multiple repeated measures ANOVAs. Bland Altman plots assessed agreement between methods. Compared to the diary [825.5 minutes (795.1, 856.0)], the Choi [843.0 (95% CI 812.6, 873.5)] and Troiano [839.1 (808.7, 869.6)] algorithms slightly overestimated wear-time, whereas the sensor [774.4 (743.9, 804.9)] underestimated it, although only the sensor differed significantly from the diary (P < .0001). Upon adjustment for average daily wear-time, there were no statistically significant differences between the wear-time methods in regards to minutes per day of moderate to vigorous physical activity (MVPA), vigorous PA, and moderate PA. Bland Altman plots indicated the Troiano and Choi algorithms were similar to the diary and within ≤ 0.5% of each other for wear-time and MVPA. The Choi or Troiano algorithms offer a valid and efficient alternative to diaries for the estimation daily wear-time in larger-scale studies of MVPA during pregnancy, and reduce burden for study participants and research staff.
Authors: Ehrlich, Samantha F; Casteel, Amanda J; Crouter, Scott E; Hibbing, Paul R; Hedderson, Monique M; Brown, Susan D; Galarce, Maren; Coe, Dawn P; Bassett, David R; Ferrara, Assiamira
J Meas Phys Behav. 2020 Jun;3(2):110-117.
Behavioural and psychosocial factors associated with 5-year weight trajectories within the PORTAL Overweight/Obesity Cohort
The purpose of this study was to model weight trajectories over a 5-year time period (2012-2016) and their association with behavioural and psychosocial characteristics and health care-related experiences using data from the Patient Outcomes Research to Advance Learning (PORTAL) overweight/obesity cohort. Weight trajectories for each eligible patient in the PORTAL overweight/obesity cohort (n = 2864) were identified first using growth modelling; trajectories were then grouped using a hierarchical cluster analysis. Weight trajectory clusters that emerged were compared on demographics, and predictors of cluster membership were examined. Clusters were also compared on responses to a survey assessing health behaviours, quality of life, and health care experience completed in 2015 by 49% of the total sample (n = 1391). Seven distinct weight trajectory clusters were identified: (a) significant weight loss then maintenance; (b) higher stable weight; (c) moderate stable weight; (d) steady weight loss then relapse; (e) weight gain then weight loss; (f) steady weight gain then maintenance; and (g) lower stable weight. Age, sex, race/ethnicity, and body mass index at baseline predicted patient’s weight trajectory (P < .001). Over two thirds of patients maintained their weight over the 5-year period. Significant weight loss then maintenance, weight gain then weight loss, and higher stable weight patients were more likely to report receiving weight counselling from their provider. Patients in the significant weight loss then maintenance and lower stable weight clusters were more likely to be physically active than the other clusters. Findings suggest variability in patterns of weight change among adults with overweight or obesity who have access to health care and that these patterns differ on demographic, behavioural and psychosocial factors, and health care experience.
Authors: Fitzpatrick SL; Rosales AG; Brown SD; Arterburn DE; Daley MF; Horberg M; Koebnick C; Oshiro C; Young DR
Obes Sci Pract. 2020 Jun;6(3):272-281. Epub 2020-02-27.
A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial
Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child’s risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks’ gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks’ gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232. Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed. Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. US National Institutes of Health.
Authors: Ferrara A; Hedderson MM; Brown SD; Ehrlich SF; Tsai AL; Feng J; Galarce M; Marcovina S; Catalano P; Quesenberry CP
Lancet Diabetes Endocrinol. 2020 06;8(6):490-500.
Association between Objective Activity Intensity and Heart Rate Variability: Cardiovascular Disease Risk Factor Mediation (CARDIA)
We evaluated the associations between accelerometer-estimated physical activity (PA) intensity and heart rate variability (HRV) and examined mediation of these associations by glycemic control indices and other cardiovascular disease risk factors. Data were from 1668 participants (X[Combining Overline]age = 45.9 ± 3.5 yr, 58.0% female, 39.9% black) who participated in year 20 (2005-2006) of the Coronary Artery Risk Development in Young Adults Fitness Study. The ActiGraph 7164 estimated participants’ mean minutes per day of vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) over 7 d. Three sequential 10-s 12-lead ECG strips were used to derive standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Mediators representing glycemic control indices included fasting glucose, fasting insulin, and 2-h oral glucose tolerance, with other mediators being traditional cardiovascular disease risk factors. Multiple linear regression assessed independent associations of PA intensity with HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV association attributable to physiological mediators. Participants averaged 2.7 ± 6.2 min·d, 33.0 ± 22.0 min·d, and 360.2 ± 83.8 min·d of VPA, MPA, and LPA, respectively, with mean values for SDNN (32.6 ± 22.4 ms) and rMSSD (34.0 ± 24.8 ms) similar. After adjustment for demographic and lifestyle behaviors, VPA was associated with both HRV metrics (SDNN: std beta = 0.06 [0.03, 0.10]; rMSSD: std beta = 0.08 [0.05, 0.12]) and LPA with rMSSD only (std beta = 0.05 [0.01, 0.08]). Fasting insulin and glucose mediated 11.6% to 20.7% of the association of VPA and LPA with HRV, with triglycerides also potentially mediating these associations (range, 9.6%-13.4%). Accelerometer-estimated VPA was associated with higher (i.e., improved) HRV. Light-intensity PA also demonstrated a positive association. Mediation analyses suggested these associations may be most attributable to glucose-insulin dynamics.
Authors: Pope ZC; Gabriel KP; Whitaker KM; Chen LY; Schreiner PJ; Jacobs DR; Sternfeld B; Carr JJ; Lloyd-Jones DM; Pereira MA
Med Sci Sports Exerc. 2020 06;52(6):1314-1321.
Prenatal Depression and Diet Quality During Pregnancy
Maternal nutrition during pregnancy has a significant effect on the health of the offspring and mother, highlighting the need for identifying factors that may affect diet during pregnancy. Research in nonpregnant and pregnant populations suggest depression may play a role. To investigate the relationship between prenatal depression and diet quality during pregnancy overall and by race/ethnicity and to explore the relationships between prenatal depression and the 12 Healthy Eating Index 2010 dietary components. A cross-sectional secondary analysis of a cohort study of Kaiser Permanente Northern California women entering prenatal care between October 2011 and April 2013. Participants included 1,160 adult pregnant women. Poor diet quality was defined as a Healthy Eating Index 2010 score in the lowest quartile. Logistic regression was used to assess the relationship between prenatal depression (defined as a depression diagnosis, Patient Health Questionnaire score of 10 or greater or antidepressant medication dispensing between the last menstrual period and completion of the food frequency questionnaire) and poor diet quality overall and by race/ethnicity. Relationships between prenatal depression and each of the 12 Healthy Eating Index 2010 dietary components were assessed using t-tests and linear regression analyses. One hundred fifty-nine (14%) participants had prenatal depression. Women with prenatal depression had nearly two times the odds of poor diet quality (odds ratio 1.80, 95% CI 1.23 to 2.60) compared with women without prenatal depression, after adjusting for potential confounders. Differences emerged by race/ethnicity; after adjusting for potential confounders the adjusted odds of poor diet quality were significant only among Hispanic women. Hispanic women with prenatal depression had an increased odds of poor diet quality compared with Hispanic women without prenatal depression (odds ratio 2.66, 95% CI 1.15 to 6.06). Women with prenatal depression had a higher consumption of empty calories (from solid fats, alcohol, and added sugars; threshold for counting alcohol >13 g/1,000 kcal) (P=0.01) and lower consumption of greens and beans (P<0.05), total fruit (P<0.01), and whole fruit (P<0.01), compared with women without prenatal depression. Except for empty calories, these findings remained after adjusting for potential confounders. Study findings suggest that women with prenatal depression are at a higher risk of poor diet quality compared with women without prenatal depression, and the relationship is stronger among Hispanic women. Nutrition counseling interventions for women with depression should consider the use of culturally sensitive materials and target limiting empty calories from solid fats, alcohol, and added sugars and encourage eating more greens, beans, and fruit.
Authors: Avalos LA; Caan B; Nance N; Zhu Y; Li DK; Quesenberry C; Hyde RJ; Hedderson MM
J Acad Nutr Diet. 2020 06;120(6):972-984. Epub 2020-02-13.
Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial
Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.
Authors: Ferrara A; McDonald JC; Brown SD; Alexander JG; Christian-Herman JL; Fisher S; Quesenberry CP
Prev Chronic Dis. 2020 May 28;17:E38. Epub 2020-05-28.
Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral-host interaction with implications for disease intervention
HPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub-Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epidemiologic studies in the U.S. and internationally. Combining five U.S. studies, we measured HPV35 positivity and, in Northern California, observed HPV35 type-specific population prevalence and estimated 5-year risk of developing precancer when HPV35-positive. HPV35 genetic variation was examined for differences in carcinogenicity in 1053 HPV35+ cervical specimens from a U.S. cohort and an international collection. African-American women had more HPV35 (12.1% vs 5.1%, P
Authors: Pinheiro M; Raine-Bennett T; Mirabello L; et al.
Int J Cancer. 2020 May 04.
Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study
Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals.
Authors: Cabeza de Baca T; Prather AA; Lin J; Sternfeld B; Adler N; Epel ES; Puterman E
Mol Psychiatry. 2020 05;25(5):1141-1153. Epub 2019-08-27.
A study of type-specific HPV natural history and implications for contemporary cervical cancer screening programs
HPV testing is replacing cytology for cervical cancer screening because of greater sensitivity and superior reassurance following negative tests for the dozen HPV genotypes that cause cervical cancer. Management of women testing positive is unresolved. The need for identification of individual HPV genotypes for clinical use is debated. Also, it is unclear how long to observe persistent infections when precancer is not initially found. In the longitudinal NCI-Kaiser Permanente Northern California Persistence and Progression (PaP) Study, we observed the clinical outcomes (clearance, progression to CIN3+, or persistence without progression) of 11,573 HPV-positive women aged 30-65 yielding 14,158 type-specific infections. Risks of CIN3+ progression differed substantially by type, with HPV16 conveying uniquely elevated risk (26% of infections with seven-year CIN3+ risk of 22%). The other carcinogenic HPV types fell into 3 distinct seven-year CIN3+ risk groups: HPV18, 45 (13% of infections, risks >5%, with known elevated cancer risk); HPV31, 33, 35, 52, 58 (39%, risks >5%); and HPV39, 51, 56, 59, 68 (23%, risks
Authors: Demarco M; Raine-Bennett TR; Schiffman M; et al.
EClinicalMedicine. 2020 May;22:100293. Epub 2020-04-25.
The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism
Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well-defined etiology. We sought to determine parental age associations with ASD-related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced parental age with clinical ASD diagnosis, Social Responsiveness Scale, or Vineland Adaptive Behavior Scales scores. Instead, increased odds of ASD were found with paternal age
Authors: Lyall K; Croen LA; Volk HE; et al.
Autism Res. 2020 Apr 21.
Reservations Regarding O-RADS Recommendations
Authors: Suh-Burgmann E; Flanagan T; Brasic N
Radiology. 2020 04;295(1):248-249. Epub 2020-02-25.
A Study of Partial Human Papillomavirus Genotyping in Support of the 2019 ASCCP Risk-Based Management Consensus Guidelines
The 2019 ASCCP Risk-Based Management Consensus Guidelines include recommendations for partial human papillomavirus (HPV) genotyping in management of abnormal cervical cancer screening results. The guidelines are based on matching estimates of cervical intraepithelial neoplasia (CIN) 3+ risk to consensus clinical action thresholds. In support of the guidelines, this analysis addresses the risks predicted by individual identification of HPV 16 and HPV 18. Risk estimates were drawn from a subset of women in the Kaiser Permanente Northern California screening program, whose residual cervical specimens were HPV typed as part of the HPV Persistence and Progression study. We calculated risk of CIN 3+ to assess how identification of HPV 16, HPV 18, or 12 other "high-risk" HPV types would influence recommended clinical management of new abnormal screening results, taking into account current cytologic results and recent screening history. Immediate and/or 5-year risks of CIN 3+ were matched to clinical actions identified in the guidelines. Identification of HPV 16 at the first visit including HPV testing elevated immediate risk of diagnosing CIN 3+ sufficiently to mandate colposcopic referral even when cytology was Negative for Intraepithelial Lesions or Malignancy and to support a preference for treatment of cytologic high-grade squamous intraepithelial lesion. HPV 18 less clearly elevated CIN 3+ risk. Identification of HPV 16 clearly mandated consideration in clinical management of new abnormal screening results. HPV 18 positivity must be considered as a special situation because of established disproportionate risk of invasive cancer. More detailed genotyping and use beyond initial management will be considered in guideline updates.
Authors: Demarco M; Raine-Bennett TR; Schiffman M; et al.
J Low Genit Tract Dis. 2020 Apr;24(2):144-147.
Genetic Contributions to Maternal and Neonatal Vitamin D Levels
Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1 We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N = 179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy.
Authors: Traglia M; Windham GC; Pearl M; Poon V; Eyles D; Jones KL; Lyall K; Kharrazi M; Croen LA; Weiss LA
Genetics. 2020 04;214(4):1091-1102. Epub 2020-02-11.
Maternal infection and antibiotic use in pregnancy and the risk of childhood obesity in offspring: a birth cohort study
The reported association between maternal antibiotic use and childhood obesity, if true, could change obstetric practice. However, it is unclear whether the reported association was due to antibiotics, or underlying infection or both. To examine the independent contributions of maternal infection and antibiotic use separately, we conducted a birth cohort study among Kaiser Permanente Northern California (KPNC) members. The study consisted of 145,393 mother-child dyads. The KPNC electronic medical records provided data on maternal infections, antibiotic use during pregnancy, and longitudinal anthropometric measurements throughout childhood. Obesity was defined by BMI using CDC criteria. Mixed effects logistic regression for repeated measurements was used to analyze multiple BMI measurements per child (five measurements per child on average). After controlling for confounders using propensity score methodology, there was no increased risk associated with maternal antibiotic use during pregnancy once underlying infection was controlled for: OR = 0.97 (95% CI: 0.92-1.01). There was also no association with timing of use or use of broad-spectrum antibiotics, nor a dose-response relationship. In contrast, maternal untreated infection (without antibiotic use) during pregnancy was associated with a statistically significant risk of childhood obesity compared with mothers without infection: odds ratio (OR) = 1.09 (95% confidence interval (CI): 1.03-1.16). The association was stronger for GBS positive infection (OR = 1.16) than GBS negative infections (OR = 1.08). These results were further confirmed by a discordant sibling study. This discordant sibling study allowed additional control of unmeasured confounders including genetic, maternal intrauterine, and familiar factors. The consistent findings from this sibling study enhances the reproducibility of our findings. It is maternal infection, NOT antibiotic use, during pregnancy that is associated with increased risk of childhood obesity. While use of antibiotics should always be judicious, in the context of preventing childhood obesity, the focus should be on reducing maternal infections during pregnancy.
Authors: Li DK; Chen H; Ferber J; Odouli R
Int J Obes (Lond). 2020 04;44(4):771-780. Epub 2019-12-05.
Food insecurity and the extremes of childhood weight: defining windows of vulnerability
Weight extremes and food insecurity (FIS) represent public-health challenges, yet their associations in childhood remain unclear. We aimed to investigate the longitudinal time-specific relationship between FIS and risk of overweight/obesity and underweight in kindergarten through 8th grade. In the prospective Early Childhood Longitudinal Study-Kindergarten Cohort (1998-2007) of 6368 children, household FIS was assessed by the validated US Household Food Security Survey Module in kindergarten, 3rd, 5th and 8th grades. Multivariable linear-regression and Poisson-regression models were computed. Compared with children experiencing food security (FS), children exposed to FIS in 5th grade had 0.19 [95% confidence interval (CI): 0.07-0.30] and 0.17 (0.06-0.27) higher body mass index z-score (BMIZ) in the 5th and 8th grades, respectively, whereas FIS in the 8th grade was associated with a 0.29 (0.19-0.40) higher BMIZ at the same wave, after adjusting for covariates and FIS at earlier waves. Children with FIS vs FS had 27% (relative risk: 1.27, 95% CI: 1.07-1.51), 21% (1.21, 1.08-1.35) and 28% (1.28, 1.07-1.53) higher risk of overweight/obesity in the 3rd, 5th and 8th grades, respectively, adjusting for covariates and FIS at prior wave(s). Children with FIS vs FS in kindergarten had a 2.76-fold (1.22-6.25) higher risk of underweight in the 8th grade. Proximal exposure to household FIS was associated with a higher risk of overweight/obesity in the 3rd, 5th and 8th grades. FIS in kindergarten was associated with a risk of underweight in the 8th grade. Thus, FIS coexists in weight extremes during vulnerable early-life windows in the USA, similarly to the global burden of FIS.
Authors: Zhu Y; Mangini LD; Hayward MD; Forman MR
Int J Epidemiol. 2020 04 01;49(2):519-527.
The impact of breast cancer on physical activity from midlife to early older adulthood and predictors of change post-diagnosis
To examine physical activity (PA) patterns from pre- to post-diagnosis, and compare these changes to women without breast cancer. To determine pre-diagnosis predictors of PA change, post-diagnosis, in breast cancer survivors (BCS). Data were from 2314 Study of Women’s Health Across the Nation (SWAN) participants, average age of 46.4 ± 2.7 years at baseline (1996-1997). In Pink SWAN, 151 women who reported an incident breast cancer diagnosis over 20 years were classified as BCS; the remaining 2163 women were controls. LOESS plots and linear mixed models were used to illustrate and compare PA changes (sports/exercise [primary measure] and total PA) from pre- to post-diagnosis (or corresponding period) in BCS versus controls. Adjusted linear regression models were used to determine pre-diagnosis predictors of at-risk post-diagnosis PA change patterns (consistently low and decreased PA). No differences in pre- to post-diagnosis PA (or corresponding period) were observed in BCS versus controls. Among BCS, the odds of at-risk post-diagnosis PA change patterns was 2.50 (95% CI 0.96-6.48) times higher for those who reported sleep problems at ≥ 50% (compared to 0%) of pre-diagnosis visits and 3.49 (95% CI 1.26-9.65) times higher for those who were overweight or obese at all (compared to no) pre-diagnosis visits. No other statistically significant predictors were noted. Age-related declines in PA were not amplified by a breast cancer diagnosis. Given the beneficial role of PA across the cancer control continuum, efforts to increase or maintain adequate PA, post-diagnosis, should be continued. While age-related physical activity declines were not amplified breast cancer diagnosis, efforts to identify breast cancer survivors at increased risk for post-diagnosis physical activity declines (or maintenance of low activity) may be a high-yield strategy to improve prognosis and quality of life.
Authors: Pettee Gabriel K; Sternfeld B; Colvin AB; Lucas AR; Karvonen-Gutierrez CA; Gold EB; Crawford S; Greendale GA; Avis NE
J Cancer Surviv. 2020 Mar 30.
Association Between Maternal Exposure to Magnetic Field Nonionizing Radiation During Pregnancy and Risk of Attention-Deficit/Hyperactivity Disorder in Offspring in a Longitudinal Birth Cohort
An association between maternal exposure to magnetic field (MF) nonionizing radiation during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) has been reported in both animal and human studies. To determine whether maternal exposure to high levels of MF nonionizing radiation is associated with an increased risk of ADHD in offspring by using more accurate measurements of MF nonionizing radiation levels and physician-diagnosed ADHD, rather than self-reports, and to determine whether the association differs for the subtypes of ADHD with or without immune-related comorbidities. A longitudinal birth cohort study was conducted at Kaiser Permanente Northern California among 1482 mother-child pairs whose mothers were participants of an existing birth cohort and whose level of exposure to MF nonionizing radiation was captured during pregnancy in 2 studies conducted from October 1, 1996, to October 31, 1998, and from May 1, 2006, to February 29, 2012. The offspring were followed up from May 1, 1997, to December 31, 2017. All participating women wore a monitoring meter for 24 hours during pregnancy to capture the level of exposure to MF nonionizing radiation from any sources. Physician-diagnosed ADHD and immune-related comorbidities of asthma or atopic dermatitis up to 20 years of age in offspring captured in the Kaiser Permanente Northern California electronic medical record from May 1, 1997, to December 31, 2017. Confounders were ascertained during in-person interviews during pregnancy. Among the 1454 mother-child pairs (548 white [37.7%], 110 African American [7.6%], 325 Hispanic [22.4%], 376 Asian or Pacific Islander [25.9%], and 95 other or unknown [6.5%]; mean [SD] maternal age, 31.4 [5.4] years]), 61 children (4.2%) had physician-diagnosed ADHD. Using Cox proportional hazards regression to account for follow-up time and confounders, compared with children whose mothers had a low level of exposure to MF nonionizing radiation during pregnancy, children whose mothers were exposed to higher levels of MF nonionizing radiation had more than twice the risk of ADHD (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.06-3.81). The association was stronger for ADHD that persisted into adolescence (≥12 years of age), with an aHR of 3.38 (95% CI, 1.43-8.02). When the subtypes of ADHD were examined, the association existed primarily for ADHD with immune-related comorbidities (asthma or atopic dermatitis), with an aHR of 4.57 (95% CI, 1.61-12.99) for all ADHD cases and an aHR of 8.27 (95% CI, 1.96-34.79) for persistent cases of ADHD. Consistent with the emerging literature, this study suggests that in utero exposure to high levels of MF nonionizing radiation was associated with an increased risk of ADHD, especially ADHD with immune-related comorbidity. The findings should spur more research to examine the biological association of in utero MF exposure with risk of ADHD in offspring, given that almost everyone is exposed to it.
Authors: Li DK; Chen H; Ferber JR; Hirst AK; Odouli R
JAMA Netw Open. 2020 03 02;3(3):e201417. Epub 2020-03-02.
Cytological sampling of fallopian tubes using a hysteroscopic catheter: A multi-center study
To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016-August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device’s ability to detect malignancy in high risk populations is warranted.
Authors: Powell CB; Littell RD; Landen CN; Pramanik S; Hamilton IC; Suh-Burgmann EJ
Gynecol Oncol. 2020 03;156(3):636-640. Epub 2020-01-07.
Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability
Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population-based, case-control study among a sample of children born during 2000-2003 in Southern California. We examined neonatal thyroid-stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early-onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln-transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj-OR: 1.00, 95% CI: 0.79-1.26) nor ID (adj-OR = 1.01, 95% CI: 0.73-1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj-OR: 0.50, 95% CI: 0.26-0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444-455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research.
Authors: Ames JL; Windham GC; Lyall K; Pearl M; Kharrazi M; Yoshida CK; Van de Water J; Ashwood P; Croen LA
Autism Res. 2020 03;13(3):444-455. Epub 2019-12-10.
Understanding childhood obesity in the US: the NIH environmental influences on child health outcomes (ECHO) program
Few resources exist for prospective, longitudinal analysis of the relationships between early life environment and later obesity in large diverse samples of children in the United States (US). In 2016, the National Institutes of Health launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate influences of environmental exposures on child health and development. We describe demographics and overweight and obesity prevalence in ECHO, and ECHO’s potential as a resource for understanding how early life environmental factors affect obesity risk. In this cross-sectional study of 70 extant US and Puerto Rico cohorts, 2003-2017, we examined age, race/ethnicity, and sex in children with body mass index (BMI) data, including 28,507 full-term post-birth to <2 years and 38,332 aged 2-18 years. Main outcomes included high BMI for age <2 years, and at 2-18 years overweight (BMI 85th to <95th percentile), obesity (BMI???95th percentile), and severe obesity (BMI???120% of 95th percentile). The study population had diverse race/ethnicity and maternal demographics. Each outcome was more common with increasing age and varied with race/ethnicity. High BMI prevalence (95% CI) was 4.7% (3.5, 6.0) <1 year, and 10.6% (7.4, 13.7) for 1 to <2 years; overweight prevalence increased from 13.9% (12.4, 15.9) at 2-3 years to 19.9% (11.7, 28.2) at 12 to <18 years. ECHO has the statistical power to detect relative risks for 'high' BMI ranging from 1.2 to 2.2 for a wide range of exposure prevalences (1-50%) within each age group. ECHO is a powerful resource for understanding influences of chemical, biological, social, natural, and built environments on onset and trajectories of obesity in US children. The large sample size of ECHO cohorts adopting a standardized protocol for new data collection of varied exposures along with longitudinal assessments will allow refined analyses to identify drivers of childhood obesity.
Authors: Tylavsky FA; Ferrara A; Hedderson MM; Zhu Y; Trasande L; et al.
Int J Obes (Lond). 2020 03;44(3):617-627. Epub 2019-10-24.
Trivalent inactivated influenza vaccine (IIV3) during pregnancy and six-month infant development
Despite recommendations by professional organizations that all pregnant women receive inactivated influenza vaccine, safety concerns remain a barrier. Our objective was to assess the effect of trivalent influenza vaccines (IIV3) during pregnancy on parent report 6-month infant development. We conducted a multi-site prospective birth cohort study during the 2010-2011 influenza season and followed pregnant women and their newborns through 6 months of age. Information on IIV3 during pregnancy was ascertained from the EHR and self-report. The Ages and Stages Questionnaire-3 (ASQ-3) was completed by the mother to assess 6-month infant neurodevelopment in five domains (communication, gross motor, fine motor, problem-solving, and personal adaptive skills). Scores for each domain above the cut-off point indicating typical development were categorized as “on schedule” while scores in the zones indicating the need for either monitoring or further assessment were categorized as “not on schedule”. Multivariable logistic regression was conducted. Of the 1225 infant-mother pairs, 65% received IIV3 during pregnancy. In bivariate analysis, infants of women who received IIV3 during pregnancy were moderately-less likely to need monitoring or further assessment in the personal social domain compared with infants of unvaccinated women (10.0% vs. 14.1%, p = 0.033; crude OR (cOR): 0.68(95%CI:0.48,0.97)). However, after controlling for potential confounders, the findings were no longer statistically significant (aOR:0.72,95%CI: 0.49,1.06,p = 0.46). No significant unadjusted or adjusted associations emerged in any other ASQ-3 domain. There was no significant association between IIV3 exposure during pregnancy and 6-month infant development. Studies of IIV3 during pregnancy to assess longer-term developmental outcomes are indicated.
Authors: Avalos LA; Zerbo O; Li DK; et al.
Vaccine. 2020 02 28;38(10):2326-2332. Epub 2020-02-05.
Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference
This cohort study sought to estimate the differences in risk of delivering infants who were small or large for gestational age (SGA or LGA, respectively) according to exercise during the first trimester of pregnancy (vs. no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex- and gestational-age-specific birthweight distributions of the 2017 US Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI: 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI: 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal-weight women, but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA but only among underweight and normal-weight women. Any vigorous exercise reduced the risk of LGA in underweight and normal-weight women only and was not associated with SGA risk.
Authors: Ehrlich SF; Neugebauer RS; Feng J; Hedderson MM; Ferrara A
Am J Epidemiol. 2020 02 28;189(2):133-145.
Mutations in the HPV16 genome induced by APOBEC3 are associated with viral clearance
HPV16 causes half of cervical cancers worldwide; for unknown reasons, most infections resolve within two years. Here, we analyze the viral genomes of 5,328 HPV16-positive case-control samples to investigate mutational signatures and the role of human APOBEC3-induced mutations in viral clearance and cervical carcinogenesis. We identify four de novo mutational signatures, one of which matches the COSMIC APOBEC-associated signature 2. The viral genomes of the precancer/cancer cases are less likely to contain within-host somatic HPV16 APOBEC3-induced mutations (Fisher’s exact test, P = 6.2 x 10-14), and have a 30% lower nonsynonymous APOBEC3 mutation burden compared to controls. We replicate the low prevalence of HPV16 APOBEC3-induced mutations in 1,749 additional cases. APOBEC3 mutations also historically contribute to the evolution of HPV16 lineages. We demonstrate that cervical infections with a greater burden of somatic HPV16 APOBEC3-induced mutations are more likely to be benign or subsequently clear, suggesting they may reduce persistence, and thus progression, within the host.
Authors: Zhu B; Raine-Bennett T; Mirabello L; et al.
Nat Commun. 2020 Feb 14;11(1):886. Epub 2020-02-14.
Association of Depression, Anxiety, and Trauma With Cannabis Use During Pregnancy
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Goler NC; Alexeeff SE; Ridout KK; Avalos LA
JAMA Netw Open. 2020 02 05;3(2):e1921333. Epub 2020-02-05.
The Effect of Gestational Weight Gain Across Reproductive History on Maternal Body Mass Index in Midlife: The Study of Women’s Health Across the Nation
Background: Excessive weight gain during pregnancy is common and has been shown to be associated with increased long-term maternal weight. However, less is known on whether there is a cumulative effect of excessive gestational weight gain (GWG) over multiple pregnancies. Methods: Data from the Study of Women’s Health Across the Nation were used, restricted to parous women with no history of stillbirth or premature birth. The effect of the number of excessive GWG pregnancies on body mass index (BMI) in midlife (age 42-53) was analyzed using multivariable linear regression. Fully adjusted models included parity, inadequate GWG, demographic, and behavioral characteristics. Results: The 1181 women included in this analysis reported a total of 2693 births. Overall, 466 (39.5%) were categorized as having at least one pregnancy with excessive GWG. The median BMI at midlife was 26.0 kg/m2 (interquartile range 22.5-31.1). In fully adjusted models, each additional pregnancy with excessive GWG was associated with 0.021 higher estimated log BMI (p = 0.031). Among women with 1-3 births, adjusted mean (95% confidence interval) BMI for those with 0, 1, 2, and 3 excessive GWG pregnancies was 25.4 (24.9-25.9), 26.8 (26.1-27.5), 27.5 (26.6-28.4), and 28.8 (27.3-30.5), respectively. Conclusions: In this multiethnic study of women with a history of term live births, the number of pregnancies with excessive GWG was associated with increased maternal BMI in midlife. Our findings suggest that prevention of excessive GWG at any point in a woman’s reproductive history can have an impact on long-term maternal health.
Authors: Hutchins F; Abrams B; Brooks M; Colvin A; Moore Simas T; Rosal M; Sternfeld B; Crawford S
J Womens Health (Larchmt). 2020 02;29(2):148-157. Epub 2019-11-27.
Sexual function, menopausal symptoms, depression and cancer worry in women with BRCA mutations
Assess sexual function, menopausal symptoms, and depression in women with BRCA mutations associated with oophorectomy and menopause status. Women age 40 and older with BRCA mutations completed a questionnaire with validated measures of sexual activity, menopausal symptoms, depression, and cancer worry. These measures were compared between those with intact ovaries and those who had undergone pre- or post-menopausal risk-reducing salpingo-oophorectomy (RRSO). Of the 244 women, 21 had intact ovaries and 223 had undergone RRSO. Women with intact ovaries had less menopausal symptoms (Menopausal Symptom Checklist (MSCL) score 14 versus 23, P = .01) but more cancer worry than women who had undergone RRSO (median Cancer Worry Scale (CWS) score 5 versus 4, P < .0001) with no significant difference in sexual activity or function. Compared with women with postmenopausal RRSO, women with premenopausal RRSO were more likely to be sexually active (56.3% versus 42.0%, P =.04) but had similar sexual functioning, including frequency, pleasure and discomfort. Women with premenopausal RRSO were also more likely to report menopausal symptoms (MSCL score 26 versus 19, P = .04) and depression (PHQ-8 score 4 versus 2, P < .001). Factors associated with sexual activity included younger age, lower BMI, living with a partner, and lower depression scores. Higher current depression score was associated with history of depression and more menopausal symptoms. Risk-reducing surgery decreases cancer risk and worry in women with BRCA mutations. Among women undergoing oophorectomy, factors such as age and history of depression were related to reduced sexual activity and increased depression, but menopausal status was not related.
Authors: Powell CB; Alabaster A; Le A; Stoller N; Armstrong MA; Raine-Bennett T
Psychooncology. 2020 02;29(2):331-338. Epub 2019-11-22.
Individualized Relative Intensity Physical Activity Accelerometer Cut-points
Physical activity (PA) intensity is expressed as either absolute or relative intensity. Absolute intensity refers to the energy required to perform an activity. Relative intensity refers to a level of effort that takes into account how hard an individual is working relative to their maximum capacity. We sought to develop methods for obtaining individualized relative-intensity accelerometer cut points using data from a maximal graded exercise treadmill test (GXT) so that each individual has their own cut point. A total of 2363 men and women 38 to 50 yr old from the CARDIA fitness study wore ActiGraph 7164 accelerometers during a maximal GXT and for seven consecutive days in 2005-2006. Using mixed-effects regression models, we regressed accelerometer counts on heart rate as a percentage of maximum (%HRmax) and on RPE. Based on these two models, we obtained a moderate-intensity (%HRmax = 64% or RPE = 12) count cut point that is specific to each participant. We applied these subject-specific cut points to the available CARDIA accelerometer data. Using RPE, the mean moderate-intensity accelerometer cut point was 4004 (SD = 1120) counts per minute. On average, cut points were higher for men (4189 counts per minute) versus women (3865 counts per minute) and were higher for Whites (4088 counts per minute) versus African Americans (3896 counts per minute). Cut points were correlated with body mass index (rho = -0.11) and GXT duration (rho = 0.33). Mean daily minutes of absolute- and relative-intensity moderate to vigorous PA were 34.1 (SD = 31.1) min·d and 9.1 (SD = 18.2) min·d, respectively. RPE cut points were higher than those based on %HRmax. This is likely due to some participants ending the GXT before achieving their HRmax. Accelerometer-based relative-intensity PA may be a useful measure of intensity relative to maximal capacity.
Authors: Siddique J; Sternfeld B; Freedson P; et al.
Med Sci Sports Exerc. 2020 02;52(2):398-407.
Neonatal jaundice in association with autism spectrum disorder and developmental disorder
To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2-5 years into: ASD (n = 636), DD (n = 777), or controls (POP; n = 926). Neonatal jaundice (n = 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35-37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not ≥38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted.
Authors: Cordero C; Schieve LA; Croen LA; Engel SM; Maria Siega-Riz A; Herring AH; Vladutiu CJ; Seashore CJ; Daniels JL
J Perinatol. 2020 02;40(2):219-225. Epub 2019-08-06.
Association Between Objective Activity Intensity & Heart Rate Variability: CVD Risk Factor Mediation (CARDIA)
We evaluated the associations between accelerometer-estimated physical activity (PA) intensity and heart rate variability (HRV) and examined mediation of these associations by glycemic control indices and other cardiovascular disease (CVD) risk factors. Data were from 1,668 participants (X[Combining Overline]age=45.9±3.5 years, 58.0% female, 39.9% black) who participated in Year 20 (2005-06) of the Coronary Artery Risk Development in Young Adults (CARDIA) Fitness Study. The ActiGraph 7164 estimated participants’ mean min/day of vigorous-intensity PA (VPA), moderate-intensity PA (MPA), and light-intensity PA (LPA) over seven days. Three sequential 10-sec 12-lead ECG strips were used to derive standard deviation of all normal RR intervals (SDNN) and root mean square of all successive RR intervals (rMSSD) HRV. Mediators representing glycemic control indices included fasting glucose, fasting insulin, and 2-hour oral glucose tolerance, with other mediators being traditional CVD risk factors. Multiple linear regression assessed independent associations of PA intensity with HRV per 1-SD. Mediation analyses computed the proportion of the PA-HRV association attributable to physiological mediators. Participants averaged 2.7±6.2, 33.0±22.0, and 360.2±83.8 min/day of VPA, MPA, and LPA, respectively, with mean values for SDNN (32.6±22.4 ms) and rMSSD (34.0±24.8 ms) similar. After adjustment for demographic and lifestyle behaviors, VPA was associated with both HRV metrics (SDNN: std beta=0.06 [0.03, 0.10]; rMSSD: std beta=0.08, [0.05, 0.12]) and LPA with rMSSD only (std beta=0.05, [0.01, 0.08]). Fasting insulin and glucose mediated 11.6%-20.7% of the association of VPA and LPA with HRV, with triglycerides also potentially mediating these associations (range: 9.6%-13.4%). Accelerometer-estimated VPA was associated with higher (i.e., improved) HRV. LPA also demonstrated a positive association. Mediation analyses suggested these associations may be most attributable to glucose-insulin dynamics.
Authors: Pope ZC; Gabriel KP; Whitaker KM; Chen LY; Schreiner PJ; Jacobs DR; Sternfeld B; Carr JJ; Lloyd-Jones DM; Pereira MA
Med Sci Sports Exerc. 2020 Jan 06.
Sex Hormone-binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes: A Longitudinal Study and Meta-analysis
This study investigated the prospective associations of circulating levels of sex hormone-binding globulin (SHBG) levels with cardiometabolic biomarkers and risk of gestational diabetes (GDM) during pregnancy. It also examines the longitudinal trajectory of SHBG in women with and without GDM. We conducted a nested case-control study of 107 incident GDM cases and 214 matched controls within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The cohort enrolled non-obese and obese women aged 18-40 years with a singleton pregnancy between 8 and 13 weeks of gestation from 2009 to 2013. GDM was ascertained via medical records review. Blood samples were drawn four times at gestational weeks 10-14, 15-26, 23-31, and 33-39. The prospective associations between SHBG levels and cardiometabolic biomarkers were examined using the Spearman partial correlation among the controls. The longitudinal trajectories of SHBG levels were examined among the cases and the controls. Meta-analysis of prospective studies were performed to examine the association between SHBG levels and GDM risk. SHBG levels at gestational weeks 10-14 were significantly inversely associated with fasting insulin (r = -0.17, P = 0.01) and insulin resistance as measured by HOMA-IR (r = -0.17, P = 0.01) at gestational week 15-26. SHBG at gestational weeks 10-14 and 15-26 was lower in cases than controls (mean ± standard deviation: (204.0 ± 97.6) vs. (220.9 ± 102.5) nmol/L, P = 0.16 and (305.6 ± 124.3) vs. (322.7 ± 105.1) nmol/L, P = 0.14, respectively), yet the differences were not significant. In the meta-analysis, SHBG was 41.5 nmol/L (95% confidence interval: 23.9, 59.1, P < 0.01) significantly lower among women with GDM than without, and each 50 nmol/L increase in SHBG was significantly associated with an odds ratio of 0.85 (95% confidence interval: 0.76-0.95, P = 0.01) for GDM. Lower SHBG levels in early pregnancy were prospectively associated with higher high insulin levels and insulin resistance in mid-pregnancy and subsequent risk of GDM, independent of adiposity. SHBG may serve as a marker for the identification of high-risk pregnancies during early pregnancy.
Authors: Li, Meng-Ying; Rawal, Shristi; Hinkle, Stefanie N; Zhu, Ye-Yi; Tekola-Ayele, Fasil; Tsai, Michael Y; Liu, Si-Min; Zhang, Cui-Lin
Matern Fetal Med. 2020 Jan;2(1):2-9. Epub 2020-01-24.
Factors Influencing Participation in Biospecimen Research among Parents of Youth with Mental Health Conditions
Biospecimens are tools that have the potential to improve early identification and treatment for autism spectrum disorders (ASD) and bipolar disorders (BPD). Unfortunately, most biobanks lack racial/ethnic diversity. One challenge to including a diverse sample of youth is recruiting and engaging families. We sought to better understand facilitators and barriers to participation in biospecimen research among a diverse group of parents of youth with ASD and BPD. The current study involved 3 Mental Health Research Network sites. At each site, parents participated in an interview that explored attitudes and beliefs about genetic research. Interviews were audio-recorded, and audio files were transcribed and coded using content analysis. A total of 58 interviews were conducted. Four challenges emerged: (1) contacting and engaging potential research participants, (2) motivating potential participants to read recruitment and consent materials, (3) motivating participation in research, in general, and (4) motivating participation in research involving biospecimen donation, specifically. Participants were eager to participate as long as the research process involved trust, clarity, and flexibility. Future research involving youth with mental health conditions would benefit from implementing multimodal strategies for recruitment and data collection and sharing knowledge gained by the research with study participants.
Authors: Owen-Smith AA; Sesay MM; Lynch FL; Massolo M; Cerros H; Croen LA
Public Health Genomics. 2020;23(3-4):122-132. Epub 2020-07-22.
Family Environment, Neurodevelopmental Risk, and the Environmental Influences on Child Health Outcomes (ECHO) Initiative: Looking Back and Moving Forward
The family environment, with all its complexity and diverse components, plays a critical role in shaping neurodevelopmental outcomes in children. Herein we review several domains of the family environment (family socioeconomic status, family composition and home environment, parenting behaviors and interaction styles, parental mental health and functioning, and parental substance use) and discuss how these domains influence neurodevelopment, with particular emphasis on mental health outcomes. We also highlight a new initiative launched by the National Institutes of Health, the Environmental influences on Child Health Outcomes (ECHO) program. We discuss the role that ECHO will play in advancing our understanding of the impact of the family environment on children’s risk for psychiatric outcomes. Lastly, we conclude with important unanswered questions and controversies in this area of research, highlighting how ECHO will contribute to resolving these gaps in our understanding, clarifying relationships between the family environment and children’s mental health.
Authors: Bush NR; Avalos LA; Posner J; et al.
Front Psychiatry. 2020;11:547. Epub 2020-06-19.
Leisure Time Physical Activity, Sedentary Time in Pregnancy, and Infant Weight at Approximately 12 Months
Background: Maternal leisure time physical activity (LTPA) and sedentary time during pregnancy may influence programming of infant growth in a sex-specific manner. Materials and Methods: Participants (N = 35,212) from the Danish National Birth Cohort reported moderate/vigorous LTPA (hours/week) in early (conception to mean 16 weeks of gestation) and late pregnancy (mean 31 weeks of gestation to delivery) during interviews at 16 weeks of gestation and 6 months postpartum. Participants reported screen time at work and time spent watching television/videos (hours/day) in early pregnancy. Infant weight at 12 months of age was reported by mothers. Weight-for-length was categorized using sex-specific international standards. Results:Participants reported on average 1 hour per week of early pregnancy moderate/vigorous LTPA, 0.5 hour per week of late pregnancy LTPA, and 3 hours per day of early pregnancy sedentary time. Early pregnancy LTPA category was not associated with infant weight (p for trend = 0.62). There were suggested associations of early pregnancy sedentary time above the first quartile with greater odds of infant underweight (odds ratio = 1.15-1.27; p for trend = 0.27). Associations were similar in male and female infants. Conclusions: There is no clear relationship between early or late pregnancy LTPA and infant weight at 12 months in our study. Maternal early pregnancy sedentary time may be associated with infant underweight at 12 months.
Authors: Badon SE; Littman AJ; Chan KCG; Williams MA; Kirkegaard H; Nohr EA; Enquobahrie DA
Womens Health Rep (New Rochelle). 2020;1(1):123-131. Epub 2020-05-12.
Plasma Prolactin and Progesterone Levels and the Risk of Gestational Diabetes: A Prospective and Longitudinal Study in a Multiracial Cohort
Objective: Prolactin and progesterone are implicated in glucose homeostasis in and outside of pregnancy. However, their associations with gestational diabetes (GDM) risk were not well-understood. This study investigates this question in a prospective and longitudinal cohort. Methods: This is a nested case-control study of 107 incident GDM cases and 214 matched non-GDM controls within the NICHD Fetal Growth Studies-Singleton Cohort. Blood samples were collected at gestational weeks 10-14, 15-26, 23-31, and 33-39. The odds ratios (OR) of GDM were estimated using conditional logistic regression. The longitudinal changes in prolactin and progesterone were estimated using linear mixed-effects models. Results: Compared to controls, cases have significantly higher prolactin levels at weeks 10-14 (median: 50.4 vs. 42.1 ng/mL), and significantly lower progesterone levels at weeks 10-14 (median: 109.4 vs. 126.5 nmol/L). Prolactin levels at weeks 10-14 were significantly and positively associated with GDM risk; the adjusted ORs across increasing quartiles were 1.00, 1.13, 1.80, 2.33 (p-trend = 0.02). A similar but slightly attenuated association was observed at weeks 15-26 (p-trend = 0.05). Progesterone was not associated with GDM risk at either time points. Longitudinal changes in prolactin and progesterone between the first two visits were not associated with GDM risk. In addition, prolactin was significantly and positively associated with insulin and C-peptide levels at weeks 10-14, and significantly and inversely associated with C-peptide levels at weeks 15-26; progesterone was significantly and inversely associated with glucose and insulin levels. Conclusions: This study provided the first prospective evidence of a positive association between prolactin levels in early pregnancy and GDM risk.
Authors: Li M; Song Y; Rawal S; Hinkle SN; Zhu Y; Tekola-Ayele F; Ferrara A; Tsai MY; Zhang C
Front Endocrinol (Lausanne). 2020;11:83. Epub 2020-02-27.
Identifying hypertension in pregnancy using electronic medical records: The importance of blood pressure values
To incorporate blood pressure (BP), diagnoses codes, and medication fills from electronic medical records (EMR) to identify pregnant women with hypertension. A retrospective cohort study of singleton pregnancies at three US integrated health delivery systems during 2005-2014. Women were considered hypertensive if they had any of the following: (1) ≥2 high BPs (≥140/90 mmHg) within 30 days during pregnancy (High BP); (2) an antihypertensive medication fill in the 120 days before pregnancy and a hypertension diagnosis from 1 year prior to pregnancy through 20 weeks gestation (Treated Chronic Hypertension); or (3) a high BP, a hypertension diagnosis, and a prescription fill within 7 days during pregnancy (Rapid Treatment). We described characteristics of these pregnancies and conducted medical record review to understand hypertension presence and severity. Of 566,624 pregnancies, 27,049 (4.8%) met our hypertension case definition: 24,140 (89.2%) with High BP, 5,409 (20.0%) with Treated Chronic Hypertension, and 5,363 (19.8%) with Rapid Treatment (not mutually exclusive). Of hypertensive pregnancies, 19,298 (71.3%) received a diagnosis, 9,762 (36.1%) received treatment and 11,226 (41.5%) had a BP ≥ 160/110. In a random sample (n = 55) of the 7,559 pregnancies meeting the High BP criterion with no hypertension diagnosis, clinical statements about hypertension were found in medical records for 58% of them. Incorporating EMR BP identified many pregnant women with hypertension who would have been missed by using diagnosis codes alone. Future studies should seek to incorporate BP to study treatment and outcomes of hypertension in pregnancy.
Authors: Chen L; Avalos LA; Neugebauer R; Badon SE; Dublin S; et al.
Pregnancy Hypertens. 2020 Jan;19:112-118. Epub 2020-01-03.
Early Life Exposure to Air Pollution and Autism Spectrum Disorder: Findings from a Multisite Case-Control Study
Epidemiologic studies have reported associations between prenatal and early postnatal air pollution exposure and autism spectrum disorder (ASD); however, findings differ by pollutant and developmental window. We examined associations between early life exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone in association with ASD across multiple US regions. Our study participants included 674 children with confirmed ASD and 855 population controls from the Study to Explore Early Development, a multi-site case-control study of children born from 2003 to 2006 in the United States. We used a satellite-based model to assign air pollutant exposure averages during several critical periods of neurodevelopment: 3 months before pregnancy; each trimester of pregnancy; the entire pregnancy; and the first year of life. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for study site, maternal age, maternal education, maternal race/ethnicity, maternal smoking, and month and year of birth. The air pollution-ASD associations appeared to vary by exposure time period. Ozone exposure during the third trimester was associated with ASD, with an OR of 1.2 (95% CI: 1.1, 1.4) per 6.6 ppb increase in ozone. We additionally observed a positive association with PM2.5 exposure during the first year of life (OR = 1.3 [95% CI: 1.0, 1.6] per 1.6 µg/m increase in PM2.5). Our study corroborates previous findings of a positive association between early life air pollution exposure and ASD, and identifies a potential critical window of exposure during the late prenatal and early postnatal periods.
Authors: McGuinn LA; Croen LA; Daniels JL; et al.
Epidemiology. 2020 01;31(1):103-114.
Primary Care Physicians’ Experiences With and Strategies for Managing Electronic Messages
The increasing use of electronic communications has enhanced access to physicians for patients and clinical staff. Primary care physicians (PCPs) have anecdotally identified electronic inbox management as a new source of work-related stress. To describe PCPs’ experiences managing their electronic inboxes and to characterize the array of management strategies developed by individual physicians and practice groups. This qualitative study was conducted in 8 medical centers of a large group practice with more than 4 million patients in diverse settings and a mature electronic health record. The group encourages patients to use portal secure messaging to enhance access to their physicians and the care experience. Semistructured interviews were conducted with 24 internists and family medicine physicians identified via snowball sampling. Interviews were conducted July through November 2018. Data analysis was conducted between November 2018 and April 2019. Audio recorded interviews were transcribed and analyzed using thematic analysis to identify major themes and subthemes. The 24 participants (12 women [50.0%]; mean [SD] age, 45.5 [6.5] years), including 9 department chiefs and 15 PCPs, had a mean (SD) of 16.8 (7.8) years since medical school graduation. Participants described substantial changes in medical practice due to electronic communication, including perceived patient expectations to receive rapid responses to portal secure messages. They described portal secure messaging as useful for building relationships with patients, but also reported that electronic message management has created new stressors, including erosion of work-life boundaries and anxiety associated with unlimited inbox volume. Individual PCPs used a diverse array of strategies, including multitasking during and outside work and delegating to medical assistants. Chiefs described group-level strategies, including reserving clinic time for inbox management, coverage systems for vacation and sick days, physician-to-physician training, and interdisciplinary teams to share messaging work. Individual physicians and local practice groups have developed a wide array of strategies for electronic inbox management. The volume of electronic messages and PCPs’ perceptions that patients expect rapid responses have created new stressors in primary care practice. Medical groups and health systems can support PCPs by facilitating knowledge transfer among physicians about inbox management strategies and further developing team structures for inbox coverage.
Authors: Lieu TA; Altschuler A; Weiner JZ; East JA; Moeller MF; Prausnitz S; Reed ME; Warton EM; Goler N; Awsare S
JAMA Netw Open. 2019 12 02;2(12):e1918287. Epub 2019-12-02.
Racial Disparities in Route of Hysterectomy for Benign Indications Within an Integrated Health Care System
Authors: Zaritsky E; Ojo A; Tucker LY; Raine-Bennett TR
JAMA Netw Open. 2019 Dec 02;2(12):e1917004. Epub 2019-12-02.
Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research
The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns. Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research. We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring. For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring. The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. https://doi.org/10.1289/EHP5133.
Authors: Pellizzari ED; Woodruff TJ; Boyles RR; Kannan K; Beamer PI; Buckley JP; Wang A; Zhu Y; Bennett DH; (Environmental influences on Child Health Outcomes)
Environ Health Perspect. 2019 12;127(12):126001. Epub 2019-12-18.
Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S
To examine racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI category. In a consortium of three U.S. integrated health care systems, 4,906,238 individuals aged ≥20 years during 2012-2013 were included. Diabetes and prediabetes were ascertained by diagnosis and laboratory results; antihyperglycemic medications were also included for diabetes ascertainment. The age-standardized diabetes and prediabetes prevalence estimates were 15.9% and 33.4%, respectively. Diabetes but not prediabetes prevalence increased across BMI categories among all racial/ethnic groups (P for trend < 0.001). Racial/ethnic minorities reached a given diabetes prevalence at lower BMIs than whites; Hawaiians/Pacific Islanders and Asians had a diabetes prevalence of 24.6% (95% CI 24.1-25.2%) in overweight and 26.5% (26.3-26.8%) in obese class 1, whereas whites had a prevalence of 23.7% (23.5-23.8%) in obese class 2. The age-standardized prediabetes prevalence estimates in overweight among Hispanics (35.6% [35.4-35.7%]), Asians (38.1% [38.0-38.3%]), and Hawaiians/Pacific Islanders (37.5% [36.9-38.2%]) were similar to those in obese class 4 among whites (35.3% [34.5-36.0%]), blacks (36.8% [35.5-38.2%]), and American Indians/Alaskan Natives (34.2% [29.6-38.8%]). In adjusted models, the strength of association between BMI and diabetes was highest among whites (relative risk comparing obese class 4 with normal weight 7.64 [95% CI 7.50-7.79]) and lowest among blacks (3.16 [3.05-3.27]). The association between BMI and prediabetes was less pronounced. Racial/ethnic minorities had a higher burden of diabetes and prediabetes at lower BMIs than whites, suggesting the role of factors other than obesity in racial/ethnic disparities in diabetes and prediabetes risk and highlighting the need for tailored screening and prevention strategies.
Authors: Zhu Y; Ferrara A; et al.
Diabetes Care. 2019 12;42(12):2211-2219. Epub 2019-09-19.
Detection of early stage ovarian cancer in a large community cohort
Although detecting ovarian cancer at early stage is a highly meaningful clinical goal, no studies have evaluated early stage disease presentation in a large community-based population and how it differs from that of late stage disease. Electronic medical records were evaluated for women diagnosed with ovarian or fallopian tube cancer in 2016 and 2017 to identify the first imaging study to detect disease. Women being followed prior to diagnosis for known genetic risk from BRCA or other mutation were excluded. The visit in which the imaging test was ordered and related encounters were reviewed to determine the indication for imaging. Patient characteristics, presenting symptoms and duration, and modality of first abnormal imaging were compared for early vs late stage ovarian cancer and by provider specialty. Of 540 women with ovarian cancer, 190 (35%) were diagnosed with early stage disease, of whom 141 (74%) were symptomatic, with 45% of women presenting to internists, 33% to gynecologists, and 20% to emergency medicine physicians. Pelvic ultrasonography detected only 23% of late stage cases whereas pelvic ultrasonography and abdominal pelvic computed tomography (CT) each detected 47% of early stage cases. While abdominal pain and bloating were common to both women with early and late stage cancer, women with early stage disease were younger (58 vs 64 years, P < .0001), more likely to present to gynecologists (33% vs 15%, P < .001) and complained more often of a palpable mass (17% vs 6%, P < .0001) or postmenopausal bleeding (11% vs 5%, P < .001). Excluding women with genetic predisposition to ovarian cancer known prior to diagnosis, approximately three out of four cases of early stage ovarian cancer are detected as the result of evaluation of symptoms and one in four cases are detected incidentally. Abdominal pelvic CT and pelvic ultrasonography each detect an equal proportion of early stage cases. In contrast to late stage presentation, women diagnosed with early stage disease present more often with complaints of a palpable mass or postmenopausal bleeding, particularly to gynecologists.
Authors: Suh-Burgmann EJ; Alavi M
Cancer Med. 2019 11;8(16):7133-7140. Epub 2019-09-30.
A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort
Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown. We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors. Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years. Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.
Authors: Lin Y; Zhu Y; Wu J; Hinkle SN; Rawal S; Han J; Weir NL; Tsai MY; Zhang C
Epidemiology. 2019 11;30 Suppl 2:S10-S16.
Community-based service use in preschool children with autism spectrum disorder and associations with insurance status
ASD-related services can improve outcomes for children, but less is known about service outside of school settings during preschool age. We aimed to describe amount and category of community-based service use among 3-5-year-old children with ASD and examine differences by health insurance. We used cross-sectional data on 792 children with ASD diagnoses in the Study to Explore Early Development, a community-based study of neurodevelopment with enrollment between 2012-2016. Mothers reported current child service use and insurance status at study entry. We used log-Poisson and logistic regression to compare service use by insurance group. Nearly 40% of children were not receiving community-based services at study entry. Children with public insurance had fewer total services than children with private or both insurances. After adjustment for sociodemographic confounders, insurance status was not associated with types of different categories of community-based services. However, children with public insurance alone were least likely to receive community-based behavioral therapy and most likely to receive psychotropic medication compared to other insurances. Many preschool-aged children do not receive community-based services, with receipt associated with insurance type. Increasing access and availability for evidence-based service, especially for beneficiaries of public insurance, may improve service use and outcomes.
Authors: Rubenstein, Eric; Croen, Lisa; Lee, Li-Ching; Moody, Eric; Schieve, Laura A; Soke, Gnakub N; Thomas, Kathleen; Wiggins, Lisa; Daniels, Julie
Res Autism Spectr Disord. 2019 Oct;66. Epub 2019-06-15.
Air pollution, neighborhood deprivation, and autism spectrum disorder in the Study to Explore Early Development
To examine whether neighborhood deprivation modifies the association between early life air pollution exposure and autism spectrum disorder (ASD), we used resources from a multisite case-control study, the Study to Explore Early Development. Cases were 674 children with confirmed ASD born in 2003-2006; controls were 855 randomly sampled children born during the same time period and residents of the same geographic areas as cases. Air pollution was assessed by roadway proximity and particulate matter <2.5 μm (PM2.5) exposure during pregnancy and first year of life. To characterize neighborhood deprivation, an index was created based on eight census tract-level socioeconomic status-related parameters. The continuous index was categorized into tertiles, representing low, moderate, and high deprivation. Logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Neighborhood deprivation modified (Pfor interaction = 0.08) the association between PM2.5 exposure during the first year of life and ASD, with a stronger association for those living in high (OR = 2.42, 95% CI = 1.20, 4.86) rather than moderate (OR=1.21, 95% CI = 0.67, 2.17) or low (OR=1.46, 95% CI = 0.80, 2.65) deprivation neighborhoods. Departure from additivity or multiplicativity was not observed for roadway proximity or exposures during pregnancy. These results provide suggestive evidence of interaction between neighborhood deprivation and PM2.5 exposure during the first year of life in association with ASD.
Authors: McGuinn LA; Croen LA; Daniels JL; et al.
Environ Epidemiol. 2019 Oct;3(5).
Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development
Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD.
Authors: Croen LA; Zerbo O; Ames JL; et al.
Autism Res. 2019 10;12(10):1551-1561. Epub 2019-07-17.
Simple Adnexal Cysts: SRU Consensus Conference Update on Follow-up and Reporting.
This multidisciplinary consensus update aligns prior Society of Radiologists in Ultrasound (SRU) guidelines on simple adnexal cysts with recent large studies showing exceptionally low risk of cancer associated with simple adnexal cysts. Most small simple cysts do not require follow-up. For larger simple cysts or less well-characterized cysts, follow-up or second opinion US help to ensure that solid elements are not missed and are also useful for assessing growth of benign tumors. In postmenopausal women, reporting of simple cysts greater than 1 cm should be done to document their presence in the medical record, but such findings are common and follow-up is recommended only for simple cysts greater than 3-5 cm, with the higher 5-cm threshold reserved for simple cysts with excellent imaging characterization and documentation. For simple cysts in premenopausal women, these thresholds are 3 cm for reporting and greater than 5-7 cm for follow-up imaging. If a cyst is at least 10%-15% smaller at any time, then further follow-up is unnecessary. Stable simple cysts at initial follow-up may benefit from a follow-up at 2 years due to measurement variability that could mask growth. Simple cysts that grow are likely cystadenomas. If a previously suspected simple cyst demonstrates papillary projections or solid areas at follow-up, then the cyst should be described by using standardized terminology. These updated SRU consensus recommendations apply to asymptomatic patients and to those whose symptoms are not clearly attributable to the cyst. These recommendations can reassure physicians and patients regarding the benign nature of simple adnexal cysts after a diagnostic-quality US examination that allows for confident diagnosis of a simple cyst. Patients will benefit from less costly follow-up, less anxiety related to these simple cysts, and less surgery for benign lesions.
Authors: Levine D; Suh-Burgmann EJ; Brown DL; et al.
Radiology. 2019 Nov;293(2):359-371. doi: 10.1148/radiol.2019191354. Epub 2019 Sep 24.
Walking for health during pregnancy: A literature review and considerations for future research
Walking is the most commonly chosen type of physical activity (PA) during pregnancy and provides several health benefits to both mother and child. National initiatives have promoted the importance of walking in general, but little emphasis is directed toward pregnant women, the majority of whom are insufficiently active. Pregnant women face a variety of dynamic barriers to a physically active lifestyle, some of which are more commonly experienced during specific times throughout the pregnancy experience. Walking is unique in that it appears resistant to a number of these barriers that limit other types of PA participation, and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are unavailable. Preliminary intervention work suggests that walking programs can be effectively adopted into a typical pregnancy lifestyle. However, a great deal of work remains to administer successful pregnancy walking interventions, including developing and using validated methods of PA and walking assessment. This narrative review discusses the unique advantages of walking during pregnancy, provides recommendations for future intervention work, and outlines the need for pregnancy-focused community walking initiatives. Standard search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review.
Authors: Connolly CP; Conger SA; Montoye AHK; Marshall MR; Schlaff RA; Badon SE; Pivarnik JM
J Sport Health Sci. 2019 Sep;8(5):401-411. Epub 2018-11-17.
Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies
Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low ( Authors: Zhu Y; Li M; Rahman ML; Hinkle SN; Wu J; Weir NL; Lin Y; Yang H; Tsai MY; Ferrara A; Zhang C PLoS Med. 2019 09;16(9):e1002910. Epub 2019-09-13.
Enhanced Recovery After Surgery to Change Process Measures and Reduce Opioid Use After Cesarean Delivery: A Quality Improvement Initiative
To evaluate implementation of an enhanced recovery after surgery (ERAS) program for patients undergoing elective cesarean delivery by comparing opioid exposure, multimodal analgesia use, and other process and outcome measures before and after implementation. An ERAS program was implemented among patients undergoing elective cesarean delivery in a large integrated health care delivery system. We conducted a pre-post study of ERAS implementation to compare changes in process and outcome measures during the 12 months before and 12 months after implementation. The study included 4,689 patients who underwent an elective cesarean delivery in the 12 months before (pilot sites: March 1, 2015-February 29, 2016, all other sites: October 1, 2015-September 30, 2016), and 4,624 patients in the 12 months after (pilot sites: April 1, 2016-March 31, 2017, all other sites: November 1, 2016-October 31, 2017) ERAS program implementation. After ERAS implementation mean inpatient opioid exposure (average daily morphine equivalents) decreased from 10.7 equivalents (95% CI 10.2-11.3) to 5.4 equivalents (95% CI 4.8-5.9) controlling for age, race-ethnicity, prepregnancy body mass index, patient reported pain score, and medical center. The use of multimodal analgesia (ie, acetaminophen and neuraxial anesthesia) increased from 9.7% to 88.8%, the adjusted risk ratio (RR) for meeting multimodal analgesic goals was 9.13 (RR comparing post-ERAS with pre-ERAS; 95% CI 8.35-10.0) and the proportion of time patients reported acceptable pain scores increased from 82.1% to 86.4% (P<.001). Outpatient opioids dispensed at hospital discharge decreased from 85.9% to 82.2% post-ERAS (P<.001) and the average number of dispensed pills decreased from 38 to 26 (P<.001). The hours to first postsurgical ambulation decreased by 2.7 hours (95% CI -3.1 to -2.4) and the hours to first postsurgical solid intake decreased by 11.1 hours (95% CI -11.5 to -10.7). There were no significant changes in hospital length of stay, surgical site infections, hospital readmissions, or breastfeeding rates. Implementation of an ERAS program in patients undergoing elective cesarean delivery was associated with a reduction in opioid inpatient and outpatient exposure and with changes in surgical process measures of care without worsened surgical outcomes.
Authors: Hedderson M; Campbell C; Quesenberry C; Liu V; et al.
Obstet Gynecol. 2019 09;134(3):511-519.
Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities
Neonatal opioid withdrawal syndrome (NOWS) has risen in prevalence from 1.2 per 1000 births in 2000 to 5.8 per 1000 births in 2012. Symptoms in neonates may include high-pitched cry, tremors, feeding difficulty, hypertonia, watery stools, and breathing problems. However, little is known about the neurodevelopmental consequences of prenatal opioid exposure in infancy, early childhood, and middle childhood. Even less is known about the cognitive, behavioral, and academic outcomes of children who develop NOWS. We review the state of the literature on the neurodevelopmental consequences of prenatal opioid exposure with a particular focus on studies in which NOWS outcomes were examined. Aiming to reduce the incidence of prenatal opioid exposure in the near future, we highlight the need for large studies with prospectively recruited participants and longitudinal designs, taking into account confounding factors such as socioeconomic status, institutional variations in care, and maternal use of other substances, to independently assess the full impact of NOWS. As a more immediate solution, we provide an agenda for future research that leverages the National Institutes of Health Environmental Influences on Child Health Outcomes program to address many of the serious methodologic gaps in the literature, and we answer key questions regarding the short- and long-term neurodevelopmental health of children with prenatal opioid exposure.
Authors: Conradt E; Croen LA; Hedderson MM; Lester BM; et al.
Pediatrics. 2019 Sep;144(3).
Pre- and Early Pregnancy Onset Depression and Subsequent Rate of Gestational Weight Gain
Background:Depression is associated with weight change outside of pregnancy. We assessed associations of prepregnancy or early pregnancy onset depression with gestational weight gain (GWG) rate overall and according to Institute of Medicine (IOM) recommendations. Materials and Methods:Depression from 6 months prepregnancy through 20 weeks gestation was identified in a health care system in northern California with perinatal depression screening (2011-2016; n = 87,600). GWG rate (lbs/week) was calculated using weight at delivery and at diagnosis or depression screening ≤20 weeks. Results:Compared to women without prepregnancy or early pregnancy depression, women with prepregnancy onset depression had 11% greater risk of GWG rate
Authors: Badon SE; Hedderson MM; Hyde RJ; Quesenberry CP; Avalos LA
J Womens Health (Larchmt). 2019 09;28(9):1237-1245. Epub 2019-05-07.
Bidirectional 10-year associations of accelerometer-measured sedentary behavior and activity categories with weight among middle-aged adults
Although higher sedentary behavior (SB) with low light intensity (LPA) and moderate-to-vigorous intensity physical activity (MVPA) are thought to increase risk for obesity, other data suggest excess weight may precede these behaviors in the causal pathway. We aimed to investigate 10-year bidirectional associations between SB and activity with weight. Analysis included 886 CARDIA participants (aged 38-50 years, 62% female, 38% black) with weight and accelerometry ( ≥ 4 days with ≥ 10 h/day) collected in 2005-6 (ActiGraph 7164) and 2015-6 (ActiGraph wGT3X-BT). Accelerometer data were calibrated, harmonized, and expressed as counts per minute (cpm) and time-dependent intensity categories (min/day of SB, LPA, and MVPA; SB and MVPA were also separated into long-bout and short-bout categories). Linear regression models were constructed to estimate adjusted associations of baseline activity with 10-year change in weight and vice versa. When activity categories were the independent variables, standardized regression coefficients (βstd.) estimated associations of replacing SB with a one SD increase in other categories, adjusted for accelerometer wear time. Over 10-years, weight increased by a mean 2.55 ± 8.05 kg and mean total activity decreased by 50 ± 153 cpm. In adjusted models, one SD higher baseline mean total activity (βstd. = -1.4 kg, p
Authors: Barone Gibbs B; Aaby D; Siddique J; Reis JP; Sternfeld B; Whitaker K; Pettee Gabriel K
Int J Obes (Lond). 2019 Aug 28.
A Seat at the Table: Strategic Engagement in Service Activities for Early Career Faculty From Underrepresented Groups in the Academy
Many academic institutions strive to promote more diverse and inclusive campuses for faculty, staff, and students. As part of this effort, these institutions seek to include individuals from historically underrepresented groups (URGs)-such as women, people from racial/ethnic minority populations, persons with disabilities-on committees and in other service activities. However, given the low number of faculty members from URGs at many institutions, these faculty members tend to receive more requests to provide service to the institution or department (e.g., serving on committees, mentoring) than their counterparts from majority groups. Faculty members from URGs, especially early-career faculty, thus risk becoming overburdened with providing service at the expense of working on other scholarly activities required for promotion and tenure (i.e., conducting research, publishing). Although many scholars and others have written about this “minority tax” and its implications for early-career faculty from underrepresented racial/ethnic minority groups, fewer have published about how this tax extends beyond racial/ethnic minorities to women and persons with disabilities. Further, the literature provides scant practical advice on how to avoid overburdening early-career faculty from URGs. Here, a group of multidisciplinary early- and mid-career faculty members from URGs seek to provide their peers from URGs with practical strategies for both evaluating the appropriateness of service requests and declining those that are not a good fit. The authors also provide institutional leaders with actionable recommendations to prevent early-career faculty from URGs from becoming overburdened with service.
Authors: Carson TL; Aguilera A; Brown SD; Peña J; Butler A; Dulin A; Jonassaint CR; Riley I; Vanderbom K; Molina KM; Cené CW
Acad Med. 2019 08;94(8):1089-1093.
Unbounded-Parent-Physician Communication in the Era of Portal Messaging
Authors: Lieu TA; Freed GL
JAMA Pediatr. 2019 Jul 29.
Scientific abstracts: Featured research at the 2019 Society of Family Planning Annual Meeting
Authors: Teal S; Haider S; Harris L; Hubacher D; Raine-Bennett T
Contraception. 2019 Jul 23.
An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk: The Early Markers for Autism Study
The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes. Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis. Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39-2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups. Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.
Authors: Heuer LS; Croen LA; Jones KL; Yoshida CK; Hansen RL; Yolken R; Zerbo O; DeLorenze G; Kharrazi M; Ashwood P; Van de Water J
Biol Psychiatry. 2019 May 15.
Viral coinfection analysis using a MinHash toolkit
Human papillomavirus (HPV) is a common sexually transmitted infection associated with cervical cancer that frequently occurs as a coinfection of types and subtypes. Highly similar sublineages that show over 100-fold differences in cancer risk are not distinguishable in coinfections with current typing methods. We describe an efficient set of computational tools, rkmh, for analyzing complex mixed infections of related viruses based on sequence data. rkmh makes extensive use of MinHash similarity measures, and includes utilities for removing host DNA and classifying reads by type, lineage, and sublineage. We show that rkmh is capable of assigning reads to their HPV type as well as HPV16 lineage and sublineages. Accurate read classification enables estimates of percent composition when there are multiple infecting lineages or sublineages. While we demonstrate rkmh for HPV with multiple sequencing technologies, it is also applicable to other mixtures of related sequences.
Authors: Dawson ET; Raine-Bennett T; Durbin R; et al.
BMC Bioinformatics. 2019 Jul 12;20(1):389. Epub 2019-07-12.
A prospective study of artificially sweetened beverage intake and cardiometabolic health among women at high risk
Artificially sweetened beverages (ASBs) are commonly consumed and recommended for individuals at high risk for cardiometabolic diseases; however, the health effects of ASBs remain contradictory. Given that cross-sectional analyses are subject to reverse causation, prospective studies with long-term follow-up are needed to evaluate associations between ASBs and cardiometabolic health, especially among high-risk individuals. The aim of this study was to examine associations of ASB intake and cardiometabolic health among high-risk women with prior gestational diabetes mellitus (GDM). We included 607 women with GDM from the Danish National Birth Cohort (DNBC; 1996-2002) who completed a clinical exam 9-16 y after the DNBC pregnancy for the Diabetes & Women’s Health (DWH) Study (2012-2014). We assessed ASB intake using FFQs completed during the DNBC pregnancy and at the DWH Study clinical exam. We examined cardiometabolic outcomes at the DWH clinical exam. We estimated percentage differences in continuous cardiometabolic markers and RRs for clinical endpoints in association with ASB intake both during pregnancy and at follow-up adjusted for prepregnancy BMI, diet, and lifestyle factors. Sensitivity analyses to account for reverse causation were performed. In pregnancy and at follow-up, 30.4% and 36.4% of women regularly (≥2 servings/wk) consumed ASB, respectively. Consumption of ASBs, both during pregnancy and at follow-up, was associated with higher glycated hemoglobin (HbA1c), insulin, HOMA-IR, triglycerides, liver fat, and adiposity and with lower HDL at follow-up. After adjustment for covariates, particularly prepregnancy BMI, the majority of associations between ASB intake in pregnancy and outcomes at follow-up became null with the exception of HbA1c. ASB intake at follow-up (≥1 serving/d compared with <1 serving/mo) was associated with higher HbA1c (6.5%; 95% CI: 1.9, 11.3; P-trend = 0.007); however, associations were not upheld in sensitivity analyses for reverse causation. Among Danish women with a history of GDM, ASB intake was not significantly associated with cardiometabolic profiles.
Authors: Hinkle SN; Zhu Y; Zhang C; et al.
Am J Clin Nutr. 2019 07 01;110(1):221-232.
A Randomized Study of Values Affirmation to Promote Interest in Diabetes Prevention Among Women With a History of Gestational Diabetes
The objective of this study was to test whether 2 interventions promote interest in diabetes prevention among women with a history of gestational diabetes mellitus, who face high lifetime risk for diabetes. We designed an email outreach message promoting an existing preventive lifestyle program. The message incorporated values affirmation, a theory-based intervention that can improve openness to health information but typically relies on a writing exercise less practical in health care settings. In a 3-arm randomized study, 237 women with elevated body mass index and a history of gestational diabetes mellitus were randomized to read an outreach message containing either no affirmation (control) or 1 of 2 affirmations, streamlined to remove the typical writing exercise: either a values affirmation prompting reflection on any personal value, or a parenting affirmation prompting reflection on caregiving-related values. Outcomes included demonstrating interest in the lifestyle program (seeking information about it or intending to join) and seeking publicly-available health information about diabetes prevention. Compared with control, participants randomized to the values affirmation more frequently demonstrated interest in the lifestyle program (59.0% vs. 74.4%; adjusted relative risk: 1.31; 95% confidence interval: 1.04-1.66) and sought information about diabetes prevention (59.0% vs. 73.4%; adjusted relative risk: 1.22; 95% confidence interval: 0.97-1.54). The parenting affirmation yielded no significant differences in either outcome. A streamlined values affirmation, designed for feasibility in a health care setting, can promote interest in diabetes prevention among women at high risk. Research is needed to evaluate its effects on diabetes prevention program enrollment and clinical outcomes.
Authors: Brown SD; Fotuhi O; Grijalva CS; Tsai AL; Quesenberry CP; Ritchie JL; Cohen GL; Ferrara A
Med Care. 2019 07;57(7):528-535.
Understanding periviable birth: A microeconomic alternative to the dysregulation narrative
Periviable infants (i.e., those born in the 20th through 26th weeks of gestation) suffer much morbidity and approximately half die in the first year of life. Attempts to explain and predict these births disproportionately invoke a “dysregulation” narrative. Research inspired by this narrative has not led to efficacious interventions. The clinical community has, therefore, urged novel approaches to the problem. We aim to provoke debate by offering the theory, inferred from microeconomics, that risk tolerant women carry, without cognitive involvement, high risk fetuses farther into pregnancy than do other women. These extended high-risk pregnancies historically ended in stillbirth but modern obstetric practices now convert a fraction to periviable births. We argue that this theory deserves testing because it suggests inexpensive and noninvasive screening for pregnancies that might benefit from the costly and invasive interventions clinical research will likely devise.
Authors: Catalano R; Bruckner T; Avalos LA; Stewart H; Karasek D; Kariv S; Gemmill A; Saxton K; Casey J
Soc Sci Med. 2019 07;233:281-284. Epub 2017-12-12.
Risk factors for low birth weight among rural and urban Malaysian women
Low birth weight prevalence in Malaysia remains high. Socioeconomic background may lead to differences in physical activity and maternal nutritional status, which may play an important role in birth outcomes. This prospective cross-sectional study aimed to identify rural-urban differences in risk factors for low birth weight among women in Malaysia. Pregnant women at ≥20 weeks of gestation in urban and rural Malaysia (n = 437) completed questionnaires on sociodemographic characteristics and physical activity. Weight and middle-upper arm circumference were measured. Infant birth outcomes were extracted from medical records. The overall prevalence of low birth weight infants was 6.38%. Rural women had more low birth weight infants than urban women (9.8% vs 2.0%, p = 0.03). Findings showed rural women were less sedentary (p = 0.003) and participated in more household/caregiving activities (p = 0.036), sports activities (p = 0.01) and less occupational activity (p < 0.001) than urban women. Logistic regression revealed that older age (OR = 1.395, 95% Cl = 1.053 to 1.846), low parity (OR = 0.256, 95% Cl = 0.088-0.747) and low middle-upper arm circumference (OR = 0.738, 95% Cl = 0.552 to 0.987) increased the risk of low birth weight infants in rural, but not in urban women. We observed differences in risk factors for low birth weight between urban and rural pregnant women. Age, malnutrition and low parity were risk factors for low birth weight among rural pregnant women. Our findings suggest that rural pregnant women with low nutritional status should be encouraged to monitor their middle-upper arm circumference consistently throughout pregnancy. Improving nutritional status in rural pregnant women may reduce the risk of low birth weight infants in this population.
Authors: Kaur S; Ng CM; Badon SE; Jalil RA; Maykanathan D; Yim HS; Jan Mohamed HJ
BMC Public Health. 2019 Jun 13;19(Suppl 4):539. Epub 2019-06-13.
Lack of Standardized Terminology in Ultrasound Reports for Ovarian Cysts
Authors: Suh-Burgmann E; Herrinton L
JAMA Intern Med. 2019 06 01;179(6):847-848.
Associations of pre-pregnancy body mass index, middle-upper arm circumference, and gestational weight gain
An optimal gestational weight gain is essential for maternal health and to reduce adverse birth outcomes. Current guidelines to monitor gestational weight gain are based on pre-pregnancy body mass index (BMI). However, middle-upper arm circumference (MUAC) is increasingly used as an alternative nutritional status measure for pregnant women. Hence, this study aimed to determine associations of MUAC and pre-pregnancy BMI with gestational weight gain rate among Malaysian pregnant women. A cross-sectional study was conducted among 444 pregnant women (≥20 weeks gestation). Women completed questionnaires on sociodemographic data, maternal characteristics and pre-pregnancy weight. Height, current weight and MUAC were measured at study visit (from 1st February 2016 to 31st January 2017). About a third (34.24%) of pregnant women were overweight or obese prior to pregnancy. MUAC was inversely associated with an inadequate rate of gestational weight gain (OR = 0.77; 95% CI: 0.68, 0.87) as compared to normal gestational weight gain. In contrast, a higher MUAC was associated with a higher odds ratio (OR = 1.28; 95% CI: 1.11, 1.49) of having excessive rate of gestational weight. No associations were found for pre-pregnancy BMI categories for gestational weight gain rate. Our findings revealed that women with low MUAC were more likely to have an inadequate gestational weight gain rate during pregnancy whereas higher MUAC was associated with an excessive gestational weight gain rate. MUAC may be a useful indicator of nutritional status associated with GWG. Routine measurement of MUAC in pregnant women may help health professionals, particularly in middle-income countries, to counsel women about gestational weight gain.
Authors: Ng CM; Badon SE; Dhivyalosini M; Hamid JJM; Rohana AJ; Teoh AN; Satvinder K
Sex Reprod Healthc. 2019 Jun;20:60-65. Epub 2019-03-19.
Perceived and objective characteristics of the neighborhood environment are associated with accelerometer-measured sedentary time and physical activity, the CARDIA Study
We investigated cross-sectional and longitudinal associations of neighborhood environment characteristics with accelerometer-measured sedentary time (SED), light-intensity physical activity (LPA), and moderate-to-vigorous intensity physical activity (MVPA). Participants were 2120 men and women in the year 20 (2005-2006) and year 30 CARDIA exams (2015-2016). Year 20 neighborhood characteristics included neighborhood cohesion, resources for physical activity, poverty, and racial residential segregation. Physical activity was measured by accelerometer at years 20 and 30. Multivariable linear regression models examined associations of standardized neighborhood measures at year 20 with SED, LPA, and MVPA assessed that year, and with 10-year changes in SED, LPA, and MVPA. Cross-sectionally, a one standard deviation (SD) increase in cohesion was associated with 4.06 less SED min/day (95% CI: -7.98, -0.15), and 4.46 more LPA min/day (95% CI: 0.88, 8.03). Each one SD increase in resources was associated with 1.19 more MVPA min/day (95% CI: 0.06, 2.31). A one SD increase in poverty was associated with 11.18 less SED min/day (95% CI: -21.16, -1.18) and 10.60 more LPA min/day (95% CI: 1.79, 19.41) among black men. No neighborhood characteristic was associated with 10-year changes in physical activity in the full sample; however, a one SD increase in cohesion was associated with a 10-year decrease of 25.44 SED min/day (95% CI: -46.73, -4.14) and an increase of 19.0 LPA min/day (95% CI, 1.89, 36.10) in black men. Characteristics of the neighborhood environment are associated with accelerometer-measured physical activity. Differences were observed by race and sex, with more robust findings observed in black men.
Authors: Whitaker KM; Xiao Q; Pettee Gabriel K; Gordon Larsen P; Jacobs DR; Sidney S; Reis JP; Barone Gibbs B; Sternfeld B; Kershaw K
Prev Med. 2019 06;123:242-249. Epub 2019-03-30.
Maternal diabetes and hypertensive disorders in association with autism spectrum disorder
Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.
Authors: Cordero C; Windham GC; Schieve LA; Fallin MD; Croen LA; Siega-Riz AM; Engel SM; Herring AH; Stuebe AM; Vladutiu CJ; Daniels JL
Autism Res. 2019 06;12(6):967-975. Epub 2019-04-10.
Newborn vitamin D levels in relation to autism spectrum disorders and intellectual disability: A case-control study in california
Vitamin D deficiency has been increasing concurrently with prevalence of autism spectrum disorders (ASD), and emerging evidence suggests vitamin D is involved in brain development. Most prior studies of ASD examined vitamin D levels in children already diagnosed, but a few examined levels during perinatal development, the more likely susceptibility period. Therefore, we examined newborn vitamin D levels in a case-control study conducted among births in 2000-2003 in southern California. Children with ASD (N?=?563) or intellectual disability (ID) (N?=?190) were identified from the Department of Developmental Services and compared to population controls (N?=?436) identified from birth certificates. 25-hydroxyvitamin D (25(OH)D) was measured in archived newborn dried blood spots by a sensitive assay and corrected to sera equivalents. We categorized 25(OH) D levels as deficient (<50?nmol/L), insufficient (50-74?nmol/L), and sufficient (?75?nmol/L), and also examined continuous levels, using logistic regression. The adjusted odds ratios (AOR) and 95% confidence intervals for ASD were 0.96 (0.64-1.4) for 25(OH)D deficiency (14% of newborns) and 1.2 (0.86-1.6) for insufficiency (26% of newborns). The AORs for continuous 25(OH)D (per 25?nmol/L) were 1.0 (0.91-1.09) for ASD and 1.14 (1.0-1.30) for ID. Thus, in this relatively large study of measured newborn vitamin D levels, our results do not support the hypothesis of lower 25(OH)D being associated with higher risk of ASD (or ID), although we observed suggestion of interactions with sex and race/ethnicity. 25(OH)D levels were relatively high (median 84?nmol/L in controls), so results may differ in populations with higher prevalence of low vitamin D levels. Autism Res 2019, 12: 989-998. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied whether vitamin D levels measured at birth were related to whether a child later developed autism (or low IQ). Our results did not show that children with autism, or low IQ, overall had lower vitamin D levels at birth than children without autism. Vitamin D levels were fairly high, on average, in these children born in Southern California.
Authors: Windham GC; Pearl M; Anderson MC; Poon V; Eyles D; Jones KL; Lyall K; Kharrazi M; Croen LA
Autism Res. 2019 06;12(6):989-998. Epub 2019-03-18.
Strategies for Building Delivery Science in an Integrated Health Care System
Health systems today have increasing opportunities and imperatives to conduct delivery science, which is applied research that evaluates clinical or organizational practices that systems can implement or encourage. Examples include research on eliminating racial/ethnic disparities in hypertension management and on identifying the types of patients who can successfully use video visits. Clinical leaders and researchers often face barriers to delivery science, including limited funding, insufficient leadership support, lack of engagement between operational and research leaders, limited pools of research expertise, and lack of pathways to identify and develop ideas. We describe five key strategies we employed to address these barriers and develop a portfolio of delivery science programs in Kaiser Permanente Northern California. This portfolio now includes small and medium-sized grant programs, training programs for postdoctoral research fellows and experienced physician researchers, and a dedicated team that partners with clinicians to develop high-priority ideas and conduct small projects. Most of our approaches are consistent with frameworks used to develop delivery science by other health systems; some are innovative. Most of these strategies are adaptable by other health systems prepared to make long-range organizational commitments to mechanisms that foster partnerships between clinical leaders and researchers.
Authors: Lieu TA; Madvig PR
J Gen Intern Med. 2019 06;34(6):1043-1047. Epub 2019-01-25.
Factors associated with recruitment, surveillance participation, and retention in an observational study of pregnant women and influenza
This report describes the results of recruitment efforts and the subsequent participation of pregnant women in study activities in a 2010-2012 observational study focused on influenza illness and vaccination in California and Oregon, USA. Socio-demographic and health characteristics extracted from electronic medical records were compared among pregnant women who enrolled in the study, refused to participate, or were never reached for study invitation. These characteristics plus additional self-reported information were compared between women who enrolled in two study tracks: a prospective cohort vs. women enrolled following an acute respiratory illness (ARI) medical encounter. The characteristics of women who participated in weekly ARI surveillance (cohort enrollees, year one) and a 6-month follow-up interview (all enrollees) were also examined. In year one, we reached 51% (6938/13,655) of the potential participants we tried to contact by telephone, and 20% (1374/6938) of the women we invited agreed to join the prospective cohort. Women with chronic medical conditions, pregnancy complications, and medical encounters for ARI (prior to pregnancy or during the study period) were more likely to be reached for recruitment and more likely to enroll in the cohort. Twenty percent of cohort enrollees never started weekly surveillance reports; among those who did, reports were completed for 55% of the surveillance weeks. Receipt of the influenza vaccine was higher among women who joined the cohort (76%) than those who refused (56%) or were never reached (54%). In contrast, vaccine uptake among medical enrollees in year one (54%; 53/98) and two (52%; 79/151) was similar to other pregnant women in those years. Study site, white race, non-Hispanic ethnicity, and not having a child aged < 13 years at home were most consistently associated with joining as a cohort or medical enrollee and completing study activities after joining. We observed systematic differences in socio-demographic and health characteristics across different levels of participant engagement and between cohort and medical enrollees. More methodological research and innovation in conducting prospective observational studies in this population are needed, especially when extended participant engagement and ongoing surveillance are required.
Authors: Thompson MG; Li DK; Bozeman S; et al.
BMC Pregnancy Childbirth. 2019 May 08;19(1):161. Epub 2019-05-08.
Epigenetic marks of prenatal air pollution exposure found in multiple tissues relevant for child health
Prenatal air pollution exposure has been linked to many adverse health conditions in the offspring. However, little is known about the mechanisms underlying these associations. Epigenetics may be one plausible biologic link. Here, we sought to identify site-specific and global DNA methylation (DNAm) changes, in developmentally relevant tissues, associated with prenatal exposure to nitrogen dioxide (NO2) and ozone (O3). Additionally, we assessed whether sex-specific changes in methylation exist and whether DNAm changes are consistently observed across tissues. Genome-scale DNAm measurements were obtained using the Infinium HumanMethylation450k platform for 133 placenta and 175 cord blood specimens from Early Autism Risk Longitudinal Investigation (EARLI) neonates. Ambient NO2 and O3 exposure levels were based on prenatal address locations of EARLI mothers and the Environmental Protection Agency’s AirNOW monitoring network using inverse distance weighting. We computed sample-level aggregate methylation measures for each of 5 types of genomic regions including genome-wide, open sea, shelf, shore, and island regions. Linear regression was performed for each genomic region; per-sample aggregate methylation measures were modeled as a function of quantitative exposure level with covariate adjustment. In addition, bumphunting was performed to identify differentially methylated regions (DMRs) associated with prenatal O3 and NO2 exposures in each tissue and by sex, with adjustment for technical and biological sources of variation. We identified global and locus-specific changes in DNA methylation related to prenatal exposure to NO2 and O3 in 2 developmentally relevant tissues. Neonates with increased prenatal O3 exposure had lower aggregate levels of DNAm at CpGs located in open sea and shelf regions of the genome. We identified 6 DMRs associated with prenatal NO2 exposure, including 3 sex-specific. An additional 3 sex-specific DMRs were associated with prenatal O3 exposure levels. DMRs initially detected in cord blood samples (n = 4) showed consistent exposure-related changes in DNAm in placenta. However, the DMRs initially detected in placenta (n = 5) did not show DNAm differences in cord blood and, thus, they appear to be tissue-specific. We observed global, locus, and sex-specific methylation changes associated with prenatal NO2 and O3 exposures. Our findings support DNAm is a biologic target of prenatal air pollutant exposures and highlight epigenetic involvement in sex-specific differential susceptibility to environmental exposure effects in 2 developmentally relevant tissues.
Authors: Ladd-Acosta C; Feinberg JI; Brown SC; Lurmann FW; Croen LA; Hertz-Picciotto I; Newschaffer CJ; Feinberg AP; Fallin MD; Volk HE
Environ Int. 2019 05;126:363-376. Epub 2019-02-28.
Prenatal exposure to endocrine disrupting chemicals in relation to autism spectrum disorder and intellectual disability
Exposure to endocrine disruptors is unavoidable. Many such compounds are suspected to impact neurologic development of children, but most studies conducted have considered effects of individual chemicals in isolation. Because exposures co-occur, it is important to consider their health impacts in a single regression framework. We applied Bayesian statistical tools (including shared mean and mixture priors for 25 unique chemicals) to study independent associations of endocrine disruptor biomarkers with autism spectrum disorder (ASD) (n = 491) and intellectual disability (n = 155), compared with 373 general population controls, in the Early Markers for Autism study. We measured biomarkers in maternal serum collected and stored from midpregnancy and considered them individually or as a class (i.e., summed polychlorinated biphenyls). We adjusted all models for original matching factors (child sex and month and year of birth), maternal age, maternal race/ethnicity, parity, and maternal education at the time samples were collected. We estimated the change in the odds of ASD or intellectual disability per 1 SD increase in the z-score of measured biomarker concentration for each chemical. Odds of ASD and intellectual disability did not change with increasing concentration for any specific endocrine disruptor. The effect estimates for each chemical were centered on or near an odds ratio of 1.00 in both models where we applied a shared mean or a mixture prior. Our mixtures analyses do not suggest an independent relationship with ASD or intellectual disability with any of the 25 chemicals examined together in this mixtures analysis.
Authors: Hamra GB; Lyall K; Windham GC; Calafat AM; Sjödin A; Volk H; Croen LA
Epidemiology. 2019 05;30(3):418-426.
Iodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States
Although it is generally acknowledged that exposure to iodine contrast agents can interfere with thyroid function, little is known about the incidence of iodine-induced hypothyroidism in young children (younger than the age of 4 years). This was a retrospective cohort study to estimate the incidence rate of detected hypothyroidism in a US-based general population of pediatric patients exposed to an iodinated contrast agent. The study was conducted in Kaiser Permanente Northern California, an integrated health care delivery system. This study included 2320 pediatric patients younger than 4 years of age who had a diagnostic procedure with an iodinated contrast agent during years 2008 to 2016. Among 2320 young children who met our study criteria, we identified 34 who met the initial criteria to be a case of hypothyroidism. The incidence density ratio for all hypothyroidism in iodine contrast agent-exposed patients was 1.33 per 1000 person months (95% confidence interval, 0.9-1.8). Most cases appeared to have subclinical hypothyroidism. The rate was higher for the probably iodine-induced cases (0.90 per 1000 person months) compared with cases with a possible alternate etiology (0.43 per 1000 person months), for males compared with females, and among children who had a heart catheterization compared with those with a computed tomography scan. It was also highest among the youngest children (younger than 3 months old), and decreased with increasing age. Our finding of hypothyroidism in young children exposed to iodine contrast agents (1.33 per 1000 person months [95% confidence interval, 0.9-1.8]) is broadly consistent with the sparse literature on this outcome.
Authors: Jick SS; Hedderson M; Xu F; Cheng Y; Palkowitsch P; Michel A
Issues Ment Health Nurs. 2019 Nov;40(11):988-989. Epub 2019-08-05.
Gestational weight gain and optimal wellness (GLOW): rationale and methods for a randomized controlled trial of a lifestyle intervention among pregnant women with overweight or obesity
Excess gestational weight gain (GWG) is common among women with overweight or obesity, increasing their risks for pregnancy complications, delivering a large infant, and postpartum weight retention. To date, only intensive interventions have had success and few interventions have been designed for implementation in healthcare settings. We describe the development, rationale, and methods of GLOW (GestationaL Weight Gain and Optimal Wellness), a randomized controlled trial evaluating the efficacy of a lifestyle intervention to prevent excess GWG among racially/ethnically diverse women with overweight or obesity in an integrated healthcare delivery system. Participants in Kaiser Permanente Northern California will be randomized, within 2 weeks of completing a study baseline clinic visit at 10 weeks’ gestation, to either usual medical care or a multi-component pregnancy lifestyle intervention adapted from the Diabetes Prevention Program (target N = 400). Informed by focus groups with patients and designed to be feasible in a clinical setting, the intervention will include 13 weekly individual sessions (11 delivered by telephone) focused on behavior change for weight management, healthy eating, physical activity, and stress management. Outcomes will be assessed in women and their infants from randomization to 12 months postpartum. The primary outcome is GWG. Secondary outcomes include changes in diet and physical activity during pregnancy and infant birthweight. Exploratory outcomes include cardiometabolic profile assessed via pregnancy blood samples and cord blood samples; and postpartum weight retention and infant anthropometrics up to 12 months of age. The trial includes systematic approaches to enhance intervention fidelity, intervention adherence, and participant retention in trial assessments. GLOW is among few trials targeting excess GWG among diverse women with overweight or obesity in a healthcare setting, with long-term maternal and infant outcomes assessed up to 12 months after delivery. This evaluation of a multi-component intervention is designed to produce generalizable results to inform potential adoption of the intervention in clinical settings. ClinicalTrials.gov ( NCT02130232 ): submitted April 30, 2014; posted May 5, 2014.
Authors: Brown SD; Hedderson MM; Ehrlich SF; Galarce MN; Tsai AL; Quesenberry CP; Ferrara A
BMC Pregnancy Childbirth. 2019 Apr 30;19(1):145. Epub 2019-04-30.
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
Authors: Küpers LK; Croen LA; Felix JF; et al.
Nat Commun. 2019 04 23;10(1):1893. Epub 2019-04-23.
Preventing Perinatal Depression to Improve Maternal and Child Health-a Health Care Imperative
Authors: Avalos LA; Flanagan T; Li DK
JAMA Pediatr. 2019 04 01;173(4):313-314.
Poor diet quality in pregnancy is associated with increased risk of excess fetal growth: a prospective multi-racial/ethnic cohort study
Nutritional perturbations during pregnancy may impact fetal and long-term childhood growth, although there are limited data on overall diet quality. We investigated whether diet quality, measured by the Healthy Eating Index-2010 (HEI-2010), during pregnancy was related to birthweight z-score (BWZ) and the clinically relevant birth outcomes of large- and small-for-gestational age (LGA and SGA). In a prospective cohort of 2269 multi-racial/ethnic women from the Pregnancy Environment and Lifestyle Study (2014-2017), dietary intake was assessed by a food frequency questionnaire during early pregnancy. Offspring BWZ and LGA or SGA were derived based on gestational age-, sex-, and racial/ethnic-specific birthweight distributions. Multivariable linear and Poisson regression with robust standard errors were used. About 80% of women did not achieve good diet quality (HEI-2010?
Authors: Zhu Y; Hedderson MM; Sridhar S; Xu F; Feng J; Ferrara A
Int J Gynaecol Obstet. 2020 Jan;148 Suppl 1:42-58.
Developing a Prognostic Information System for Personalized Care in Real Time
Electronic medical records hold promise to transform clinical practice. However, technological and other barriers may preclude using them to guide care in real time. We used the Virtual Data Warehouse (VDW) to develop a tool that enables physicians to generate real-time, personalized prognostic information about survival after cancer. Patients with cancer often ask their oncologists, “Have you ever seen a patient like me?” To help oncologists answer this question, we developed a prototype Prognostic Information System (PRISM), a web-based tool that gathers data about the index patient from Kaiser Permanente’s clinical information systems, selects a historical cohort of similar patients, and displays the survival curve of the similar patients relative to key points in their treatment course. The prototype was developed by a multidisciplinary team with expertise in oncology, research, and technology. We have completed two rounds of user testing and refinement. Successful development rested on: (1) executive support and a clinical champion; (2) collaboration among experts from multiple disciplines; (3) starting with simple cases rather than ambitious ones; (4) extensive research experience with the Virtual Data Warehouse, related databases, and an existing query tool; and (5) following agile software development principles, especially iterative user testing. Clinical data stored in health care systems’ electronic medical records can be used to personalize clinical care in real time. Development of prognostic information systems can be accelerated by collaborations among researchers, technology specialists, and clinicians and by use of existing technology like the Virtual Data Warehouse.
Authors: Lieu TA; Neugebauer R; Van Den Eeden SK; Baer DM; et al.
EGEMS (Wash DC). 2019 Mar 25;7(1):2. Epub 2019-03-25.
Maternal Gestational Weight Gain, Obesity, and the Timing of Pubertal Onset in Daughters
Early puberty is associated with adverse health outcomes, but little is known regarding early life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005-06. Using Weibull regression models accommodating interval censoring, and adjusting for important confounders, we found that excessive GWG was associated with increased risk of early thelarche (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.26-1.78) and early pubarche (HR: 1.35; 95% CI: 1.10-1.66). Inadequate GWG was associated with early thelarche (HR: 1.36; 95% CI: 1.08-1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30) (HR: 2.01; 95% CI: 1.53-2.63; HR: 2.08; 95% CI: 1.45-2.98, respectively]. Similar associations were found for pubarche outcome. Inclusion of girls’ prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy may help prevent early pubertal onset and subsequent negative health outcomes.
Authors: Aghaee S; Laurent CA; Deardorff J; Ferrara A; Greenspan LC; Quesenberry CP; Kushi LH; Kubo A
Am J Epidemiol. 2019 Mar 15.
Changes in body composition and weight during the menopause transition
The relation between the menopause transition (MT) and changes in body composition or weight remains uncertain. We hypothesized that, independent of chronological aging, the MT would have a detrimental influence on body composition. Participants were from the longitudinal Study of Women’s Health Across the Nation (SWAN) cohort. We assessed body composition by dual energy x-ray absorptiometry. Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of outcomes as a function of time before or after the final menstrual period (FMP). Covariates were age at FMP, race, study site, and hormone therapy. Fat and lean mass increased prior to the MT. At the start of the MT, rate of fat gain doubled, and lean mass declined; gains and losses continued until 2 years after the FMP. After that, the trajectories of fat and lean mass decelerated to zero slope. Weight climbed linearly during premenopause without acceleration at the MT. Its trajectory became flat after the MT. Accelerated gains in fat mass and losses of lean mass are MT-related phenomena. The rate of increase in the sum of fat mass and lean mass does not differ between premenopause and the MT; thus, there is no discernable change in rate of weight gain at the start of the MT. NIH, Department of Health and Human Services (DHHS), through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women’s Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).
Authors: Greendale GA; Sternfeld B; Huang M; Han W; Karvonen-Gutierrez C; Ruppert K; Cauley JA; Finkelstein JS; Jiang SF; Karlamangla AS
JCI Insight. 2019 03 07;4(5). Epub 2019-03-07.
Health Care Service Utilization and Cost Among Adults with Autism Spectrum Disorders in a U.S. Integrated Health Care System
To compare health care utilization patterns and cost among insured adults with autism spectrum disorder (ASD), adults with attention-deficit and hyperactivity disorder (ADHD), and adults with neither condition (general population [GP] controls). We conducted a case-control study among adults (≥18 years) who were members of Kaiser Permanente Northern California (KPNC) for at least 9 months each year from 2008 to 2012. Cases (N = 1507) were adults with an ASD diagnosis (ICD-9-CM 299.0-299.8) recorded in the electronic medical record on at least two separate occasions by December 31, 2012. Two control groups, adults with ADHD (N = 9042) defined by ICD-9-CM code 314 and GP (N = 15,070), were randomly selected and frequency matched to cases on gender and age. Health care utilization and cost data were obtained from KPNC databases for the year 2012. Compared with adults with ADHD, adults with ASD had significantly higher utilization of outpatient visits for primary care (74.2% vs. 66.6%), mental health (43.3% vs. 33.2%), and laboratory services (60.9% vs. 54.4%). Hospitalizations for ambulatory care sensitive diagnoses (5.4% vs. 2.3%) were less frequent overall but more common among adults with ASD than with ADHD. Group differences were larger comparing adults with ASD with GP controls. Gynecology visits and screening for cervical cancer were significantly less common among women with ASD than among women with ADHD (35% vs. 50%) or GP (35% vs. 49%). Total annual mean healthcare costs for adults with ASD were 20% higher than costs for adults with ADHD and double costs for GP. Adults with ASD had significantly higher rates of utilization across most health care service areas compared with adults with ADHD or GP; however, women with ASD were significantly less likely to have gynecology visits and have screening for cervical cancer. We conducted a study among adults (≥18 years) who were members of Kaiser Permanente Northern California (KPNC) from 2008 to 2012. We compared how often people attended different types of health care and costs of health care among adults with autism spectrum disorder (ASD), adults with attention-deficit and hyperactivity disorder (ADHD), and adults with neither condition (general population [GP] controls). The study included 1507 adults with ASD, 9042 with ADHD but not ASD, and 15,070 GP controls with no ASD or ADHD. Health care and cost data were obtained from KPNC databases for the year 2012. The study found that adults with ASD used more outpatient visits for primary care, mental health, and laboratory services than adults with ADHD. Gynecology visits and screening for cervical cancer were less common among women with ASD than among women with ADHD or GP. Health care costs for adults with ASD were higher than costs for adults with ADHD and costs for GP. In conclusion, adults with ASD had higher rates of use of most health care service areas than adults with ADHD or GP; however, women with ASD were less likely to have gynecology visits and have screening for cervical cancer.
Authors: Zerbo, Ousseny; Qian, Yinge; Ray, Thomas; Sidney, Steve; Rich, Steve; Massolo, Maria; Croen, Lisa A
Autism Adulthood. 2019 Mar 01;1(1):27-36. Epub 2019-03-11.
Trends in marijuana use among pregnant women with and without nausea and vomiting in pregnancy, 2009-2016
Cross-sectional studies indicate an elevated prevalence of prenatal marijuana use in women with nausea and vomiting in pregnancy (NVP). However, it is unknown whether differences in marijuana use by NVP status have persisted over time as marijuana becomes more acceptable and accessible and prenatal use increases overall. We compared trends in prenatal marijuana use by NVP status in the first trimester of pregnancy using data from Kaiser Permanente Northern California’s (KPNC) large healthcare system. The sample comprised KPNC pregnant women aged ≥12 who completed a self-administered questionnaire on marijuana use and a urine toxicology test for cannabis during standard prenatal care from 2009 to 2016. The annual prevalence of marijuana use via self-report or toxicology by NVP status was estimated using Poisson regression with a log link function, adjusting for sociodemographics and parity. We tested for linear trends and differences in trends by NVP. Of 220,510 pregnancies, 38,831 (17.6%) had an NVP diagnosis. Prenatal marijuana use was elevated each year among women with NVP. The adjusted prevalence of use increased significantly from 2009 to 2016 at an annual rate of 1.086 (95%CI = 1.069-1.104) among women with NVP, from 6.5% (95%CI = 5.7%-7.2%) to 11.1% (95%CI = 0.2%-12.0%), and 1.069 (95%CI = 1.059-1.080) among women without NVP, from 3.4% (95%CI = 3.2%-3.7%) to 5.8% (95%CI = 5.5%-6.1%). Trends did not vary by NVP status. The prevalence of prenatal marijuana use has remained elevated over time among women with NVP. Clinicians should ask pregnant patients about their reasons for marijuana use and treat NVP with evidence-based interventions.
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Avalos LA; Alexeeff S; Conway A; Armstrong MA; Weisner C; Campbell CI; Goler N
Drug Alcohol Depend. 2019 03 01;196:66-70. Epub 2019-01-18.
Timing of household food insecurity exposures and asthma in a cohort of US school-aged children
Food insecurity is positively associated with asthma, the most common chronic childhood disease, yet directionality is unclear. The objective was to determine the association between exposure to food insecurity in early childhood and the odds of asthma later in childhood. Data from four waves of the Early Childhood Longitudinal Study-Kindergarten (ECLS-K) cohort, a prospective, dual-frame, multistage probability cluster sampling study of school-aged US children were entered in multivariate logistic regression models, adjusted for covariates. Exposures to food insecurity were based on parental responses to the validated USDA 18-item module at each wave. Public and private primary and secondary schools between 1998 and 2007. At its inception (1999), the ECLS-K had 20 578 kindergarteners; by the spring of eighth grade (2007), the cohort dropped to 9725 due to attrition. Children missing an exposure, outcome or confounding variable were excluded, final n=6731. Child’s diagnosis of asthma by a healthcare professional as reported by the parent. Household food insecurity (vs food security) in the year before kindergarten and in second grade had a higher odds of asthma by 18% (95% CI 1.17 to 1.20) and 55% (95% CI 1.51 to 1.55). After removing asthmatics before third grade from the model, food insecurity in second grade was associated with higher odds of asthma at fifth or eighth grades (OR 1.55; 95% CI 1.53 to 1.58), whereas food insecurity in the year before kindergarten had a lower odds at fifth or eighth grades. Food insecurity in the year before kindergarten and in second grade were associated with a higher odds of asthma in third grade. Food insecurity in second grade retained the signal for increased odds of asthma after third and through eighth grades. Additional research is needed to explore childhood windows of vulnerability to asthma.
Authors: Mangini LD; Hayward MD; Zhu Y; Dong Y; Forman MR
BMJ Open. 2019 02 22;8(11):e021683. Epub 2019-02-22.
Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women
Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1-4, B1-4, C1-4, D1-4) which may have differential cervical cancer risk. A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI. A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1-4 and C1-4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0-4.7); A4 in East Asia (6.6, 3.1-14.1) and North America (3.8, 1.7-8.3); and D in North (6.2, 4.1-9.3) and South/Central America (2.2, 0.8-5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5-6.5; 12.1, 5.7-25.6, respectively). HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal.
Authors: Clifford GM; Raine-Bennett T; Mirabello L; et al.
Papillomavirus Res. 2019 Feb 06;7:67-74. Epub 2019-02-06.
Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain in Relation to Autism Spectrum Disorder and other Developmental Disorders in Offspring
Most prior studies examining maternal pre-pregnancy body mass index (BMI) in relation to offspring autism spectrum disorders (ASD) have reported an association, though findings are not uniform and few have also examined gestational weight gain (GWG). Therefore, we examined both in the Study to Explore Early Development, a multi-site case-control study of children born in 2003-2006. Children identified from clinics, schools, and birth certificates were enrolled at ages 2-5 year and using standardized developmental evaluations, classified as: ASD, other developmental delays (DD), or population-based controls. Maternal height, weight, and GWG were self-reported during the telephone interview. Three primary weight risk factors were examined: (a) Pre-pregnancy BMI, classified as underweight to obese, (b) GWG continuous and categorized as quintiles, and (c) Institute of Medicine clinical weight-gain recommendations. Odds ratios adjusted (AOR) for sociodemographic and prenatal factors were calculated among term singletons, comparing the ASD (n = 540) or DD (n = 720) groups to the control group (n = 776). The AOR of ASD and maternal obesity was 1.37 (95%CI 0.98-1.92). Associations with higher GWG were stronger (Quintile5 vs. Quintile3 AOR = 1.58, 95%CI 1.08-2.31), and particularly so among overweight/obese women (AOR = 1.90, 95%CI 0.98-3.68). DD was associated with maternal overweight and obesity (obesity AOR = 1.48, 95%CI 1.08-2.02), but not with total GWG or clinical recommendations. High maternal BMI and GWG are risk factors for other pregnancy and child outcomes, and our results suggest they may also represent modifiable risk factors for neurodevelopmental outcomes. Autism Res 2019, 12: 316-327 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In a large, national study, we found that children with autism were more likely than unaffected children to have mothers with higher weight gain during pregnancy; risk of autism may be even stronger if mothers were also overweight before pregnancy. Children with other developmental delays were more likely to have mothers who were overweight or obese before pregnancy, but not who gained more weight during pregnancy. Overweight and weight gain may represent factors that could be modified.
Authors: Windham GC; Anderson M; Lyall K; Daniels JL; Kral TVE; Croen LA; Levy SE; Bradley CB; Cordero C; Young L; Schieve LA
Behav Ther. 2019 03;50(2):446-458. Epub 2018-08-16.
Pregnancy-Associated Cancer: A U.S. Population-Based Study
The incidence of pregnancy-associated cancer (PAC) is expected to increase as more women delay childbearing until later ages. However, information on frequency and incidence of PAC is scarce in the United States. We identified pregnancies among women aged 10-54 years during 2001-2013 from five U.S. health plans participating in the Cancer Research Network (CRN) and the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). We extracted information from the health plans’ administrative claims and electronic health record databases, tumor registries, and infants’ birth certificate files to estimate the frequency and incidence of PAC, defined as cancer diagnosed during pregnancy and up to 1 year postpartum. We identified 846 PAC events among 775,709 pregnancies from 2001 to 2013. The overall incidence estimate was 109.1 (95% confidence interval [CI]?=?101.8-116.7) per 100,000 pregnancies. There was an increase in the incidence between 2002 and 2012 (the period during which complete data were available), from 75.0 (95% CI?=?54.9-100.0) per 100,000 pregnancies in 2002 to 138.5 (95% CI?=?109.1-173.3) per 100,000 pregnancies in 2012. The most common invasive cancers diagnosed were breast (n?=?208, 24.6%), thyroid (n?=?168, 19.9%), melanoma (n?=?93, 11.0%), hematologic (n?=?87, 10.3%), and cervix/uterus (n?=?74, 8.7%). Our study provides contemporary incidence estimates of PAC from a population-based cohort of U.S. women. These estimates provide the data needed to help develop clinical and public health policies aimed at diagnosing PAC at an early stage and initiating appropriate therapeutic interventions in a timely manner.
Authors: Cottreau CM; Dashevsky I; Andrade SE; Li DK; Nekhlyudov L; Raebel MA; Ritzwoller DP; Partridge AH; Pawloski PA; Toh S
J Womens Health (Larchmt). 2019 02;28(2):250-257. Epub 2018-10-10.
Dietary Quality and Glycemic Control Among Women with Gestational Diabetes Mellitus
Poor dietary quality, measured by the Healthy Eating Index 2010 (HEI-2010), is associated with risk of gestational diabetes mellitus (GDM) and type 2 diabetes. The aim was to investigate the association between dietary quality and glycemic control in women with GDM. The study included 1220 women with GDM. Dietary quality was calculated by HEI-2010 score from a Food Frequency Questionnaire administered shortly after GDM diagnosis; higher scores indicate higher dietary quality. Subsequent glycemic control was defined as ?80% of all capillary glucose measurements meeting recommended clinical targets below 95?mg/dL for fasting, and below 140?mg/dL 1-hour glucose after meals. As compared with Quartile 1 of HEI-2010 score, Quartiles 2, 3, and 4 showed increased adjusted odds of overall optimal glycemic control (odds ratio [95% confidence interval] 1.90 [1.34-2.70], 1.77 [1.25-2.52], and 1.55 [1.09-2.20], respectively). Increased odds of glycemic control were observed in Quartiles 2, 3, and 4 as compared with Quartile 1 of HEI-2010 score for 1-hour postbreakfast and 1-hour postdinner. Mean capillary glucose was lower in Quartiles 2, 3, and 4 of HEI-2010 score when compared with Quartile 1 for 1-hour postdinner (p?=?0.03). Clinicians should be aware that even a small improvement in diet quality may be beneficial for the achievement of improved glycemic control in women with GDM. Clinical Trials.gov number, NCT01344278.
Authors: Gadgil MD; Ehrlich SF; Zhu Y; Brown SD; Hedderson MM; Crites Y; Ferrara A
J Womens Health (Larchmt). 2019 02;28(2):178-184. Epub 2018-10-30.
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
Authors: Kilpeläinen TO; Sternfeld B; Loos RJF; et al.
Nat Commun. 2019 01 22;10(1):376. Epub 2019-01-22.
Prenatal exposure to extremely low frequency magnetic field and its impact on fetal growth
Studies on the effect of prenatal exposure to magnetic field (MF) on fetal growth is inconclusive and subject to some methodological limitations, particularly in measurement of MF exposure. The present study aimed to examine the association between maternal extremely low frequency MF (ELF-MF) exposure during pregnancy and fetal growth in offspring. A total of 128 pregnant women were recruited at their 3rd trimester and asked to wear an EMDEX Lite meter for 24 h to capture daily ELF-MF exposure. Time-weighted average (TWA), P50, and P75 of personal 24-h measurements were used to evaluate prenatal ELF-MF exposure. The medians of these measurements were used as cut-off points of high and low prenatal ELF-MF exposure. Fetal growth was measured by infant’s birth weight, skinfold thickness of triceps, abdomen, and back, and circumference of head, upper arm, and abdomen. These measures were conducted within 24-h after birth. Generalized Linear Model was used to examine the association between maternal ELF-MF level and fetal growth indices after potential confounders were adjusted for. Compared with girls with lower prenatal ELF-MF exposure, girls with higher exposure had a lower birth weight, thinner skinfold of triceps, abdomen and back, and smaller circumference of head, upper arm and abdomen in all three ELF-MF matrices. The differences were statistically significant for birth weight and most other growth measurements (P < 0.05). These measures had no significant difference between higher and lower prenatal ELF-MF exposure in boys except back skinfold thickness. Prenatal exposure to higher ELF-MF levels was associated with decreased fetal growth in girls, but not in boys.
Authors: Ren Y; Chen J; Miao M; Li DK; Liang H; Wang Z; Yang F; Sun X; Yuan W
Environ Health. 2019 01 11;18(1):6. Epub 2019-01-11.
Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men
Exposure to bisphenol A (BPA) has been shown to impact human sperm quality. The epigenetic mechanisms underlying the effect remain unknown. The acetylcholinesterase (ACHE) gene is a sperm-expressed gene encoding the acetylcholine hydrolyzing enzyme acetylcholinesterase and participates in the apoptosis of cells, including sperm. This study aimed to examine whether BPA exposure is associated with the hydroxymethylation level of the sperm ACHE gene. A total of 157 male factory workers were studied, among whom 74 had BPA exposure in the workplace (BPA exposure group) and 83 had no BPA exposure in the workplace (control group). Urine samples were collected for BPA measurement and semen samples were collected to assay for ACHE hydroxymethylation. Sperm ACHE hydroxymethylation level was higher in the BPA exposure group (p = 0.041) compared to the control group. When subjects were categorized according to tertiles of detected BPA level, higher ACHE hydroxymethylation levels were observed for the lowest, middle, and top tertiles compared to those with BPA below the limit of detection (LOD). In a linear regression analysis adjusted for confounders, a positive linear association between urine BPA concentration and 5-hydroxymethylcytosine (5hmC) rate of the sperm ACHE gene was observed, although the association did not reach statistical significance in all categories after being stratified by the BPA tertile. In conclusion, 5hmC of the sperm ACHE gene was positively associated with BPA exposure, which may provide supportive evidence for BPA’s effects on male fertility or other health endpoints.
Authors: Song X; Miao M; Zhou X; Li D; Tian Y; Liang H; Li R; Yuan W
Int J Epidemiol. 2019 04 01;48(2):423-432.
Associations of Accelerometer-Measured Sedentary Time and Physical Activity With Prospectively Assessed Cardiometabolic Risk Factors: The CARDIA Study
Background Isotemporal substitution examines the effect on health outcomes of replacing sedentary time with light-intensity physical activity or moderate-to-vigorous intensity physical activity; however, existing studies are limited by cross-sectional study designs. Methods and Results Participants were 1922 adults from the CARDIA (Coronary Artery Risk Development in Young Adults) study. Linear regression examined the associations of sedentary, light-intensity physical activity, and moderate-to-vigorous intensity physical activity at year 20 (2005-2006) with waist circumference, blood pressure, glucose, insulin, triglycerides, high-density lipoprotein cholesterol, and a composite risk score at year 30 (2015-2016). Models then examined change in activity with change in cardiometabolic risk over the same 10-year period. Replacing 30 min/day of sedentary time with 30 min/day of light-intensity physical activity at year 20 was associated with a lower composite risk score (-0.01 SD [95% CI, -0.02, -0.00]) at year 30, characterized by lower waist circumference (0.15 cm [95% CI, -0.27, 0.02]), insulin (0.20 ?U/mL [95% CI, -0.35, -0.04]), and higher high-density lipoprotein cholesterol (0.20 mg/dL [95% CI, 0.00, 0.40]; all P<0.05). An increase of 30 min/day in MVPA from year 20 to year 30, when replacing an equivalent increase in sedentary time, was associated with a decrease in the composite risk score (-0.08 [95% CI, -0.13, -0.04]) over the same 10 years, characterized by a decrease in waist circumference (1.52 cm [95% CI, -2.21, -0.84]), insulin (-1.13 ?U/mL [95% CI, -1.95, -0.31]), triglycerides (-6.92 mg/dL [95% CI, -11.69, -2.15]), and an increase in high-density lipoprotein cholesterol (1.59 mg/dL [95% CI, 0.45, 2.73]; all P<0.05). Conclusions Replacement of sedentary time with light-intensity physical activity or moderate-to-vigorous intensity physical activity is associated with improved cardiometabolic health 10 years later.
Authors: Whitaker KM; Pettee Gabriel K; Buman MP; Pereira MA; Jacobs DR; Reis JP; Gibbs BB; Carnethon MR; Staudenmayer J; Sidney S; Sternfeld B
J Am Heart Assoc. 2019 02 19;8(4):e010586.
Family history of immune conditions and autism spectrum and developmental disorders: Findings from the study to explore early development
Numerous studies have reported immune system disturbances in individuals with autism and their family members; however, there is considerable variability in findings with respect to the specific immune conditions involved, their timing, and the family members affected and little understanding of variation by autism subphenotype. Using data from the Study to Explore Early Development (SEED), a multi-site case-control study of children born 2003-2006 in the United States, we examined the role of family history of autoimmune diseases, asthma, and allergies in autism spectrum disorder (ASD) as well as other developmental disorders (DD). We investigated maternal immune conditions during the pregnancy period, as well as lifetime history of these conditions in several family members (mother, father, siblings, and study child). Logistic regression analyses included 663 children with ASD, 984 children with DD, and 915 controls ascertained from the general population (POP). Maternal history of eczema/psoriasis and asthma was associated with a 20%-40% increased odds of both ASD and DD. Risk estimates varied by specific ASD subphenotypes in association with these exposures. In addition, children with ASD were more likely to have a history of psoriasis/eczema or allergies than POP controls. No association was observed for paternal history or family history of these immune conditions for either ASD or DD. These data support a link between maternal and child immune conditions and adverse neurodevelopmental outcomes, and further suggest that associations may differ by ASD phenotype of the child. Autism Research 2019, 12: 123-135. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multi-site study in the US-the Study to Explore Early Development-we found that women with a history of eczema/psoriasis and asthma are more likely to have children with ASD or DD. In addition, children with ASD are more likely to have a history of psoriasis/eczema or allergies than typically developing children. These data support a link between maternal and child immune conditions and adverse neurodevelopmental outcomes.
Authors: Croen LA; Qian Y; Ashwood P; Daniels JL; Fallin D; Schendel D; Schieve LA; Singer AB; Zerbo O
Autism Res. 2019 01;12(1):123-135. Epub 2018-08-10.
A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36?months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change)?>?0.1, p?
Authors: Mordaunt CE; Croen LA; Fallin MD; et al.
Mol Autism. 2019;10:36. Epub 2019-10-24.
Identification and validation of uterine perforation, intrauterine device expulsion, and breastfeeding in four health care systems with electronic health records
To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion. Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum. The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled. Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.
Authors: Anthony MS; Getahun D; Schoendorf J; et al.
Clin Epidemiol. 2019;11:635-643. Epub 2019-07-23.
Incremental Cost of Prematurity by Week of Gestational Age
Objective This study was aimed to compare health care costs and utilization at birth through 1 year, between preterm and term infants, by week of gestation. Methods A cross-sectional study of infants born at ≥ 23 weeks of gestational age (GA) at Kaiser Permanente Northern California facilities between 2000 and 2011, using outcomes data from an internal neonatal registry and cost estimates from an internal cost management database. Adjusted models yielded estimates for cost differences for each GA group. Results Infants born at 25 to 37 weeks incur significantly higher birth hospitalization costs and experience significantly more health care utilization during the initial year of life, increasing progressively for each decreasing week of gestation, when compared with term infants. Among all very preterm infants (≤ 32 weeks), each 1-week decrease in GA is associated with incrementally higher rates of mortality and major morbidities. Conclusion We provide estimates of potential cost savings that could be attributable to interventions that delay or prevent preterm delivery. Cost differences were most extreme at the lower range of gestation (≤ 30 weeks); however, infants born moderately preterm (31-36 weeks) also contribute substantially to the burden, as they represent a higher proportion of total births.
Authors: Walsh EM; Li SX; Black LK; Kuzniewicz M
AJP Rep. 2019 Jan;9(1):e76-e83. Epub 2019-03-19.
Diagnostic thresholds for pregnancy hyperglycemia, maternal weight status and the risk of childhood obesity in a diverse Northern California cohort using health care delivery system data
To estimate the risk of childhood obesity associated with the various criteria proposed for diagnosis of gestational diabetes (GDM), and the joint effects with maternal BMI. Cohort study of 46,396 women delivering at the Kaiser Permanente Northern California health care delivery system in 1995-2004 and their offspring, followed through 5-7 years of age. Pregnancy hyperglycemia was categorized according to the screening and oral glucose tolerance test values proposed for the diagnosis of GDM by the International Association of the Diabetes and Pregnancy Study Group (IADPSG), Carpenter Coustan (CC), and the National Diabetes Data Group (NDDG). Childhood obesity was defined by the International Obesity Task Force’s age and sex-specific BMI cut-offs. Poisson regression models estimated the risks of childhood obesity associated with each category of pregnancy glycemia compared to normal screening, and the joint effects of maternal BMI category and GDM by the CC and the IADPSG criteria. Compared with normal screening, increased risks of childhood obesity were observed for abnormal screening [RR (95% CI): 1.30 (1.22, 1.38)], 1+ abnormal values by the IADPSG or CC [1.47 (1.36, 1.59) and 1.48 (1.37, 1.59), respectively], and 2+ values by CC or NDDG [1.52 (1.39, 1.67) and 1.60 (1.43, 1.78), respectively]. Compared to obese women without GDM, obese women with GDM defined by the CC criteria had significantly increased risk of childhood obesity [1.20 (1.07, 1.34)], which was also observed for GDM by the IADSPG [1.18 (1.07, 1.30)], though GDM did not significantly increase the risk of childhood obesity among normal weight or overweight women. The risk of childhood obesity starts to increase at levels of pregnancy glycemia below those used to diagnose GDM and the effect of GDM on childhood obesity risk appears more pronounced in women with obesity. Interventions to reduce obesity and pregnancy hyperglycemia are warranted.
Authors: Ehrlich SF; Hedderson MM; Xu F; Ferrara A
PLoS One. 2019;14(5):e0216897. Epub 2019-05-10.
A Randomized Controlled Trial of mHealth Mindfulness Intervention for Cancer Patients and Informal Cancer Caregivers: A Feasibility Study Within an Integrated Health Care Delivery System
To assess feasibility and preliminary efficacy of a mobile/online-based (mHealth) mindfulness intervention for cancer patients and their caregivers to reduce distress and improve quality of life (QoL). Two-arm randomized controlled trial within Kaiser Permanente Northern California targeting cancer patients who received chemotherapy and their informal caregivers. The intervention group received a commercially available mindfulness program for 8 weeks. The wait-list control group received usual care. We assessed feasibility using retention and adherence rates and obtained participant-reported data on distress, QoL, sleep, mindfulness, and posttraumatic growth before and immediately after the intervention. Ninety-seven patients (median age 59 years; female 69%; 65% whites) and 31 caregivers (median age 63 years; female 58%; 77% whites) were randomized. Among randomized participants, 74% of the patients and 84% of the caregivers completed the study. Among those in the intervention arm who initiated the mindfulness program, 65% practiced at least 50% of the days during the intervention period. We observed significantly greater improvement in QoL among patients in the intervention arm compared with controls. Caregivers in the intervention group experienced increased mindfulness compared with controls. Participants appreciated the convenience of the intervention and the mindfulness skills they obtained from the program. We demonstrated the feasibility of conducting a randomized trial of an mHealth mindfulness intervention for cancer patients and their informal caregivers. Results from fully powered efficacy trials would inform the potential for clinicians to use this scalable intervention to help improve QoL of those affected by cancer and their caregivers.
Authors: Kubo A; Kurtovich E; McGinnis M; Aghaee S; Altschuler A; Quesenberry C; Kolevska T; Avins AL
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419850634.
Links between age at menarche, antral follicle count, and body mass index in African American and European American women
To examine the relationships between age at menarche, antral follicle count (AFC), and body mass index (BMI) in a multi-ethnic population of women. Community-based, cross-sectional study. Academic setting. A total of 245 African American women and 273 European American women, aged 25-45 years, with regular menstrual cycles and no reproductive disorders. The ethnicity of these women was self-reported and genetically validated. The AFCs were measured by transvaginal ultrasound during the early follicular phase. Anthropometric measurements were taken, and age at menarche was gathered by questionnaire. Determination of the associations between age of menarche and adult AFC and BMI. Earlier age of menarche was associated with both higher BMIs and higher AFCs in adulthood, with control for female age. The antral follicle difference between early (<12 years) vs. late (?15 years) initiation of menarche in both white and black women was +3.81 and +3.34 follicles, respectively, which is equivalent to an approximately 20% difference in AFC. This study provides the first evidence that timing of menarche may influence AFC. Because of limited studies on African American women, this work provides additional needed data and may enhance our ability to prospectively screen and better treat various diseases associated with the female reproductive lifespan.
Authors: Schuh SM; Kadie J; Rosen MP; Sternfeld B; Reijo Pera RA; Cedars MI
Fertil Steril. 2019 04;111(4):629-640.
Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED)
Immune system abnormalities have been widely reported among children with autism spectrum disorder (ASD), which may increase the risk of childhood infections. The Study to Explore Early Development (SEED) is a multisite case-control study of children aged 30-69 months, born in 2003-2006. Cases are children previously diagnosed and newly identified with ASD enrolled from education and clinical settings. Children with a previously diagnosed non-ASD developmental condition were included in the developmental delay/disorder (DD) control group. The population (POP) control group included children randomly sampled from birth certificates. Clinical illness from infection during the first 28 days (“neonatal,” from medical records) and first three years of life (caregiver report) in cases was compared to DD and POP controls; and between cases with and without regression. Children with ASD had greater odds of neonatal (OR = 1.8; 95%CI: 1.1, 2.9) and early childhood infection (OR = 1.7; 95%CI: 1.5, 1.9) compared to POP children, and greater odds of neonatal infection (OR = 1.5; 95%CI: 1.1, 2.0) compared to DD children. Cases with regression had 1.6 times the odds (95%CI: 1.1, 2.3) of caregiver-reported infection during the first year of life compared to cases without regression, but neonatal infection risk and overall early childhood infection risk did not differ. Our results support the hypothesis that children with ASD are more likely to have infection early in life compared to the general population and to children with other developmental conditions. Future studies should examine the contributions of different causes, timing, frequency, and severity of infection to ASD risk. Autism Research 2019, 12: 136-146. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at infections during early childhood in relation to autism spectrum disorder (ASD). We found that children with ASD were more likely to have an infection in the first 28 days of life and before age three compared to children with typical development. Children with ASD were also more likely than children with other developmental delays or disorders to have an infection in the first 28 days of life.
Authors: Sabourin KR; Reynolds A; Schendel D; Rosenberg S; Croen LA; Pinto-Martin JA; Schieve LA; Newschaffer C; Lee LC; DiGuiseppi C
Autism Res. 2019 01;12(1):136-146. Epub 2018-11-26.
The impact of gene expression profile testing on confidence in chemotherapy decisions and prognostic expectations
Little is known about whether gene expression profile (GEP) testing and specific recurrence scores (e.g., medium risk) improve women’s confidence in their chemotherapy decision or perceived recurrence risk. We evaluate the relationship between these outcomes and GEP testing. We surveyed women eligible for GEP testing (stage I or II, Gr1-2, ER+, HER2-) identified through the Surveillance, Epidemiology, and End Results (SEER) Registry of Washington or Kaiser Permanente Northern California from 2012 to 2016, approximately 0-4 years from diagnosis (N?=?904, RR?=?45.4%). Confidence in chemotherapy was measured as confident (Very, completely) versus Not Confident (Somewhat, A little, Not At All); perceived risk recurrence was recorded numerically (0-100%). Women reported their GEP test receipt (Yes, No, Unknown) and risk recurrence score (High, Intermediate, Low, Unknown). In our analytic sample (N?=?833), we propensity score weighted the three test receipt cohorts and used propensity weighted multivariable regressions to examine associations between the outcomes and the three test receipt cohorts, with receipt stratified by score. 29.5% reported an unknown GEP test receipt; 86% being confident. Compared to no test receipt, an intermediate score (aOR 0.34; 95% CI 0.20-0.58), unknown score (aOR 0.09; 95% CI 0.05-0.18), and unknown test receipt (aOR 0.37; 95% CI 0.24-0.57) were less likely to report confidence. Most women greatly overestimated their recurrence risk regardless of their test receipt or score. GEP testing was not associated with greater confidence in chemotherapy decisions. Better communication about GEP testing and the implications for recurrence risk may improve women’s decisional confidence.
Authors: Panattoni L; Lieu TA; Jayasekera J; O'Neill S; Mandelblatt JS; Etzioni R; Phelps CE; Ramsey SD
Breast Cancer Res Treat. 2019 Jan;173(2):417-427. Epub 2018-10-10.
Weight estimation among multi-racial/ethnic infants and children aged 0-5·9 years in the USA: simple tools for a critical measure
In resource-constrained facilities or during resuscitation, immediate paediatric weight estimation remains a fundamental challenge. We aimed to develop and validate weight estimation models based on ulna length and forearm width and circumference measured by simple and portable tools; and to compare them against previous methods (advanced paediatric life support (APLS), Theron and Traub-Johnson formulas). Cross-sectional analysis of anthropometric measurements. Four ulna- and forearm-based weight estimation models were developed in the training set (n 1016). Assessment of bias, precision and accuracy was examined in the validation set (n 457). National Children’s Study-Formative Research in Anthropometry (2011-2012). Multi-racial/ethnic infants and children aged <6 years (n 1473). Developed Models 1-4 had high predictive precision (R 2=0·91-0·97). Mean percentage errors between predicted and measured weight were significantly smaller across the developed models (0·1-0·7 %) v. the APLS, Theron and Traub-Johnson formulas (-1·7, 9·2 and -4·9 %, respectively). Root-mean-squared percentage error was overall smaller among Models 1-4 v. the three existing methods (range=7·5-8·7 v. 9·8-13·3 %). Further, Models 1-4 were within 10 and 20 % of actual weight in 72-87 and 95-99 % of the weight estimations, respectively, which outperformed any of the three existing methods. Ulna length, forearm width and forearm circumference by simple and portable tools could serve as valid and reliable surrogate measures of weight among infants and children aged <6 years with improved precision over the existing age- or length-based methods. Further validation of these models in physically impaired or non-ambulatory children is warranted.
Authors: Zhu Y; Hernandez LM; Dong Y; Himes JH; Caulfield LE; Kerver JM; Arab L; Voss P; Hirschfeld S; Forman MR
Public Health Nutr. 2019 01;22(1):147-156. Epub 2018-10-18.
Bisphenol A and pubertal height growth in school-aged children
Bisphenol A (BPA) is an environmental endocrine disruptor and is found in many consumer products. Studies suggest that BPA may perturb pubertal development, although evidence on BPA-influenced pubertal height growth is scarce. A total of 754 children aged 9-18 years from three schools (one elementary, one middle, and one high school) in Shanghai were included in this longitudinal study. Height was measured at enrolment (visit 1) and, subsequently, at 19 months after enrolment (visit 2). Age- and sex-specific Z scores for height were calculated (height Z score?=?[participant’s height-sex- and age-specific population height mean]/sex- and age-specific population height standard deviation). Urine samples were collected at enrolment to measure BPA concentrations. We used multiple linear regression models or general estimating equation models (GEE) to estimate associations between urine BPA level and height Z score. The geometric mean of urine BPA concentrations was 1.6??g/L (95%CI: 1.4, 1.8) or 1.2??g/g creatinine (95%CI: 1.0, 1.3). An inverse association between urine BPA level and height was observed in boys. After adjustment for potential confounders, height Z score at enrolment in boys decreased by 0.49 for the highest exposure level (above 10.9??g/g creatinine as the 90th percentile), compared with the lowest BPA exposure (below 0.2??g/g creatinine as the 25th percentile) (95%CI: -0.96, -0.01; p-trend?=?0.024). The inverse association remained between BPA exposure and height Z score at visit 2. The GEE model showed that a 1-unit increase in log10-transformed BPA concentrations was associated with a 0.15-point decrease in height Z score over the follow-up (95%CI: -0.30, -0.01). BPA was not associated with height growth in girls. Our findings indicate an inverse association between urine BPA level and height growth in boys. These findings need to be confirmed in further studies.
Authors: Wang Z; Liang H; Tu X; Yuan W; Zhou Z; Jin L; Miao M; Li DK
J Expo Sci Environ Epidemiol. 2019 01;29(1):109-117. Epub 2018-09-05.
Brief Report: Maternal Opioid Prescription from Preconception Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in Children
Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child’s risk of ASD, developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features in the Study to Explore Early Development, a case-control study of neurodevelopment. Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions. Odds for ASD and ASD/DD were non-significantly elevated for first trimester prescriptions. Work exploring mechanisms and timing between peri-pregnancy opioid use and child neurodevelopment is needed.
Authors: Rubenstein E; Young JC; Croen LA; DiGuiseppi C; Dowling NF; Lee LC; Schieve L; Wiggins LD; Daniels J
J Autism Dev Disord. 2019 Jan;49(1):376-382.
Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls
Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.
Authors: Sweeten TL; Croen LA; Windham GC; Odell JD; Stubbs EG; Torres AR
J Autism Dev Disord. 2019 Jan;49(1):410-414.
Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women’s Health Across the Nation
Background Measures of subclinical atherosclerosis are predictors of future cardiovascular outcomes as well as of physical and cognitive functioning. The menopausal transition is associated with accelerated progression of atherosclerosis in women. The prospective association between a healthy lifestyle during the midlife and subclinical atherosclerosis is unclear. Methods and Results Self-reported data on smoking, diet, and physical activity from 1143 women in the Study of Women’s Health Across the Nation were used to construct a 10-year average Healthy Lifestyle Score ( HLS ) during the midlife. Markers of subclinical atherosclerosis were measured 14 years after baseline and included common carotid artery intima-media thickness ( CCA – IMT ), adventitial diameter ( CCA – AD ), and carotid plaque. The associations of average HLS with CCA – IMT and CCA – AD were estimated using linear models; the association of average HLS with carotid plaque was estimated using cumulative logit models. Average HLS was associated with smaller CCA – IMT and CCA – AD in the fully adjusted models ( P=0.0031 and <0.001, respectively). Compared with participants in the lowest HLS level, those in the highest level had 0.024 mm smaller CCA - IMT (95% confidence interval: -0.048, 0.000), which equals 17% of the SD of CCA - IMT , and 0.16 mm smaller CCA - AD (95% confidence interval: -0.27, -0.04), which equals 24% of the SD of CCA - AD . Among the 3 components of the HLS , abstinence from smoking had the strongest association with subclinical atherosclerosis. Conclusions Healthy lifestyle during the menopausal transition is associated with less subclinical atherosclerosis, highlighting the growing recognition that the midlife is a critical window for cardiovascular prevention in women.
Authors: Wang D; Sternfeld B; Baylin A; et al.
J Am Heart Assoc. 2018 12 04;7(23):e010405.
Antenatal and Intrapartum Risk Factors for Hypoxic-Ischemic Encephalopathy in a US Birth Cohort
To identify risk factors for hypoxic-ischemic encephalopathy (HIE) within a recent US birth cohort. In a retrospective cohort study of 44 572 singleton infants ?36 weeks of gestation born at Kaiser Permanente Northern California in 2008-2015, we identified all infants with HIE based on the presence of 3 inclusion criteria: clinical signs of neonatal encephalopathy, NICU admission, and either a 10-minute Apgar of??5 or a base excess of ?-15?mmol/L. Neonatal acidemia was defined as a base excess of ?-12?mmol/L. We ascertained antenatal and intrapartum complications from electronic records. Multivariable analysis was performed using logistic regression. There were 45 infants (1.0 per 1000) with HIE and 197 (4.4 per 1000) with neonatal acidemia. Of the infants with HIE, 64% had an intrapartum complication consisting of a sentinel event (36%), clinical chorioamnionitis (40%), or both (11%). Risk factors for HIE on multivariable analysis were sentinel event (relative risk [RR], 16.1; 95% CI, 8.4-33) and clinical chorioamnionitis (RR, 5.2; 95% CI, 2.7-9.9). After removing the 16 infants with HIE who were exposed to a sentinel event from multivariate analysis, maternal age of??35 years (RR, 2.5; 95% CI, 1.1-5.6) and a urinary tract infection during pregnancy (RR, 2.6; 95% CI, 1.0-6.5) emerged as potential antenatal risk factors for HIE. A significant proportion of HIE is preceded by a sentinel event, emphasizing the importance of developing improved methodologies to predict and prevent this perinatal complication. Strategies focused on reducing other complications such as clinical chorioamnionitis and/or maternal pyrexia may also improve our ability to prevent HIE.
Authors: Parker SJ; Kuzniewicz M; Niki H; Wu YW
J Pediatr. 2018 12;203:163-169. Epub 2018-09-27.
Risk of cardiovascular disease in women with BRCA1 and BRCA2 mutations
Estimate the prevalence of cardiovascular disease risk factors and endpoints in women with BRCA mutations. Women, age 40 and older, with BRCA mutations identified in Kaiser Permanente Northern California completed a questionnaire and underwent a lipid and fasting glucose panel. Bivariable analysis of clinical and demographic factors was performed. The Atherosclerotic Cardiovascular Disease (ASCVD) calculator was used to predict 10-year risk of a cardiovascular event. Of the 233 women, 19 women had intact ovaries (median age 56.0) and 214 had undergone risk-reducing salpingo-oophorectomy (RRSO). Among the 108 women with RRSO under age 50 (median age 51.0), compared to the 106 women who had RRSO at or over age 50 (median age 63.5) 6.5% vs 10.4% reported diabetes (p = 0.30), 23.2% versus 28.3% had elevated fasting blood glucose (p = 0.39), 21.3% versus 34.0% reported hypertension (p = 0.04) with median systolic blood pressure of 118 mmHg versus 125.5 mmHg (p < 0.009), 25% versus 32% reported hyperlipidemia (p = 0.40), and 42% versus 49% had any abnormal lipid test (p = 0.28). An elevated 10-year ASCVD risk of over 10% was seen in 6.1% versus 24.8% respectively (p = 0.0001). Women who underwent RRSO at age of 50 and over, had higher ASCVD 10-year risk than women who underwent RRSO at younger ages most likely owing to older age at study entry. The ASCVD risks for women with BRCA mutation who had RRSO did not suggest increased risk associated with being a BRCA mutation carrier.
Authors: Powell CB; Alabaster A; Armstrong MA; Stoller N; Raine-Bennett T
Gynecol Oncol. 2018 12;151(3):489-493. Epub 2018-10-10.
Maternal exposure to bisphenol A and anogenital distance throughout infancy: A longitudinal study from Shanghai, China
Bisphenol A (BPA) is one of the most common endocrine-disrupting compounds (EDCs) with a ubiquitous presence. Both animal and human studies have reported the association between maternal exposure to BPA and anogenital distance (AGD) in offspring. However, the results are conflicting and the longitudinal effect is unknown. We aimed to examine the effect of maternal exposure to BPA on AGD in offspring in a longitudinal birth cohort from birth to 1?year of age. BPA was assayed using urine samples collected at 12-16 gestational weeks from 982 pregnant participants who later delivered infants. Infants’ AGDs (AGDap [anus-penis] and AGDas [anus-scrotum] for boys, AGDac [anus-clitoris] and AGDaf [anus-fourchette] for girls) were measured at birth, and at 6 and 12?months of age. Multiple linear regression analysis was conducted to examine the associations between maternal exposure to BPA and offspring’s AGDs. Then generalized estimating equation (GEE) model was applied to make use of the repeated measurements of AGDs and examine the overall effect of maternal exposure to BPA. Compared to boys with undetected maternal BPA, those with detected BPA were more likely to have shorter AGDap and AGDas at 6 and 12?months. However, the differences were statistically significant for AGDap and AGDas only at 12?months (2.87 and 4.12?mm shorter, respectively). In GEE models, similar patterns were observed. Boys in the higher quartiles were more likely to have shorter AGDap and AGDas than those in the first quartile. However, statistically significant differences were only observed in boys in the third quartile. For girls, these associations were not observed regardless of the timing of measurements (at birth, 6?months and 12?months). Maternal exposure to BPA was associated with shortened AGDap and AGDas in boys at age 12?months but not in girls, which suggests a gender specific effect of BPA exposure on offspring’s development.
Authors: Sun X; Li D; Liang H; Miao M; Song X; Wang Z; Zhou Z; Yuan W
Environ Int. 2018 12;121(Pt 1):269-275. Epub 2018-09-14.
Central Obesity Increases the Risk of Gestational Diabetes Partially Through Increasing Insulin Resistance
This study examined the associations of central obesity measures, waist to hip ratio (WHR) and waist circumference (WC), in early pregnancy with subsequent risk of gestational diabetes mellitus (GDM) and evaluated the potential mediating role of insulin resistance markers. Within the prospective Pregnancy Environment and Lifestyle Study cohort of 1,750 women, WC and hip circumference were measured at gestational weeks 10 to 13. In a nested case-control study within the cohort, 115 GDM cases and 230 controls had fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adiponectin measurements at gestational weeks 16 to 19. Poisson and conditional logistic regression models were used, adjusting for established risk factors for GDM, including prepregnancy overweight or obesity. For women with WHR
Authors: Zhu Y; Hedderson MM; Quesenberry CP; Feng J; Ferrara A
Obesity (Silver Spring). 2018 Nov 21.
Longitudinal Maternal Vitamin D Status during Pregnancy Is Associated with Neonatal Anthropometric Measures
Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother⁻offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies⁻Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10⁻14, 15⁻26, 23⁻31, and 33⁻39 GW and categorized as 75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10⁻14 GW, 16.8% and 49.2% of women had 25(OH)D
Authors: Francis EC; Hinkle SN; Song Y; Rawal S; Donnelly SR; Zhu Y; Chen L; Zhang C
Nutrients. 2018 Nov 02;10(11). Epub 2018-11-02.
Prospective Validation of a Standardized Ultrasonography-Based Ovarian Cancer Risk Assessment System
To evaluate the performance of a system that standardizes ovarian cancer risk assessment and reporting on ultrasonography. We conducted a prospective community-based cohort study of average-risk women undergoing ultrasonography in 2016 using a reporting system that requires adnexal masses to be categorized as 1, 2, 3, or X based on standardized ultrasound criteria including size, presence of solid components, and vascularity assessed by Doppler. With a median follow-up of 18 months, the risk of ovarian cancer or borderline tumor diagnosis for each category was determined. Among 43,606 women undergoing ultrasonography, 6,838 (16%) had an abnormal adnexal mass reported: 70% were category 1, 21% category 2, 3.7% category 3, and 5.4% category X. Among these women, 89 (1.3%) were subsequently diagnosed with ovarian cancer and 59 (0.9%) with borderline tumors. The risks of ovarian cancer diagnosis associated with masses reported as categories 1, 2, 3, and X were 0.2% (95% CI 0.05-0.3%), 1.3% (95% CI 0.7-1.9%), 6.0% (95% CI 3.0-8.9%), and 13.0% (95% CI 9.5-16.4%), respectively; risks of either ovarian cancer or borderline tumor were 0.4% (95% CI 0.2-0.6%), 2.3% (95% CI 1.6-3.1%), 10.4% (95% CI 6.6-14.1%), and 18.9% (95% CI 14.9-23.0%) respectively. Among 36,768 (84%) women with normal or benign adnexal findings reported, 38 women were diagnosed with ovarian cancer, for a risk of 0.1% (95% CI 0.07-0.14%). In a community-based setting with low ovarian cancer prevalence, our standardized reporting system differentiated adnexal masses into four categories with distinct levels of risk with 9-10% of women having higher risk masses and 70% of women having masses associated with a risk of cancer similar to that of normal ultrasound findings. The system supports risk-based management by providing clinicians a more consistent assessment of risk based on ultrasound characteristics.
Authors: Suh-Burgmann E; Flanagan T; Osinski T; Alavi M; Herrinton L
Obstet Gynecol. 2018 11;132(5):1101-1111.
Long-term postmenopausal estrogen therapy may be associated with increased risk of breast cancer: a cohort study
Reports of a role of postmenopausal estrogen replacement therapy in the development of breast cancer have been inconsistent. Although many epidemiologic studies have failed to show an association between short-term use of estrogen and breast cancer, there are indications that long-term use may present an increased risk. We undertook a long-term, retrospective cohort study of the incidence of breast cancer in women who had taken long-term estrogen (average 17.2 years), compared to women who had not taken estrogen. Subjects were 454 women born between 1900 and 1915, who were members of a large health maintenance organization in northern California. By the end of 1995, 26 (11.2%) of estrogen users developed breast cancer, as did 9 (4.1%) of the nonusers; the relative risk (RR) for estrogen use was 2.8 [95% confidence interval (95% CI) 1.3-5.9]. Adjustment for age and multiple breast cancer risk factors, including breast cancer surveillance, reduced the RR for estrogen to 2.0 (95% CI 0.9-4.5). We conclude that long-term estrogen use is associated with a substantially increased risk of breast cancer.
Authors: Ettinger B; Quesenberry C; Schroeder DA; Friedman G
Menopause. 2018 11;25(11):1191-1194.
Continuation of postmenopausal hormone replacement therapy: comparison of cyclic versus continuous combined schedules
Discontinuation of hormone replacement therapy (HRT) is much more common than what is reported in randomized, double-blind clinical trials. Our purpose in this retrospective study, using a prescription database, was to compare the continuation rate among women who took cyclic combination therapy adding progesterone to estrogen (CYC-PERT) or continuous combined estrogen progestin therapy (CC-PERT). The study subjects were 1,532 women, ≥45 years old, who initially filled index prescriptions for 0.625 mg conjugated estrogens. They were divided into two groups (CYC-PERT = 644, CC-PERT = 888) on the basis of coprescribed medroxyprogesterone. We found that for all women initiating therapy, 35-40% did not return for a refill and 76-81% stopped therapy within 3 years. Those prescribed CC-PERT initially were more likely to stop than those prescribed CYC-PERT (rate ratio [RR] = 1.20; 95% confidence interval [CI] = 1.06-1.35). Adjustments for age, year of starting medication, cost of medication, and prescriber specialty did not affect the difference in discontinuation between the two regimens (RR 1.18, 95% CI = 1.04-1.34). We conclude that the likelihood of women continuing HRT beyond 3 years of initiation is low. Furthermore, compared with CYC-PERT users, those receiving CC-PERT have a slightly higher probability of discontinuation. Efforts should be made to understand why three quarters of women beginning HRT will stop it long before it can provide major long-term benefit.
Authors: Ettinger B; Li DK; Klein R
Menopause. 2018 11;25(11):1187-1190.
The Utility and Cross-Validation of a Composite Physical Activity Score in Relation to Cardiovascular Health Indicators: Coronary Artery Risk Development in Young Adults
Single-method assessment of physical activity (PA) has limitations. The utility and cross-validation of a composite PA score that includes reported and accelerometer-derived PA data has not been evaluated. Participants attending the Year 20 exam were randomly assigned to the derivation (two-thirds) or validation (one-third) data set. Principal components analysis was used to create a composite score reflecting Year 20 combined reported and accelerometer PA data. Generalized linear regression models were constructed to estimate the variability explained (R2) by each PA assessment strategy (self-report only, accelerometer only, composite score, or self-report plus accelerometer) with cardiovascular health indicators. This process was repeated in the validation set to determine cross-validation. At Year 20, 3549 participants (45.2 [3.6] y, 56.7% female, and 53.5% black) attended the clinic exam and 2540 agreed to wear the accelerometer. Higher R2 values were obtained when combined assessment strategies were used; however, the approach yielding the highest R2 value varied by cardiovascular health outcome. Findings from the cross-validation also supported internal study validity. Findings support continued refinement of methodological approaches to combine data from multiple sources to create a more robust estimate that reflects the complexities of PA behavior.
Authors: Pettee Gabriel K; Pérez A; Jacobs DR; Lee J; Kohl HW; Sternfeld B
J Phys Act Health. 2018 11 01;15(11):847-856. Epub 2018-10-19.
Omega 3 polyunsaturated fatty acids and healthy ageing
Authors: Zhu Y; Ferrara A; Forman MR
BMJ. 2018 10 17;363:k4263. Epub 2018-10-17.
A Pre-Pregnancy Biomarker Risk Score Improves Prediction of Future Gestational Diabetes
Previous studies have not examined the ability of multiple preconception biomarkers, considered together, to improve prediction of gestational diabetes mellitus (GDM). To develop a preconception biomarker risk score and assess its association with subsequent GDM. A nested case-control study among a cohort of women with serum collected as part of a health examination (1984 to 1996) and subsequent pregnancy (1984 to 2009). Biomarkers associated with GDM were dichotomized into high/low risk. Integrated health care system. Two controls were matched to each GDM case (n = 256 cases) on year and age at examination, age at pregnancy, and number of pregnancies between examination and index pregnancy. GDM. High-risk levels of sex hormone-binding globulin (SHBG; <44.2 nM), glucose (>90 mg/dL), total adiponectin (<7.2 μg/mL), and homeostasis model assessment-estimated insulin resistance (>3.9) were independently associated with 2.34 [95% confidence interval (CI): 1.50, 3.63], 2.03 (95% CI: 1.29, 3.19), 1.83 (95% CI: 1.16, 2.90), and 1.67 (95% CI: 1.07, 2.62) times the odds of GDM and included in the biomarker risk score. For each unit increase in the biomarker risk score, odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36). A biomarker risk score including only SHBG and glucose was sufficient to improve prediction beyond established risk factors (age, race/ethnicity, body mass index, family history of diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002). The improved, predictive ability of the biomarker risk score beyond established risk factors suggests clinical use of the biomarker risk score in identifying women at risk for GDM before conception for targeted prevention strategies.
Authors: Badon SE; Zhu Y; Sridhar SB; Xu F; Lee C; Ehrlich SF; Quesenberry CP; Hedderson MM
J Endocr Soc. 2018 Oct 01;2(10):1158-1169. Epub 2018-09-13.
Hyperbilirubinemia, Phototherapy, and Childhood Asthma
Our aim was to quantify the associations of both hyperbilirubinemia and phototherapy with childhood asthma using a population-based cohort with total serum bilirubin (TSB) levels. Retrospective cohort study of infants born at ?35 weeks’ gestation in the Kaiser Permanente Northern California health system (n = 109?212) from 2010 to 2014. Cox models were used to estimate hazard ratios (HRs) for a diagnosis of asthma. In the study, 16.7% of infants had a maximum TSB level of ?15 mg/dL, 4.5% of infants had a maximum TSB level of ?18 mg/dL, and 11.5% of infants received phototherapy. Compared with children with a maximum TSB level of 3 to 5.9 mg/L, children with a TSB level of 9 to 11.9 mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL were at an increased risk for asthma (HR: 1.22 [95% confidence interval (CI): 1.11-1.3], HR: 1.18 [95% CI: 1.08-1.29], and HR: 1.30 [95% CI: 1.18-1.43], respectively). Children with a TSB level of ?18 mg/dL were not at an increased risk for asthma (HR: 1.04; 95% CI: 0.90-1.20). In propensity-adjusted analyses, phototherapy was not associated with asthma (HR: 1.07; 95% CI: 0.96-1.20). Modest levels of hyperbilirubinemia were associated with an increased risk of asthma, but an association was not seen at higher levels. No dose-response relationship was seen. Using phototherapy to prevent infants from reaching these modest TSB levels is unlikely to be protective against asthma.
Authors: Kuzniewicz MW; Niki H; Walsh EM; McCulloch CE; Newman TB
Pediatrics. 2018 10;142(4). Epub 2018-09-12.
Childhood Seizures After Phototherapy
: media-1vid110.1542/5804915133001PEDS-VA_2018-0648Video Abstract BACKGROUND AND OBJECTIVES: In a recent Danish study, researchers found an increased risk of childhood epilepsy after phototherapy but only in boys. We investigated this association in a Kaiser Permanente Northern California cohort. From 499?642 infants born at ?35 weeks’ gestation in 1995-2011 followed for ?60 days, we excluded 1773 that exceeded exchange transfusion thresholds and 1237 with seizure diagnoses at <60 days. We ascertained phototherapy, covariates, and outcomes from electronic records and existing databases. Our primary outcome was ?1 encounter with a seizure diagnosis plus ?1 prescription for an antiepileptic drug. We used Cox and Poisson models to adjust for bilirubin levels and other confounding variables. A total of 37?683 (7.6%) infants received any phototherapy. The mean (SD) follow-up time was 8.1 (5.2) years. The crude incidence rate per 1000 person-years of the primary outcome was 1.24 among phototherapy-exposed children and 0.76 among those unexposed (rate ratio: 1.63; 95% confidence interval [CI]: 1.44 to 1.85). The adjusted hazard ratio (aHR) was 1.22 (95% CI: 1.05 to 1.42; P = .009). Boys were at higher risk of seizures overall (aHR = 1.18; 95% CI: 1.10 to 1.27) and had a higher aHR for phototherapy (1.33; 95% CI: 1.10 to 1.61) than girls (1.07; 95% CI: 0.84 to 1.37), although effect modification by sex was not statistically significant (P = .17). The adjusted 10-year excess risks per 1000 were 2.4 (95% CI: 0.6 to 4.1) overall, 3.7 (95% CI: 1.2 to 6.1) in boys, and 0.8 (95% CI: -1.7 to 3.2) in girls. Phototherapy in newborns is associated with a small increased risk of childhood seizures, even after adjusting for bilirubin values, and the risk is more significant in boys.
Authors: Newman TB; Wu YW; Kuzniewicz MW; Grimes BA; McCulloch CE
Pediatrics. 2018 10;142(4).
Contraception after Abortion and Risk of Repeated Unintended Pregnancy among Health Plan Members
Optimizing access to effective contraception at the time of abortion can reduce repeated unintended pregnancies. To assess contraception initiation and repeated unintended pregnancies among women receiving abortions in Kaiser Permanente Northern California (KPNC) facilities and through outside contracted facilities. A retrospective cohort study was conducted using a randomized proportional sample of women aged 15 to 44 years having abortions in KPNC, to determine contraception initiation within 90 days. Demographic and clinical characteristics (age, race/ethnicity, gravidity, parity, contraceptive method initiated, and pregnancies within 12 months) were collected from electronic health records. Descriptive statistics, χ2 tests, t-tests, and logistic regression models assessed predictors of long-acting reversible contraception (LARC) initiation and having another unintended pregnancy within 12 months of abortion. Women having abortions from contracted facilities were significantly less likely to initiate LARC within 90 days compared with those receiving abortions in KPNC facilities (11.99% vs 19.10%, p = 0.012). Significant factors associated with 90-day LARC initiation included abortions in KPNC facilities (adjusted odds ratio [aOR] = 1.87, p = 0.007) and gravidity of 3 or more. Women initiating short-acting or no contraception were significantly more likely to have an unintended pregnancy within 12 months of the abortion than those initiating LARC (aOR = 3.66, p = 0.005; no contraception vs LARC, aOR = 3.75, p = 0.005). In response to this study, KPNC now provides reimbursement for LARC in all outside abortion contracts, internalized more abortions in KPNC facilities, and strengthened clinical recommendations for immediate, effective postabortion contraception, especially LARC.
Authors: Postlethwaite D; Merchant M; Alabaster A; Raine-Bennett T
Perm J. 2018 Sep 10;22. Epub 2018-09-10.
The Seveso accident: A look at 40 years of health research and beyond.
A 1976 chemical factory explosion near Seveso, Italy exposed residents to high levels of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a known human carcinogen and potent endocrine disruptor. It is highly lipophilic and has a long half-life in humans. Much of what we know and can learn about the risks of dioxin exposure on human health arose from the tragic circumstances of Seveso. This review aims to describe the Seveso accident, summarize the results of 40 years of research on the health of the Seveso population since the accident, and discuss next-stage research on the health of Seveso residents, their children, and grandchildren.
Authors: Eskenazi, Brenda B; Warner, Marcella M; Brambilla, Paolo P; Signorini, Stefano S; Ames, Jennifer J; Mocarelli, Paolo P
Environment international. 2018 Sep 01;121(Pt 1):71-84. Epub 2018-09-01.
Data Enclaves for Sharing Information Derived From Clinical and Administrative Data
Authors: Platt R; Lieu T
JAMA. 2018 08 28;320(8):753-754.
Placental gross shape differences in a high autism risk cohort and the general population
A growing body of evidence suggests that prenatal environment is important in Autism Spectrum Disorder (ASD) etiology. In this study, we compare placental shape features in younger siblings of children with ASD, who themselves are at high ASD risk, to a sample of low risk peers. Digital photographs of the fetal placenta surface and of the sliced placental disk from 129 high ASD risk newborns and from 267 newborns in the National Children’s Study Vanguard pilot were analysed to extract comparable measures of placental chorionic surface shape, umbilical cord displacement and disk thickness. Placental thickness measures were moderately higher in siblings of ASD cases. The placentas of ASD-case siblings were also rounder and more regular in perimeter than general population placentas. After stratification by sex, these across-group differences persisted for both sexes but were more pronounced in females. No significant differences were observed in cord insertion measures. Variations in placental shape features are generally considered to reflect flexibility in placental growth in response to changes in intrauterine environment as the placenta establishes and matures. Reduced placental shape variability observed in high ASD risk siblings compared to low-risk controls may indicate restricted ability to compensate for intrauterine changes.
Authors: Park BY; Misra DP; Moye J; Miller RK; Croen L; Fallin MD; Walker C; Newschaffer CJ; Salafia CM; National Children’s Study Consortium
PLoS ONE. 2018;13(8):e0191276. Epub 2018-08-22.
Cross-genetic determination of maternal and neonatal immune mediators during pregnancy
The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.
Authors: Traglia M; Croen LA; Jones KL; Heuer LS; Yolken R; Kharrazi M; DeLorenze GN; Ashwood P; Van de Water J; Weiss LA
Genome Med. 2018 08 22;10(1):67. Epub 2018-08-22.
Association of Nausea and Vomiting in Pregnancy With Prenatal Marijuana Use
Use of marijuana, an antiemetic, is increasing among pregnant women,1,2 and data from 2 small surveys3,4 indicate that women self-report using marijuana to alleviate nausea and vomiting in pregnancy (NVP). To date, only 1 epidemiologic study5 has examined whether women with NVP are at elevated risk of using marijuana. The study of 4735 pregnant women in Hawaii5 from 2009 through 2011 found that self-reported prenatal marijuana use was more prevalent among those with (3.7%) vs without (2.3%) self-reported severe nausea during pregnancy. We used data from a large California health care system with standard universal screening for prenatal marijuana use via self-report and urine toxicologic tests from January 1, 2009, through December 31, 2016, to test whether prenatal marijuana use is elevated among females with a diagnosis of NVP. Methods:Kaiser Permanente Northern California (KPNC) is a multispecialty health care system serving more than 4 million members representative of the Northern California area. The sample consisted of pregnant females 12 years or older in KPNC who completed a self-reported substance use questionnaire and urine toxicologic test in the first trimester (at approximately?8 weeks gestation) during standard prenatal care. All positive toxicologic test findings were confirmed with a laboratory test result. The institutional review board of KPNC approved this study and waived the need for informed consent. Nausea and vomiting during the first trimester of pregnancy (90 days from last menstrual period) was based on International Classification of Disease, Ninth Revision, Clinical Modification, and Tenth Revision, Clinical Modification, diagnostic codes in the electronic health record and categorized as severe (hyperemesis gravidarum [codes 643.00, 643.03, 643.10, 643.13, O21.0, and O21.1]), mild (other NVP diagnoses [codes 536.2, 643.80, 643.90, 643.93, 787.01, 787.02, 787.03, G43.A0, O21.9, R11.0, R11.10, R11.11, and R11.2]), or none. We estimated the adjusted odds of prenatal marijuana use among females with NVP using multilevel logistic regression, controlling for age, race/ethnicity, median neighborhood household income, year, and self-reported marijuana use in the year before pregnancy from the universal screening questionnaire for prenatal substance use. We used in the PROC GLIMMIX procedure in SAS software (version 9.3; SAS Institute, Inc) for all analyses, and 2-sided P?
Authors: Young-Wolff KC; Sarovar V; Tucker LY; Avalos LA; Conway A; Armstrong MA; Goler N
JAMA Intern Med. 2018 Aug 20.
Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen
Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, has been shown to alter DNA methylation. However, little information is available about the effect of BPA exposure on DNA hydroxymethylation in humans. The objective of the present study was to examine whether BPA exposure was associated with DNA hydroxymethylation in human semen samples. We measured urine BPA levels and LINE-1 hydroxymethylation in 158 male factory workers selected from an occupational cohort study conducted in China between 2004 and 2008. Among them, there were 72 male workers with occupational BPA exposure (BPA-exposed group) and 86 male workers without occupational BPA exposure (unexposed group). Multivariate linear regression models were used to examine the association of exposure to BPA with LINE-1 hydroxymethylation. LINE-1 was more highly hydroxymethylated in the BPA-exposed group than in the unexposed group (median 12.97% vs. 9.68%, respectively; p < 0.05), after adjusting for the potential confounders. The medians of 5-hydroxymethylcytosine (5hmC) generally increased with increasing urine BPA levels: 8.79%, 12.16%, 11.53%, and 13.45%, for undetected BPA and corresponding tertiles for the detected BPA, respectively. After analysis using data at individual level, our findings indicated that BPA exposure was associated with alterations of sperm LINE-1 hydroxymethylation, which might have implications for understanding the mechanisms underlying BPA-induced adverse effects on male reproductive function.
Authors: Tian Y; Zhou X; Miao M; Li DK; Wang Z; Li R; Liang H; Yuan W
Int J Environ Res Public Health. 2018 Aug 17;15(8). Epub 2018-08-17.
AHR gene-dioxin interactions and birthweight in the Seveso Second Generation Health Study.
Background: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is proposed to interfere with fetal growth via altered activity of the aryl hydrocarbon receptor (protein: AHR; gene: AHR) pathway which regulates diverse biological and developmental processes including xenobiotic metabolism. Genetic variation in AHR is an important driver of susceptibility to low birthweight in children exposed to prenatal smoking, but less is known about these genetic interactions with TCDD, AHR’s most potent xenobiotic ligand.Methods: The Seveso Women’s Health Study (SWHS), initiated in 1996, is a cohort of 981 Italian women exposed to TCDD from an industrial explosion in July 1976. We measured TCDD concentrations in maternal serum collected close to the time of the accident. In 2008 and 2014, we followed up the SWHS cohort and collected data on birth outcomes of SWHS women with post-accident pregnancies. We genotyped 19 single nucleotide polymorphisms (SNPs) in AHR among the 574 SWHS mothers. Results: Among 901 singleton births, neither SNPs nor TCDD exposure alone were significantly associated with birthweight. However, we found six individual SNPs in AHR which adversely modified the association between maternal TCDD and birthweight, implicating gene-environment interaction. We saw an even stronger susceptibility to TCDD due to interaction when we examined the joint contribution of these SNPs in a risk allele score. These SNPs were all located in noncoding regions of AHR, particularly in proximity to the promoter. Conclusions: This is the first study to demonstrate that genetic variation across the maternal AHR gene may shape fetal susceptibilities to TCDD exposure.
Authors: Ames, Jennifer J; Warner, Marcella M; Mocarelli, Paolo P; Brambilla, Paolo P; Signorini, Stefano S; Siracusa, Claudia C; Huen, Karen K; Holland, Nina N; Eskenazi, Brenda B
International journal of epidemiology. 2018 Aug 14;162(Pt 1):55-62. Epub 2018-08-14.
Research Gaps in Gestational Diabetes Mellitus: Executive Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop
The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on research gaps in gestational diabetes mellitus (GDM) with a focus on 1) early pregnancy diagnosis and treatment and 2) pharmacologic treatment strategies. This article summarizes the proceedings of the workshop. In early pregnancy, the appropriate diagnostic criteria for the diagnosis of GDM remain poorly defined, and an effect of early diagnosis and treatment on the risk of adverse outcomes has not been demonstrated. Despite many small randomized controlled trials of glucose-lowering medication treatment in GDM, our understanding of medication management of GDM is incomplete as evidenced by discrepancies among professional society treatment guidelines. The comparative effectiveness of insulin, metformin, and glyburide remains uncertain, particularly with respect to long-term outcomes. Additional topics in need of further research identified by workshop participants included phenotypic heterogeneity in GDM and novel and individualized treatment approaches. Further research on these topics is likely to improve our understanding of the pathophysiology and treatment of GDM to improve both short- and long-term outcomes for mothers and their children.
Authors: Wexler DJ; Ferrara A; Catalano PM; et al.
Obstet Gynecol. 2018 08;132(2):496-505.
Breastfeeding and growth during infancy among offspring of mothers with gestational diabetes mellitus: a prospective cohort study
Breastfeeding (BF) may protect against obesity and type 2 diabetes mellitus in children exposed to maternal diabetes in utero, but its effects on infant growth among this high-risk group have rarely been evaluated. The objective of this study was to evaluate BF intensity and duration in relation to infant growth from birth through 12 months among offspring of mothers with gestational diabetes mellitus (GDM). Prospective cohort of 464 GDM mother-infant dyads (28% White, 36% Hispanic, 26% Asian, 8% Black, 2% other). Weight and length measured at birth, 6-9 weeks, 6 months and 12 months. Categorized as intensive BF or formula feeding (FF) groups at 6-9 weeks (study baseline), and intensity from birth through 12 months as Group 1: consistent exclusive/mostly FF, Group 2: transition from BF to FF within 3-9 months and Group 3: consistent exclusive/mostly BF. Multivariable mixed linear regression models estimated adjusted mean (95% confidence interval) change in z-scores; weight-for-length (WLZ), weight-for-age and length-for-age. Compared with intensive BF at 6-9 weeks, FF showed greater increases in WLZ-scores from 6 to 9 weeks to 6 months [+0.38 (0.13 to 0.62) vs. +0.02 (-0.15 to 0.19); p = 0.02] and birth to 12 months [+1.11 (0.87 to 1.34) vs. +0.53 (0.37 to 0.69); p < 0.001]. For 12-month intensity and duration, Groups 2 and 3 had smaller WLZ-score increases than Group 1 from 6 to 9 weeks to 6 months [-0.05 (-0.27 to 0.18) and +0.07 (-0.19 to 0.23) vs. +0.40 (0.15 to 0.64); p = 0.01 and 0.07], and birth to 12 months [+0.60 (0.39 to 0.82) and +0.59 (0.33 to 0.85) vs. +0.97 (0.75 to 1.19); p < 0.05]. Among offspring of mothers with GDM, high intensity BF from birth through 1 year is associated with slower infant ponderal growth and lower weight gain.
Authors: Gunderson EP; Greenspan LC; Faith MS; Hurston SR; Quesenberry CP; SWIFT Offspring Study Investigators
Pediatr Obes. 2018 08;13(8):492-504. Epub 2018-04-24.
Health Care Utilization in the First Month after Birth and Its Relationship to Newborn Weight Loss and Method of Feeding
Guidelines recommend closer outpatient follow-up for exclusively breastfed newborns, especially those with pronounced weight loss, because of increased risk of hyperbilirubinemia and dehydration that might require readmission. Our objective was to determine how feeding method and weight loss are associated with neonatal health care utilization. A retrospective cohort study conducted at Northern California Kaiser Permanente hospitals in 2009-2013 assessed 143,889 neonates to study the inpatient method of feeding as well as inpatient and outpatient weights. The main outcome measures were inpatient and outpatient health care utilization in the 30 days after birth. Newborn weight loss and feeding method were both associated with utilization. Exclusively breastfed newborns had higher readmission rates than those exclusively formula fed for both vaginal (4.3% compared to 2.1%) (P < .001) and cesarean deliveries (2.1% compared to 1.5%) (P = .025). Those exclusively breastfed also had more neonatal outpatient visits compared to those exclusively formula fed for both vaginal (means of 3.0 and 2.3, P < .001) and cesarean deliveries (means of 2.8 and 2.2, P < .001). Among vaginally delivered newborns of all feeding types, newborns with weight loss >10% at discharge had a relative risk of readmission of 1.10 (95% confidence interval [CI],1.00, 1.20) compared to those with <8% weight loss at discharge; among the subset weighed as inpatients or outpatients between 48 and 72 hours, those with >10% weight loss between 48-72 hours had a relative risk of readmission of 2.11 (95% CI, 1.95, 2.26) compared to those with <8% weight loss at 48-72 hours. Exclusive breastfeeding and weight loss are associated with increased neonatal health care utilization. Improving clinical management of exclusively breastfed neonates with pronounced weight loss might reduce health care utilization.
Authors: Flaherman V; Schaefer EW; Kuzniewicz MW; Li SX; Walsh EM; Paul IM
Acad Pediatr. 2018 08;18(6):677-684. Epub 2017-12-02.
Scientific abstracts featured research at the 2018 North American Forum on Family Planning
The Society of Family Planning (SFP), Planned Parenthood Federation of America (PPFA), and the Association of Reproductive Health Professionals (ARHP) are delighted to host the eighth annual North American Forum on Family Planning (the Forum) in New Orleans, LA, from October 20� 22, 2018. This dynamic multidisciplinary meeting is a stimulating opportunity for investigators in the areas of contraception, abortion, and sexual and reproductive health to gather to share research, learn, and develop new ideas. The Forum features presentations of unpublished research, clinical practice updates and thought-provoking breakout sessions that help us stay engaged with the most current evidence and give us the tools to make a difference in the medically, socially, and politically complex sphere of family planning. A record total of 312 scientific abstracts were submitted this year, and reviewed by a panel of 59 family planning experts. The Forum’s Scientific Committee accepted 105 abstracts for poster presentation. The Committee selected 20 of the top-ranked abstracts for oral presentation, and is proud to present four outstanding abstracts in a plenary session for all attendees. These abstracts, described briefly below, detail research from diverse investigators using a spectrum of investigative methodologies, from basic laboratory science to n tionwide integrated knowledge translation.
Authors: Teal S; Borrero S; Hubacher D; Madden T; Raine-Bennett T
Contraception. 2018 Jul 19.
Comparison of Collaborative Versus Single-Site Quality Improvement to Reduce NICU Length of Stay
There is unexplained variation in length of stay (LOS) across NICUs, suggesting that there may be practices that can optimize LOS. Three groups of NICUs in the California Perinatal Quality Care Collaborative were followed: (1) collaborative centers participating in an 18-month collaborative quality improvement project to optimize LOS for preterm infants; (2) individual centers aiming to optimize LOS; and (3) nonparticipants. Our aim in the collaborative project was to decrease postmenstrual age (PMA) at discharge for infants born between 27 + 0 and <32 weeks' gestational age by 3 days. A secondary outcome was "early discharge," the proportion of infants discharged from the hospital before 36 + 5 weeks' PMA. The balancing measure of readmissions within 72 hours was tracked for the collaborative group. From 2013 to 2015, 8917 infants were cared for in 20 collaborative NICUs, 19 individual project NICUs, and 71 nonparticipants. In the collaborative group, the PMA at discharge decreased from 37.8 to 37.5 weeks (P = .02), and early discharge increased from 31.6% to 41.9% (P = .006). The individual project group had no significant change. Nonparticipants had a decrease in PMA from 37.5 to 37.3 weeks (P = .01) but no significant change in early discharge (39.8% to 43.6%; P = .24). There was no significant change in readmissions over time in the collaborative group. A structured collaborative project that was focused on optimizing LOS led to a 3-day decrease in LOS and was more effective than individualized quality improvement efforts.
Authors: Lee HC; Kuzniewicz M; Sharek PJ; et al.
Pediatrics. 2018 07;142(1). Epub 2018-06-13.
The Relationship Between Prescription Copayments and Contraceptive Adherence in a New-user Cohort
Contraceptive nonadherence is an important contributor to unintended pregnancy in the United States. While the elimination of patient cost sharing has been cited as means to improve contraceptive access, little is known about the relationship between cost sharing and ongoing adherence and continuation of chosen methods. The purpose of this study was to examine the relationship between copayment amount and adherence to pharmacy-dispensed contraception in young women. We conducted a retrospective cohort study of 39,142 women ages 19-29 with a new prescription for the contraceptive pill, patch, or ring at Kaiser Permanente Northern California during 2011-2014. We examined 12-month nonadherence as measured by timely prescription refills and used multivariable Cox proportional hazards models to assess the association between copayment amount and the risk of nonadherence. Ninety-four percent of women used the pill, and 6% used the patch or ring. Forty percent of patients had no copayment and 25% had a copayment of ≥$30. Nearly 75% of women were nonadherent during the study period. In 2013 and 2014, women with a copayment had a 9% increased risk of nonadherence (adjusted hazard ratio, 1.09; 95% confidence interval, 1.04, 1.14) compared with women with no copayment. Prescription copayments may serve as a barrier to adherence of pharmacy-dispensed contraception. Given recent changes to Affordable Care Act contraceptive coverage requirement, these findings can be used to support state-level and health system-level policies for no-cost contraception, and to determine the potential public health impact of this policy change.
Authors: Marshall C; Schmittdiel J; Chandra M; Calhoun A; Raine-Bennett T
Med Care. 2018 07;56(7):577-582.
Gestational Diabetes Mellitus and Renal Function: A Prospective Study With 9- to 16-Year Follow-up After Pregnancy
To examine whether gestational diabetes mellitus (GDM), independent of subsequent diabetes, is an early risk factor for renal impairment long term after the index pregnancy. In the Diabetes & Women’s Health (DWH) study (2012-2016), we examined the independent and joint associations of GDM and subsequent diabetes with long-term renal function among 607 women with and 619 women without GDM in the Danish National Birth Cohort (DNBC) index pregnancy (1996-2002). At median follow-up of 13 years after the index pregnancy, serum creatinine (mg/dL) and urinary albumin (mg/L) and creatinine (mg/dL) were measured, from which estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (UACR) (mg/g) were derived. Compared with women without GDM or subsequent diabetes, women with a GDM history had significantly higher eGFR even if they had not subsequently developed diabetes (adjusted β-coefficient [95% CI] = 3.3 [1.7, 5.0]). Women who had a GDM history and later developed diabetes (n = 183) also had significantly higher UACR [exponent β = 1.3 [95% CI 1.1, 1.6]) and an increased risk of elevated UACR (≥20 mg/g) [adjusted relative risk [95% CI] = 2.3 [1.1, 5.9]) compared with women with neither. After adjusting for potential confounders including prepregnancy BMI and hypertension, GDM without subsequent diabetes was not related to UACR. Women who develop GDM in pregnancy were more likely to show increased eGFR levels 9-16 years postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. However, only those who subsequently developed diabetes showed overt renal damage as evidenced by elevated UACR.
Authors: Rawal S; Zhu Y; Zhang C; et al.
Diabetes Care. 2018 07;41(7):1378-1384. Epub 2018-05-04.
Genetic Variants in CPA6 and PRPF31 are Associated with Variation in Response to Metformin in Individuals with Type 2 Diabetes
Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to identify common and rare variants associated with HbA1c response to metformin treatment and followed up these findings in four replication cohorts. Common variants in PRPF31 and CPA6 were associated with worse and better metformin response, respectively (P < 5 × 10-6), and meta-analysis in independent cohorts displayed similar associations with metformin response (P = 1.2 × 10-8 and P = 0.005, respectively). Previous studies have shown that PRPF31(+/-) knockout mice have increased total body fat (P = 1.78 × 10-6) and increased fasted circulating glucose (P = 5.73 × 10-6). Furthermore, rare variants in STAT3 associated with worse metformin response (q <0.1). STAT3 is a ubiquitously expressed pleiotropic transcriptional activator that participates in the regulation of metabolism and feeding behavior. Here, we provide novel evidence for associations of common and rare variants in PRPF31, CPA6, and STAT3 with metformin response that may provide insight into mechanisms important for metformin efficacy in T2D.
Authors: Rotroff DM; Hedderson MM; ACCORD/ACCORDion Investigators; et al.
Diabetes. 2018 07;67(7):1428-1440. Epub 2018-04-12.
A Tailored Letter Based on Electronic Health Record Data Improves Gestational Weight Gain Among Women With Gestational Diabetes: The Gestational Diabetes’ Effects on Moms (GEM) Cluster-Randomized Controlled Trial
Evaluate whether a tailored letter improved gestational weight gain (GWG) and whether GWG mediated a multicomponent intervention’s effect on postpartum weight retention among women with gestational diabetes mellitus (GDM). A cluster-randomized controlled trial of 44 medical facilities (n = 2,014 women) randomized to usual care or a multicomponent lifestyle intervention delivered during pregnancy (tailored letter) and postpartum (13 telephone sessions) to reduce postpartum weight retention. The tailored letter, using electronic health record (EHR) data, recommended an end-of-pregnancy weight goal tailored to prepregnancy BMI and GWG trajectory at GDM diagnosis: total GWG at the lower limit of the IOM range if BMI ≥18.5 kg/m2 or the midpoint if <18.5 kg/m2 and weight maintenance if women had exceeded this. The outcomes for this study were the proportion of women meeting the Institute of Medicine (IOM) guidelines for weekly rate of GWG from GDM diagnosis to delivery and meeting the end-of-pregnancy weight goal. The tailored letter significantly increased the proportion of women meeting the IOM guidelines (72.6% vs. 67.1%; relative risk 1.08 [95% CI 1.01-1.17]); results were similar among women with BMI <25.0 kg/m2 (1.07 [1.00-1.15]) and ≥25.0 kg/m2 (1.08 [0.98-1.18]). Thirty-six percent in the intervention vs. 33.0% in usual care met the end-of-pregnancy weight goal (1.08 [0.99-1.18]); the difference was statistically significant among women with BMI <25.0 kg/m2 (1.28 [1.05-1.57]) but not ≥25.0 kg/m2 (0.99 [0.87-1.13]). Meeting the IOM guidelines mediated the effect of the multicomponent intervention in reducing postpartum weight retention by 24.6% (11.3-37.8%). A tailored EHR-based letter improved GWG, which mediated the effect of a multicomponent intervention in reducing postpartum weight retention.
Authors: Hedderson MM; Brown SD; Ehrlich SF; Tsai AL; Zhu Y; Quesenberry CP; Crites Y; Ferrara A
Diabetes Care. 2018 07;41(7):1370-1377. Epub 2018-04-18.
Associations Between Maternal Obesity and Pregnancy Hyperglycemia and Timing of Pubertal Onset in Adolescent Girls: A Population-Based Study
Early puberty is associated with adverse health outcomes. We investigated whether in utero exposure to maternal obesity is associated with daughters’ pubertal timing using 15,267 racially/ethnically diverse Kaiser Permanente Northern California members aged 6-11 years with pediatrician-assessed Tanner staging (2003-2017). We calculated maternal body mass index (BMI; weight (kg)/height (m)2) during pregnancy from the electronic health record data. Using a proportional hazards model with interval censoring, we examined the associations between maternal obesity and girls’ pubertal timing, as well as effect modification by race/ethnicity and mediation by prepubertal BMI. Maternal obesity (BMI ≥30) and overweight (BMI 25-29.9) were associated with earlier onset of breast development in girls (hazard ratio (HR) = 1.39 (95% confidence interval (CI): 1.30, 1.49) and HR = 1.21 (95% CI: 1.13, 1.29), respectively), after adjustment for girl’s race/ethnicity, maternal age, education, parity, and smoking during pregnancy. There was interaction by race/ethnicity for associations between maternal obesity and girls’ pubic hair onset: Associations were strongest among Asian and non-Hispanic white girls (HR = 1.53 (95% CI: 1.24, 1.90) and HR = 1.34 (95% CI: 1.18, 1.52), respectively) and absent for African-American girls. Adjustment for girl’s prepubertal BMI only slightly attenuated associations. Our results suggest the importance of maternal metabolic factors during pregnancy in the timing of girls’ puberty and potential differences in the associations by race/ethnicity.
Authors: Kubo A; Deardorff J; Laurent CA; Ferrara A; Greenspan LC; Quesenberry CP; Kushi LH
Am J Epidemiol. 2018 07 01;187(7):1362-1369.
Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development
The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.
Authors: Schieve LA; Tian L; Dowling N; Croen L; Hoover-Fong J; Alexander A; Shapira SK
J Autism Dev Disord. 2018 07;48(7):2379-2395.
Maternal sedentary behavior during pre-pregnancy and early pregnancy and mean offspring birth size: a cohort study
Sedentary behavior is associated with adverse health outcomes in the general population. Whether sedentary behavior during pregnancy is associated with newborn outcomes, such as birth size, is not established, and previous studies have been inconsistent. While previous research suggests that male and female fetuses respond differently to maternal behaviors, such as physical activity, the role of infant sex in sedentary behavior-birth size associations has not been examined. Participants in the Omega study, a cohort in Washington State (1996-2008), reported leisure time sedentary behavior (non-work time spent sitting), light intensity physical activity, and moderate/vigorous leisure time physical activity duration in the year before pregnancy (N = 1373) and in early pregnancy (N = 1535, mean 15 weeks). Offspring birth size was abstracted from delivery records. Non-parametric calibration weighting was used to assign adjustment weight (matching the distribution of sociodemographic and medical characteristics of the full cohort (N = 4128)) to participants with available sedentary behavior data. Weighted linear regression models were used to estimate mean differences in offspring birthweight, head circumference, and ponderal index (birthweight/length3) associated with leisure time sedentary behavior. Regression models were run overall and stratified by offspring sex. Isotemporal substitution modeling was used to determine mean differences in birthweight associated with replacing sedentary behavior with light or moderate/vigorous physical activity. On average, women spent 2.3 and 2.6 h/day in leisure time sedentary behavior during pre- and early pregnancy, respectively. There were no associations of pre-pregnancy leisure time sedentary behavior with mean birthweight, head circumference, or ponderal index (adjusted β = - 12, 95% CI: -28, 4.1; β = 0.0, 95% CI: -0.04, 0.1; and β = 0.1, 95% CI: -0.2, 0.4, respectively). Early pregnancy sedentary behavior was not associated with mean birth size. Associations of sedentary behavior with mean birth size did not differ by offspring sex. Replacing sedentary time with light or moderate/vigorous physical activity was not associated with mean birthweight. We did not observe associations of maternal sedentary behavior during pre- or early pregnancy with mean offspring birth size. Pre-pregnancy and early pregnancy sedentary behavior may have important adverse effects on maternal health, but our results do not support associations with mean offspring birth size.
Authors: Badon SE; Littman AJ; Chan KCG; Williams MA; Enquobahrie DA
BMC Pregnancy Childbirth. 2018 Jun 27;18(1):267. Epub 2018-06-27.
A Longitudinal Study of Thyroid Markers across Pregnancy and the Risk of Gestational Diabetes
Triiodothyronine (T3) is the biologically-active thyroid hormone involved in glucose metabolism. fT3:fT4 ratio, a marker indicating conversion of free thyroxine (fT4) to free T3 (fT3), is also implicated in glucose homeostasis. To examine associations of fT3 and fT3:fT4 ratio with gestational diabetes (GDM). In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and fT3:fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10-14) and second (weeks 15-26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. 12 U.S. clinical centers. 107 GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2,802 women. GDM diagnosis ascertained from medical records. Both fT3 and fT3:fT4 ratio were positively associated with GDM; aOR (95% CI) comparing the highest vs. lowest fT3 quartile was 4.25 (1.67,10.80) at first and 3.89 (1.50, 10.10) at second trimester. Similarly, the corresponding risk estimates for fT3:fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Isolated hypothyroxinemia in the second, but not first trimester, was significantly related to increased GDM risk; aOR (95% CI) comparing hypothyroxinemic women to euthyroid was 2.97 (1.07,8.24). Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.
Authors: Rawal S; Zhu Y; Zhang C; et al.
J Clin Endocrinol Metab. 2018 Jun 07.
A prospective and longitudinal study of plasma phospholipid saturated fatty acid profile in relation to cardiometabolic biomarkers and the risk of gestational diabetes
Data on saturated fatty acids (SFAs) in relation to metabolic function and glucose homeostasis remain controversial. Such data are lacking among pregnant women. We prospectively investigated objectively measured individual and subclasses of plasma phospholipid SFAs throughout pregnancy in relation to cardiometabolic markers and gestational diabetes mellitus (GDM) risk. Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort of 2802 singleton pregnancies, 107 GDM cases were ascertained via medical record review and matched to 214 non-GDM controls on age, race/ethnicity, and gestational week (GW) at blood collection. Individual plasma phospholipid SFA concentrations were repeatedly measured throughout pregnancy at GWs 10-14, 15-26, 23-31, and 33-39 and also grouped into subclasses of even- or odd-chain SFAs. From GW 10, even-chain SFA concentrations were significantly higher among women who later developed GDM, whereas odd-chain SFAs were significantly lower among GDM cases compared with controls. At GWs 10-14, the SFA palmitic acid (16:0) was positively associated with impaired insulin resistance and cardiometabolic markers and the risk of GDM [adjusted OR comparing the highest with the lowest quartile (aORQ4-Q1): 4.76; 95% CI: 1.72, 13.10; P-trend = 0.001]. In contrast, odd-chain SFAs were inversely related to the previously mentioned markers and GDM risk [aORQ4-Q1 for pentadecanoic acid (15:0): 0.32; 95% CI: 0.11, 0.92; P-trend = 0.025; for heptadecanoic acid (17:0): 0.20; 95% CI: 0.07, 0.58; P-trend = 0.003]. Women with high (median or greater) even-chain SFA concentrations and low (less than median) odd-chain SFAs had a 9.43-fold (95%: CI 3.26-, 27.30-fold) increased risk compared with women with low even-chain and high odd-chain SFA concentrations. Similar results were observed at GWs 15-26. The study provided one of the first lines of evidence suggesting that circulating concentrations of SFAs varying by SFA chain length, as early as GWs 10-14, were significantly and differentially associated with subsequent risk of GDM. Our findings highlight the importance of assessing objectively measured, individual, and subclasses of SFAs to investigate their distinct biological and pathophysiologic roles in glucose homeostasis and cardiometabolic outcomes. This study was registered at www.clinicaltrials.gov as NCT00912132.
Authors: Zhu Y; Tsai MY; Sun Q; Hinkle SN; Rawal S; Mendola P; Ferrara A; Albert PS; Zhang C
Am J Clin Nutr. 2018 Jun 01;107(6):1017-1026.
Comparison of Two Generations of ActiGraph Accelerometers: The CARDIA Study
This study aimed to examine the comparability of the ActiGraph 7164 and wGT3X-BT wear time, count-based estimates, and average time per day in physical activity of different intensities. We studied 87 Coronary Artery Risk Development in Young Adults (CARDIA) participants 48-60 yr of age who simultaneously wore the 7164 and wGT3X-BT accelerometers at the waist in 2015-2016, with wear time of ≥4 of 7 d, ≥10 h·d for both monitors. Freedson cutpoints (counts per minute) were used to define sedentary (<100), light (100-1951), moderate (1952-5724), and vigorous activity (≥5725). Agreement was evaluated using paired-difference tests, intraclass correlation coefficients, and Bland-Altman plots. Given systematic differences in count-based estimates between monitors, a calibration formula applied to the wGT3X-BT values was obtained by linear regression. Total detected wear time minutes per day was nearly identical between the 7164 and the wGT3X-BT (881.5 ± 70.9 vs 880.3 ± 78.1, P = 0.72). The wGT3X-BT values were calibrated to the 7164 values by dividing counts by 1.088. After calibration, no differences were observed between the 7164 and the wGT3X-BT in total counts per day (310,184 ± 129,189 vs 307,085 ± 135,362, P = 0.48), average counts per min per day (349.5 ± 139.5 vs 346.5 ± 147.2, P = 0.54), sedentary (513.2 ± 93.6 vs 509.6 ± 98.6, P = 0.23), light (335.3 ± 81.5 vs 338.7 ± 81.1, P = 0.22), moderate (31.0 ± 21.9 vs 30.3 ± 23.4, P = 0.31), or moderate-to-vigorous minutes per day (33.1 ± 24.6 vs 32.0 ± 26.0, P = 0.13). A significant difference was observed for vigorous minutes per day (0.2 ± 1.0 vs 0.0 ± 0.3, P < 0.01); however, the absolute difference was marginal. Intraclass correlation coefficients showed excellent agreement for all measures (0.95-0.99). After applying a calibration formula, the 7164 and wGT3X-BT were comparable for total wear time, count-based estimates, and average minutes per day in sedentary, light, moderate, and moderate-to-vigorous activity. Findings illustrate a novel methodological approach to facilitate accelerometer data harmonization.
Authors: Whitaker KM; Pettee Gabriel K; Jacobs DR; Sidney S; Sternfeld B
Med Sci Sports Exerc. 2018 06;50(6):1333-1340.
Plasma concentrations of lipids during pregnancy and the risk of gestational diabetes mellitus: A longitudinal study
Abnormal lipid profiles have been associated with gestational diabetes mellitus (GDM), but studies with longitudinal measures of lipids throughout pregnancy are sparse. The aim of the present study was to characterize longitudinal changes in lipid profiles throughout pregnancy and prospectively examine the associations of plasma lipid concentrations with risk of GDM. This study was a nested case-control study including 107 GDM cases and 214 matched non-GDM controls from participants in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies – Singleton cohort. Blood samples were collected longitudinally at Gestational Weeks (GW) 10-14, 15-26 (fasting sample), 23-31, and 33-39. Plasma concentrations of triglycerides, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured by enzymatic assays. Low-density lipoprotein cholesterol (LDL-C) was calculated using Friedewald’s formula. Plasma triglycerides, total cholesterol, and LDL-C increased as pregnancy progressed. At GW 10-14, the adjusted odds ratios (aORs) of GDM comparing the highest versus lowest quartile were 3.15 (95% confidence interval [CI] 1.38-7.15; P trend = 0.002) for triglycerides and 0.44 (95% CI 0.18-1.09; P trend = 0.045) for HDL-C. At GW 15-26, the aORs were 6.57 (95% CI 2.25-19.17; P trend = 0.001) for triglycerides and 0.23 (95% CI 0.08-0.63; P trend = 0.005) for HDL-C. No significant associations were observed for total cholesterol and LDL-C concentrations with risk of GDM. Higher plasma triglyceride and lower HDL-C concentrations in early and mid-pregnancy were significantly associated with a greater risk of GDM. Total cholesterol and LDL-C concentrations during pregnancy were not significantly associated with GDM risk.
Authors: Bao W; Dar S; Zhu Y; Wu J; Rawal S; Li S; Weir NL; Tsai MY; Zhang C
J Diabetes. 2018 Jun;10(6):487-495. Epub 2017-09-29.
Large-Scale Implementation of Structured Reporting of Adnexal Masses on Ultrasound
The aim of this article is to describe the development and implementation of structured reporting of adnexal mass findings on pelvic ultrasound in a large integrated health care delivery system. A structured reporting system that includes standardized terminology for describing adnexal masses on ultrasound was developed by a multidisciplinary team of radiologists, gynecologists, and gynecologic oncologists on the basis of literature review and internal data. The system uses a reporting template that requires radiologists to assign abnormal adnexal masses to one of five possible categories on the basis of standardized criteria: category 0, 1, 2, or 3 for masses <10 cm, to reflect increasing concern for malignancy, and category X for masses >10 cm. Unique predefined hashtags were linked to each category to enable electronic data extraction, and a hard stop feature was installed that prevents reports from being finalized without a category designation. In 2014, after a 3-month pilot study, large-scale implementation was supported by an educational campaign consisting of web-based conferences, e-mail announcements, and local presentations. Clinical management recommendations on the basis of category and other clinical factors were provided in a separate practice resource for clinicians. Analysis of adherence revealed that 93% of the approximately 12,000 reports describing abnormal adnexal masses in 2016 included category designations. Feedback from referring providers via an anonymous survey indicated high levels of satisfaction with reports. Multidisciplinary collaboration and leveraging of technology enabled large-scale implementation of structured reporting with high levels of adherence among radiologists and improved satisfaction among referring providers.
Authors: Suh-Burgmann EJ; Flanagan T; Lee N; Osinski T; Sweet C; Lynch M; Caponigro M; Mehta J; Alavi M; Herrinton LJ
J Am Coll Radiol. 2018 May;15(5):755-761. Epub 2018-03-20.
Recent Intrauterine device use and the risk of precancerous cervical lesions and cervical cancer
Understanding the effect of contraceptives on the development of precancerous lesions of the cervix and cervical cancer may provide information that is valuable to women in contraceptive decision-making. The purpose of this study was to evaluate the association between recent intrauterine device (IUD) use (by type) and cervical intraepithelial neoplasia 2, 3, adenocarcinoma in situ or cancer (CIN2+ or CIN3+). Case-control study of 17,559 women age 18-49 with incident CIN2+ cases and 5:1 age-matched, incidence-density selected controls (N=87,378) who were members of Kaiser Permanente Northern California Healthcare System from 1996-2014. Recent IUD use, within 18 months prior to index, was the exposure of interest. We identified 1,657 IUD users among the cases and 7,925 IUD users among controls. After adjusting for sexually transmitted infection testing, smoking, HPV vaccination, hormonal contraceptive use, parity, race and number of outpatient healthcare system visits, IUD use was associated with an increased rate of CIN2+ [rate ratio (RR) 1.12, 95% confidence interval (1.05-1.18), p
Authors: Averbach S; Silverberg MJ; Leyden W; Smith-McCune K; Raine-Bennett T; Sawaya GF
Contraception. 2018 Apr 16.
Automated Cervical Screening and Triage, Based on HPV Testing and Computer-Interpreted Cytology
State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict women at highest risk. Those with the highest-risk HPV types or abnormal cytology are commonly referred to colposcopy; however, expert cytology services are critically lacking in many regions. To permit completely automatable cervical screening/triage, we designed and validated a novel triage method, a cytologic risk score algorithm based on computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We compared it with abnormal cytology in predicting precancer among 1839 women testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente Northern California (KPNC). Precancer outcomes were ascertained by record linkage. As additional validation, we compared the algorithm prospectively with cytology results among 243 807 women screened at KPNC (2016-2017). All statistical tests were two-sided. Among HPV-positive women, the algorithm matched the triage performance of abnormal cytology. Combined with HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred 91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring 38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and 37.4%, respectively, for typing and cytology triage). In the 2016-2017 validation, the predicted risk scores strongly correlated with cytology (P < .001). High-quality cervical screening and triage performance is achievable using this completely automated approach. Automated technology could permit extension of high-quality cervical screening/triage coverage to currently underserved regions.
Authors: Yu K; Raine-Bennett TR; Schiffman M; et al.
J Natl Cancer Inst. 2018 Apr 11.
Psychiatric and Medical Conditions in Transition-Aged Individuals With ASD
Children with autism spectrum disorder (ASD) have a variety of medical and psychiatric conditions and an increased use of health care services. There is limited information about the prevalence of psychiatric and medical conditions in adolescents and young adults with ASD. Our objective was to describe the frequency of medical and psychiatric conditions in a large population of diverse, insured transition-aged individuals with ASD. Participants included Kaiser Permanente Northern California members who were enrolled from 2013 to 2015 and who were 14 to 25 years old. Individuals with ASD (n = 4123) were compared with peers with attention-deficit/hyperactivity disorder (n = 20 615), diabetes mellitus (n = 2156), and typical controls with neither condition (n = 20 615). Over one-third (34%) of individuals with ASD had a co-occurring psychiatric condition; the most commonly reported medical conditions included infections (42%), obesity (25%), neurologic conditions (18%), allergy and/or immunologic conditions (16%), musculoskeletal conditions (15%), and gastrointestinal (11%) conditions. After controlling for sex, age, race, and duration of Kaiser Permanente Northern California membership, most psychiatric conditions were significantly more common in the ASD group than in each comparison group, and most medical conditions were significantly more common in the ASD group than in the attention-deficit/hyperactivity disorder and typical control groups but were similar to or significantly less common than the diabetes mellitus group. Although more research is needed to identify factors contributing to this excess burden of disease, there is a pressing need for all clinicians to approach ASD as a chronic health condition requiring regular follow-up and routine screening and treatment of medical and psychiatric issues.
Authors: Davignon MN; Qian Y; Massolo M; Croen LA
Pediatrics. 2018 04;141(Suppl 4):S335-S345.
Efficacy of Subthreshold Newborn Phototherapy During the Birth Hospitalization in Preventing Readmission for Phototherapy
Treatment of jaundiced newborns with subthreshold phototherapy (phototherapy given to newborns with bilirubin levels below those recommended in American Academy of Pediatrics [AAP] guidelines) is common. However, the use of subthreshold phototherapy may have risks and increase costs, and, to date, it has not been systematically studied in newborns. To estimate the efficacy of subthreshold phototherapy for newborns with total serum bilirubin (TSB) levels from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold during the birth hospitalization in preventing readmissions for phototherapy, and to identify predictors of readmission for phototherapy. Retrospective cohort study of 25 895 newborns born at 35 or more weeks’ gestation, born in 1 of 16 Kaiser Permanente Northern California hospitals from January 1, 2010, through December 31, 2014, with at least 1 TSB level from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold and not exceeding the threshold during the birth hospitalization. Data were analyzed from November 1, 2015, to November 28, 2017. Subthreshold phototherapy during the birth hospitalization. Readmission for phototherapy. Among 25 895 newborns with qualifying TSB levels from 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold, 4956 (19.1%) received subthreshold phototherapy and 241 of these (4.9%) were readmitted for phototherapy compared with 2690 of 20 939 untreated newborns (12.8%) (unadjusted odds ratio [OR], 0.35; 95% CI, 0.30-0.40). In a logistic regression model, adjustment for confounding variables, including gestational age, race/ethnicity, formula feedings per day, and the difference between the TSB level and the phototherapy threshold, strengthened the association (OR, 0.28; 95% CI, 0.19-0.40). Estimated numbers needed to treat ranged from 60.8 in the lowest quintile of predicted risk to 6.3 in the highest quintile. Newborns who received formula feedings had lower adjusted odds of readmission for phototherapy compared with exclusively breastfed newborns (OR, 0.58; 95% CI, 0.47-0.72 for >0 to <2 formula feedings per day; OR, 0.24; 95% CI, 0.21-0.27 for ≥6 formula feedings per day). Subthreshold phototherapy was associated with a 22-hour longer length of stay (95% CI, 16-28 hours). Subthreshold phototherapy during the birth hospitalization is effective in preventing readmissions for phototherapy; however, for each readmission prevented, many newborns require phototherapy who would otherwise not need it.
Authors: Wickremasinghe AC; Kuzniewicz MW; McCulloch CE; Newman TB
JAMA Pediatr. 2018 04 01;172(4):378-385.
Association between paternal alcohol consumption before conception and anogenital distance of offspring
There are limited studies on the effects of paternal alcohol consumption, before conception, on the reproductive development of offspring. Anogenital distance (AGD), the distance from the center of the anus to the genitals, is a sensitive biomarker of reproductive hormone abnormalities during the critical developmental window. The relationship between paternal alcohol consumption and AGD of human offspring has not been studied yet. This cohort study included 1,292 pregnant women recruited in Shanghai. An in-person interview was conducted to collect information on demographic characteristics of couples, and husbands’ lifestyles, including drinking habits. AGD (boys, AGD-AP [anus-penis], AGD-AS [anus-scrotum]; girls, AGD-AC [anus-clitoris], AGD-AF [anus-fourchette]) measurements were performed at birth, and at 6 and 12 months of age. Multiple linear regression analysis was conducted to determine the association between paternal alcohol consumption before conception, and the AGDs of offspring. Data included AGD measurements of infants at birth (N = 980), at 6 months (N = 592, 60.4%), and at 12 months (N = 543, 55.4%). Boys in the paternal alcohol-exposed group had shorter AGDs, irrespective of the areas measured (AGD-AP and AGD-AS) and time of measurements, than those in the unexposed group. However, only the differences in AGD-AP at birth and AGD-AS at 6 months were statistically significant. For girls, the associations were similar at birth; however, the AGD-AC and AGD-AF were longer in the paternal alcohol-exposed group than the unexposed group at 12 months. Our findings provide first, but preliminary evidence, that paternal alcohol consumption within 3 months before conception may be associated with shorter AGD in the offspring, especially in boys, which indicates that paternal alcohol drinking may have an adverse effect on their reproductive development. Further studies should be conducted to validate these results.
Authors: Xia R; Jin L; Li D; Liang H; Yang F; Chen J; Yuan W; Miao M
Alcohol Clin Exp Res. 2018 Apr;42(4):735-742. Epub 2018-02-14.
Racial disparities in family-provider interactions for pediatric asthma care
Black and Latino children experience significantly worse asthma morbidity than their white peers for multifactorial reasons. This study investigated differences in family-provider interactions for pediatric asthma, based on race/ethnicity. This was a cross-sectional study of parent surveys of asthmatic children within the Population-Based Effectiveness in Asthma and Lung Diseases Network. Our study population comprised 647 parents with survey response data. Data on self-reported race/ethnicity of the child were collected from parents of the children with asthma. Outcomes studied were responses to the questions about family-provider interactions in the previous 12 months: (1) number of visits with asthma provider; (2) number of times provider reviewed asthma medications with patient/family; (3) review of a written asthma treatment plan with provider; and (4) preferences about making asthma decisions. In multivariate adjusted analyses controlling for asthma control and other co-morbidities, black children had fewer visits in the previous 12 months for asthma than white children: OR 0.63 (95% CI 0.40, 0.99). Additionally, black children were less likely to have a written asthma treatment plan given/reviewed by a provider than their white peers, OR 0.44 (95% CI 0.26, 0.75). There were no significant differences by race in preferences about asthma decision-making nor in the frequency of asthma medication review. Black children with asthma have fewer visits with their providers and are less likely to have a written asthma treatment plan than white children. Asthma providers could focus on improving these specific family-provider interactions in minority children.
Authors: Trivedi M; Fung V; Kharbanda EO; Larkin EK; Butler MG; Horan K; Lieu TA; Wu AC
J Asthma. 2018 04;55(4):424-429. Epub 2017-07-14.
A Pilot Mobile-based Mindfulness Intervention for Cancer Patients and their Informal Caregivers
Authors: Kubo A; Altschuler A; Kurtovich E; Hendlish S; Laurent CA; Kolevska T; Li Y; Avins A
Mindfulness (N Y). 2018 Dec;9(6):1885-1894. Epub 2018-03-24.
Associations of overweight/obesity and socioeconomic status with hypertension prevalence across racial and ethnic groups
Racial/ethnic disparities in the prevalence of diagnosed hypertension are persistent but may be partially explained by racial/ethnic differences in weight category and neighborhood socioeconomic status. The authors compared hypertension prevalence rates among 4 060 585 adults with overweight or obesity across 10 healthcare systems by weight category and neighborhood education level in geographically and racially diverse individuals. Data were obtained from electronic health records. Hypertension was defined as at least two outpatient visits or one inpatient hospitalization with a coded diagnosis. Logistic regression, adjusted for age, sex, and site, with two-way interactions between race/ethnicity and weight category or neighborhood education, was used to examine the association between hypertension and race/ethnicity, with whites as the reference. Results documented that odds ratios for hypertension prevalence were greater for blacks, American Indians/Alaskan Natives, Asians, and Native Hawaiians/other Pacific Islanders compared with whites and lower for Hispanics in similar weight categories and neighborhood education levels. Although two-way interactions were statistically significant, the magnitude of the odds of hypertension compared with whites did not substantially vary across weight or neighborhood education. Hypertension odds were almost double relative to whites for blacks and Native Hawaiians/other Pacific Islanders across most weight categories and all neighborhood education levels. Odds of hypertension were about 50% greater for Asians relative to whites across weight categories. Results suggest that other factors might be associated with racial/ethnic disparities in hypertension. More research is needed to understand the many factors that may contribute to variation in diagnosed hypertension across racial/ethnic groups with overweight or obesity.
Authors: Young DR; Ferrara A; Yamamoto A; et al.
J Clin Hypertens (Greenwich). 2018 03;20(3):532-540. Epub 2018-02-12.
Bone loss in women with BRCA1 and BRCA2 mutations
Estimate the prevalence and identify risk factors for bone loss in women with BRCA mutations. Women, age 40 and older, with BRCA mutations identified from the Breast Cancer Surveillance database at Kaiser Permanente Northern California were invited to participate and undergo a dual-energy x-ray absorptiometry scan to assess for bone loss (osteopenia or osteoporosis). Multivariable logistic regression analysis was performed to assess clinical factors associated with bone loss. Of the 238 women in the final cohort, 20 women had intact ovaries (median age 54.5years) and 218 had undergone risk reducing salpingo-oophorectomy (RRSO) (median age 57). The prevalence of bone loss was 55% in the no RRSO group and 72.5% in the RRSO group (P=0.10). In multivariable analysis, only higher body mass index (OR 0.6 per 5kg/m2, 95% CI: 0.4-0.7) and nonwhite race compared to white (OR 0.5, 95% CI: 0.2-0.9) were protective for bone loss while older age (OR 1.5 per 10years, 95% CI: 1.1-2.1) and selective estrogen receptor modulator use (3.1, 95% CI: 1.2-10.1) were associated with increased odds of bone loss. Among women with RRSO, bone loss was more frequent in women who had postmenopausal (n=106) compared to women who had premenopausal RRSO (n=112), (82.1% and 63.4% respectively, P=0.002). In multivariable analysis, only BMI was protective of bone loss (OR 0.5, 95%, CI: 0.4-0.7) but neither age nor menopausal status at RRSO were associated with bone loss. Bone loss is common in women with BRCA mutations who undergo RRSO.
Authors: Powell CB; Alabaster A; Stoller N; Armstrong MA; Salyer C; Hamilton I; Raine-Bennett T
Gynecol Oncol. 2018 03;148(3):535-539.
Acute Associations between Outdoor Temperature and Premature Rupture of Membranes
Extreme ambient temperatures have been linked to preterm birth. Preterm premature rupture of membranes is a common precursor to preterm birth but is rarely studied in relation to temperature. We linked 15,381 singleton pregnancies with premature rupture of membranes from a nationwide US obstetrics cohort (2002-2008) to local temperature. Case-crossover analyses compared daily temperature during the week preceding delivery and the day of delivery to 2 control periods, before and after the case period. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence intervals (CIs) of preterm and term premature rupture of membranes for a 1°C increase in temperature during the warm (May-September) and cold (October-April) season separately after adjusting for humidity, barometric pressure, ozone, and particulate matter. During the warm season, 1°C increase during the week before delivery was associated with a 5% (95% CI, 3%, 6%) increased preterm premature rupture of membranes risk, and a 4% (95% CI, 3%, 5%) increased term premature rupture of membranes risk. During the cold season, 1°C increase was associated with a 2% decreased risk for both preterm (95% CI, 1%, 3%) and term premature rupture of membranes (95% CI, 1%, 3%). The day-specific associations for the week before delivery were similar, but somewhat stronger for days closer to delivery. Relatively small ambient temperature changes were associated with the risk of both preterm and term premature of membranes. Given the adverse consequences of premature rupture of membranes and concerns over global climate change, these findings merit further investigation. See video abstract at, https://links.lww.com/EDE/B312.
Authors: Ha S; Liu D; Zhu Y; Sherman S; Mendola P
Epidemiology. 2018 03;29(2):175-182.
Validation of an HPV DNA cervical screening test that provides expanded HPV typing
Background/Purpose
As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major question is the clinical value of identifying individual HPV types. We aimed to validate Onclarity™ (Becton Dickinson Diagnostics, Sparks MD), a nine-channel HPV test recently approved by FDA, by assessing: 1) the association of Onclarity type/channels with precancer/cancer; 2) HPV type/channel agreement between Onclarity and cobas™ (Roche Molecular Systems, Pleasanton CA), another FDA-approved test; and 3) Onclarity typing for all types/channels compared to typing results from a research assay (Linear Array™, LA, Roche).Methods.We compared Onclarity to histopathology, cobas, and LA. We tested a stratified random sample (n=9,701) of discarded routine clinical specimens that had tested positive by Hybrid Capture 2 (HC2, Qiagen, Germantown MD). A subset had already been tested by cobas and LA (n=1,965). Cervical histopathology was ascertained from electronic health records.Results.Hierarchical Onclarity channels showed a significant linear association with histologic severity. Onclarity and cobas had excellent agreement on partial typing of HPV16, HPV18, and the other twelve types as a pool (sample-weighted kappa: 0.83); cobas was slightly more sensitive for HPV18 and slightly less sensitive for the pooled high-risk types. Typing by Onclarity showed excellent agreement with types and group of types identified by LA (kappas from 0.80 for HPV39/68/35 to 0.97 for HPV16).DiscussionOnclarity typing results corresponded well to histopathology and to an already-validated HPV DNA test, and could provide additional clinical typing if such discrimination is determined to be clinically desirable.
Authors: Demarco M; Fetterman B; Lorey T; Poitras N; Raine-Bennett TR; Schiffman M; et al.
J Clin Microbiol. 2018 Feb 28.
Cost Effectiveness of Gene Expression Profile Testing in Community Practice
Purpose Gene expression profile (GEP) testing can support chemotherapy decision making for patients with early-stage, estrogen receptor-positive, human epidermal growth factor 2-negative breast cancers. This study evaluated the cost effectiveness of one GEP test, Onco type DX (Genomic Health, Redwood City, CA), in community practice with test-eligible patients age 40 to 79 years. Methods A simulation model compared 25-year societal incremental costs and quality-adjusted life-years (QALYs) of community Onco type DX use from 2005 to 2012 versus usual care in the pretesting era (2000 to 2004). Inputs included Onco type DX and chemotherapy data from an integrated health care system and national and published data on Onco type DX accuracy, chemotherapy effectiveness, utilities, survival and recurrence, and Medicare and patient costs. Sensitivity analyses varied individual parameters; results were also estimated for ideal conditions (ie, 100% testing and adherence to test-suggested treatment, perfect test accuracy, considering test effects on reassurance or worry, and lowest costs). Results Twenty-four percent of test-eligible patients had Onco type DX testing. Testing was higher in younger patients and patients with stage I disease ( v stage IIA), and 75.3% and 10.2% of patients with high and low recurrence risk scores received chemotherapy, respectively. The cost-effectiveness ratio for testing ( v usual care) was $188,125 per QALY. Considering test effects on worry versus reassurance decreased the cost-effectiveness ratio to $58,431 per QALY. With perfect test accuracy, the cost-effectiveness ratio was $28,947 per QALY, and under ideal conditions, it was $39,496 per QALY. Conclusion GEP testing is likely to have a high cost-effectiveness ratio on the basis of community practice patterns. However, realistic variations in assumptions about key variables could result in GEP testing having cost-effectiveness ratios in the range of other accepted interventions. The differences in cost-effectiveness ratios on the basis of community versus ideal conditions underscore the importance of considering real-world implementation when assessing the new technology.
Authors: Chandler Y; Schechter CB; Jayasekera J; Near A; O'Neill SC; Isaacs C; Phelps CE; Ray GT; Lieu TA; Ramsey S; Mandelblatt JS
J Clin Oncol. 2018 02 20;36(6):554-562. Epub 2018-01-08.
Human Papillomavirus DNA methylation as a biomarker for cervical precancer: Consistency across 12 genotypes and potential impact on management of HPV-positive women
Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV-positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. In this nested case-control study, we tested up to 30 cases of precancer (CIN3/AIS) and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, odds ratios, and areas under the curve (AUC). Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies. Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden’s index (0.46), compared with cytology (0.31) and a 5-type methylation assay including only previously described types (0.26). The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared to cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology- or HPV16/18-positives. HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multi-type methylation assay may serve as a triage test for HPV-positive women.
Authors: Clarke MA; Gradíssimo A; Schiffman M; Lam J; Sollecito CC; Fetterman B; Lorey T; Poitras NE; Raine-Bennett T; Castle PE; Wentzensen N; Burk RD
Clin Cancer Res. 2018 Feb 02.
Impact of Copayment Changes on Children’s Albuterol Inhaler Use and Costs after the Clean Air Act Chlorofluorocarbon Ban
To examine changes in children’s albuterol use and out-of-pocket (OOP) costs in response to increased copayments after the Food and Drug Administration banned inhalers with chlorofluorocarbon (CFC) propellants. Four health maintenance organizations (HMOs), two that increased copayments for albuterol inhalers that went from generic CFC-containing to branded CFC-free versions, and two that retained generic copayments for CFC-free inhalers (controls). We included children with asthma aged 4-17 years with commercial coverage from 2007 to 2010. Interrupted time series with comparison series. We obtained enrollee and plan characteristics from enrollment files, and utilization data from pharmacy and medical claims; OOP expenditures were extracted from pharmacy claims for two HMOs with cost data available. There were no significant differences in albuterol use between the group with increased cost-sharing and controls with respect to changes after the policy change. There was a postpolicy increase of $6.11 OOP per month per child using albuterol among those with increased cost-sharing versus $0.36 in controls; the difference between groups was significant (p < .01). Increased copayments for brand-name CFC-free albuterol after the CFC ban did not lead to a decrease in children's albuterol use, but it led to a modest increase in OOP costs.
Authors: Galbraith AA; Fung V; Li L; Butler MG; Nordin JD; Hsu J; Smith D; Vollmer WM; Lieu TA; Soumerai SB; Wu AC
Health Serv Res. 2018 02;53(1):156-174. Epub 2016-11-20.
Prenatal Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Association with Autism Spectrum Disorder and Intellectual Disability
Emerging work has examined neurodevelopmental outcomes following prenatal exposure to per- and polyfluoroalkyl substances (PFAS), but few studies have assessed associations with autism spectrum disorder (ASD). Our objective was to estimate associations of maternal prenatal PFAS concentrations with ASD and intellectual disability (ID) in children. Participants were from a population-based nested case-control study of children born from 2000 to 2003 in southern California, including children diagnosed with ASD (n=553), ID without autism (n=189), and general population (GP) controls (n=433). Concentrations of eight PFAS from stored maternal sera collected at 15-19 wk gestational age were quantified and compared among study groups. We used logistic regression to obtain adjusted odds ratios for the association between prenatal PFAS concentrations (parameterized continuously and as quartiles) and ASD versus GP controls, and separately for ID versus GP controls. Geometric mean concentrations of most PFAS were lower in ASD and ID groups relative to GP controls. ASD was not significantly associated with prenatal concentrations of most PFAS, though significant inverse associations were found for perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) [adjusted ORs for the highest vs. lowest quartiles 0.62 (95% CI: 0.41, 0.93) and 0.64 (95% CI: 0.43, 0.97), respectively]. Results for ID were similar. Results from this large case-control study with prospectively collected prenatal measurements do not support the hypothesis that prenatal exposure to PFAS is positively associated with ASD or ID. https://doi.org/10.1289/EHP1830.
Authors: Lyall K; Yau VM; Hansen R; Kharrazi M; Yoshida CK; Calafat AM; Windham G; Croen LA
Environ Health Perspect. 2018 01 02;126(1):017001. Epub 2018-01-02.
Liver Enzymes in Early to Mid-pregnancy, Insulin Resistance, and Gestational Diabetes Risk: A Longitudinal Analysis
Background: Liver enzymes may be implicated in glucose homeostasis; liver enzymes progressively change during pregnancy but longitudinal data during pregnancy in relation to insulin resistance and gestational diabetes (GDM) risk are lacking. We investigated longitudinal associations of γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT) with insulin secretion and resistance markers across early to mid-pregnancy and subsequent GDM risk. Methods: Within the prospective Pregnancy Environment and Lifestyle Study cohort, 117 GDM cases were ascertained and matched to 232 non-GDM controls in a nested case-control study. Fasting blood samples were collected at two clinic visits (CV1, gestational weeks 10-13; CV2, gestational weeks 16-19). Linear mixed model and conditional logistic regression were used, adjusting for major risk factors for GDM. Results: In repeated measure analysis, after adjusting for confounders including body mass index and waist-to-hip ratio, GGT per standard deviation increment was associated with elevated fasting glucose and HOMA-IR (% change = 1.51%, 95% CI 0.56-2.46% and 7.43%, 95% CI 1.76-13.11%, respectively) and decreased adiponectin (% change = -2.86%, 95% CI-5.53 to -0.20%) from CV1 to CV2. At CV1 and CV2, GGT levels comparing the highest versus lowest quartile were associated with 3.01-fold (95% CI 1.32-6.85) and 3.51-fold (95% CI 1.37-8.97) increased risk of GDM, respectively. Progressively increased ( Authors: Zhu Y; Hedderson MM; Quesenberry CP; Feng J; Ferrara A Front Endocrinol (Lausanne). 2018;9:581. Epub 2018-10-02.
Case-control meta-analysis of blood DNA methylation and autism spectrum disorder
Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 × 10- 7. Seven CpGs showed differences at p < 1 × 10- 5 and 48 at 1 × 10- 4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.
Authors: Andrews SV; Croen LA; Ladd-Acosta C; et al.
Mol Autism. 2018;9:40. Epub 2018-06-28.
A cohort study of maternal cardiometabolic risk factors and primary cesarean delivery in an integrated health system
Maternal cardiometabolic risk factors (i.e., hyperglycemia, pre-existing hypertension and high body mass index) impact fetal growth and risk of having a cesarean delivery. However, the independent and joint contribution of maternal cardiometabolic risk factors to primary cesarean section is unclear. We aimed to elucidate the degree to which maternal cardiometabolic risk factors contribute to primary cesarean deliveries and whether associations vary by infant size at birth in an integrated health system. A cohort study of 185,045 singleton livebirths from 2001 to 2010. Poisson regression with robust standard errors provided crude and adjusted relative risks (RR) and 95% confidence intervals (CIs) for cesarean delivery risk associated with risk factors. We then estimated the proportion of cesarean sections that could be prevented if the cardiometabolic risk factor in pregnant women were eliminated (the population-attributable risk [PAR]). In a single multivariable model, maternal cardiometabolic risk factors were independently associated with cesarean delivery: RR (95% CI) abnormal glucose screening 1.04 (1.01-1.08); gestational diabetes 1.18 (1.11-1.18) and pre-existing diabetes 1.60 (1.49-1.71); pre-existing hypertension 1.16 (1.10-1.23); overweight 1.27 (1.24-1.30); obese class I 1.46 (1.42-1.51); obese class II 1.73 (1.67-1.80); and obese class III 1.97 (1.88-2.07); adjusting for established risk factors, medical facility and year. The associations between maternal cardiometabolic risk factors and primary cesarean delivery remained among infants with appropriate weights for gestational age. The PARs were 17.4% for overweight/obesity, 7.0% for maternal hyperglycemia, 2.0% for pre-existing hypertension and 20.5% for any cardiometabolic risk factor. Maternal cardiometabolic risk factors were independently associated with risk of primary cesarean delivery, even among women delivering infants born at an appropriate size for gestational age. Effective strategies to increase the proportion of women entering pregnancy at an optimal weight with normal blood pressure and glucose before pregnancy could potentially eliminate up to 20% of cesarean deliveries.
Authors: Hedderson MM; Xu F; Sridhar SB; Han ES; Quesenberry CP; Crites Y
PLoS ONE. 2018;13(7):e0199932. Epub 2018-07-03.
Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation
Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (PPC1 = 1.4 × 10-9; PPC2 = 2.9 × 10-5; PPC3 = 3.8 × 10-5; PPC4 = 4.2 × 10-6; PPC5 = 9.9 × 10-13, PPC6 = 1.3 × 10-11) and not with sample type (PPC1-6>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P = 0.46), and estimated proportions were highly correlated between paired samples (r = 0.99). Differences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.
Authors: Dou J; Schmidt RJ; Benke KS; Newschaffer C; Hertz-Picciotto I; Croen LA; Iosif AM; LaSalle JM; Fallin MD; Bakulski KM
Epigenetics. 2018;13(1):108-116. Epub 2018-02-16.
Autism spectrum disorder and birth spacing: Findings from the study to explore early development (SEED)
Previous studies of autism spectrum disorder (ASD) and birth spacing had limitations; few examined phenotypic case subtypes or explored underlying mechanisms for associations and none assessed whether other (non-ASD) developmental disabilities (DDs) were associated with birth spacing. We assessed associations between inter-pregnancy interval (IPI) and both ASD and other DDs using data from the Study to Explore Early Development, a multi-site case-control study with rigorous case-finding and case-classification methods and detailed data collection on maternal reproductive history. Our sample included 356 ASD cases, 627 DD cases, and 524 population (POP) controls born in second or later births. ASD and DD cases were further sub-divided according to whether the child had intellectual disability (ID). ASD cases were also sub-divided by ASD symptom severity, and DD cases were subdivided by presence of some ASD symptoms (indicated on an autism screener). Odds ratios, adjusted for maternal-child sociodemographic factors, (aORs) and 95% confidence intervals were derived from logistic regression models. Among term births, ASD was associated with both IPI <18 months (aOR 1.5 [1.1-2.2]) and ≥60 months (1.5 [0.99-2.4]). Both short and long IPI associations were stronger among ASD cases with high severity scores (aORs 2.0 [1.3-3.3] and 1.8 [0.99-3.2], respectively). Associations were unchanged after adding several factors potentially related to the causal pathway to regression models. DD was not associated with either short or long IPI-overall, among term births, or in any subgroup examined. These findings extend those from previous studies and further inform recommendations on optimal pregnancy spacing. Autism Res 2018, 11: 81-94. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We investigated whether the amount of time between pregnancies was associated autism spectrum disorder (ASD) or other developmental disabilities (DD) in children. ASD was increased in second and later-born children who were conceived less than 18 months or 60 or more months after the mother's previous birth. Other DDs were not associated with birth spacing.
Authors: Schieve LA; Tian LH; Drews-Botsch C; Windham GC; Newschaffer C; Daniels JL; Lee LC; Croen LA; Danielle Fallin M
Autism Res. 2018 01;11(1):81-94. Epub 2017-11-22.
Neurocognitive and physical functioning in the Seveso Women’s Health Study.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is neurotoxic in animals but few studies have investigated its effects on the human brain. Related dioxin-like compounds have been linked to poorer cognitive and motor function in older adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in one of the highest known residential exposures to TCDD. In 1996, we initiated the Seveso Women’s Health Study, a retrospective cohort study of the health of the women who were newborn to 40 years old in 1976. Here, we investigate whether TCDD exposure is associated with physical functioning and working memory more than 20 years later. Individual TCDD concentration (ppt) was measured in archived serum collected soon after the explosion. In 1996 and 2008, we measured physical functioning (n=154) and working memory (n=459), respectively. We examined associations between serum TCDD and motor and cognitive outcomes with multivariate linear regression and semi-parametric estimators. A 10-fold increase in serum TCDD was not associated with walking speed (adjusted β=0.0006ft/s, 95% Confidence Interval (CI): -0.13, 0.13), upper body mobility (adjusted β=-0.06, 95% CI: -0.36, 0.23), or manual dexterity (adjusted β=0.34, 95% CI: -0.65, 1.33). We observed an inverted U-shaped association in grip strength, with poorer strength in the lowest and highest TCDD exposure levels. There was no association between TCDD and the Wechsler digit and spatial span tests. Neither menopause status at assessment nor developmental timing of exposure modified associations between TCDD and working memory. Our findings, in one of the only studies of TCDD’s effects on neuropsychological and physical functioning in women, do not indicate an adverse effect on these domains, with the exception of a U-shaped relationship with grip strength. Given the limited assessment and relative youth of the women at this follow-up, future work examining additional neuropsychological outcomes is warranted.
Authors: Ames, Jennifer J; Warner, Marcella M; Brambilla, Paolo P; Mocarelli, Paolo P; Satariano, William A WA; Eskenazi, Brenda B
Environmental research. 2018 Apr 01;162(Pt 1):55-62. Epub 2017-12-26.
Exposure to Magnetic Field Non-Ionizing Radiation and the Risk of Miscarriage: A Prospective Cohort Study
Magnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42-5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants’ pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.
Authors: Li DK; Chen H; Ferber JR; Odouli R; Quesenberry C
Sci Rep. 2017 12 13;7(1):17541. Epub 2017-12-13.
Autism risk classification using placental chorionic surface vascular network features
Autism Spectrum Disorder (ASD) is one of the fastest-growing developmental disorders in the United States. It was hypothesized that variations in the placental chorionic surface vascular network (PCSVN) structure may reflect both the overall effects of genetic and environmentally regulated variations in branching morphogenesis within the conceptus and the fetus’ vital organs. This paper provides sound evidences to support the study of ASD risks with PCSVN through a combination of feature-selection and classification algorithms. Twenty eight arterial and 8 shape-based PCSVN attributes from a high-risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas were examined for ranked relevance using a modified version of the random forest algorithm, called the Boruta method. Principal component analysis (PCA) was applied to isolate principal effects of arterial growth on the fetal surface of the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation was performed to establish error statistics. The Boruta method selected 15 arterial attributes as relevant, implying the difference in high and low ASD risk can be explained by the arterial features alone. The five principal features obtained through PCA, which accounted for about 88% of the data variability, indicated that PCSVNs associated with placentas of high-risk ASD pregnancies generally had fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, and smaller branch angles than their population-based counterparts. We developed a set of methods to explain major PCSVN differences between placentas associated with high risk ASD pregnancies and those selected from the general population. The research paradigm presented can be generalized to study connections between PCSVN features and other maternal and fetal outcomes such as gestational diabetes and hypertension.
Authors: Chang JM; Croen L; et al.
BMC Med Inform Decis Mak. 2017 Dec 06;17(1):162. Epub 2017-12-06.
Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder
Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.
Authors: Andrews SV; Ellis SE; Bakulski KM; Sheppard B; Croen LA; Hertz-Picciotto I; Newschaffer CJ; Feinberg AP; Arking DE; Ladd-Acosta C; Fallin MD
Nat Commun. 2017 10 24;8(1):1011. Epub 2017-10-24.
Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium
Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.
Authors: Sharp GC; Falahi F; Relton CL; et al.
Hum Mol Genet. 2017 10 15;26(20):4067-4085.
Scaling of the surface vasculature on the human placenta
The networks of veins and arteries on the chorionic plate of the human placenta are analyzed in terms of Voronoi cells derived from these networks. Two groups of placentas from the United States are studied: a population cohort with no prescreening, and a cohort from newborns with an elevated risk of developing autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the two cohorts collapse onto a single distribution, indicating common mechanisms for the formation of the complete vasculatures, but which have different levels of activity in the two cohorts.
Authors: Leonard AS; Lee J; Schubert D; Croen LA; Fallin MD; Newschaffer CJ; Walker CK; Salafia CM; Morgan SP; Vvedensky DD
Phys Rev E. 2017 Oct;96(4-1):040401. Epub 2017-10-02.
Offspring risk of obesity in childhood, adolescence and adulthood in relation to gestational diabetes mellitus: a sex-specific association
Animal data suggest sexually dimorphic programming of obesity in response to altered intrauterine environment, but the longitudinal impact of gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in humans is unclear. We conducted a prospective analysis of 15 009 US individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were followed from 1996 (ages 9-14 years) through 2010. Height and weight from validated questionnaires were used to derive body mass index (BMI) at different ages. Obesity during childhood (< 18 years) and adulthood (≥ 18 years) were defined using the International Obesity Task Force and the World Health Organization criteria. GDM exposure was identified through self-reported questionnaires from mothers. Relative risks were estimated using multivariable log-binomial regression models with generalized estimating equations accounting for clustering within the same family. Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and had increased risk of obesity; the adjusted relative risk [RR, 95% confidence interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early adulthood. No significant association between obesity and maternal GDM was observed among female participants (RR = 0.97, 95% CI: 0.71-1.33). The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring.
Authors: Li S; Zhu Y; Yeung E; Chavarro JE; Yuan C; Field AE; Missmer SA; Mills JL; Hu FB; Zhang C
Int J Epidemiol. 2017 10 01;46(5):1533-1541.
Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes
To assess recent trends of administering adjuvant gemcitabine-docetaxel (GD) chemotherapy for Stage I uterine leiomyosarcoma, and to compare disease-free and overall survival between women who received and did not receive adjuvant GD chemotherapy. All patients diagnosed with Stage I uterine leiomyosarcoma in a California-Colorado population-based health plan inclusive of 2006-2013 were included in a retrospective cohort. Adjuvant GD chemotherapy rates, clinico-pathologic characteristics and survival estimates were assessed. Of 111 women with Stage I uterine leiomyosarcoma, 33 received adjuvant GD (median 4cycles), 77 received no chemotherapy, and 1 patient excluded for non-GD chemotherapy. GD-chemotherapy and no-chemotherapy groups were similar with respect to age, stage (IA/IB), uterine weight, mitotic index, body mass index, and Charlson comorbidity score. Non-Hispanic white women were twice as likely to receive adjuvant chemotherapy as non-white or Hispanic women (37.7 vs. 17.1%, P=0.02). The proportion of women receiving adjuvant GD chemotherapy increased from 6.5% in 2006-2008 to 46.9% in 2009-2013 (P<0.001). There was no significance difference in unadjusted Kaplan-Meyer estimated disease-free (P=0.95) or overall survival (P=0.43) between GD-chemotherapy and no-chemotherapy cohorts. Corresponding adjusted Cox proportional hazard ratios for adjuvant GD chemotherapy compared to no chemotherapy were 1.01 (95% confidence interval [CI] 0.57-1.80, P=0.97) for recurrence and 1.28 (95% CI 0.69-2.36, P-0.48) for mortality. Use of adjuvant GD chemotherapy for Stage I uterine leiomyosarcoma has increased significantly in the last decade, despite unclear benefit. Compared to no chemotherapy, 4-6cycles of adjuvant GD chemotherapy does not appear to alter survival outcomes.
Authors: Littell RD; Tucker LY; Raine-Bennett T; Palen TE; Zaritsky E; Neugebauer R; Embry-Schubert J; Lentz SE
Gynecol Oncol. 2017 10;147(1):11-17. Epub 2017-07-24.
Urine leakage during sexual activity among ethnically diverse, community-dwelling middle-aged and older women
Urinary incontinence is associated with decreased female sexual function, but little is known about the prevalence, predictors, and impact of urine leakage during sexual activity among women in the community. The purpose of this study was to evaluate the prevalence and impact of urine leakage during sex in ethnically diverse, community-dwelling midlife and older women. Urinary incontinence and sexual function were assessed by structured questionnaire in a multiethnic, community-based cohort of women enrolled in Kaiser Permanente Northern California, an integrated healthcare delivery system in California. All women were aged 40-80 years and sampled from 1 of 4 racial/ethnic groups (20% black, 20% Latina, 20% Asian, and 40% non-Latina white). Differences in frequency, bother, and fear of urine leakage during sexual activity were examined among women with monthly, weekly, and daily urinary incontinence and across different types of urinary incontinence (stress, urgency, mixed, and other type urinary incontinence), with the use of chi-square tests. Independent risk factors for urine leakage during sexual activity were identified through multivariable logistic regression. Of the 509 women who reported being sexually active and having at least monthly urinary incontinence, 127 of them (25%) reported experiencing any urine leakage during sex during the past 3 months. Nineteen percent of the women reported being subjectively bothered by leakage during sex, and 16% of them reported restricting sexual activity because of fear of leakage. Women with more frequent underlying urinary incontinence were more likely to report experiencing or being bothered by leakage during sex and restricting sexual activity because of fear of leakage (P<.001 for all). Participants with predominantly stress or mixed type urinary incontinence were more likely to report experiencing leakage during sex and being subjectively bothered by this leakage (P<.002 for all). Factors independently associated with leakage during sex were depression (odds ratio,1.96; 95% confidence interval, 1.20-3.20), symptomatic pelvic organ prolapse (odds ratio, 2.10; 95% confidence interval, 1.11-3.98), mixed vs urgency type urinary incontinence (odds ratio, 3.16; 95% confidence interval, 1.70-5.88), stress vs urgency type urinary incontinence (odds ratio, 1.94; 95% confidence interval, 1.01-3.70), and frequency of sexual activity (odds ratio, 1.6395% confidence interval, 1.05-2.55), but not age or race/ethnicity. Up to a quarter of women with at least monthly urinary incontinence in the community may experience urine leakage during sexual activity. Many incontinent women who leak urine during sex remain sexually active, which indicates that the preservation of sexual function should still be a priority in this population. Among incontinent women, depression, pelvic organ prolapse, and stress mixed-type urinary incontinence may be associated with urine leakage during sexual activity.
Authors: Munaganuru N; Van Den Eeden SK; Creasman J; Subak LL; Strano-Paul L; Huang AJ
Am J Obstet Gynecol. 2017 10;217(4):439.e1-439.e8. Epub 2017-06-08.
Spontaneous and indicated preterm delivery risk is increased among overweight and obese women without prepregnancy chronic disease
To investigate the independent impact of prepregnancy obesity on preterm delivery among women without chronic diseases by gestational age, preterm category and parity. A retrospective cohort study. Data from the Consortium on Safe Labor (CSL) in the USA (2002-08). Singleton deliveries at ≥23 weeks of gestation in the CSL (43 200 nulliparas and 63 129 multiparas) with a prepregnancy body mass index (BMI) ≥18.5 kg/m2 and without chronic diseases. Association of prepregnancy BMI and the risk of preterm delivery was examined using Poisson regression with normal weight as reference. Preterm deliveries were categorised by gestational age (extremely, very, moderate to late) and category (spontaneous, indicated, no recorded indication). Relative risk of spontaneous preterm delivery was increased for extremely preterm among obese nulliparas (1.26, 95% CI: 0.94-1.70 for overweight; 1.88, 95% CI: 1.30-2.71 for obese class I; 1.99, 95% CI: 1.32-3.01 for obese class II/III) and decreased for moderate to late preterm delivery among overweight and obese multiparas (0.90, 95% CI: 0.83-0.97 for overweight; 0.87, 95% CI: 0.78-0.97 for obese class I; 0.79, 95% CI: 0.69-0.90 for obese class II/III). Indicated preterm delivery risk was increased with prepregnancy BMI in a dose-response manner for extremely preterm and moderate to late preterm among nulliparas, as it was for moderate to late preterm delivery among multiparas. Prepregnancy BMI was associated with increased risk of preterm delivery even in the absence of chronic diseases, but the association was heterogeneous by preterm categories, gestational age and parity. Obese nulliparas without chronic disease had higher risk for spontaneous delivery <28 weeks of gestation.
Authors: Kim SS; Mendola P; Zhu Y; Hwang BS; Grantz KL
BJOG. 2017 Oct;124(11):1708-1716. Epub 2017-04-01.
Intimate Partner Violence, Smoking, and Pregnancy: What Can We Do to Help?
Authors: Young-Wolff KC; McCaw B; Avalos LA
J Womens Health (Larchmt). 2017 Sep 22.
Maternal and Paternal Infertility Disorders and Treatments and Autism Spectrum Disorder: Findings from the Study to Explore Early Development
Previous studies of associations between ASD and conception using assisted reproductive technology (ART) are inconsistent and few studies have examined associations with other infertility treatments or infertility disorders. We examined associations between ASD and maternal/paternal infertility disorders and numerous maternal treatments among 1538 mother-child pairs in the Study to Explore Early Development, a population-based case-control study. ASD was associated with any female infertility diagnosis and several specific diagnoses: blocked tubes, endometriosis, uterine-factor infertility, and polycystic ovarian syndrome. Stratified analyses suggested associations were limited to/much stronger among second or later births. The findings were not explained by sociodemographic factors such as maternal age or education or multiple or preterm birth. ASD was not associated with ART or non-ART infertility treatments.
Authors: Schieve LA; Drews-Botsch C; Harris S; Newschaffer C; Daniels J; DiGuiseppi C; Croen LA; Windham GC
J Autism Dev Disord. 2017 Sep 12.
Prenatal Alcohol Exposure in Relation to Autism Spectrum Disorder: Findings from the Study to Explore Early Development (SEED)
Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report. Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk. These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.
Authors: Singer AB; DiGuiseppi C; Daniels JL; et al.
Paediatr Perinat Epidemiol. 2017 Sep 07.
HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis
Although most cervical human papillomavirus type�16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected�case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.
Authors: Mirabello L; Yeager M; Yu K; Clifford GM; Xiao Y; Zhu B; Cullen M; Boland JF; Wentzensen N; Nelson CW; Raine-Bennett T; Chen Z; Bass S; Song L; Yang Q; Steinberg M; Burdett L; Dean M; Roberson D; Mitchell J; Lorey T; Franceschi S; Castle PE; Walker J; Zuna R; Kreimer AR; Beachler DC; Hildesheim A; Gonzalez P; Porras C; Burk RD; Schiffman M
Cell. 2017 Sep 07;170(6):1164-1174.e6.
Validation of Self-Reported Diagnosis of Gestational Diabetes at Six Weeks Postpartum
Self-report is often used in identifying gestational diabetes events in epidemiologic studies; however, validity data are limited, with little to no data on self-reported severity or treatment. We aimed to assess the validity of self-reported gestational diabetes diagnosis and evaluate the accuracy of glucose diagnosis results and gestational diabetes treatment self-reported at 6-week postpartum. Data were from 82 and 83 women with and without gestational diabetes, respectively, within the prospective National Institute Child Health and Human Development Fetal Growth Studies-Singletons (2009-2013). Medical record data were considered the gold standard. Sensitivity was 95% (95% confidence interval [CI] = 88, 98), and specificity was 100% (95% CI = 96, 100); four women with gestational diabetes incorrectly reported not having the disease, and none of the women without gestational diabetes reported having gestational diabetes. Sensitivity did not vary substantially across maternal characteristics including race/ethnicity. For women who attempted to recall their values (84/159 women), self-reported glucose challenge test results did not differ from the medical records (median difference: 0; interquartile range: 0-0 mg/dl). Medical records indicated that 42 (54%) of 78 women with confirmed gestational diabetes were treated by diet only and 33 (42%) were treated by medication. All 42 women with diet-treated gestational diabetes correctly reported having had diet and lifestyle modification, and 28 (85%) of 33 women with medication-treated gestational diabetes indicated postpartum that they had medication treatment. At 6-week postpartum, regardless of race/ethnicity or socioeconomic status, women accurately recalled whether they had gestational diabetes and, as applicable, their treatment method.
Authors: Hinkle SN; Rawal S; Zhu Y; Grewal J; Albert PS; Zhang C
Epidemiology. 2017 Sep;28(5):747-752.
Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case-Control Study in California
Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders. Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID). We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses. Geometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0.56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2.58, 95% CI: 0.86, 7.79 and AOR=2.64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID. Contrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. https://doi.org/10.1289/EHP1079.
Authors: Lyall K; Croen LA; Weiss LA; Kharrazi M; Traglia M; Delorenze GN; Windham GC
Environ Health Perspect. 2017 Aug 30;125(8):087023. Epub 2017-08-30.
Rates and Predictors of Vaccinations Among Inflammatory Bowel Disease Patients Receiving Anti-Tumor Necrosis Factor Agents
As an important quality measure, the rates of recommended immunizations among immunocompromised inflammatory bowel disease (IBD) patients in community practice have not been well studied. This study sought to investigate the rates and predictors of recommended immunizations and screening tests among IBD patients receiving anti-tumor necrosis factor (TNF) therapy in a large integrated healthcare organization. We conducted a retrospective cohort study of 1401 IBD patients on anti-TNF therapy between 2010 and 2013 within the Kaiser Permanente Northern California healthcare system. The rates of vaccinations and screening tests were quantified, and the associated predictors were investigated. Vaccination rates for influenza and pneumococcus were 43.5 and 24.1%, respectively. The majority of patients (73.7%) received hepatitis B screening and/or vaccine. Patients receiving infliximab had higher rates of pneumococcal vaccine (P = 0.002), hepatitis B screening (P < 0.001), and tuberculin skin test (P < 0.001) compared with patients receiving adalimumab. Older patient age (≥50 years) was associated with higher likelihood of having HBsAg test (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0, P = 0.002), influenza vaccine (OR 2.6 [2.1-3.4], P < 0.001), and pneumococcal vaccine (OR 4.0 [3.0-5.3], P < 0.001). In contrast, older providers (≥50 years) were associated with significantly lower likelihood of their patients' having hepatitis A and B screening tests, and pneumococcal vaccination. The rates of immunizations for IBD patients receiving anti-TNF treatment were lower than recommended. Structured reminders for vaccinations and education for both patients and providers (older physicians in particular) may prove beneficial in improving immunization rates among immunocompromised IBD patients.
Authors: Pham HV; Hasan I; Udaltsova N; Pham K; Abramson O; Armstrong MA; Postlethwaite D; Li D
Dig Dis Sci. 2017 Aug 23.
Healthy Lifestyle During Early Pregnancy and Risk of Gestational Diabetes Mellitus
Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4). Regression models were used to determine relative risk of GDM (n = 140 cases) in relation to healthy lifestyle. Twenty percent of participants had a healthy diet, 66% were physically active, 95% were nonsmokers, and 55% had low stress. Each 1-point increase in lifestyle score was associated with a 21% lower risk of GDM (95% confidence interval: 0.65, 0.96) after adjustment for age, race, and nulliparity. Adjustment for prepregnancy body mass index, prepregnancy physical activity, and prepregnancy smoking attenuated the associations slightly. Associations were similar in normal-weight and overweight/obese women. In this study, a composite measure of healthy lifestyle during early pregnancy was associated with substantially lower GDM risk. Public health messaging and interventions promoting multiple aspects of a healthy lifestyle during early pregnancy should be considered for GDM prevention.
Authors: Badon SE; Enquobahrie DA; Wartko PD; Miller RS; Qiu C; Gelaye B; Sorensen TK; Williams MA
Am J Epidemiol. 2017 Aug 1;186(3):326-333. doi: 10.1093/aje/kwx095.
Scientific abstracts featured research at the 2017 North American Forum on Family Planning
Authors: Espey E; Teal S; Borrero S; Raine-Bennett T; Finer L
Contraception. 2017 Aug 01.
Peripubertal dietary flavonol and lignan intake and age at menarche in a longitudinal cohort of girls
BackgroundDietary phytoestrogens may alter hormonal activity in childhood. Flavonols and lignans are the most prevalent phytoestrogens in the Western diet. We examined whether higher intake of flavonols and lignans was associated with later age at menarche in a prospective study of young girls.MethodsIn all, 1,044 girls aged 6-8 years (mean 7.3 years) with two to four 24-h dietary recalls during their baseline year were followed up for 11 years until the attainment of menarche in the Breast Cancer and Environment Research Project (BCERP). Associations of age at menarche with quintiles of phytoestrogens were assessed using hazard ratios (HR) and 95% confidence intervals (CIs) from Cox proportional hazards models, controlling for body mass index and other covariates.ResultsThe highest quintile of flavonol intake was associated with a later age at menarche, compared with the lowest quintile (adjusted HR: 0.80, 95% CI: (0.66-1.00). For lignans, there was a later age in overweight girls (HR: 0.56, 95% CI=0.40-0.80).ConclusionThese dietary bioactives may reflect a healthy diet, and foods high in phytoestrogens may influence the timing of menarche.
Authors: Mervish NA; Teitelbaum SL; Pajak A; Windham GC; Pinney SM; Kushi LH; Biro FM; Wolff MS
Pediatr Res. 2017 Aug;82(2):201-208. Epub 2017-06-14.
Urinary bisphenol A and pubertal development in Chinese school-aged girls: a cross-sectional study
Animal studies suggest that bisphenol A (BPA) may perturb pubertal development in females. However, evidence from human studies is limited. This was a cross-sectional study to investigate the association between BPA exposure and pubertal development in school-aged girls. A total of 655 girls aged 9-18 years were selected from three schools in Shanghai, from May to June 2011. We collected one single spot urine sample from each girl. Urine BPA concentrations were measured by modified high-performance liquid chromatography and categorized according to LOD and the median of those above LOD. Pubertal development status was assessed by using Tanner staging, and age at menarche was collected as a milestone for mid-puberty. Modified Poisson regression was used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs). After adjustment for potential confounders, girls with detected BPA were more likely to have delayed menarche, a mid-puberty event, compared with girls with undetectable BPA; the prevalence ratios (PR) were 0.73 (0.56, 0.95) for those with moderate BPA(LOD-median) and 0.72 (0.52, 0.99) for those with high BPA(>median), respectively. Girls aged 9-12 years with detected BPA were more likely to have reached pubic hair stage 2, the indicator of pubarche; while among girls aged >15 years, those with detected BPA were less likely to have reached pubic hair stage 5, the late stage of pubic hair development. BPA exposure was associated with alterations in the timing of pubertal development. Results in the present study should be interpreted with caution because of its cross-sectional nature and the limited sample size in each age group.
Authors: Miao M; Wang Z; Liu X; Liang H; Zhou Z; Tan H; Yuan W; Li DK
Environ Health. 2017 07 27;16(1):80. Epub 2017-07-27.
Demographic and Clinical Characteristics Associated with Engagement in Behavioral Health Treatment Among Children with Autism Spectrum Disorders
This study investigates demographic and clinical factors associated with initiation, continuation, and adherence to behavioral health treatment (BHT) among children with autism spectrum disorder. Among 293 insured children referred for applied behavior analysis (ABA) based BHT, 23% never initiated treatment. Among those initiating treatment, 31% discontinued treatment within 1 year of treatment initiation, and only 15% received 80% or more of recommended treatment hours. Younger age at referral to treatment, private health insurance, and receiving more than 10 h/week of BHT were associated with treatment engagement. Co-occurring psychiatric and medical conditions were related to treatment discontinuation among children 5 years or older. These findings suggest specific subgroups that may benefit from additional support with engaging in recommended behavioral health treatment.
Authors: Croen LA; Shankute N; Davignon M; Massolo ML; Yoshida C
J Autism Dev Disord. 2017 Jul 26.
Chronic and Acute Ozone Exposure in the Week Prior to Delivery Is Associated with the Risk of Stillbirth
Chronic and acute air pollution has been studied in relation to stillbirth with inconsistent findings. We examined stillbirth risk in a retrospective cohort of 223,375 singleton deliveries from 12 clinical sites across the United States. Average criteria air pollutant exposure was calculated using modified Community Multiscale Air Quality models for the day of delivery and each of the seven days prior, whole pregnancy, and first trimester. Poisson regression models using generalized estimating equations estimated the relative risk (RR) of stillbirth and 95% confidence intervals (CI) in relation to an interquartile range increase in pollutant with adjustment for temperature, clinical, and demographic factors. Ozone (O₃) was associated with a 13-22% increased risk of stillbirth on days 2, 3, and 5-7 prior to delivery in single pollutant models, and these findings persisted in multi-pollutant models for days 5 (RR = 1.22, CI = 1.07-1.38) and 6 (RR = 1.18, CI = 1.04-1.33). Whole pregnancy and first trimester O₃ increased risk 18-39% in single pollutant models. Maternal asthma increased stillbirth risk associated with chronic PM2.5 and carbon monoxide exposures. Both chronic and acute O₃ exposure consistently increased stillbirth risk, while the role of other pollutants varied. Approximately 8000 stillbirths per year in the US may be attributable to O₃ exposure.
Authors: Mendola P; Ha S; Pollack AZ; Zhu Y; Seeni I; Kim SS; Sherman S; Liu D
Int J Environ Res Public Health. 2017 07 06;14(7). Epub 2017-07-06.
Leveraging EHRs for patient engagement: perspectives on tailored program outreach
Electronic health records (EHRs) present healthcare delivery systems with scalable, cost-effective opportunities to promote lifestyle programs among patients at high risk for type 2 diabetes, yet little consensus exists on strategies to enhance patient engagement. We explored patient perspectives on program outreach messages containing content tailored to EHR-derived diabetes risk factors-a theory-driven strategy to increase the persuasiveness of health communications. Convergent mixed methods. Within an integrated healthcare delivery system, women with a history of gestational diabetes participated in 1 of 6 ethnic-specific focus groups to elicit diverse perspectives and a survey yielding quantitative data to contextualize qualitative responses. The sample included 35 participants (80% racial/ethnic minorities; mean age = 36 years). Themes regarding tailored messages centered on diabetes risk communication (opposing attitudes about whether to feature diabetes risk factors), privacy (how and whether patient data should be accessed), authenticity (perceiving messages as personalized vs generically computer generated), and preferences for messages sent by one’s personal physician. Trust in the medical profession and perceived risk for diabetes were similar to levels reported in comparable samples. Patient reactions highlight the challenges of leveraging EHRs for tailored messages. Some viewed messages as caring reminders to take preventive action and others raised concerns over intrusiveness. Optimal lifestyle program outreach to improve quality of care for women at high risk for diabetes may require communication from personal physicians, careful development to mitigate concerns over privacy and authenticity, and techniques to counteract the threatening nature of personalized risk communication.
Authors: Brown SD; Grijalva CS; Ferrara A
Am J Manag Care. 2017 Jul 01;23(7):e223-e230. Epub 2017-07-01.
Maternal dietary intakes of refined grains during pregnancy and growth through the first 7 y of life among children born to women with gestational diabetes
Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking.Objective:We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM).Design:The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass indexzscores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors.Results:Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98;P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth.Conclusions:Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with offspring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted.
Authors: Zhu Y; Zhang C; et al.
Am J Clin Nutr. 2017 Jul;106(1):96-104. Epub 2017-06-07.
Medical Conditions in the First Years of Life Associated with Future Diagnosis of ASD in Children
This study examines medical conditions diagnosed prior to the diagnosis of autism spectrum disorder (ASD). Using a matched case control design with 3911 ASD cases and 38,609 controls, we found that 38 out of 79 medical conditions were associated with increased ASD risk. Developmental delay, mental health, and neurology conditions had the strongest associations (ORs 2.0-23.3). Moderately strong associations were observed for nutrition, genetic, ear nose and throat, and sleep conditions (ORs 2.1-3.2). Using machine learning methods, we clustered children based on their medical conditions prior to ASD diagnosis and demonstrated ASD risk stratification. Our findings provide new evidence indicating that children with ASD have a disproportionate burden of certain medical conditions preceding ASD diagnosis.
Authors: Alexeeff SE; Yau V; Qian Y; Davignon M; Lynch F; Crawford P; Davis R; Croen LA
J Autism Dev Disord. 2017 Jul;47(7):2067-2079.
Maternal consumption of artificially sweetened beverages during pregnancy, and offspring growth through 7 years of age: a prospective cohort study
Artificial sweeteners are widely replacing caloric sweeteners. Data on long-term impact of artificially sweetened beverage (ASB) consumption during pregnancy on offspring obesity risk are lacking. We prospectively investigated intake of ASBs and sugar-sweetened beverages (SSBs) during pregnancy in relation to offspring growth through age 7 years among high-risk children born to women with gestational diabetes. In a prospective study of 918 mother-singleton child dyads from the Danish National Birth Cohort, maternal dietary intake was assessed by a food frequency questionnaire during pregnancy. Offspring body mass index z-scores (BMIZ) and overweight/obesity status were derived using weight and length/height at birth, 5 and 12 months and 7 years. Linear regression and Poisson regression with robust standard errors were used, adjusting for major risk factors. Approximately half of women reported consuming ASBs during pregnancy and 9% consumed daily. Compared to never consumption, daily ASB intake during pregnancy was positively associated with offspring large-for-gestational age [adjusted relative risk (aRR) 1.57; 95% CI: 1.05, 2.35 at birth], BMIZ (adjusted β 0.59; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years. Per-serving-per-day substitution of ASBs with water during pregnancy was related to a lower overweight/obesity risk at 7 years (aRR 0.83; 95% CI: 0.76, 0.91), whereas SSB substitution with ASBs was not related to a lower risk (aRR 1.14; 95% CI: 1.00, 1.31). Our findings illustrated positive associations between intrauterine exposure to ASBs and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted.
Authors: Zhu Y; Zhang C; et al.
Int J Epidemiol. 2017 Jun 06.
Variants in Pharmacokinetic Transporters and Glycaemic Response to Metformin: A MetGen Meta-Analysis
Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.
Authors: Dujic T; van der Heijden AA; Pearson ER; et al.
Clin Pharmacol Ther. 2017 Jun;101(6):763-772. Epub 2017-02-03.
Minimally Invasive Hysterectomy and Power Morcellation Trends in a West Coast Integrated Health System
To examine trends in minimally invasive hysterectomy and power morcellation use over time and associated clinical characteristics. We conducted a trend analysis and retrospective cohort study of all women 18 years of age and older undergoing hysterectomy for benign conditions at Kaiser Permanente Northern California collected from electronic health records. Generalized estimating equations and Cochran-Armitage testing were used to assess the primary outcomes, hysterectomy incidence, and proportion of hysterectomies by surgical route and power morcellation. Logistic regression analysis was used to assess secondary outcomes, clinical characteristics, and complications associated with surgical route. There were 31,971 hysterectomies from 2008 to 2015; the incidence decreased slightly from 2.86 (95% confidence interval [CI] 2.85-2.87) to 2.60 (95% CI 2.59-2.61) per 1,000 women (P<.001). Minimally invasive hysterectomies increased from 39.8% to 93.1%, almost replacing abdominal hysterectomies entirely (P<.001). Vaginal hysterectomies decreased slightly from 26.6% to 23.4% (P<.001). The proportion of nonrobotic laparoscopic hysterectomies with power morcellation increased steadily from 3.7% in 2008 to a peak of 11.4% in 2013 and decreased to 0.02% in 2015 (P<.001). Robot-assisted laparoscopic hysterectomies remained a small proportion of all hysterectomies comprising 7.8% of hysterectomies in 2015. Women with large uteri (greater than 1,000 g) were more likely to receive abdominal hysterectomies than minimally invasive hysterectomy (adjusted relative risk 11.62, 95% CI 9.89-13.66) and laparoscopic hysterectomy with power morcellation than without power morcellation (adjusted relative risk 5.74, 95% CI 4.12-8.00). Laparoscopic supracervical hysterectomy was strongly associated with power morcellation use (adjusted relative risk 43.89, 95% CI 37.55-51.31). A high minimally invasive hysterectomy rate is primarily associated with uterine size and can be maintained without power morcellation.
Authors: Zaritsky E; Tucker LY; Neugebauer R; Chou T; Flanagan T; Walter AJ; Raine-Bennett T
Obstet Gynecol. 2017 Jun;129(6):996-1005.
Ambient air pollution and risk of gestational hypertension
Air pollution has been linked to hypertension in the general population, but data on gestational hypertension (GH) are limited. We investigated air pollutants and toxics during preconception and early gestation in relation to GH risk in the Consortium on Safe Labor/Air Quality and Reproductive Health Study (2002-2008). Modified Community Multiscale Air Quality models estimated air pollution exposures among 6,074 singleton pregnancies with GH and 199,980 normotensives. Generalized estimating equations estimated relative risks per interquartile-range increment for pollutants and high exposure (≥75th percentile) for toxics, after adjustment for major risk factors. For an interquartile-range increment, GH risk was significantly increased by 18% for sulfur dioxide during the three months preconception; and 17% for nitrogen oxides, 10% for particulate matter <2.5 μm, 7% for particulate matter <10 μm, and 22% for sulfur dioxide during gestational weeks 1-20. High exposures to several polycyclic aromatic hydrocarbons both during preconception and the first trimester were significantly associated with 8%-20% higher GH risk. Further, preconceptional exposures to several volatile organic compounds were significantly associated with 11%-19% higher risk. Our findings suggest early exposures to criteria air pollutants, particularly from transport emissions, and high exposure to several air toxics during preconception may increase GH risk.
Authors: Zhu Y; Zhang C; Liu D; Ha S; Kim SS; Pollack A; Mendola P;
Am J Epidemiol. 2017 May 4. doi: 10.1093/aje/kwx097. [Epub ahead of print]
Are Health Plan Design and Prior Use of Long-Acting Reversible Contraception Associated with Pregnancy Intention?
In 2007, high-deductible plans were added to the primarily nondeductible Kaiser Permanente Northern California (KPNC) integrated health plan, which had covered 100% of device and procedure costs of long-acting reversible contraception (LARC) for members regardless of prescription/visit copay amount. We hypothesized that nondeductible plans and prior LARC use decreased unintended pregnancy. The purpose of this study was to determine if health plan design (nondeductible vs. deductible) and LARC use before pregnancy were associated with pregnancy intention. In this retrospective cohort study, women aged 15-44 as of the index date of June 30, 2010 were followed from January 1, 2010 to December 31, 2012 for evidence of pregnancy (n = 65,989). Health plan design, copays, contraceptive method used most recently before the pregnancy, and self-reported pregnancy intention status (intended, mistimed, unwanted) were obtained from electronic medical records. Logistic regression models were developed to determine if various health plan designs, copays, or prior LARC use were associated with pregnancy intention, controlling for potential confounders such as age, race/ethnicity, marital status, education/income, parity, and comorbidities. In all models, LARC use before pregnancy versus non-LARC use was significantly related to intended pregnancies (all models: odds ratio [OR] = 2.26, 95% confidence interval [CI] 2.06-2.48). Women with deductible plans with healthcare spending accounts (HSA) were more likely to report intended pregnancies versus women with nondeductible plans (all models: OR = 1.2, 95% CI 1.04-1.30). In stratified analyses, high income/high education was a significant predictor of intended pregnancy regardless of race/ethnicity. LARC use before pregnancy and having an HSA were associated with intended pregnancy.
Authors: Armstrong MA; Postlethwaite DA; Darbinian JA; McCoy M; Law A
J Womens Health (Larchmt). 2017 May;26(5):450-460. Epub 2016-10-18.
Predictors of Breastfeeding Initiation and Maintenance in an Integrated Healthcare Setting
The American Academy of Pediatrics recommends exclusive breastfeeding to age 6 months. Although breastfeeding rates in the United States have been increasing over time, further improvements are needed to meet Healthy People 2020 targets. Research aim: This study examined predictors of breastfeeding initiation and maintenance among a population of insured pregnant women. Participants were 1,149 pregnant women enrolled in the Pregnancy and Influenza Project in two Kaiser Permanente regions in 2010-2011. Data were collected through interviews at enrollment and 1 month and 6 months postpartum and through participants’ electronic medical records. Nearly all (99%) women reported initiating breastfeeding. Rates of exclusive breastfeeding were 70% and 54% at 1 month and 6 months, respectively; an additional 22% and 23% of women reported supplementing breastfeeding with formula. Of the women who supplemented, the mean ( SD) infant age at formula introduction was 53 (62) days. Of those who had stopped breastfeeding, the mean ( SD) infant age at cessation was 85 (59) days. Higher maternal education level, better maternal self-rated health, prenatal folic acid use, absence of chronic medical conditions, and infant full-term birth were significantly associated with breastfeeding maintenance. Although rates of breastfeeding in this population were higher than national rates, a significant number of women stopped breastfeeding or introduced formula earlier than recommended. Two to 3 months postpartum may be a critical period warranting additional encouragement or intervention by healthcare providers. Mothers’ education attainment, maternal health factors, and gestational age at delivery may predict likelihood of breastfeeding maintenance.
Authors: Henninger ML; Avalos LA; Pregnancy and Influenza Project Workgroup; et al.
J Hum Lact. 2017 May;33(2):256-266. Epub 2017-03-23.
The Pregnancy Environment and Lifestyle Study (PETALS): a population-based longitudinal multi-racial birth cohort
Increasing recognition has been received regarding the proven and suggested links between multi-level environmental exposures on a broad scale (e.g., chemical, clinical, behavioral, physical and social) and health deficits originated from the critical window of development. However, such prospective human data are limited. In 2016, the National Institutes of Health funded 35 centers comprising 84 extant cohorts for the Environmental Influences on Child Health Outcomes (ECHO) pediatric cohorts program. The Pregnancy Environment and Lifestyle Study (PETALS) is one of the cohorts at the participating centers of Kaiser Permanente Northern California (KPNC). PETALS was originally funded by the National Institute of Environmental Health Sciences to establish a longitudinal birth cohort of 3,350 mother-infant pairs and conduct a nested case-control study of 300 women with gestational diabetes (GDM) and 600 matched controls to investigate the associations between phenol exposures in first and second trimesters and GDM risk and the related outcome of infant macrosomia. This paper describes the prospective cohort design of PETALS, current research activities, and cohort profile of enrolled women who delivered as of February 2016. Women are enrolled from the KPNC membership. Fasting blood draw, urine collection, anthropometric measurements, and questionnaires on health history and lifestyle are completed at baseline and follow-up clinic visits with targeted windows of 10-13 and 16-19 weeks of gestation, respectively. Further, women’s clinical and health assessments before and after the index pregnancy in addition to their children’s birth outcomes and health information can be abstracted from electronic health records, allowing future follow-up. Study data could also be linked and extended to a myriad of additional observational data including environmental and area-level databases and census data. In this racially- and ethnically-diverse pregnancy cohort, the generated biospecimen and data repository will establish a comprehensive framework which may provide unique opportunities to address a multitude of research questions on the intrauterine environment and adverse pregnancy and birth outcomes in a representative multi-racial/ethnic population with generalizable findings.
Authors: Zhu Y; Hedderson MM; Feng J; Mevi AA; Ferrara A
BMC Pregnancy Childbirth. 2017 04 17;17(1):122. Epub 2017-04-17.
Maternal healthy lifestyle during early pregnancy and offspring birthweight: differences by offspring sex
PURPOSE: Individual maternal lifestyle factors during pregnancy have been associated with offspring birthweight; however, associations of combined lifestyle factors with birthweight and potential differences by offspring sex have not been examined.
MATERIALS AND METHODS: Participants (N = 2924) were identified from a pregnancy cohort in Washington state. Lifestyle factors during early pregnancy were dichotomized based on Alternate Healthy Eating Index score ≥62, leisure time physical activity (LTPA) ≥ 150 min/week, not smoking during pregnancy and Perceived Stress Scale score ≤3, then combined into a lifestyle score (0-4). Regression models were run overall and stratified by offspring sex, prepregnancy overweight/obese (BMI ≥25 kg/m2) and prepregnancy LTPA.
RESULTS: Overall, 20% of participants had healthy diet, 95% were nonsmokers, 55% had low stress levels, and 66% were physically active. Lifestyle score was not associated with birthweight (β = 3.3 g; 95% CI: -14.5, 21.0); however, associations differed by offspring sex (p = .009). For each unit increase in lifestyle score, there was a suggested 22.4 g higher birthweight (95% CI: -2.7, 47.6) among males and 14.6 g lower birthweight (95% CI: -39.9, 10.7) among females. Prepregnancy BMI and LTPA did not modify associations.
CONCLUSIONS: Healthy lifestyle score in early pregnancy may be associated with greater birthweight among male offspring, but lower birthweight among female offspring.
Authors: Badon SE; Miller RS; Qiu C; Sorensen TK; Williams MA; Enquobahrie DA
J Matern Fetal Neonatal Med. 2017 Apr 3:1-7. doi: 10.1080/14767058.2017.1309383.
Outcomes of Admissions for Preterm Labor
Objective This study aims to quantitate the incidence of preterm labor (PTL) admissions and determine the frequency and predictors of preterm delivery (PTD) during these admissions. Study Design Retrospective cohort of singleton pregnancies within Kaiser Permanente Northern California, 2001 to 2011. PTL admissions were defined as inpatient encounters > 24 hours with an International Classification of Diseases, 9th Revision code for PTL. Results Total study population was 365,897 with PTL admission rate 11%. PTD occurred in 85% of pregnancies with PTL admission. Delivery occurred within 48 hours of admission in 96% ≥34 weeks, 67% 31 to 33 weeks, and 51.9% <31 weeks. Predictors of delivery during PTL admission included gestational age 34 to 36 weeks (adjusted odds ratio [aOR], 6.90), chorioamnionitis (aOR, 105.58), and preterm rupture of membranes (aOR 19.29). Conclusion We demonstrate a high rate of PTD per PTL admission in a highly integrated health care system. More work is needed to determine optimal practices for hospitalization and treatment of women diagnosed with PTL.
Authors: Kuzniewicz MW; Black L; Walsh EM; Li SX; Greenberg M
AJP Rep. 2017 Apr;7(2):e106-e113. Epub 2017-06-22.
A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis
Current algorithms for management of neonatal early-onset sepsis (EOS) result in medical intervention for large numbers of uninfected infants. We developed multivariable prediction models for estimating the risk of EOS among late preterm and term infants based on objective data available at birth and the newborn’s clinical status. To examine the effect of neonatal EOS risk prediction models on sepsis evaluations and antibiotic use and assess their safety in a large integrated health care system. The study cohort includes 204 485 infants born at 35 weeks’ gestation or later at a Kaiser Permanente Northern California hospital from January 1, 2010, through December 31, 2015. The study compared 3 periods when EOS management was based on (1) national recommended guidelines (baseline period [January 1, 2010, through November 31, 2012]), (2) multivariable estimates of sepsis risk at birth (learning period [December 1, 2012, through June 30, 2014]), and (3) the multivariable risk estimate combined with the infant’s clinical condition in the first 24 hours after birth (EOS calculator period [July 1, 2014, through December 31, 2015]). The primary outcome was antibiotic administration in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS. The study cohort included 204 485 infants born at 35 weeks’ gestation or later: 95 343 in the baseline period (mean [SD] age, 39.4 [1.3] weeks; 46 651 male [51.0%]; 37 007 white, non-Hispanic [38.8%]), 52 881 in the learning period (mean [SD] age, 39.3 [1.3] weeks; 27 067 male [51.2%]; 20 175 white, non-Hispanic [38.2%]), and 56 261 in the EOS calculator period (mean [SD] age, 39.4 [1.3] weeks; 28 575 male [50.8%]; 20 484 white, non-Hispanic [36.4%]). In a comparison of the baseline period with the EOS calculator period, blood culture use decreased from 14.5% to 4.9% (adjusted difference, -7.7%; 95% CI, -13.1% to -2.4%). Empirical antibiotic administration in the first 24 hours decreased from 5.0% to 2.6% (adjusted difference, -1.8; 95% CI, -2.4% to -1.3%). No increase in antibiotic use occurred between 24 and 72 hours after birth; use decreased from 0.5% to 0.4% (adjusted difference, 0.0%; 95% CI, -0.1% to 0.2%). The incidence of culture-confirmed EOS was similar during the 3 periods (0.03% in the baseline period, 0.03% in the learning period, and 0.02% in the EOS calculator period). Readmissions for EOS (within 7 days of birth) were rare in all periods (5.2 per 100 000 births in the baseline period, 1.9 per 100 000 births in the learning period, and 5.3 per 100 000 births in the EOS calculator period) and did not differ statistically (P = .70). Incidence of adverse clinical outcomes, including need for inotropes, mechanical ventilation, meningitis, and death, was unchanged after introduction of the EOS calculator. Clinical care algorithms based on individual infant estimates of EOS risk derived from a multivariable risk prediction model reduced the proportion of newborns undergoing laboratory testing and receiving empirical antibiotic treatment without apparent adverse effects.
Authors: Kuzniewicz MW; Puopolo KM; Fischer A; Walsh EM; Li S; Newman TB; Kipnis P; Escobar GJ
JAMA Pediatr. 2017 Apr 01;171(4):365-371.
Cardiometabolic Risk Factors Among 1.3 Million Adults With Overweight or Obesity, but Not Diabetes, in 10 Geographically Diverse Regions of the United States, 2012-2013
Various phenotypes of overweight and obesity pose various health risks. The objective of this study was to determine the prevalence of 4 commonly measured cardiometabolic risk factors (CRFs) among adults with overweight or obesity, but not diabetes, at the time of the study. We analyzed data for 1,294,174 adults (aged ≥20 y) who were members of one of 4 integrated health systems. Each cohort member had a body mass index in 2012 or 2013 that indicated overweight or obesity. We determined the presence of 4 CRFs within 1 year of the first BMI measurement: elevated blood pressure (systolic ≥130 mm Hg or diastolic >85 mm Hg or ICD-9-CM [International Classification of Diseases, Ninth Revision, Clinical Modification] diagnosis code 401.0-405.9); elevated triglycerides (≥150 mg/dL or ICD-9-CM 272.1); low high-density lipoprotein cholesterol (<40 mg/dL for men or <50 mg/dL for women or ICD-9-CM 272.5); and prediabetes (fasting glucose 100-125 mg/dL or HbA1c 5.7%-6.4% or ICD-9-CM 790.2x). We tested the risk of having 1 or more CRFs after adjusting for obesity class and demographic characteristics with multivariable logistic regression. Among participants with overweight (52.5% of the sample), 18.6% had none of the 4 CRFs. Among the 47.5% of participants with obesity, 9.6% had none; among participants with morbid obesity, 5.8% had none. Age was strongly associated with CRFs in multivariable analysis. Almost 10% of participants with obesity had no CRFs. Overweight or obesity increases cardiometabolic risk, but the number and type of CRFs varied substantially by age, even among participants with morbid obesity.
Authors: Nichols GA; Horberg M; Koebnick C; Young DR; Waitzfelder B; Sherwood NE; Daley MF; Ferrara A
Prev Chronic Dis. 2017 Mar 09;14:E22. Epub 2017-03-09.
Over-the-Counter Access to Oral Contraceptives for Adolescents
Oral contraceptives (OCs) are used by millions of women in the U.S. The requirement to obtain OCs by prescription from a clinician may serve as a barrier to contraceptive initiation and continuation for women, in particular adolescents. Over-the-counter (OTC) availability would reduce this barrier and could further reduce unintended pregnancy rates. This review explores the scientific issues and regulatory processes involved in switching OCs to OTC status for minor adolescents. We review: (1) the regulatory criteria for switching a drug to OTC status; (2) risk of pregnancy and safety during use of OCs including combined oral contraceptives and progestin-only pills for adolescents; (3) the ability of adolescents to use OCs consistently and correctly; (4) OTC access to OCs and potential effect on sexual risk behaviors; and (5) the potential for reduced opportunities for clinicians to counsel and provide recommended reproductive health care to adolescents. We find strong scientific rationale for including adolescents in any regulatory change to switch OCs to OTC status. OCs are safe and highly effective among adolescents; contraindications are rarer among adolescents compared to adult women. Ready access to OCs, condoms, and emergency contraception increases their use without increasing sexual risk behaviors.
Authors: Upadhya KK; Santelli JS; Raine-Bennett TR; Kottke MJ; Grossman D
J Adolesc Health. 2017 Mar 06.
A Clinical Prediction Rule for Rebound Hyperbilirubinemia Following Inpatient Phototherapy
The American Academy of Pediatrics provides little guidance on when to discontinue phototherapy in newborns treated for hyperbilirubinemia. We sought to develop a prediction rule to estimate the probability of rebound hyperbilirubinemia after inpatient phototherapy. Subjects for this retrospective cohort study were infants born in 2012 to 2014 at ≥35 weeks’ gestation at 16 Kaiser Permanente Northern California hospitals who received inpatient phototherapy before age 14 days. We defined rebound as the return of total serum bilirubin (TSB) to phototherapy threshold within 72 hours of phototherapy termination. We used stepwise logistic regression to select predictors of rebound hyperbilirubinemia and devised and validated a prediction score by using split sample validation. Of the 7048 infants treated with inpatient phototherapy, 4.6% had rebound hyperbilirubinemia. Our prediction score consisted of 3 variables: gestational age <38 weeks (adjusted odds ratio [aOR] 4.7; 95% confidence interval [CI], 3.0-7.3), younger age at phototherapy initiation (aOR 0.51 per day; 95% CI, 0.38-0.68), and TSB relative to the treatment threshold at phototherapy termination (aOR 1.5 per mg/dL; 95% CI, 1.4-1.7). The model performed well with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.86-0.91) in the derivation data set and 0.88 (95% CI, 0.86-0.90) in the validation data set. Approximately 70% of infants had scores <20, which correspond to a <4% probability of rebound hyperbilirubinemia. The risk of rebound hyperbilirubinemia can be quantified according to an infant's gestational age, age at phototherapy initiation, and TSB relative to the treatment threshold at phototherapy termination.
Authors: Chang PW; Kuzniewicz MW; McCulloch CE; Newman TB
Pediatrics. 2017 Mar;139(3). Epub 2017-02-14.
Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability
Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are neurodevelopmental toxicants, but few studies have examined associations with autism spectrum disorder (ASD). We aimed to determine whether prenatal exposure to PCBs and OCPs influences offspring risk of ASD and intellectual disability without autism (ID). We conducted a population-based case-control study among Southern California births, including children with ASD (n = 545) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR) criteria and ID (n = 181), as well as general population (GP) controls (n = 418). Concentrations of 11 PCB congeners and 2 OCPs measured in banked second-trimester serum samples were compared between the diagnostic groups. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses. Geometric mean levels of several PCB congeners were higher in the ASD group than in the ID and GP groups. ASD risk was elevated for a number of PCB congeners, particularly for the highest vs. lowest quartile of PCB138/158 (AOR = 1.79; 95% CI: 1.10, 2.71) and PCB153 (AOR = 1.82; 95% CI: 1.10, 3.02), and for highest deciles of other congeners in secondary analyses. PCB138/158 was also associated with increased ID (AOR = 2.41; 95% CI: 1.18, 4.91), though no trend was suggested. OCPs were not associated with increased risk of ASD in primary analyses, whereas nonmonotonic increases in risk of ID were found with p,p´-DDE. Our results suggest higher levels of some organochlorine compounds during pregnancy are associated with ASD and ID. Citation: Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, Windham GC. 2017. Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect 125:474-480; https://dx.doi.org/10.1289/EHP277.
Authors: Lyall K; Croen LA; Sjödin A; Yoshida CK; Zerbo O; Kharrazi M; Windham GC
Environ Health Perspect. 2017 Mar;125(3):474-480. Epub 2016-08-23.
Parents’ Perspectives on How to Improve the Childhood Vaccination Process
Few national studies have asked parents how to improve the childhood vaccination process. We surveyed a nationally representative online panel of parents on how to improve this process, rationales for nonstandard approaches, and alternatives to the standard schedule. Twelve percent of the 1222 respondents reported using nonstandard approaches: 3.2% used a specific schedule, 6.0% had no specific schedule, and 2.5% declined all vaccinations. The most common rationales were that too many vaccines are given at once, and discomfort with vaccine ingredients. Regarding how to improve the process, parents using the standard schedule most often said nothing could be improved (51%), or better vaccine information (22%). Those using nonstandard approaches most often would have liked more choice (40%) or better vaccine information (26%). Parents’ experiences with the vaccination process could be improved by offering information prior to visits, giving more information about side effects, and allowing more flexibility about vaccine scheduling.
Authors: Lieu TA; Zikmund-Fisher BJ; Chou C; Ray GT; Wittenberg E
Clin Pediatr (Phila). 2017 Mar;56(3):238-246. Epub 2016-07-20.
Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants
Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal midpregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large-scale maternal and fetal genetic study of the midpregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project. Levels of PCB (polychlorinated biphenyl) and PBDE (polybrominated diphenyl ether) congeners showed high maternal and fetal estimated SNP-based heritability (h2g) accounting for 39-99% of the total variance. Genome-wide association analyses identified significant maternal loci for p,p’-DDE (P = 7.8 × 10-11) in the CYP2B6 gene and for BDE-28 (P = 3.2 × 10-8) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P = 4.6 × 10-8) and PCB187 (P = 2.8 × 10-8), near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment. Negative associations were observed for BDE-100, BDE153, and the sum of PBDEs with ASD, partly explained by genome-wide additive genetic effects that predicted PBDE levels. Our results support genetic control of midgestational biomarkers for environmental exposures by nonoverlapping maternal and fetal genetic determinants, suggesting that future studies of environmental risk factors should take genetic variation into consideration. The independent influence of fetal genetics supports previous hypotheses that fetal genotypes expressed in placenta can influence maternal physiology and the transplacental transfer of organohalogens.
Authors: Traglia M; Croen LA; Lyall K; Windham GC; Kharrazi M; DeLorenze GN; Torres AR; Weiss LA
G3 (Bethesda). 2017 Feb 24.
Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes
To assess the association of regular, unsupervised sports and exercise during pregnancy, by intensity level, with glycaemic control in women with gestational diabetes (GDM). Prospective cohort study of 971 women who, shortly after being diagnosed with GDM, completed a Pregnancy Physical Activity Questionnaire assessing moderate and vigorous intensity sports and exercise in the past 3 months. Self-monitored capillary glucose values were obtained for the 6-week period following the questionnaire, with optimal glycaemic control defined≥80% values meeting the targets<5.3mmol/L for fasting and <7.8mmol/L 1-hour after meals. Logistic regression estimated the odds of achieving optimal control; linear regression estimated activity level-specific least square mean glucose, as well as between-level mean glucose differences. For volume of moderate intensity sports and exercise ([MET×hours]/week), the highest quartile, compared to the lowest, had significantly increased odds of optimal control (OR=1.82 [95% CI: 1.06-3.14] P=0.03). There were significant trends for decreasing mean 1-hour post breakfast, lunch and dinner glycaemia with increasing quartile of moderate activity (all P<0.05). Any participation in vigorous intensity sports and exercise was associated with decreased mean 1-hour post breakfast and lunch glycaemia (both P<0.05). No associations were observed for fasting. Higher volumes of moderate intensity sports and exercise, reported shortly after GDM diagnosis, were significantly associated with increased odds of achieving glycaemic control. Clinicians should be aware that unsupervised moderate intensity sports and exercise performed in mid-pregnancy aids in subsequent glycaemic control among women with GDM.
Authors: Ehrlich SF; Hedderson MM; Brown SD; Sternfeld B; Chasan-Taber L; Feng J; Adams J; Ching J; Crites Y; Quesenberry CP; Ferrara A
Diabetes Metab. 2017 Feb 23.
The impact of preterm birth <37 weeks on parents and families: a cross-sectional study in the 2 years after discharge from the neonatal intensive care unit
Little is known about the quality of life of parents and families of preterm infants after discharge from the neonatal intensive care unit (NICU). Our aims were (1) to describe the impact of preterm birth on parents and families and (2) and to identify potentially modifiable determinants of parent and family impact. We surveyed 196 parents of preterm infants <24 months corrected age in 3 specialty clinics (82% response rate). Primary outcomes were: (1) the Impact on Family Scale total score; and (2) the Infant Toddler Quality of Life parent emotion and (3) time limitations scores. Potentially modifiable factors were use of community-based services, financial burdens, and health-related social problems. We estimated associations of potentially modifiable factors with outcomes, adjusting for socio-demographic and infant characteristics using linear regression. Median (inter-quartile range) infant gestational age was 28 (26-31) weeks. Higher Impact on Family scores (indicating worse effects on family functioning) were associated with taking ≥3 unpaid hours/week off from work, increased debt, financial worry, unsafe home environment and social isolation. Lower parent emotion scores (indicating greater impact on the parent) were also associated with social isolation and unpaid time off from work. Lower parent time limitations scores were associated with social isolation, unpaid time off from work, financial worry, and an unsafe home environment. In contrast, higher parent time limitations scores (indicating less impact) were associated with enrollment in early intervention and Medicaid. Interventions to reduce social isolation, lessen financial burden, improve home safety, and increase enrollment in early intervention and Medicaid all have the potential to lessen the impact of preterm birth on parents and families.
Authors: Lakshmanan A; Agni M; Lieu T; Fleegler E; Kipke M; Friedlich PS; McCormick MC; Belfort MB
Health Qual Life Outcomes. 2017 Feb 16;15(1):38. Epub 2017-02-16.
Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996-2014
Despite concern for adverse perinatal outcomes in women with diabetes mellitus before pregnancy, recent data on the prevalence of pregestational type 1 and type 2 diabetes mellitus in the United States are lacking. The purpose of this study was to estimate changes in the prevalence of overall pregestational diabetes mellitus (all types) and pregestational type 1 and type 2 diabetes mellitus and to estimate whether changes varied by race-ethnicity from 1996-2014. We conducted a cohort study among 655,428 pregnancies at a Northern California integrated health delivery system from 1996-2014. Logistic regression analyses provided estimates of prevalence and trends. The age-adjusted prevalence (per 100 deliveries) of overall pregestational diabetes mellitus increased from 1996-1999 to 2012-2014 (from 0.58 [95% confidence interval, 0.54-0.63] to 1.06 [95% confidence interval, 1.00-1.12]; Ptrend <.0001). Significant increases occurred in all racial-ethnic groups; the largest relative increase was among Hispanic women (121.8% [95% confidence interval, 84.4-166.7]); the smallest relative increase was among non-Hispanic white women (49.6% [95% confidence interval, 27.5-75.4]). The age-adjusted prevalence of pregestational type 1 and type 2 diabetes mellitus increased from 0.14 (95% confidence interval, 0.12-0.16) to 0.23 (95% confidence interval, 0.21-0.27; Ptrend <.0001) and from 0.42 (95% confidence interval, 0.38-0.46) to 0.78 (95% confidence interval, 0.73-0.83; Ptrend <.0001), respectively. The greatest relative increase in the prevalence of type 1 diabetes mellitus was in non-Hispanic white women (118.4% [95% confidence interval, 70.0-180.5]), who had the lowest increases in the prevalence of type 2 diabetes mellitus (13.6% [95% confidence interval, -8.0 to 40.1]). The greatest relative increase in the prevalence of type 2 diabetes mellitus was in Hispanic women (125.2% [95% confidence interval, 84.8-174.4]), followed by African American women (102.0% [95% confidence interval, 38.3-194.3]) and Asian women (93.3% [95% confidence interval, 48.9-150.9]). The prevalence of overall pregestational diabetes mellitus and pregestational type 1 and type 2 diabetes mellitus increased from 1996-1999 to 2012-2014 and racial-ethnic disparities were observed, possibly because of differing prevalence of maternal obesity. Targeted prevention efforts, preconception care, and disease management strategies are needed to reduce the burden of diabetes mellitus and its sequelae.
Authors: Peng TY; Ehrlich SF; Crites Y; Kitzmiller JL; Kuzniewicz MW; Hedderson MM; Ferrara A
Am J Obstet Gynecol. 2017 Feb;216(2):177.e1-177.e8. Epub 2016-10-15.
The impact of high apparent temperature on spontaneous preterm delivery: a case-crossover study
The impact of high apparent temperature on spontaneous preterm delivery: a case-crossover studyBACKGROUND: Despite the prediction that temperatures are expected to increase in the future, little is known about the health effects of increasing temperatures on pregnant women. The objective of this study was to investigate the impact of apparent temperature on spontaneous preterm delivery (PTD).METHODS: A case-crossover study of 14,466 singleton spontaneous preterm deliveries occurring between January 1, 1995 and December 31, 2009 among Kaiser Permanente Northern California (KPNC) members was conducted. Preterm deliveries were identified through KPNC’s Electronic Health Records (EHR) data. Data on gestational age at delivery, infant sex, and maternal address were also extracted from KPNC’s EHR and linked to meteorologic and air pollution monitoring data based on residential zip code.RESULTS: An 11.6% (95% CI: 4.1, 19.7) increase in spontaneous PTD was associated with a 10 °F (5.6 °C) increase in weekly average (lag06) apparent temperature, during the warm season. During the cold season, increases in apparent temperature did not significantly impact the overall effect of spontaneous PTD (6.2%, (95% CI: -3.0, 16.2) per 10 °F (5.6 °C) increase in weekly average (lag06) apparent temperature). Significant differences in the relationship between apparent temperature and spontaneous PTD emerged for region, gestational age and infant sex, during the cold season. No significant differences emerged for air pollutants.CONCLUSIONS: Our findings provide evidence for an increase in the odds of spontaneous PTD associated with increases in apparent temperature, especially during the warm season.
Authors: Avalos LA; Chen H; Li DK; Basu R
Environ Health. 2017 Feb 01;16(1):5. Epub 2017-02-01.
Newborn Weight Loss During Birth Hospitalization and Breastfeeding Outcomes Through Age 1 Month
Weight loss is universal for exclusively breastfed newborns in the first few days after birth. Many newborns exclusively breastfed during birth hospitalization receive formula in the first month after discharge and thus cease exclusive breastfeeding. However, the relationship between early weight loss and subsequent cessation of breastfeeding and exclusive breastfeeding is unknown. Research aim: This study aimed to determine the relationship between newborn weight loss and duration and exclusivity of breastfeeding among newborns breastfed exclusively during the birth hospitalization. Retrospective cohort study at Kaiser Permanente Northern California hospitals between 2009 and 2013. The main predictor variable was weight loss during birth hospitalization. The main outcomes were cessation of breastfeeding and cessation of exclusive breastfeeding in the first 25 days after discharge. Among our sample, 83,344 were exclusively breastfed during birth hospitalization. At 25 days after discharge, 15.6%, 95% confidence interval (CI) [14.6%, 16.6%], of those delivered vaginally and 17.6%, 95% CI [14.5%, 20.6%], of those delivered by cesarean section were estimated to have completely ceased breastfeeding; 57.0%, 95% CI [55.5%, 58.4%], and 57.9%, 95% CI [53.6%, 61.8%], respectively, had ceased exclusive breastfeeding. Survival curves depicting rates of breastfeeding cessation through 1 month did not differ by degree of weight loss or by weight loss trajectory. However, curves depicting rates of exclusive breastfeeding demonstrated significantly more formula use among those with more weight loss at discharge. Among those exclusively breastfed during birth hospitalization, weight loss nomograms may help identify newborns at higher risk of cessation of exclusive breastfeeding. Lactation support targeted to those with exacerbated weight loss trajectories may improve duration of exclusive breastfeeding.
Authors: Flaherman VJ; Schaefer EW; Kuzniewicz MK; Li S; Walsh E; Paul IM
J Hum Lact. 2017 Feb;33(1):225-230. Epub 2017-01-20.
Patient perceptions of a decision support tool to assist with young women’s contraceptive choice
Contraceptive decision support tools (DSTs) have been suggested as a way to provide patient-centered contraceptive care, but little is known about the role they play in women’s decision-making. The aim of this study is to understand patients’ perceptions of the value of a contraceptive DST. We conducted 21 semi-structured interviews with unmarried women aged 18-29 from an integrated health care system who viewed the DST. Thematic analysis was conducted to identify common themes in the participants’ experience. Four themes were identified: Informative; Narrowing down options; Tool vs. doctor; and Preparation for a clinical visit. In general, participants felt the tool was valuable because it provided them relevant information and facilitated their decision-making process by narrowing down contraceptive options. Participants felt the tool could prepare them for a visit with their health care provider by helping them identify questions for their provider, but also saw distinctions between the DST and what their provider could offer. Contraceptive DSTs are valuable to their users when they include information on contraceptive attributes women deem important and allow for user-driven tailoring. Contraceptive DSTs may address patient informational needs and can serve as a complement to provider counseling.
Authors: Marshall C; Nuru-Jeter A; Guendelman S; Mauldon J; Raine-Bennett T
Patient Educ Couns. 2017 Feb;100(2):343-348. Epub 2016-08-24.
Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation
Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD.
Authors: Jones KL; Croen LA; Yoshida CK; Heuer L; Hansen R; Zerbo O; DeLorenze GN; Kharrazi M; Yolken R; Ashwood P; Van de Water J
Mol Psychiatry. 2017 Feb;22(2):273-279. Epub 2016-05-24.
The impact of maternal factors on the association between temperature and preterm delivery
Few studies have examined maternal modifiers of temperature and adverse birth outcomes because of lack of data. We assessed the relationship between apparent temperature, preterm delivery (PTD) and maternal demographics, medical and mental health conditions, and behaviors. A time-stratified case-crossover analysis was conducted using 14,466 women who had a PTD (20 to less than 37 gestational weeks) from 1995 to 2009 using medical records from a large health maintenance organization in Northern California. Effect modifiers considered by stratification included several maternal factors: age, race/ethnicity, depression, hypertension, diabetes, smoking, alcohol use, pre-pregnancy body mass index, and Medicaid status. Apparent temperature data for women who had a monitor located within 20km of their residential zip codes were included. All analyses were stratified by warm (May 1 through October 31) and cold (November 1 through April 30) seasons. For every 10 F (5.6 C) increase in average cumulative weekly apparent temperature (lag06), a greater risk was observed for births occurring during the warm season (11.63%; 95% CI: 4.08, 19.72%) compared to the cold season (6.18%; -2.96, 16.18%), especially for mothers who were younger, Black, Hispanic, underweight, smoked or consumed alcohol during pregnancy, or had pre-existing /gestational hypertension, diabetes, or pre-eclampsia. Our findings suggest that warmer apparent temperatures exacerbate the risk of PTD, particularly for subgroups of more vulnerable women.
Authors: Basu R; Chen H; Li DK; Avalos LA
Environ Res. 2017 Jan 02;154:109-114. Epub 2017-01-02.
Urine bisphenol A and pubertal development in boys
Bisphenol A (BPA) is an environmental endocrine disruptor and is found in many consumer products. Animal studies suggest that BPA may perturb pubertal development in males, although studies in humans are limited. This study investigated the association between BPA exposure and pubertal onset and progression among school-aged boys in Shanghai, China. A total of 671 boys aged 9-18 years from three schools (one elementary, one middle, and one high school) in Shanghai were enrolled in a cross-sectional study. Tanner stages for genital and pubic hair development and testicular volume were assessed by a specifically trained physician. Information concerning spermarche was self-reported. Urine samples were collected to examine peripubertal BPA exposure levels. Associations between BPA exposure and pubertal development, as indicated by the presence of different milestones in early puberty, mid-puberty and late puberty, were assessed using Poisson multivariate regression to derive adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs). Earlier onset of genital and pubic hair development was observed in boys with moderate BPA exposure compared with those exposed to the least BPA; the adjusted PRs were 1.31 (95%CI:1.03, 1.68) and 1.28 (95%CI:1.02, 1.60) for onset of genital maturation and pubic hair development, respectively. A similar trend was seen for onset of testicular development, although the association was not statistically significant. Conversely, compared with the lowest level of BPA exposure, moderate BPA exposure was associated with delayed presence of the late stage of genital development, with an adjusted PR of 0.78 (95%CI: 0.65, 0.92). A suggestive inverse association was also observed between BPA exposure and late progression of testicular development. Our findings indicate an association between peripubertal BPA exposure and earlier pubertal onset, but delayed pubertal progression, in boys. Longitudinal studies of male pubertal development with periodic follow-up are needed to verify these results.
Authors: Wang Z; Li D; Miao M; Liang H; Chen J; Zhou Z; Wu C; Yuan W
Int J Hyg Environ Health. 2017 Jan;220(1):43-50. Epub 2016-10-15.
Risk of Type 2 Diabetes Mellitus following Gestational Diabetes Pregnancy in Women with Polycystic Ovary Syndrome
This study examines gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) and the risk of type 2 diabetes mellitus (DM) following GDM pregnancy. A cohort of 988 pregnant women with PCOS who delivered during 2002-2005 was examined to determine the prevalence and predictors of GDM, with follow-up through 2010 among those with GDM to estimate the risk of DM. Of the 988 pregnant women with PCOS, 192 (19%) developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the incidence of DM was 2.8 (95% confidence interval (CI) 1.9-4.2) per 100 person-years and substantially higher for those who received pharmacologic treatment for GDM (6.6 versus 1.5 per 100 person-years, p < 0.01). The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic treatment for GDM (adjusted hazard ratio 4.1, 95% CI 1.8-9.6). The five-year incidence of DM was 13.1% overall and also higher in the pharmacologic treatment subgroup (27.0% versus 7.1%, p < 0.01). The strongest predictors of GDM among women with PCOS included Asian race and prepregnancy obesity. Pharmacologic treatment of GDM is associated with fourfold higher risk of subsequent DM.
Authors: Lo JC; Yang J; Gunderson EP; Hararah MK; Gonzalez JR; Ferrara A
J Diabetes Res. 2017;2017:5250162. Epub 2017-12-20.
Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men
Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19.37% increase) in BPA-exposed men, with 72.69% of genome regions harboring 5hmc. A total of 9,610 differential 5hmc regions (DhMRs) were revealed in BPA-exposed men relative to controls, which were mainly located in intergenic and intron regions. These DhMRs were composed of 8,670 hyper-hMRs and 940 hypo-hMRs, affecting 2,008 genes and the repetitive elements. The hyper-hMRs affected genes were enriched in pathways associated with nervous system, development, cardiovascular diseases and signal transduction. Additionally, enrichment of 5hmc was observed in the promoters of eight maternally expressed imprinted genes in BPA-exposed sperm. Some of the BPA-affected genes, for example, MLH1, CHD2, SPATA12 and SPATA20 might participate in the response to DNA damage in germ cells caused by BPA. Our analysis showed that enrichment of 5hmc both in promoters and gene bodies is higher in the genes whose expression has been detected in human sperm than those whose expression is absent. Importantly, we observed that BPA exposure affected the 5hmc level in 11.4% of these genes expressed in sperm, and in 6.85% of the sperm genome. Finally, we also observed that BPA exposure tends to change the 5hmc enrichment in the genes which was previously reported to be distributed with the trimethylated Histone 3 (H3K27me3, H3K4me2 or H3K4me3) in sperm. Thus, these results suggest that BPA exposure likely interferes with gene expression via affecting DNA hydroxymethylation in a way partially dependent on trimethylation of H3 in human spermatogenesis. Our current study reveals a new mechanism by which BPA exposure reduces human sperm quality.
Authors: Zheng H; Zhou X; Li DK; Yang F; Pan H; Li T; Miao M; Li R; Yuan W
PLoS ONE. 2017;12(6):e0178535. Epub 2017-06-05.
A Survey of Parents with Children on the Autism Spectrum: Experience with Services and Treatments
Autism spectrum disorders (ASD) are lifelong neurodevelopmental disorders, and little is known about how parents address the health and psychosocial consequences of ASD. Few studies have examined use of various treatments and services in a large, diverse sample of children with ASD and their families. This paper presents methods to create an autism research resource across multiple large health delivery systems and describes services and treatments used by children with ASD and their families. Four study sites conducted a Web survey of parents of children and adolescents with ASD who were members of Kaiser Permanente. We tabulated data distributions of survey responses and calculated χ2 statistics for differences between responders and nonresponders. The children of the 1155 respondents were racially and ethnically diverse (55% white, 6% black, 5% Asian, 9% multiracial, 24% Hispanic) and representative of the total population invited to participate with respect to child sex (83% male), child age (57% < 10 years), and ASD diagnosis (64% autistic disorder). The most frequently used services and treatments were Individualized Education Programs (85%), family physician visits (78%), and occupational and speech therapy (55% and 60%, respectively). Home-based programs frequently included implementation of social skills training (44%) and behavior management (42%). Prescription medication use was high (48%). Caregivers reported disruption of personal and family routines because of problem behaviors. These survey data help to elucidate parents' experiences with health services for their children with ASD and serve as a potential resource for future research.
Authors: Becerra TA; Massolo ML; Yau VM; Owen-Smith AA; Lynch FL; Crawford PM; Pearson KA; Pomichowski ME; Quinn VP; Yoshida CK; Croen LA
Perm J. 2017;21.
Perceived psychosocial stress and gestational weight gain among women with gestational diabetes
Growing evidence links perceived stress-a potentially modifiable psychosocial risk factor-with health behaviors and obesity. Yet little is known about the relationship between stress during pregnancy and gestational weight gain, particularly among women with pregnancy complications. We conducted a cross-sectional analysis to examine associations between psychosocial stress during pregnancy and gestational weight gain among women with gestational diabetes. We used baseline data from the Gestational Diabetes’s Effects on Moms (GEM) study: 1,353 women with gestational diabetes who delivered a term singleton within Kaiser Permanente Northern California were included. Perceived stress near the time of gestational diabetes diagnosis was measured using the validated Perceived Stress Scale (PSS10). Gestational weight gain was categorized according to the 2009 Institute of Medicine recommendations. Binomial regression analyses adjusted for gestational age and maternal age at the time of gestational diabetes diagnosis, and race/ethnicity and estimated rate ratios (RR) and their 95% confidence interval (CI). Among women with a normal pregravid Body Mass Index (BMI 18.5-24.9 kg/m2), there was a significant association between high (Q4) PSS score and risk of both exceeding and gaining below the Institute of Medicine recommendations compared to those with lower stress (Q1) [adjusted RR = 2.16 95% CI 1.45-3.21; RR = 1.39 95% CI 1.01-1.91, respectively.] Among women with pregravid overweight/obesity (BMI≥25 kg/m2), there was no association. Although the temporal relationship could not be established from this study, there may be a complex interplay between psychosocial stress and gestational weight gain among women with gestational diabetes. Further studies examining stress earlier in pregnancy, risk of developing gestational diabetes and excess/inadequate gestational weight gain are warranted to clarify these complex relationships.
Authors: Kubo A; Ferrara A; Brown SD; Ehrlich SF; Tsai AL; Quesenberry CP; Crites Y; Hedderson MM
PLoS ONE. 2017;12(3):e0174290. Epub 2017-03-28.
Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study
Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution.
Authors: Park BY; Lee BK; Burstyn I; Tabb LP; Keelan JA; Whitehouse AJO; Croen LA; Fallin MD; Hertz-Picciotto I; Montgomery O; Newschaffer CJ
Mol Autism. 2017;8:3. Epub 2017-01-31.
Psychotropic Medication Use among Insured Children with Autism Spectrum Disorder
This study examined psychotropic medication use among 7901 children aged 1-17 with autism spectrum disorder (ASD) in five health systems, comparing to matched cohorts with no ASD. Nearly half (48.5 %) of children with ASD received psychotropics in the year observed; the most common classes were stimulants, alpha-agonists, or atomoxetine (30.2 %), antipsychotics (20.5 %), and antidepressants (17.8 %). Psychotropic treatment was far more prevalent among children with ASD, as compared to children with no ASD (7.7 % overall), even within strata defined by the presence or absence of other psychiatric diagnoses. The widespread use of psychotropics we observed, particularly given weak evidence supporting the effectiveness of these medications for most children with ASD, highlights challenges in ASD treatment and the need for greater investment in its evaluation.
Authors: Madden JM; Lakoma MD; Lynch FL; Rusinak D; Owen-Smith AA; Coleman KJ; Quinn VP; Yau VM; Qian YX; Croen LA
J Autism Dev Disord. 2017 Jan;47(1):144-154.
Infection and antibiotic use in infancy and risk of childhood obesity: a longitudinal birth cohort study
Data from previous studies have suggested a possible association between antibiotic use in infancy and risk of childhood obesity, with implications for health-care delivery and obesity prevention strategies. However, whether the observed association was due to antibiotic use or underlying infection, or both, is unclear. We aimed to disentangle the effect of antibiotic use in infancy from that of underlying infection on the risk of childhood obesity. In this longitudinal birth cohort study, we included infants in the Kaiser Permanente Northern California population born between Jan 1, 1997, and March 31, 2013. We used electronic medical records to ascertain data for antibiotic use, infection diagnosis, and anthropometric measurements (and thus BMI and obesity status) from birth up to age 18 years. We used standard mixed-effects logistic regression for repeated measurements to analyse multiple BMI measurements per child (median five measurements) and to obtain odds ratios (ORs) and 95% CIs for obesity risk. We also did a substudy in 547 same-sex twin pairs with discordant exposure status to substantiate our findings. 260 556 individuals were included in our analysis. After controlling for maternal age, race or ethnic origin, pre-pregnancy BMI, preterm delivery, low birthweight, maternal antibiotic use, and infection during pregnancy, infection without antibiotic use in infancy was associated with an increased risk of childhood obesity compared with controls without infection (OR 1·25, 95% CI 1·20-1·29). A clear dose-response relation was seen between infection episodes and risk of childhood obesity (ptrend <0·0001). By contrast, compared with infants with untreated infection, antibiotic use during infancy was not associated with risk of childhood obesity (1·01, 0·98-1·04). Neither broad-spectrum nor narrow-spectrum antibiotics were associated with risk of childhood obesity. These findings were supported by the results of the twin set analysis. Infection, but not antibiotic use, during infancy is associated with risk of childhood obesity. This finding will need to be replicated in future studies. Although our results do not rule out a potential effect of antibiotics on microbiome composition and the use of antibiotics should always be judicious, they suggest that treatment of common infections with antibiotics in infancy is unlikely to be a main contributor to childhood obesity. Kaiser Permanente Center for Effectiveness & Safety Research.
Authors: Li DK; Chen H; Ferber J; Odouli R
Lancet Diabetes Endocrinol. 2017 Jan;5(1):18-25. Epub 2016-11-01.
The autism symptom interview, school-age: A brief telephone interview to identify autism spectrum disorders in 5-to-12-year-old children
This study reports on the initial validation of the Autism Symptom Interview (ASI), School-Age, a brief (15-20 min) phone interview derived from questions from the Autism Diagnostic Interview-Revised (ADI-R). The ASI, School-Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best-estimate clinical diagnosis of ASD (n = 159) or non-ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non-ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81-0.92) and a specificity of 0.62 (95% CI = 0.53-0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74-0.88) and 0.92 (95% CI = 0.86-0.96), respectively. Internal consistency and test-retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78-88. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Authors: Bishop SL; Huerta M; Gotham K; Alexandra Havdahl K; Pickles A; Duncan A; Hus Bal V; Croen L; Lord C
Autism Res. 2017 Jan;10(1):78-88. Epub 2016-06-10.
Placental genetic variations in vitamin D metabolism and birthweight
INTRODUCTION: Vitamin D has pleiotropic functions that regulate fetal growth and development. We investigated associations of common placental genetic variations in vitamin D metabolism with birthweight.
METHODS: The study was conducted among participants (506 maternal-infant pairs) of a pregnancy cohort study. Data were collected using interviewer-administered questionnaires and post-delivery medical record abstraction. DNA, extracted from placental samples collected at delivery, was genotyped for eight single nucleotide polymorphisms (SNPs) in five vitamin D metabolism genes (CUBN, LRP2, VDR, GC, and CYP2R1). Linear and logistic regression models were used to evaluate associations of SNPs with birthweight and risk of low birthweight, respectively. Effect modification of associations by infant sex was examined using stratified analyses and interaction terms in regression models.
RESULTS: Mean (standard-deviation) birthweight among all, male, and female infants was 3482.1 (549.9), 3544.6 (579.0) and 3419.2 (512.5) grams, respectively. Each copy of the minor allele of rs2282679 (GC) was associated with a 68.6 g (95%CI:3.1134.7 g) increase in birthweight overall. Sex-specific associations were observed for SNP rs4667591 (LRP2) (p-value for interaction < 0.001). Each copy of the minor allele of rs4667591 was associated with a 124.7 g (95%CI:20.1229.0 g) increase in birthweight among female infants, and a suggested 81.6 g decrease in birthweight among male infants (95%CI:-183.7,20.5 g). DISCUSSION: Our study identified overall and sex-specific associations between placental genetic variations in vitamin D metabolism and birthweight. If confirmed by larger replication studies, observed associations may provide insight into mechanistic underpinnings of the relationships between placental vitamin D metabolism and birth size.
Authors: Workalemahu T; Badon SE; Dishi-Galitzky M; Qiu C; Williams MA; Sorensen T; Enquobahrie DA
Placenta. 2017 Feb;50:78-83. doi: 10.1016/j.placenta.2016.12.028. Epub 2016 Dec 27.
The Changing Epidemiology of Autism Spectrum Disorders
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts. Genetic and environmental factors contribute to ASD etiology, which remains incompletely understood. Research on ASD epidemiology has made significant advances in the past decade. Current prevalence is estimated to be at least 1.5% in developed countries, with recent increases primarily among those without comorbid intellectual disability. Genetic studies have identified a number of rare de novo mutations and gained footing in the areas of polygenic risk, epigenetics, and gene-by-environment interaction.Epidemiologic investigations focused on nongenetic factors have established advanced parental age and preterm birth as ASD risk factors, indicated that prenatal exposure to air pollution and short interpregnancy interval are potential risk factors, and suggested the need for further exploration of certain prenatal nutrients, metabolic conditions, and exposure to endocrine-disrupting chemicals. We discuss future challenges and goals for ASD epidemiology as well as public health implications. Expected final online publication date for the Annual Review of Public Health Volume 38 is March 20, 2017. Please see https://www.annualreviews.org/page/journal/pubdates for revised estimates.
Authors: Lyall K; Croen L; Daniels J; Fallin MD; Ladd-Acosta C; Lee BK; Park BY; Snyder NW; Schendel D; Volk HE; Windham GC; Newschaffer C
Annu Rev Public Health. 2016 Dec 21.
Parental weighting of seizure risks vs. fever risks in vaccination tradeoff decisions
As part of a survey of about vaccination beliefs, a nationally representative sample of parents of young children answered a series of tradeoff questions that asked them to choose between two vaccination approaches that differed in terms of risks of vaccine complications, number of injections, and/or vaccine effectiveness. Most parents were willing to have their children endure more injections, and many were willing to forgo disease protection, in order to reduce the rare chance of febrile seizures. Yet, most parents were unwilling to trade disease protection to reduce the risk of fever alone, even though this is correlated with the risk of febrile seizures. Vaccine risk communications need to address the heightened emotional weight that parents give to febrile seizure risk, even when the rarity of such events is explicit.
Authors: Zikmund-Fisher BJ; Wittenberg E; Lieu TA
Vaccine. 2016 Dec 07;34(50):6123-6125. Epub 2016-11-03.
Weight Change Nomograms for the First Month After Birth
Clinicians expect newborns to surpass birth weight by age 10 to 14 days, yet few studies have examined the natural history of weight change in the weeks after birth. We sought to determine the distribution of weight loss and subsequent regain during the first month, the proportion not surpassing birth weight by 14 and 21 days, and whether findings differed by delivery mode. For 161 471 singleton neonates delivered at ≥36 weeks’ gestation at Kaiser Permanente Northern California Medical Centers between 2009 and 2013 and weighing 2000 to 5000 g at birth, we extracted daily weights from inpatient electronic records and weights from outpatient visits in the first month. Quantile regression appropriate for repeated measures was used to estimate percentiles of weight change as a function of time after birth, stratified by delivery mode. After exclusions, weight data were analyzed from 143 889 newborns (76% born vaginally). Based on percentile estimates, 50% of newborns were at or above birth weight at 9 and 10 days after vaginal and cesarean delivery, respectively. Among those delivered vaginally, 14% and 5% were not back to birth weight by 14 and 21 days, respectively. For those delivered by cesarean, 24% and 8% were not back to birth weight by 14 and 21 days, respectively. It is not uncommon for newborns to be below birth weight 10 to 14 days after delivery. A larger percentage of newborns delivered by cesarean had yet to regain birth weight at every time point through 1 month.
Authors: Paul IM; Schaefer EW; Miller JR; Kuzniewicz MW; Li SX; Walsh EM; Flaherman VJ
Pediatrics. 2016 Dec;138(6). Epub 2016-11-09.
Deep sequencing of HPV16 genomes: A new high-throughput tool for exploring the carcinogenicity and natural history of HPV16 infection
For unknown reasons, there is huge variability in risk conferred by different HPV types and, remarkably, strong differences even between closely related variant lineages within each type. HPV16 is a uniquely powerful carcinogenic type, causing approximately half of cervical cancer and most other HPV-related cancers. To permit the large-scale study of HPV genome variability and precancer/cancer, starting with HPV16 and cervical cancer, we developed a high-throughput next-generation sequencing (NGS) whole-genome method. We designed a custom HPV16 AmpliSeq?panel that generated 47 overlapping amplicons covering 99% of the genome sequenced on the Ion Torrent Proton platform. After validating with Sanger, the current "gold standard" of sequencing, in 89 specimens with concordance of 99.9%, we used our NGS method and custom annotation pipeline to sequence 796 HPV16-positive exfoliated cervical cell specimens. The median completion rate per sample was 98.0%. Our method enabled us to discover novel SNPs, large contiguous deletions suggestive of viral integration (OR of 27.3, 95% CI 3.3-222, P=0.002), and the sensitive detection of variant lineage coinfections. This method represents an innovative high-throughput, ultra-deep coverage technique for HPV genomic sequencing, which, in turn, enables the investigation of the role of genetic variation in HPV epidemiology and carcinogenesis.
Authors: Cullen M; Boland JF; Schiffman M; Zhang X; Wentzensen N; Yang Q; Chen Z; Yu K; Mitchell J; Roberson D; Bass S; Burdette L; Machado M; Ravichandran S; Luke B; Machiela MJ; Andersen M; Osentoski M; Laptewicz M; Wacholder S; Feldman A; Raine-Bennett T; Lorey T; Castle PE; Yeager M; Burk RD; Mirabello L
Papillomavirus Res. 2015 Dec 1;1:3-11.
Prospective Case-Control Study of Abnormal Bleeding after Outpatient Corticosteroid Injection
This study is aimed at evaluating the incidence of bleeding among women having outpatient corticosteroid injection compared to matched controls, using mailed surveys and electronic health records. Prospective survey study of women receiving outpatient corticosteroid injection for joint or back pain (cases) compared to women matched for visit, diagnosis of joint/back pain, and age, who did not receive an injection (controls). A survey was mailed 45 days following outpatient visit, inquiring about menstrual history, abnormal bleeding, and potential risk factors. The proportion of women reporting abnormal bleeding was compared between cases and controls, and stratified by menopausal status. One thousand and sixty two surveys were mailed to 531 identified cases/control pairs, and 40% response was seen from each group. Of 379 analyzable responders, 135 (36%) were premenopausal and 244 (64%) postmenopausal. Postmenopausal women who had a corticosteroid injection were more likely to report recent abnormal bleeding compared to controls (17 vs. 7%, p = 0.02), whereas rates were similar among premenopausal women (50 vs. 43%, p = 0.39). When logistic regression was performed, injection was associated with bleeding among postmenopausal women, independent of body mass index and hormone use. Corticosteroid injection is associated with increased abnormal vaginal bleeding among postmenopausal women.
Authors: Suh-Burgmann E; Liu JY
Gynecol Obstet Invest. 2016 Nov 23.
Differences in testosterone and its precursors by sex of the offspring in meconium
Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in meconium from females (p=0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis.
Authors: Frey AJ; Park BY; Schriver ER; Feldman DR; Parry S; Croen LA; Fallin DM; Hertz-Picciotto I; Newschaffer CJ; Snyder NW
J Steroid Biochem Mol Biol. 2016 Nov 18.
A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin
One-third of type-2 diabetic patients respond poorly to metformin. Despite extensive research, the impact of genetic and nongenetic factors on long-term outcome is unknown. In this study we combine nonlinear mixed effect modeling with computational genetic methodologies to identify predictors of long-term response. In all, 1,056 patients contributed their genetic, demographic, and long-term HbA1c data. The top nine variants (of 12,000 variants in 267 candidate genes) accounted for approximately one-third of the variability in the disease progression parameter. Average serum creatinine level, age, and weight were determinants of symptomatic response; however, explaining negligible variability. Two single nucleotide polymorphisms (SNPs) in CSMD1 gene (rs2617102, rs2954625) and one SNP in a pharmacologically relevant SLC22A2 gene (rs316009) influenced disease progression, with minor alleles leading to less and more favorable outcomes, respectively. Overall, our study highlights the influence of genetic factors on long-term HbA1c response and provides a computational model, which when validated, may be used to individualize treatment.
Authors: Goswami S; Hedderson MM; Savic RM; et al.
Clin Pharmacol Ther. 2016 Nov;100(5):537-547. Epub 2016-09-23.
Phototherapy and Risk of Type 1 Diabetes
Increases in both phototherapy use and the incidence of type 1 diabetes mellitus (DM-1) have been reported. One large study has suggested a strong association between them. Our objective was to quantify any association between neonatal phototherapy and DM-1 in a northern California integrated health care system. This retrospective cohort study included 499 642 children born at ≥35 weeks’ gestation in 15 Kaiser Permanente Northern California hospitals from 1995 to 2011 and followed until March 31, 2014. We ascertained phototherapy, bilirubin levels, and other covariates from electronic records. We identified DM-1 cases using a diabetes registry and inpatient and outpatient diagnoses. We used traditional and propensity-adjusted Cox models to quantify associations. Phototherapy use increased from 2.7% in 1995 to 16.0% in 2011. DM-1 was diagnosed in 37 of 39 406 children who had received phototherapy (15.1 per 100 000 person-years; mean follow-up 6.2 years) and 712 of 460 236 who had not (18.8 per 100 000 person-years; mean follow-up 8.2 years). There was no evidence of increasing diabetes incidence. We found no association between phototherapy and DM-1 in either unadjusted analyses (incidence rate ratio 0.81; 95% confidence interval, 0.56 to 1.12) or analyses adjusted for hyperbilirubinemia and other covariates (hazard ratio 1.06; 95% confidence interval, 0.78 to 1.45). DM-1 incidence was most strongly associated with race and ethnicity, with whites at highest risk (25.6 per 100 000) and Asians at lowest risk (8.9 per 100 000). We found no evidence of increased DM-1 risk in children who had received phototherapy.
Authors: Newman TB; Wickremasinghe AC; Walsh EM; Grimes BA; McCulloch CE; Kuzniewicz MW
Pediatrics. 2016 Nov;138(5). Epub 2016-10-19.
Pleiotropic Mechanisms Indicated for Sex Differences in Autism
Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.
Authors: Mitra I; Croen LA; Weiss LA; et al.
PLoS Genet. 2016 11;12(11):e1006425. Epub 2016-11-15.
Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development
Maternal immune activity has been linked to children with autism spectrum disorder (ASD). We examined maternal occupational exposure to asthma-causing agents during pregnancy in relation to ASD risk. Our sample included 463 ASD cases and 710 general population controls from the Study to Explore Early Development whose mothers reported at least one job during pregnancy. Asthmagen exposure was estimated from a published job-exposure matrix. The adjusted odds ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96-2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in this study, but this result does not exclude some involvement of maternal exposure to asthma-causing agents in ASD.
Authors: Singer AB; Windham GC; Croen LA; Daniels JL; Lee BK; Qian Y; Schendel DE; Fallin MD; Burstyn I
J Autism Dev Disord. 2016 Nov;46(11):3458-3468.
Risk of Autism Associated With Hyperbilirubinemia and Phototherapy
Whether neonatal hyperbilirubinemia and/or phototherapy increase the risk of autism spectrum disorder (ASD) is unclear. We sought to quantify the risk of ASD associated with elevated total serum bilirubin (TSB) levels and with phototherapy. In a retrospective cohort study of 525?409 infants born at ?35 weeks’ gestation in 15 Kaiser Permanente Northern California (KPNC) hospitals, 1995-2011, we obtained all TSB levels and determined which infants received phototherapy. From the KPNC Autism Registry, we identified patients with ASD diagnosed at a KPNC Autism Center, by a clinical specialist, or by a pediatrician. We calculated Cox proportional hazard ratios (HRs) for time to diagnosis of ASD, adjusting for confounding factors. Among infants in the birth cohort, 2% had at least 1 TSB level ?20 mg/dL, and 8% received phototherapy. The rate of ASD was 13 per 1000 births. Crude analyses revealed an association between TSB ?20 and ASD (relative risk: 1.4; 95% confidence interval [CI]: 1.1-1.6), and between phototherapy and ASD (relative risk: 1.7; 95% CI: 1.5-1.8). After adjusting for confounders, TSB ?20 (HR: 1.09; 95% CI: 0.89-1.35) and phototherapy (HR: 1.10; 95% CI: 0.98-1.24) were no longer significantly associated with ASD. Independent risk factors for ASD included maternal and paternal age; maternal and paternal higher education; male sex; birth weight <2500 g or ?4200 g; and later year of birth. After adjustment for the effects of sociodemographic factors and birth weight, neither hyperbilirubinemia nor phototherapy was an independent risk factor for ASD.
Authors: Wu YW; Kuzniewicz MW; Croen L; Walsh EM; McCulloch CE; Newman TB
Pediatrics. 2016 Oct;138(4).
Effects of maternal folic acid supplementation on gene methylation and being small for gestational age
Being small for gestational age (SGA), a foetal growth abnormality, has a long-lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter-relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. We conducted a case-control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri-conception FA supplementation and also be sex-specific.
Authors: Qian YY; Li DK; et al.
J Hum Nutr Diet. 2016 Oct;29(5):643-51. Epub 2016-05-27.
Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin
Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.
Authors: Zhou K; Hedderson MM; Pearson ER; et al.
Nat Genet. 2016 Sep;48(9):1055-1059. Epub 2016-08-08.
Mismatching Among Guidelines, Providers, and Parents on Controller Medication Use in Children With Asthma
Underuse of controller medicines among children with asthma remains widespread despite national guidelines. To (1) assess provider prescribing patterns for asthma controller medications; (2) assess how frequently parents’ reports of their child’s asthma controller medicine use were mismatched with their provider’s recommendations; and (3) evaluate parent attitudes and demographic characteristics associated with these mismatches. In this cross-sectional study, we conducted linked surveys of parents and providers of children with probable persistent asthma in a Medicaid program and 4 commercial health plans in 2011. Probable persistent asthma was defined as a diagnosis of asthma and 1 or more controller medication dispensing. This study included 740 children (mean age, 8.6 years). Providers for 50% of the children reported prescribing controller medications for daily year-round use, 41% for daily use during active asthma months, and 9% for intermittent use for relief. Among parents, 72% knew which class of controller medication the provider prescribed and 49% knew the administration frequency and the medication class. Parents were less likely to report the same controller medication type as the provider, irrespective of dose and frequency, if they were Latino (odds ratio [OR], 0.23; CI, 0.057-0.90), had a household smoker (OR, 2.87; CI, 0.42-19.6), or believed the controller medicine was not helping (OR, 0.15; CI, 0.048-0.45). Mismatches between parent reports and providers intentions regarding how the child was supposed to use inhaled steroids occurred for half of the children. Efforts should focus on ways to reduce mismatches between parent and provider intentions regarding controller medication use.
Authors: Wu AC; Li L; Fung V; Kharbanda EO; Larkin EK; Butler MG; Galbraith A; Miroshnik I; Davis RL; Horan K; Lieu TA
J Allergy Clin Immunol Pract. 2016 Sep-Oct;4(5):910-6. Epub 2016-05-17.
HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women
HPV16 is a common sexually transmitted infection although few infections lead to cervical precancer/cancer; we cannot distinguish nor mechanistically explain why only certain infections progress. HPV16 can be classified into four main evolutionary-derived variant lineages (A, B, C, D) that have been previously suggested to have varying disease risks. We used a high-throughput HPV16 whole-genome sequencing assay to investigate variant lineage risk among 3215 HPV16-infected women. Using sublineages A1/A2 as the reference, we assessed all variant lineage associations with infection outcome over three or more years of follow-up: 1107 control subjects ( Authors: Mirabello L; Yeager M; Cullen M; Boland JF; Chen Z; Wentzensen N; Zhang X; Yu K; Yang Q; Mitchell J; Roberson D; Bass S; Xiao Y; Burdett L; Raine-Bennett T; Lorey T; Castle PE; Burk RD; Schiffman M J Natl Cancer Inst. 2016 Sep;108(9). Epub 2016-04-29.
Experience With Opportunistic Salpingectomy in a Large, Community-Based Health System in the United States
To evaluate the trend in uptake of salpingectomy at the time of hysterectomy and assess physicians’ attitudes toward the practice. This was a retrospective cohort study using the electronic medical record to identify women 18 years of age or older undergoing hysterectomy from June 2011 to May 2014 in a large integrated health care delivery system. The primary outcome was the change in rate of opportunistic salpingectomy over time and after a systemwide practice recommendation was issued in May 2013. Secondary outcomes included data on blood loss, operating time, and length of stay. Of the 12,143 hysterectomies performed over the 3-year study period, 7,498 were performed without oophorectomy. There was a statistically significant rise in rate of salpingectomy over time from 14.7% for June 2011 to May 2012 to 44.6% from June 2012 to May 2013 and to 72.7% from June 2013 to May 2014 (P<.001). Sixty-one percent of laparoscopic hysterectomies were performed with salpingectomy, whereas only 25% of abdominal and 17% of vaginal hysterectomies had salpingectomies. Median estimated blood loss was lower in the salpingectomy group, 100 compared with 150 mL (P<.01). There was a significantly shorter median operating time (147 compared with 154 minutes, P=.002) for laparoscopic hysterectomy with bilateral salpingectomy compared with laparoscopic hysterectomy alone. Rates of salpingectomy increased significantly over time, consistent with the high reported acceptance rate reported by health care providers and highlighting the importance of physician education to improve compliance with risk-reducing clinical strategies.
Authors: Garcia C; Martin M; Tucker LY; Lyon L; Armstrong MA; McBride-Allen S; Littell RD; Alabaster A; Raine-Bennett T; Powell CB
Obstet Gynecol. 2016 Aug;128(2):277-83.
Featured research at the 2015 North American Forum on Family Planning
Authors: Bruce L; Espey E; Borrero S; Raine-Bennett T; Finer L; Teal S
Contraception. 2015 Jul 2.
Validity of Self-Reported Pre-Pregnancy Weight and Body Mass Index Classification in an Integrated Health Care Delivery System
Self-reported weight prior to pregnancy is prone to error. We utilised a measured pre-conceptional weight from the electronic health record (EHR) to investigate error in recalled pre-pregnancy body mass index (BMI) category and compared how associations between pre-pregnancy BMI and pregnancy outcomes varied by using the two measures. We assessed differences in means, correlations, and categorisation of pre-pregnancy BMI for 5092 singleton pregnancies delivered between 2007 and 2013 in Kaiser Permanente Northern California. Associations between measured and self-reported BMI category and gestational diabetes, infant size for gestational age, and exceeding the Institute of Medicine gestational weight gain recommendations were assessed. Overall, the two measures assigned the same BMI category for 86.7% of women with higher risks of misclassification for overweight (Relative Risk (RR) 3.38, 95% Confidence Interval (CI) 2.79, 4.10), obese class I (RR 3.81, 95% CI 3.07, 4.75), and obese class II (RR 1.80, 95% CI 1.28, 2.55) women compared to normal weight women. However, associations between self-reported or measured BMI category and several pregnancy outcomes were similar. Despite misclassification, self-reported and measured pre-pregnancy weights were similarly associated with perinatal outcomes in this study population. Our results illustrate the value of the EHR for recording measured pre-pregnancy weight for use in research.
Authors: Han E; Abrams B; Sridhar S; Xu F; Hedderson M
Paediatr Perinat Epidemiol. 2016 07;30(4):314-9. Epub 2016-03-09.
Pre-pregnancy adverse lipid profile and subsequent risk of gestational diabetes
Lower low-density lipoprotein (LDL) peak diameter and a predominance of small, dense LDL are associated with type 2 diabetes, but it is unclear whether they are a risk factor for gestational diabetes mellitus (GDM). To evaluate whether prepregnancy lipid profile predicts the development of GDM during pregnancy. A nested case-control study among women who participated in a multiphasic health exam, where blood was collected and stored between 1984 and 1996, and who then had a subsequent pregnancy between 1984 and 2009. Kaiser Permanente Northern California. Cases were 254 women who developed GDM. Two controls were selected for each case and matched for year of blood draw, age at baseline, age at pregnancy, and number of intervening pregnancies. Prepregnancy LDL peak diameter and prepregnancy lipid subfraction concentrations grouped according to size, and the odds of developing GDM. Women in the lowest quartiles of LDL peak diameter and high-density lipoprotein had increased odds of GDM compared with women in the highest quartiles (odds ratio [95% CI], 2.60 [1.37-4.94] and 1.98 [1.01-3.86], respectively), in multivariable adjusted models. Being in the highest quartile of small and very small LDL subfractions also increased the odds of GDM (2.61 [1.35-5.03] and 2.44 [1.22-4.85], respectively). Lower LDL peak diameter size and high-density lipoprotein levels and higher levels of small and very small LDL subfraction groups were present years before pregnancy in women who developed GDM. A prepregnancy atherogenic lipid profile may help identify women at risk of GDM to target for prevention.
Authors: Han ES; Krauss RM; Xu F; Sridhar SB; Ferrara A; Quesenberry CP; Hedderson MM
J Clin Endocrinol Metab. 2016 Jul;101(7):2721-7. Epub 2016-04-05.
Lifestyle behaviors and ethnic identity among diverse women at high risk for type 2 diabetes
Diet and physical activity lifestyle behaviors are modifiable risk factors for type 2 diabetes and are shaped by culture, potentially influencing diabetes health disparities. We examined whether ethnic identity-the strength of attachment to one’s ethnic group, and a long-standing focus of psychological research-could help account for variations in lifestyle behaviors within a diverse population at high risk for chronic disease. Using data from the Gestational Diabetes’ Effects on Moms trial, this US-based cross-sectional study included 1463 pregnant women (74% from minority ethnic/racial groups; 46% born outside the US) with gestational diabetes (GDM), a common pregnancy complication conferring high risk for type 2 diabetes after delivery. Mixed linear regression models examined whether ethnic identity is associated with lifestyle behaviors after adjusting for demographic, clinical, and acculturative characteristics (e.g., nativity and length of residence in the US). In the overall sample, a one-unit increase in ethnic identity score was significantly associated with 3% greater fiber intake, 4% greater fruit/vegetable intake, 11% greater total activity, and 11% greater walking (p values < 0.01). Within ethnic/racial groups, a one-unit increase in ethnic identity score was significantly associated with 17% greater fiber intake among Filipina women; 5% lower total caloric intake among non-Hispanic White women; and 40% greater total activity, 35% greater walking, and 8% greater total caloric intake among Latina women (p values ≤ 0.03). Results from this large study suggest that ethnic group attachment is associated with some lifestyle behaviors, independent of acculturation indicators, among young women with GDM who are at high risk for type 2 diabetes. Stronger ethnic identity may promote certain choices known to be associated with reduced risk of type 2 diabetes. Prospective research is needed to clarify the temporal nature of associations between ethnic identity and modifiable diabetes risk factors.
Authors: Brown SD; Ehrlich SF; Kubo A; Tsai AL; Hedderson MM; Quesenberry CP; Ferrara A
Soc Sci Med. 2016 07;160:87-93. Epub 2016-05-14.
Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder
The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child’s primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.
Authors: DiGuiseppi CG; Croen LA; Schendel DE; et al.
Disabil Health J. 2016 Jul;9(3):544-51. Epub 2016-01-29.
The role of human papillomavirus (HPV) genotyping in cervical cancer screening: A large-scale evaluation of the cobas HPV test
The cobas?HPV Test ("cobas", Roche Molecular Systems) detects HPV16 and HPV18 individually, and a pool of 12 other high-risk (HR) HPV types. The test is approved for 1) ASC-US triage to determine need for colposcopy, 2) combined screening with cytology ("co-testing"), and 3) primary HPV screening. To assess the possible value of HPV16/18 typing, >17,000 specimens from a longitudinal cohort study of initially HPV-positive women (HC2, Qiagen) were retested with cobas. To study accuracy, cobas genotyping results were compared to those of an established method, the LINEAR ARRAY HPV Genotyping Test (LA, Roche Molecular Systems). Clinical value of the typing strategy was evaluated by linking the cobas results (supplemented by other available typing results) to 3-year cumulative risks of CIN3+. Grouped hierarchically (HPV16, else HPV18, else other HR types, else negative), the kappa statistic for agreement between cobas and LA was 0.86 (95%CI=0.86-0.87). In all 3 scenarios, HPV16-positive women were at much higher 3-year risk of CIN3+ than HPV16-negative women: women aged 21 and older with ASC-US (14.5%, 95%CI=13.5%-15.5% versus 3.5%, 95%CI=3.3%-3.6%); women aged 30 and older that were HPV-positive cytology-negative (10.3%, 95%CI=9.6%-11.1% versus 2.3%, 95%CI=2.2%-2.4%); and all women 25 and older that were HPV-positive (18.5%, 95%CI=17.8%-19.2% versus 4.3%, 95%CI=4.2%-4.4%). The cobas and LA results show excellent agreement. The data support HPV16 typing. HPV16 typing is useful in the management of HPV- positive/cytology-negative women in co-testing, of all HPV-positive women in primary HPV testing, and perhaps in the management of HPV-positive women with ASC-US.
Authors: Schiffman M; Boyle S; Raine-Bennett T; Katki HA; Gage JC; Wentzensen N; Kornegay JR; Apple R; Aldrich C; Ehrlich HA; Tam T; Befano B; Burk RD; Castle PE
Cancer Epidemiol Biomarkers Prev. 2015 Jun 18.
Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes
Objectives To estimate the associations of moderate and vigorous intensity exercise during pregnancy with the rate of gestational weight gain (GWG) from gestational diabetes (GDM) diagnosis to delivery, overall and stratified by prepregnancy overweight/obesity. Methods Prospective cohort study with physical activity reported shortly after the GDM diagnosis and prepregnancy weight and post-diagnosis GWG obtained from electronic health records (n = 1055). Multinomial logistic regression models in the full cohort and stratified by prepregnancy overweight/obesity estimated associations of moderate and vigorous intensity exercise with GWG below and above the Institute of Medicine’s (IOM) prepregnancy BMI-specific recommended ranges for weekly rate of GWG in the second and third trimesters. Results In the full cohort, any participation in vigorous intensity exercise was associated with decreased odds of GWG above recommended ranges as compared to no participation [odds ratio (95 % confidence interval): 0.63 (0.40, 0.99)], with a significant trend for decreasing odds of excess GWG with increasing level of vigorous intensity exercise. Upon stratification by prepregnancy overweight/obesity, significant associations were only observed for BMI ≥ 25.0 kg/m(2): any vigorous intensity exercise, as compared to none, was associated with 54 % decreased odds of excess GWG [0.46 (0.27, 0.79)] and significant trends were detected for decreasing odds of GWG both below and above the IOM’s recommended ranges with increasing level of vigorous exercise (both P ≤ 0.03). No associations were observed for moderate intensity exercise. Conclusions for Practice In women with GDM, particularly overweight and obese women, vigorous intensity exercise during pregnancy may reduce the odds of excess GWG.
Authors: Ehrlich SF; Sternfeld B; Krefman AE; Hedderson MM; Brown SD; Mevi A; Chasan-Taber L; Quesenberry CP; Ferrara A
Matern Child Health J. 2016 Jun;20(6):1247-57.
Association Between Laboratory Calibration of a Serum Bilirubin Assay, Neonatal Bilirubin Levels, and Phototherapy Use
The American Academy of Pediatrics treatment recommendations for neonatal jaundice are based on age-specific total serum bilirubin (TSB) levels. In May 2012, Ortho Clinical Diagnostics adjusted the calibrator values for Vitros Chemistry Products BuBc Slides (Ortho Clinical Diagnostics), a widely used method to quantify TSB, after concerns of positively biased results. To investigate the association between recalibration of a reflectance spectrophotometry serum bilirubin assay and TSB levels and phototherapy use among newborns. Descriptive study comparing TSB levels and phototherapy use before and after recalibration at Kaiser Permanente Northern California, a large, integrated health care delivery system. The study evaluated live births at or after 35 weeks’ gestation at 12 facilities that used universal serum bilirubin screening before (January 1, 2010, through April 30, 2012; n = 61 677) and after (July 1, 2012, through December 31, 2013; n = 42 571) recalibration. The analysis took place in December 2015. Recalibration of bilirubin testing instruments. Proportions of newborns with (1) at least 1 TSB value at or above 15 mg/dL; (2) at least 1 TSB level exceeding the American Academy of Pediatrics phototherapy threshold; (3) phototherapy during the birth hospitalization; and (4) at least 1 readmission for phototherapy. In 104 420 infants (61 677 in the prerecalibration period and 42 511 in the postrecalibration period), a TSB was obtained in 99.2% of infants during birth and in 99.5% of infants within the first 30 days after birth. The postrecalibration period was associated with a 1.25 mg/dL (95% CI, 1.19-1.31; P < .001) decrease in mean maximum TSB, which led to a 39% relative reduction (from 20.4% to 12.4%) in infants with a TSB level of 15 mg/dL or more and a 51% relative reduction (from 9.3% to 4.5%) in infants with a TSB level that was at or above the American Academy of Pediatrics phototherapy threshold. Phototherapy during birth hospitalizations was reduced by 59% (absolute risk reduction, 5.5%; 95% CI, 4.7%-6.1%) and readmissions for phototherapy by 53% (absolute risk reduction, 1.8%; 95% CI, 1.4%-2.3%). Modest recalibration-induced reductions in mean TSB concentrations was associated with a significant reduction in the percentage of infants with clinically significant hyperbilirubinemia. Current laboratory accuracy standards are insufficient to detect biases that can have significant clinical effect. These data underline the need for increased integration of laboratory expertise into clinical guidelines and to support international initiatives to standardize laboratory measurements.
Authors: Kuzniewicz MW; Greene DN; Walsh EM; McCulloch CE; Newman TB
JAMA Pediatr. 2016 Jun 01;170(6):557-61.
Leisure Time Physical Activity and Gestational Diabetes Mellitus in the Omega Study
PURPOSE: Findings of studies investigating associations of leisure time physical activity (LTPA) with gestational diabetes mellitus (GDM) risk have been inconsistent. We investigated associations of LTPA with GDM and whether these associations differ by prepregnancy overweight/obese status or gestational weight gain category.
METHODS: Participants (N = 3209) of the Omega study, a pregnancy cohort study in Washington State (1996-2008), reported LTPA duration (h·wk) and energy expenditure (MET·h·wk) in the year before pregnancy and in early pregnancy. Diagnoses of GDM were abstracted from medical records. Poisson regression models were used to determine relative risks of GDM across tertiles of prepregnancy or early pregnancy LTPA duration and energy expenditure. Stratified analyses and interaction terms were used to assess effect modification by prepregnancy overweight/obese status (BMI ≥25 kg·m) or gestational weight gain category (adequate or excessive).
RESULTS: Each tertile increase in prepregnancy LTPA duration or energy expenditure was associated with 15% (95% CI = 0.72-1.00) and 19% (95% CI = 0.69-0.96) lower risk of GDM, respectively. Each tertile increase in early pregnancy LTPA duration or energy expenditure was associated with 16% (95% CI = 0.72-0.97) and 17% (95% CI = 0.72-0.95) lower risk of GDM, respectively. LTPA during both prepregnancy and early pregnancy was associated with a 46% reduced risk of GDM (95% CI = 0.32-0.89) compared with inactivity during both periods. LTPA-GDM associations were similar by prepregnancy BMI and gestational weight gain.
CONCLUSION: Our results support a role for the promotion of physical activity before and during pregnancy in the prevention of GDM.
Authors: Badon SE; Wartko PD; Qiu C; Sorensen TK; Williams MA; Enquobahrie DA
Neonatal Phototherapy and Infantile Cancer
To determine whether neonatal phototherapy is associated with cancer in the first year after birth. We analyzed a data set from the California Office of Statewide Health Planning and Development that was created by linking birth certificates, death certificates, and hospital discharge abstracts up to age 1 year. Subjects were 5?144?849 infants born in California hospitals at ?35 weeks’ gestation from 1998 to 2007. We used International Classification of Diseases, Ninth Revision codes to identify phototherapy at <15 days and discharge diagnoses of cancer at 61 to 365 days. We adjusted for potential confounding variables by using traditional and propensity-adjusted logistic regression models. Cancer was diagnosed in 58/178?017 infants with diagnosis codes for phototherapy and 1042/4?966?832 infants without such codes (32.6/100?000 vs 21.0/100?000; relative risk 1.6; 95% confidence interval [CI], 1.2-2.0, P = .002). In propensity-adjusted analyses, associations were seen between phototherapy and overall cancer (adjusted odds ratio [aOR] 1.4; 95% CI, 1.1-1.9), myeloid leukemia (aOR 2.6; 95% CI, 1.3-5.0), and kidney cancer (aOR 2.5; 95% CI, 1.2-5.1). The marginal propensity-adjusted absolute risk increase for cancer after phototherapy in the total population was 9.4/100?000 (number needed to harm of 10?638). Because of the higher baseline risk of cancer in infants with Down syndrome, the number needed to harm was 1285. Phototherapy may slightly increase the risk of cancer in infancy, although the absolute risk increase is small. This risk should be considered when making phototherapy treatment decisions, especially for infants with bilirubin levels below current treatment guidelines.
Authors: Wickremasinghe AC; Kuzniewicz MW; Grimes BA; McCulloch CE; Newman TB
Pediatrics. 2016 Jun;137(6).
Retrospective Cohort Study of Phototherapy and Childhood Cancer in Northern California
To investigate the association between neonatal phototherapy use and childhood cancer. This retrospective cohort study included 499?621 children born at ?35 weeks’ gestation from 1995 to 2011 in Kaiser Permanente Northern California hospitals, who survived to hospital discharge and were followed ?60 days. We obtained data on home and inpatient phototherapy, covariates, and cancer incidence from electronic records. We used propensity-adjusted Cox and Poisson models to control for confounding and unequal follow-up times. There were 60 children with a diagnosis of cancer among 39?403 exposed to phototherapy (25 per 100?000 person-years), compared with 651 of 460?218 unexposed children (18 per 100?000 person-years; incidence rate ratio [IRR] 1.4; P = .01). Phototherapy was associated with increased rates of any leukemia (IRR 2.1; P = .0007), nonlymphocytic leukemia (IRR 4.0; P = .0004), and liver cancer (IRR 5.2; P = .04). With adjustment for a propensity score that incorporated bilirubin levels, chromosomal disorders, congenital anomalies, and other covariates, associations were no longer statistically significant: Adjusted hazard ratios (95% confidence intervals) were 1.0 (0.7-1.6) for any cancer, 1.6 (0.8-3.5) for any leukemia, 1.9 (0.6-6.9) for nonlymphocytic leukemia, and 1.4 (0.2-12) for liver cancer. Upper limits of 95% confidence intervals for adjusted 10-year excess risk were generally <0.1% but reached 4.4% for children with Down syndrome. Although phototherapy use was associated with increased cancer rates (particularly nonlymphocytic leukemia), control for confounding variables eliminated or attenuated the associations. Nonetheless, the possibility of even partial causality suggests that avoiding unnecessary phototherapy may be prudent.
Authors: Newman TB; Wickremasinghe AC; Walsh EM; Grimes BA; McCulloch CE; Kuzniewicz MW
Pediatrics. 2016 Jun;137(6).
Perinatal Obstetric Office Depression Screening and Treatment: Implementation in a Health Care System
Perinatal depression affects between 12% and 20% of pregnant and postpartum women and is underdiagnosed. The American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force recently recommended universal perinatal depression screening. We discuss challenges to instituting universal screening, describe the development and implementation between 2007 and 2014 of Kaiser Permanente Northern California’s successful program, and highlight key measures of success. A quality improvement system approach with four steps guided development: 1) identify and use best practices, 2) identify champions and educate clinicians, 3) use data that drive performance, and 4) streamline office workflow. Clinical success was determined by at least 50% improvement in depression care metrics from diagnosis to 120 days afterward. Depression diagnoses, Patient Health Questionnaire-9 scores, medication dispensation, and treatment for all births in 2014 (N=37,660) were extracted from electronic health records. Ninety-six percent of pregnant and postpartum women were screened at least once. Fourteen percent screened positive for depression (Patient Health Questionnaire-9 score of 10 or greater). Approximately 6% of pregnant and postpartum women had severe depression with a Patient Health Questionnaire-9 of 15 or greater and a depression diagnosis, and 80% of these women received treatment. Forty percent of women with a depression diagnosis demonstrated improved symptoms. Kaiser Permanente Northern California’s universal perinatal depression screening program can serve as a model for the feasibility and clinical effectiveness of universal depression screening in obstetric care.
Authors: Flanagan T; Avalos LA
Obstet Gynecol. 2016 May;127(5):911-5.
Development and Implementation of an Early-Onset Sepsis Calculator to Guide Antibiotic Management in Late Preterm and Term Neonates
Authors: Kuzniewicz MW; Walsh EM; Li S; Fischer A; Escobar GJ
Jt Comm J Qual Patient Saf. 2016 May;42(5):232-9.
Improved Perinatal Depression Screening, Treatment, and Outcomes With a Universal Obstetric Program
To evaluate whether universal prenatal and early postnatal screening for depression leads to increased detection, subsequent intervention, and improved depressive symptom outcomes. We conducted a population-based retrospective cohort study of 97,678 pregnant Kaiser Permanente Northern California members during three phases of the Universal Perinatal Depression Screening Program (preimplementation, rollout, fully implemented) from 2007 through 2014. Depression screening scores (Patient Health Questionnaire-9), depression diagnoses, individual counseling visits, demographic characteristics, and medication dispensings were extracted from electronic health records and pharmacy databases. The percentage of women screened, new depression diagnoses, and women receiving treatment were compared among the three phases (tests of trend). Changes in depressive symptom scores up to 6 months postpartum were assessed (rollout and fully implemented phases). A significant increase emerged in the percentage of women screened over the three phases ranging from less than 1% (n=122) (preimplementation) to 98% (n=41,124) (fully implemented) (P<.001). Identification of a new depression diagnosis increased from 8.2% (n=1,341) (preimplementation) to 11.5% (n=4,943) (fully implemented) (P<.001). Although the observed percentage of women receiving treatment decreased (60.9% [preimplementation] to 47.1% [fully implemented]), significant increases in the expected percentage of women receiving treatment emerged (42.6% [preimplementation] to 47.1% [fully implemented]; P<.05). Similar trends were noted for women with Patient Health Questionnaire-9 scores of 15 or greater (greater severity), highlighting an increase in expected percentage of women receiving treatment (5.9% [preimplementation] to 81.9% [fully implemented]; P<.05). In the fully implemented phase, improvements in depressive symptoms up to 6 months postpartum were noted. These data provide evidence of benefit for universal perinatal depression screening programs regarding depression identification and treatment receipt and suggest improvement in symptom outcomes for women in screening programs, especially among integrated health care systems.
Authors: Avalos LA; Raine-Bennett T; Chen H; Adams AS; Flanagan T
Obstet Gynecol. 2016 May;127(5):917-25.
Breast cancer multigene testing trends and impact on chemotherapy use
A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b) correlations between Recurrence Score (RS) and chemotherapy, and c) whether test introduction was associated with a reduction in chemotherapy use. Retrospective cohort study. The Kaiser Permanente Northern California tumor registry and electronic health records from 2005 to 2012 were used to identify HR+, human epidermal growth factor receptor 2 negative, node-negative cancers. Analyses used logistic regression with propensity score matching and 2-level logistic regression. Of the 7004 patients who met guidelines for testing, 22% were tested and 26% had chemotherapy. Test use was more likely in younger women (for ages 40-49 years vs 50-64 years: odds ratio [OR], 1.22; 95% CI, 1.04-1.44), in women with tumors sized 1.0 to 2.0 cm versus > 2 cm (OR, 1.20; 95% CI, 1.03-1.40), and in women from higher-income neighborhoods (for each $10,000 increase in area median income: OR, 1.05; 95% CI, 1.03-1.07). Among patients with low RS, 8% had chemotherapy versus 72% among patients with high RS (P < .01). In propensity score-matched analyses, testing was associated with an absolute reduction of 6.2% in the proportion of women receiving chemotherapy (95% CI, 2.9%-9.5%); the 2-level model showed a similar but nonsignificant (P = .14) association. The 21-gene test is used in a minority of eligible patients in this integrated plan. Its use appears to be associated with a modest decrease in overall chemotherapy use.
Authors: Ray GT; Mandelblatt J; Habel LA; Ramsey S; Kushi LH; Li Y; Lieu TA
Am J Manag Care. 2016 May 01;22(5):e153-60. Epub 2016-05-01.
A Description of Midlife Women Experiencing Intimate Partner Violence Using Electronic Medical Record Information
Intimate partner violence (IPV) is an important health problem affecting women of all ages, but is often not addressed during healthcare visits. To use electronic records of diagnoses and telephone advice calls to describe the clinical patterns of midlife women experiencing IPV. Using case-control methodology, women with an ICD9 diagnosis of IPV were chosen from those enrolled in 2005-2006 in Kaiser Permanente Northern California (KPNC) and matched on visit date, age, and facility with women without such a diagnosis. The study population was divided into subsets: ages 45-53 years (318 cases, 1588 controls); ages 54-64 years (200 cases, 1000 controls). Diagnoses and symptoms reported by phone that were significantly related to the cases compared with the controls were identified using multivariate logistic regression. Among women aged 45-53 years, diagnoses of anxiety (odds ratio [OR]?=?2.05) and of psychiatric problems (OR?=?1.65) and calls for head injury (OR?=?3.17), mental health problems (OR?=?2.46), and sexually transmitted diseases (OR?=?2.40) were associated with IPV. Among women aged 54-64 years, diagnoses of anxiety (OR?=?1.74) and other psychiatric problems (OR?=?1.76), injuries (other than head and neck) (OR?=?1.57), urinary tract infection (UTI; OR?=?2.31), headache (OR?=?2.06), and calls for mental health problems (OR?=?4.16) were associated with IPV. Among all women aged 45-64 years, history of prior IPV was strongly associated with subsequent diagnosis of IPV. Information available in the electronic health record of women who have been identified as experiencing IPV can be used to identify patterns of symptoms and diagnosis among midlife women. These patterns can potentially be used to improve identification of IPV in this age group. In addition to screening of all women for IPV, the presence of psychiatric problems, injuries, headache, and UTI and prior experience of IPV should prompt additional focused clinical inquiry about IPV in midlife women.
Authors: Eaton A; Temkin TL; Fireman BH; McCaw BR; Kotz KJ; Amaral D; Bhargava R
J Womens Health (Larchmt). 2016 May;25(5):498-504. Epub 2015-12-24.
Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study
Maternal pregnancy levels of the inflammatory marker C-reactive protein (CRP) has been previously associated with autism spectrum disorder (ASD) in the offspring. We conducted a population-based nested case-control study with 500 children with ASD, 235 with developmental delay (DD) and 580 general population (GP) controls to further investigate whether elevated CRP during pregnancy increases the risk of ASD. Maternal CRP concentration was measured in archived serum collected during 15-19 weeks of pregnancy and genome-wide single-nucleotide polymorphism (SNP) data were generated. The levels of CRP were compared between ASD vs GP and DD vs GP. The genetic associations with CRP were assessed via linear regression. Maternal CRP levels in mid-pregnancy were lower in mothers of ASD compared with controls. The maternal CRP levels in the upper third and fourth quartiles were associated with a 45 and 44% decreased risk of ASD, respectively. Two SNPs at the CRP locus showed strong association with CRP levels but they were not associated with ASD. No difference was found between maternal CRP levels of DD and controls. The reasons for the lower levels of CRP in mothers of ASD are not known with certainty but may be related to alterations in the immune response to infectious agents. The biological mechanisms underlying this association remain to be clarified.
Authors: Zerbo O; Croen LA; et al.
Transl Psychiatry. 2016 Apr 19;6:e783. Epub 2016-04-19.
Building the new schoolhouse: the Massachusetts school building authority.
In a 2010 special issue of New Solutions on school health and environment, Paulson and Barnett asked who is responsible for the environmental health of schools. The Massachusetts School Building Authority (MSBA), the product of liberals trying to bring organization and efficiency to school construction, is an "off-label" and only partial answer to the question. The MSBA, established in 2004, lent its ear to health and safety advocates who seized an opportunity to implement regulations, guidelines, and education reforms at the level of school construction. The MSBA’s progressiveness is a model to localities and states across the United States facing the dual crisis of attacks on public education and financial inefficiency. However, the MSBA is still in its infancy. Time will tell whether the MSBA, viewed as a limited state pilot program, can survive and expand its environmental health programs or whether its initiative is only as good as its current leadership.
Authors: Ames, Jennifer J; Levenstein, Charles C
New solutions : a journal of environmental and occupational health policy : NS. 2013 Jan 01;23(2):369-87. Epub 2016-03-12.
Sewer Gas: An Indoor Air Source of PCE to Consider During Vapor Intrusion Investigations.
The United States Environmental Protection Agency (USEPA) is finalizing its vapor intrusion guidelines. One of the important issues related to vapor intrusion is background concentrations of volatile organic chemicals (VOCs) in indoor air, typically attributed to consumer products and building materials. Background concentrations can exist even in the absence of vapor intrusion and are an important consideration when conducting site assessments. In addition, the development of accurate conceptual models that depict pathways for vapor entry into buildings is important during vapor intrusion site assessments. Sewer gas, either as a contributor to background concentrations or as part of the site conceptual model, is not routinely evaluated during vapor intrusion site assessments. The research described herein identifies an instance where vapors emanating directly from a sanitary sewer pipe within a residence were determined to be a source of tetrachloroethylene (PCE) detected in indoor air. Concentrations of PCE in the bathroom range from 2.1 to 190 ug/m3 and exceed typical indoor air concentrations by orders of magnitude resulting in human health risk classified as an "Imminent Hazard" condition. The results suggest that infiltration of sewer gas resulted in PCE concentrations in indoor air that were nearly two-orders of magnitude higher as compared to when infiltration of sewer gas was not known to be occurring. This previously understudied pathway whereby sewers serve as sources of PCE (and potentially other VOC) vapors is highlighted. Implications for vapor intrusion investigations are also discussed.
Authors: Pennell, Kelly G KG; Scammell, Madeleine Kangsen MK; McClean, Michael D MD; Ames, Jennifer J; Weldon, Brittany B; Friguglietti, Leigh L; Suuberg, Eric M EM; Shen, Rui R; Indeglia, Paul A PA; Heiger-Bernays, Wendy J WJ
Ground water monitoring & remediation. 2013 Jun 15;33(3):119-126. Epub 2016-03-12.
Field data and numerical modeling: A multiple lines of evidence approach for assessing vapor intrusion exposure risks.
USEPA recommends a multiple lines of evidence approach to make informed decisions at vapor intrusion sites because the vapor intrusion pathway is notoriously difficult to characterize. Our study uses this approach by incorporating groundwater, soil gas, indoor air field measurements and numerical models to evaluate vapor intrusion exposure risks in a Metro-Boston neighborhood known to exhibit lower than anticipated indoor air concentrations based on groundwater concentrations. We collected and evaluated five rounds of field sampling data over the period of one year. Field data results show a steep gradient in soil gas concentrations near the groundwater surface; however as the depth decreases, soil gas concentration gradients also decrease. Together, the field data and the numerical model results suggest that a subsurface feature is limiting vapor transport into indoor air spaces at the study site and that groundwater concentrations are not appropriate indicators of vapor intrusion exposure risks in this neighborhood. This research also reveals the importance of including relevant physical models when evaluating vapor intrusion exposure risks using the multiple lines of evidence approach. Overall, the findings provide insight about how the multiple lines of evidence approach can be used to inform decisions by using field data collected using regulatory-relevant sampling techniques, and a well-established 3-D vapor intrusion model.
Authors: Pennell, Kelly G KG; Scammell, Madeleine K MK; McClean, Michael D MD; Suuberg, Eric M EM; Moradi, Ali A; Roghani, Mohammadyousef M; Ames, Jennifer J; Friguglietti, Leigh L; Indeglia, Paul A PA; Shen, Rui R; Yao, Yijun Y; Heiger-Bernays, Wendy J WJ
The Science of the total environment. 2016 Jun 15;556():291-301. Epub 2016-03-12.
Health Services Utilization Among Children With and Without Autism Spectrum Disorders
Using data from multiple health systems (2009-2010) and the largest sample to date, this study compares health services use among youth with and without an autism spectrum disorder (ASD)-including preventive services not previously studied. To examine these differences, we estimated logistic and count data models, controlling for demographic characteristics, comorbid physical health, and mental health conditions. Results indicated that youth with an ASD had greater health care use in many categories, but were less likely to receive important preventive services including flu shots and other vaccinations. An improved understanding of the overall patterns of health care use among this population could enable health systems to facilitate the receipt of appropriate and effective health care.
Authors: Cummings JR; Croen LA; et al.
J Autism Dev Disord. 2016 Mar;46(3):910-20.
HPV16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer
AbstractWe have developed and evaluated a next-generation bisulfite sequencing (NGS) assay to distinguish HPV16 cervical precancer (CIN2-3; N=59) from HPV16-positive transient infections (N=40). Cervical DNA was isolated and treated with bisulfite and HPV16 methylation was quantified by (i) amplification with barcoded primers and massively parallel single molecule sequencing and (ii) site-specific pyrosequencing. Assays were evaluated for agreement using intraclass correlation coefficients (ICC). Odds ratios (OR) for high methylation vs. low methylation were calculated. Single site pyrosequencing and NGS data were correlated (ICC=0.61) and both indicated hypermethylation was associated with precancer (ORs of 2-37). Concordant NGS and pyrosequencing results yieled ORs that were stronger when compared with using either assay separately. Within the L1 region, the ORs for CIN2-3 were 14.3 and 22.4 using pyrosequencing and NGS assays, respectively; when both methods agreed the OR was 153. NGS assays provide methylation haplotypes, termed methyl-haplotypes from single molecule reads: cases had increased methyl-haplotypes with ≥1 methylated CpG site(s) per fragment compared with controls, particularly in L1 (p=3.0×10(-8)). The maximum discrimination of cases from controls for a L1 methyl-haplotype had an AUC of 0.89 corresponding to a sensitivity of 92.5% and a specificity of 73.1%. The strengthening of the OR when the two assays were concordant suggests the true association of CpG methylation with precancer is stronger than with either assay. As cervical cancer prevention moves to DNA testing methods, DNA based biomarkers, such as HPV methylation could serve as a reflex strategy to identify women at high risk for cervix cancer.
Authors: Mirabello L; Frimer M; Harari A; McAndrew T; Smith B; Chen Z; Wentzensen N; Wacholder S; Castle PE; Raine-Bennett T; Schiffman M; Burk RD
Int J Cancer. 2015 Feb 15;136(4):E146-53. Epub 2014-09-03.
The Value of Ultrasound Monitoring of Adnexal Masses for Early Detection of Ovarian Cancer
Although ultrasound has so far been found to be ineffective as a screening tool for ovarian cancer, it is commonly used as a means of evaluating or following ovarian or adnexal masses once they are detected. We review the use of serial ultrasound for the management of adnexal masses and propose an approach to monitoring based on an understanding of the overall risk of cancer among the population in question and an assessment of how the potential benefit of monitoring compares with potential risk. In our approach, masses that are symptomatic, large (>10?cm), associated with an elevated CA 125 level or overt signs of malignancy, or that are determined to have a worrisome appearance by stringent ultrasound criteria should be evaluated surgically. Women with masses that have none of these characteristics should be offered monitoring. Short-term initial ultrasound monitoring carries significant potential benefit in terms of aiding detection of early malignancy and avoidance of unnecessary surgery. However, if a mass remains stable but persistent, the potential benefit of ongoing monitoring wanes with time, whereas the potential harms, in terms of patient anxiety, cost, and the risk of incidental findings and unnecessary surgery increase. Therefore, monitoring of stable lesions should be limited in duration in order to limit potential harms from overtreatment and overdiagnosis.
Authors: Suh-Burgmann E; Kinney W
Front Oncol. 2016;6:25. Epub 2016-02-10.
Is heart rate variability associated with frequency and intensity of vasomotor symptoms among healthy perimenopausal and postmenopausal women?
Research has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function. Women (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks. Baseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up. Heart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms.
Authors: Jones SM; Guthrie KA; LaCroix AZ; Sternfeld B; Landis CA; Reed SD; Dunn A; Caan B; Cohen LS; Hunt J; Newton KM
Clin Auton Res. 2016 Feb;26(1):7-13. Epub 2015-Dec-21.
Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies
Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations. Mother-infant pairs were selected from a cohort of 1.2 million live-born deliveries (2001-2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program. Mothers with first-trimester trimethoprim-sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to (i) a primary comparison group (mothers exposed to penicillins and/or cephalosporins) and (ii) a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication during the same time period). The outcomes were cardiovascular abnormalities, cleft palate/lip, clubfoot, and urinary tract abnormalities. We first identified 7615 infants in the TMP-SUL exposure group, of which 7595 (99%) were exposed to a combination of TMP-SUL and the remaining 1% to sulfonamides alone. After matching (1:1) to the comparator groups and only including those with complete data on covariates, there were 20?064 (n?=?6688 per group) in the primary analyses. Overall, cardiovascular defects (1.52%) were the most common and cleft lip/palate (0.10%) the least common that were evaluated. Compared with penicillin/cephalosporin exposure, and no antibacterial exposure, TMP-SUL exposure was not associated with statistically significant elevated risks for cardiovascular, cleft lip/palate, clubfoot, or urinary system defects. First-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials.
Authors: Hansen C; Li DK; Davis R; et al.
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8. Epub 2015-Nov-24.
Growth and obesity through the first 7 years of life in association with levels of maternal glycemia during pregnancy: a prospective cohort study
BACKGROUND: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications.OBJECTIVE: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status.DESIGN: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring’s ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors.RESULTS: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo.CONCLUSION: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI.
Authors: Zhu Y; Olsen SF; Mendola P; Yeung EH; Vaag A; Bowers K; Liu A; Bao W; Li S; Madsen C; Grunnet LG; Granström C; Hansen S; Martin K; Chavarro JE; Hu FB; Langhoff-Roos J; Damm P; Zhang C;
Am J Clin Nutr. 2016 Mar;103(3):794-800. doi: 10.3945/ajcn.115.121780. Epub 2016 Jan 27.
Interacting effects of obesity, race, ethnicity and sex on the incidence and control of adult-onset asthma
To improve care and control for patients with adult-onset asthma, a better understanding of determinants of their risk and outcomes is important. We investigated how associations between asthma, asthma control and obesity may be modified by patient demographic characteristics. This retrospective study of adults enrolled in several health plans across the U.S. (n = 2,860,305) examined the interacting effects of obesity, age, race, and sex on adult-onset asthma and asthma control. Multivariable adjusted Cox and logistic regression models estimated hazard ratios (HR), and 95 % confidence intervals (CI) for the associations between body mass index (BMI) and study outcomes, and interactions of BMI with demographic characteristics. Compared with individuals who had a BMI <25 kg/m(2), the hazard of adult-onset asthma progressively increased with increasing BMI, from a 12 % increase among persons with a BMI of 25.0-29.9 kg/m(2) (HR 1.12, 95 % CI 1.10, 1.14) to an almost 250 % increase among persons with a BMI ?50 kg/m(2) (HR 2.49, 95 % CI 2.38, 2.60). The magnitude of the association between obesity and asthma risk was greater for women (compared with men) and lower for Blacks (compared with non-Hispanic Whites). Among individuals with asthma, obesity was associated with poorly controlled and high-risk asthma. The present study demonstrates that the magnitude of the associations between obesity and adult-onset asthma incidence and control are modified by race, age, and sex. Understanding the role of obesity in the development of adult-onset asthma will help to improve asthma treatment algorithms and to develop targeted interventions.
Authors: Koebnick C; Fischer H; Daley MF; Ferrara A; Horberg MA; Waitzfelder B; Young DR; Gould MK
Allergy Asthma Clin Immunol. 2016;12:50. Epub 2016-Oct-19.
Building a Governance Strategy for CER: The Patient Outcomes Research to Advance Learning (PORTAL) Network Experience
The Patient Outcomes Research to Advance Learning (PORTAL) Network was established with funding from the Patient-Centered Outcomes Research Institute (PCORI) in 2014. The PORTAL team adapted governance structures and processes from past research network collaborations. We will review and outline the structures and processes of the PORTAL governance approach and describe how proactively focusing on priority areas helped us to facilitate an ambitious research agenda. For years a variety of funders have supported large-scale infrastructure grants to promote the use of clinical datasets to answer important comparative effectiveness research (CER) questions. These awards have provided the impetus for health care systems to join forces in creating clinical data research networks. Often, these scientific networks do not develop governance processes proactively or systematically, and address issues only as problems arise. Even if network leaders and collaborators foresee the need to develop governance approaches, they may underestimate the time and effort required to develop sound processes. The resulting delays can impede research progress. Because the PORTAL sites had built trust and a foundation of collaboration by participating with one another in past research networks, essential elements of effective governance such as guiding principles, decision making processes, project governance, data governance, and stakeholders in governance were familiar to PORTAL investigators. This trust and familiarity enabled the network to rapidly prioritize areas that required sound governance approaches: responding to new research opportunities, creating a culture of trust and collaboration, conducting individual studies, within the broader network, assigning responsibility and credit to scientific investigators, sharing data while protecting privacy/security, and allocating resources. The PORTAL Governance Document, complete with a Toolkit of Appendices is included for reference and for adaptation by other networks. As a result of identifying project-based governance priorities (IRB approval, subcontracting, selection of new research including lead PI and participating sites, and authorship) and data governance priorities (reciprocal data use agreement, analytic plan procedures, and other tools for data governance), PORTAL established most of its governance structure by Month 6 of the 18 month project. This allowed science to progress and collaborators to experience first-hand how the structures and procedures functioned in the remaining 12 months of the project, leaving ample time to refine them and to develop new structures or processes as necessary. The use of procedures and processes with which participating investigators and their home institutions were already familiar allowed project and regulatory requirements to be established quickly to protect patients, their data, and the health care systems that act as stewards for both. As the project progressed, PORTAL was able to test and adjust the structures it put place, and to make substantive revisions by Month 17. As a result, priority processes have been predictable, transparent and effective. Strong governance practices are a stewardship responsibility of research networks to justify the trust of patients, health plan members, health care delivery organizations, and other stakeholders. Well-planned governance can reduce the time necessary to initiate the scientific activities of a network, a particular concern when the time frame to complete research is short. Effective network and data governance structures protect patient and institutional data as well as the interests of investigators and their institutions, and assures that the network has built an environment to meet the goals of the research.
Authors: Paolino AR; McGlynn EA; Lieu T; Nelson AF; Prausnitz S; Horberg MA; Arterburn DE; Gould MK; Laws RL; Steiner JF
EGEMS (Wash DC). 2016;4(2):1216. Epub 2016-03-28.
Maternal Leisure Time Physical Activity and Infant Birth Size
BACKGROUND: Associations of maternal leisure time physical activity with birth size are inconsistent. Roles of infant sex and maternal prepregnancy body mass index (BMI) in these associations have not been studied.
METHODS: Participants (N = 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported leisure time physical activity duration and energy expenditure in the year prepregnancy and in early pregnancy (mean 15 weeks gestation). Regression models estimated mean differences in infant head circumference, birthweight, and ponderal index (birthweight/length) across quartiles of pre- or early-pregnancy leisure time physical activity. We assessed effect modification by infant sex or prepregnancy overweight/obese status (BMI ≥ 25 kg/m).
RESULTS: We observed positive associations between prepregnancy leisure time physical activity and head circumference overall and among male infants. Among males, each quartile increase in prepregnancy physical activity duration was associated with 0.14 cm (95% confidence interval = 0.046, 0.24; trend P = 0.004) greater head circumference. We did not observe associations between leisure time physical activity and birthweight or ponderal index overall. Each quartile increase in pre- or early-pregnancy physical activity duration was associated with 17-23 g lower birthweight among female infants and among women with normal prepregnancy BMI.
CONCLUSIONS: We observed positive associations between prepregnancy leisure time physical activity and head circumference among male infants, and inverse associations of pre- and early-pregnancy physical activity with birthweight among female infants and women with normal prepregnancy BMI. Future studies should confirm results and elucidate mechanisms of observed associations.
Authors: Badon SE; Wander PL; Qiu C; Miller RS; Williams MA; Enquobahrie DA
Epidemiology. 2016 Jan;27(1):74-81. doi: 10.1097/EDE.0000000000000399.
Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: A Global Perspective
Despite the increasing epidemic of diabetes mellitus affecting populations at different life stages, the global burden of gestational diabetes mellitus (GDM) is not well assessed. Systematically synthesized data on global prevalence estimates of GDM are lacking, particularly among developing countries. The hyperglycemic intrauterine environment as exemplified in pregnancies complicated by GDM might not only reflect but also fuel the epidemic of type 2 diabetes mellitus (T2DM). We comprehensively reviewed available data in the past decade in an attempt to estimate the contemporary global prevalence of GDM by country and region. We reviewed the risk of progression from GDM to T2DM as well. Synthesized data demonstrate wide variations in both prevalence estimates of GDM and the risk of progression from GDM to T2DM. Direct comparisons of GDM burden across countries or regions are challenging given the great heterogeneity in screening approaches, diagnostic criteria, and underlying population characteristics. In this regard, collaborative efforts to estimate global GDM prevalence would be a large but important leap forward. Such efforts may have substantial public health implications in terms of informing health policy makers and healthcare providers for disease burden and for developing more targeted and effective diabetes prevention and management strategies globally.
Authors: Zhu Y; Zhang C;
Curr Diab Rep. 2016 Jan;16(1):7. doi: 10.1007/s11892-015-0699-x.
Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation
To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. We conducted a population-based cohort study. All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting. There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation. Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.
Authors: Raine-Bennett T; Neugebauer R; Lentz SE; et al.
Obstet Gynecol. 2016 Jan;127(1):29-39.
The Comparative Effectiveness of Diabetes Prevention Strategies to Reduce Postpartum Weight Retention in Women With Gestational Diabetes Mellitus: The Gestational Diabetes’ Effects on Moms (GEM) Cluster Randomized Controlled Trial
To compare the effectiveness of diabetes prevention strategies addressing postpartum weight retention for women with gestational diabetes mellitus (GDM) delivered at the health system level: mailed recommendations (usual care) versus usual care plus a Diabetes Prevention Program (DPP)-derived lifestyle intervention. This study was a cluster randomized controlled trial of 44 medical facilities (including 2,280 women with GDM) randomized to intervention or usual care. The intervention included mailed gestational weight gain recommendations plus 13 telephone sessions between 6 weeks and 6 months postpartum. Primary outcomes included the following: proportion meeting the postpartum goals of 1) reaching pregravid weight if pregravid BMI <25.0 kg/m(2) or 2) losing 5% of pregravid weight if BMI ?25.0 kg/m(2); and pregravid to postpartum weight change. On average, over the 12-month postpartum period, women in the intervention had significantly higher odds of meeting weight goals than women in usual care (odds ratio [OR] 1.28 [95% CI 1.10, 1.47]). The proportion meeting weight goals was significantly higher in the intervention than usual care at 6 weeks (25.5 vs. 22.4%; OR 1.17 [1.01, 1.36]) and 6 months (30.6 vs. 23.9%; OR 1.45 [1.14, 1.83]). Condition differences were reduced at 12 months (33.0 vs. 28.0%; OR 1.25 [0.96, 1.62]). At 6 months, women in the intervention retained significantly less weight than women in usual care (mean 0.39 kg [SD 5.5] vs. 0.95 kg [5.5]; mean condition difference -0.64 kg [95% CI -1.13, -0.14]) and had greater increases in vigorous-intensity physical activity (mean condition difference 15.4 min/week [4.9, 25.8]). A DPP-derived lifestyle intervention modestly reduced postpartum weight retention and increased vigorous-intensity physical activity.
Authors: Ferrara A; Brown SD; Albright CL; Tsai AL; Sternfeld B; Gordon NP; Schmittdiel JA; Gunderson EP; Mevi AA; Quesenberry CP; et al.
Diabetes Care. 2016 Jan;39(1):65-74. Epub 2015-12-09.
Altered Gut Microbiota Composition Associated with Eczema in Infants
Eczema is frequently the first manifestation of an atopic diathesis and alteration in the diversity of gut microbiota has been reported in infants with eczema. To identify specific bacterial communities associated with eczema, we conducted a case-control study of 50 infants with eczema (cases) and 51 healthy infants (controls). We performed high-throughput sequencing for V3-V4 hypervariable regions of the 16S rRNA genes from the gut fecal material. A total of 12,386 OTUs (operational taxonomic units) at a 97% similarity level were obtained from the two groups, and we observed a difference in taxa abundance, but not the taxonomic composition, of gut microbiota between the two groups. We identified four genera enriched in healthy infants: Bifidobacterium, Megasphaera, Haemophilus and Streptococcus; and five genera enriched in infants with eczema: Escherichia/Shigella, Veillonella, Faecalibacterium, Lachnospiraceae incertae sedis and Clostridium XlVa. Several species, such as Faecalibacterium prausnitzii and Ruminococcus gnavus, that are known to be associated with atopy or inflammation, were found to be significantly enriched in infants with eczema. Higher abundance of Akkermansia muciniphila in eczematous infants might reduce the integrity of intestinal barrier function and therefore increase the risk of developing eczema. On the other hand, Bacteroides fragilis and Streptococcus salivarius, which are known for their anti-inflammatory properties, were less abundant in infants with eczema. The observed differences in genera and species between cases and controls in this study may provide insight into the link between the microbiome and eczema risk.
Authors: Zheng H; Liang H; Wang Y; Miao M; Shi T; Yang F; Liu E; Yuan W; Ji ZS; Li DK
PLoS ONE. 2016;11(11):e0166026. Epub 2016-11-03.
Peripheral Blood Leukocyte Production of BDNF following Mitogen Stimulation in Early Onset and Regressive Autism
Brain-derived neurotrophic factor (BDNF) is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset autism and children who had a regressive form of autism. We show here that plasma levels of BDNF levels are increased in children with autism, especially in early onset autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with autism. This data suggest that immune cell-derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in autism.
Authors: Enstrom A; Onore C; Tarver A; Hertz-Picciotto I; Hansen R; Croen L; Van de Water J; Ashwood P
Am J Biochem Biotechnol. 2008;4(2):121-129.
Trimester-Specific Gestational Weight Gain and Infant Size for Gestational Age
Gestational weight gain is known to influence fetal growth. However, it is unclear whether the associations between gestational weight gain and fetal growth vary by trimester. In a diverse cohort of 8,977 women who delivered a singleton between 2011 and 2013, we evaluated the associations between trimester-specific gestational weight gain and infant size for gestational age. Gestational weight gain was categorized per the 2009 Institute of Medicine (IOM) recommendations; meeting the recommendations was the referent. Large for gestational age and small for gestational age were defined as birthweight > 90th percentile or <10th percentile, respectively, based on a national reference standard birthweight distribution. Logistic regression models estimated the odds of having a large or small for gestational age versus an appropriate for gestational age infant. Only gestational weight gain exceeding the IOM recommendations in the 2nd and 3rd trimesters independently increased the odds of delivering a large for gestational age infant (Odds Ratio (95% Confidence Interval): 1st: 1.17 [0.94, 1.44], 2nd: 1.47 [1.13, 1.92], 3rd: 1.70 [1.30, 2.22]). Gestational weight gain below the IOM recommendations increased the likelihood of having a small for gestational age infant in the 2nd trimester only (1.76 [1.23, 2.52]). There was effect modification, and gestational weight gain below the IOM recommendations increased the likelihood of having a small for gestational age infant in the 2nd trimester and only among women with a pre-pregnancy body mass index from 18.5-24.9 kg/m2 (2.06 [1.35, 3.15]). These findings indicate that gestational weight gain during the 2nd and 3rd trimesters is more strongly associated with infant growth. Interventions to achieve appropriate gestational weight gain may optimize infant size at birth.
Authors: Sridhar SB; Xu F; Hedderson MM
PLoS ONE. 2016;11(7):e0159500. Epub 2016-07-21.
The Patient Outcomes Research To Advance Learning (PORTAL) Network Adult Overweight and Obesity Cohort: Development and Description
The Patient-Centered Outcomes Research Institute (PCORI) created a new national network infrastructure to enable large-scale observational comparative effectiveness research across diverse clinical care settings. As part of testing the feasibility of this effort, each clinical data research network (CDRN) was required to construct cohorts of patients, including one of patients with overweight and obesity. The aim of this paper is to report on the development of the Patient Outcomes Research to Advance Learning (PORTAL) overweight and obese cohort, which includes patients from 10 health plans located across the United States. Information was gathered from each plan’s electronic health records (EHR). Eligibility included 18 years of age or older, a valid height and weight in 2012 or 2013, and body mass index (BMI) greater than 22.9 kg/m(2). Pre-diabetes and diabetes status was defined using the American Diabetes Association (ADA) criteria, using lab values of glycated hemoglobin (HbA1c) or fasting glucose available in the EHR. Hypertension was identified from the International Classification of Diseases (ICD) diagnosis codes. Individuals were classified into BMI categories: healthy weight (23.0-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), obese class 1 (30.0-34.9 kg/m(2)), obese class 2 (35.0-39.9 kg/m(2)), obese class 3 (40.0-49.0 kg/m(2)), and obese class 4 (>50.0 kg/m(2)). A cohort of 5,293,458 non-pregnant adults was created. Weight status was 20.39% (1,079,289/5,293,458) healthy weight, 40.40% (2,138,520/5,293,458) overweight, 22.78% (1,205,866/5,293,458) obese class 1, 9.86% (521,872/5,293,458) obese class 2, 5.59% (295,786/5,293,458) obese class 3, and 0.98% (52,125/5,293,458) obese class 4. Race/ethnicity was 49.02% (2,594,776/5,293,458) non-Hispanic white, 22.89% (1,211,677/5,293,458) Hispanic, 10.40% (550,608/5,293,458) Asian, 10.83% (573,506/5,293,458) black, and 6.59% (348,830/5,293,458) other. About 34.33% (1,817,438/5,293,458) met the definition of hypertension, 20.49% (1,660,940/5,293,458) of individuals met the criteria for pre-diabetes, and 14.98% (793,069/5,293,458) met criteria for diabetes. Prevalence of pre-diabetes and diabetes varied across health plans to a greater extent than expected based on hypertension prevalence and BMI status variability. This large, race, ethnic, and geographically diverse cohort will be useful for future studies of rare exposures or outcomes and differences in health care practices.
Authors: Young DR; Ferrara A; Lewis KH; et al.
JMIR Res Protoc. 2016;5(2):e87. Epub 2016-06-15.
Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders
An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance.
Authors: Grether JK; Ashwood P; Van de Water J; Yolken RH; Anderson MC; Torres AR; Westover JB; Sweeten T; Hansen RL; Kharrazi M; Croen LA
Front Neurosci. 2016;10:218. Epub 2016-05-18.
Predictors of impact of vaginal symptoms in postmenopausal women
This study aims to identify factors associated with greater impact of vaginal symptoms on the functioning and well-being of postmenopausal women. Postmenopausal women who reported vaginal dryness, itching, irritation, or pain with sexual activity completed the multidimensional Day-to-day Impact of Vaginal Aging (DIVA) questionnaire and underwent assessment of multiple sociodemographic and clinical factors that have the potential to influence the impact of vaginal symptoms. Multivariable linear regression analyses examined relationships between selected participant characteristics and DIVA scale scores assessing symptom impact on activities of daily living, emotional well-being, self-concept and body image, and sexual functioning. Among 745 symptomatic participants, the mean (SD) age was 56 (9) years, and 66% were racial/ethnic minorities. Women with comorbid depression reported greater impact of vaginal symptoms on all dimensions of functioning and well-being measured by the DIVA questionnaire (11%-22% estimated increase in impact scores associated with every three-point increase in Hospital and Anxiety Depression Scale scores). Women with urinary incontinence also reported greater impact of vaginal symptoms on activities of daily living, emotional well-being, and self-concept and body image (27%-37% estimated increase in impact scores). Age, partner status, frequency of sexual activity, general health, and body mass index also predicted greater impact on at least one domain. Findings suggest that special efforts should be made to identify and treat vaginal symptoms in postmenopausal women known to have depression or urinary incontinence, as these women may experience greater impact of vaginal symptoms on multiple domains of functioning and quality of life.
Authors: Hunter MM; Nakagawa S; Van Den Eeden SK; Kuppermann M; Huang AJ
Menopause. 2016 Jan;23(1):40-6.
Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood
Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3-5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.
Authors: Ladd-Acosta C; Feinberg AP; Daniele Fallin M; et al.
Environ Res. 2016 Jan;144(Pt A):139-48. Epub 2015-11-21.
Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus: A Prospective Cohort Study
Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). Integrated health care system. 1035 women diagnosed with GDM who delivered singletons at 35 weeks’ gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Randomized design is not feasible or desirable for clinical studies of lactation. Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. National Institute of Child Health and Human Development.
Authors: Gunderson EP; Lo JC; Sternfeld B; Quesenberry CP; Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy Investigators; et al.
Ann Intern Med. 2015 Dec 15;163(12):889-98. Epub 2015-11-24.
Pioglitazone Use and Risk of Bladder Cancer–Reply
Authors: Ferrara A; Lewis JD; Habel LA
JAMA. 2015 Dec 15;314(23):2568-9.
Maternal Infection During Pregnancy and Autism Spectrum Disorders
We conducted a nested case-control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (ORadj) = 1.15, 95 % confidence interval (CI) 0.92-1.43]. However, women with infections diagnosed during a hospital admission (ORadj = 1.48, 95 % CI 1.07-2.04), particularly bacterial infections (ORadj = 1.58, 95 % CI 1.06-2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (ORadj = 1.36, 95 % CI 1.05-1.78).
Authors: Zerbo O; Qian Y; Yoshida C; Grether JK; Van de Water J; Croen LA
J Autism Dev Disord. 2015 Dec;45(12):4015-25.
A Study of Physician Knowledge and Experience with Autism in Adults in a Large Integrated Healthcare System
We conducted an online survey of adult health care providers at Kaiser Permanente Northern California and semi-structured interviews with a subset of physicians. The survey assessed providers’ ability to recognize autism spectrum disorder (ASD), asked them to rate their autism knowledge, comfort level in treating affected patients, and evaluated training and resource needs. 922 providers completed the survey (response rate 25.3 %), and 9 were interviewed by telephone regarding their autism training and experiences caring for patients with autism. Most providers reported lacking skills and tools to care for this adult patient population. A high proportion of adult providers were not aware that they had patients with ASD. These findings underscore the need to educate physicians caring for adults with ASD.
Authors: Zerbo O; Massolo ML; Qian Y; Croen LA
J Autism Dev Disord. 2015 Dec;45(12):4002-14.
External Validation of Early Weight Loss Nomograms for Exclusively Breastfed Newborns
Nomograms that show hour-by-hour percentiles of weight loss during the birth hospitalization were recently developed to aid clinical care of breastfeeding newborns. The nomograms for breastfed neonates were based on a sample of 108,907 newborns delivered at 14 Kaiser Permanente medical centers in Northern California (United States). The objective of this study was to externally validate the published nomograms for newborn weight loss using data from a geographically distinct population. Data were compiled from the Penn State Milton S. Hershey Medical Center located in Hershey, PA. For singleton neonates delivered at ?36 weeks of gestation between January 2013 and September 2014, weights were obtained between 6 hours and 48 hours (vaginal delivery) or 60 hours (cesarean delivery) for neonates who were exclusively breastfeeding. Quantile regression methods appropriate for repeated measures were used to estimate 50th, 75th, 90th, and 95th percentiles of weight loss as a function of time after birth. These percentile estimates were compared with the published nomograms. Of the 1,587 newborns who met inclusion criteria, 1,148 were delivered vaginally, and 439 were delivered via cesarean section. These newborns contributed 1,815 weights for vaginal deliveries (1.6 per newborn) and 893 weights for cesarean deliveries (2.0 per newborn). Percentile estimates from this Penn State sample were similar to the published nomograms. Deviations in percentile estimates for the Penn State sample were similar to deviations observed after fitting the same model separately to each medical center that made up the Kaiser Permanente sample. The published newborn weight loss nomograms for breastfed neonates were externally validated in a geographically distinct population.
Authors: Schaefer EW; Flaherman VJ; Kuzniewicz MW; Li SX; Walsh EM; Paul IM
Breastfeed Med. 2015 Dec;10(10):458-63. Epub 2015-11-13.
Associations of Early and Late Gestational Weight Gain with Infant Birth Size
OBJECTIVES: Associations of gestational weight gain (GWG) during specific periods of pregnancy with infant birth size have been inconsistent. Infant sex-specific differences in these associations are unknown
METHODS: Information on GWG (kg) [total, early (<20 weeks gestation), and late (≥20 weeks gestation)] and indices of infant birth size including birthweight (BW), ponderal index (PI), crown-heel length (CHL), and head circumference (HC) was collected from 3,621 pregnant women. We calculated adjusted mean differences and 95 % confidence intervals (CIs) relating total, early and late GWG to infant birth size using multivariable linear regression procedures. We used stratified analyses and interaction terms to test whether associations differed by infant sex. RESULTS: One-kg increases in total, early or late GWG were associated with BW increases of 17.2 g (95 % CI 13.8-18.9), 14.1 g (95 % CI 10.3-18.0), and 21.0 g (95 % CI 16.7-25.4), respectively. Early GWG-BW and late GWG-BW associations were different (p = 0.026). Sex-stratified total GWG-BW associations were similar to overall results. There were sex-specific differences in early GWG-BW and late GWG-BW associations. Among females, early GWG-BW (12.0 g, 95 % CI 6.7-17.2) and late GWG-BW (24.2 g, 95 % CI 18.2-30.3) associations differed (p = 0.0042); the corresponding associations did not differ among males. Total, early, and late GWG were associated with CHL and HC, but not with PI. Associations did not differ for early or late GWG. CONCLUSIONS FOR PRACTICE: For comparable GWG, late-GWG-related BW increase is greater than early-GWG-related BW increase, particularly among female infants.
Authors: Wander PL; Sitlani CM; Badon SE; Siscovick DS; Williams MA; Enquobahrie DA
Relationship between self-reported residential indoor remodeling and semen quality: a case-control study
The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.
Authors: Miao MH; Li Z; Li DK; Yan B; Liang H; Zhi EL; Du HW; Yuan W
Asian J Androl. 2015 Nov-Dec;17(6):981-4.
Incidence of Dravet Syndrome in a US Population
De novo mutations of the gene sodium channel 1? (SCN1A) are the major cause of Dravet syndrome, an infantile epileptic encephalopathy. US incidence of DS has been estimated at 1 in 40?000, but no US epidemiologic studies have been performed since the advent of genetic testing. In a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California during 2007-2010, we electronically identified patients who received ?2 seizure diagnoses before age 12 months and who were also prescribed anticonvulsants at 24 months. A child neurologist reviewed records to identify infants who met 4 of 5 criteria for clinical Dravet syndrome: normal development before seizure onset; ?2 seizures before age 12 months; myoclonic, hemiclonic, or generalized tonic-clonic seizures; ?2 seizures lasting >10 minutes; and refractory seizures after age 2 years. SCN1A gene sequencing was performed as part of routine clinical care. Eight infants met the study criteria for clinical Dravet syndrome, yielding an incidence of 1 per 15?700. Six of these infants (incidence of 1 per 20?900) had a de novo SCN1A missense mutation that is likely to be pathogenic. One infant had an inherited SCN1A variant that is unlikely to be pathogenic. All 8 experienced febrile seizures, and 6 had prolonged seizures lasting >10 minutes by age 1 year. Dravet syndrome due to an SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ?2 prolonged febrile seizures by 1 year of age.
Authors: Wu YW; Sullivan J; McDaniel SS; Meisler MH; Walsh EM; Li SX; Kuzniewicz MW
Pediatrics. 2015 Nov;136(5):e1310-5. Epub 2015-10-05.
Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California
Findings from national surveys suggest that everyone in the US is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. To evaluate the potential effects of low environmental exposures to perchlorate on thyroid function. Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County during 2000-3, a period when much of the area’s water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 ?g/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. The median urinary perchlorate concentration was 6.5 ?g/L, about 2-times higher than in the general US population. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) (regression coefficient (B)=-0.70; 95% confidence interval (CI), -1.06, -0.34), decreasing free thyroxine (fT4) (B=-0.053; 95% CI, -0.092, -0.013), and increasing log10 thyroid stimulating hormone (B=0.071; 95% CI, 0.008, 0.133). These results suggest that environmental perchlorate exposures may impact thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment.
Authors: Steinmaus C; Pearl M; Kharrazi M; Blount BC; Miller MD; Pearce EN; Valentin-Blasini L; DeLorenze G; Hoofnagle AN; Liaw J
Environ Health Perspect. 2015 Oct 20.
The health status of adults on the autism spectrum
Compared to the general pediatric population, children with autism have higher rates of co-occurring medical and psychiatric illnesses, yet very little is known about the general health status of adults with autism. The objective of this study was to describe the frequency of psychiatric and medical conditions among a large, diverse, insured population of adults with autism in the United States. Participants were adult members of Kaiser Permanente Northern California enrolled from 2008 to 2012. Autism spectrum disorder cases (N = 1507) were adults with autism spectrum disorder diagnoses (International Classification of Diseases-9-Clinical Modification codes 299.0, 299.8, 299.9) recorded in medical records on at least two separate occasions. Controls (N = 15,070) were adults without any autism spectrum disorder diagnoses sampled at a 10:1 ratio and frequency matched to cases on sex and age. Adults with autism had significantly increased rates of all major psychiatric disorders including depression, anxiety, bipolar disorder, obsessive-compulsive disorder, schizophrenia, and suicide attempts. Nearly all medical conditions were significantly more common in adults with autism, including immune conditions, gastrointestinal and sleep disorders, seizure, obesity, dyslipidemia, hypertension, and diabetes. Rarer conditions, such as stroke and Parkinson’s disease, were also significantly more common among adults with autism. Future research is needed to understand the social, healthcare access, and biological factors underlying these observations.
Authors: Croen, Lisa A; Zerbo, Ousseny; Qian, Yinge; Massolo, Maria L; Rich, Steve; Sidney, Stephen; Kripke, Clarissa
Autism. 2015 Oct;19(7):814-23. Epub 2015-04-24.
Autism Spectrum Disorder Symptoms Among Children Enrolled in the Study to Explore Early Development (SEED)
This study examined the phenotypic profiles of children aged 30-68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive, behavioral, and social functioning and the presence of parent-reported conditions. Children with ASD and DD with ASD symptoms had mild to severe ASD risk on several measures compared to children with other DD and POP who had little ASD risk across measures. We conclude that children in SEED have varying degrees of ASD impairment and associated deficits. SEED thus provides a valuable sample to explore ASD phenotypes and inform risk factor analyses.
Authors: Wiggins LD; Croen LA; Schendel D; et al.
J Autism Dev Disord. 2015 Oct;45(10):3183-94.
Associations between Bisphenol A Exposure and Reproductive Hormones among Female Workers
The associations between Bisphenol-A (BPA) exposure and reproductive hormone levels among women are unclear. A cross-sectional study was conducted among female workers from BPA-exposed and unexposed factories in China. Women’s blood samples were collected for assay of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17?-Estradiol (E2), prolactin (PRL), and progesterone (PROG). Their urine samples were collected for BPA measurement. In the exposed group, time weighted average exposure to BPA for an 8-h shift (TWA8), a measure incorporating historic exposure level, was generated based on personal air sampling. Multiple linear regression analyses were used to examine linear associations between urine BPA concentration and reproductive hormones after controlling for potential confounders. A total of 106 exposed and 250 unexposed female workers were included in this study. A significant positive association between increased urine BPA concentration and higher PRL and PROG levels were observed. Similar associations were observed after the analysis was carried out separately among the exposed and unexposed workers. In addition, a positive association between urine BPA and E2 was observed among exposed workers with borderline significance, while a statistically significant inverse association between urine BPA and FSH was observed among unexposed group. The results suggest that BPA exposure may lead to alterations in female reproductive hormone levels.
Authors: Miao M; Yuan W; Yang F; Liang H; Zhou Z; Li R; Gao E; Li DK
Int J Environ Res Public Health. 2015 Oct;12(10):13240-50. Epub 2015-10-22.
Potential harms outweigh benefits of indefinite monitoring of stable adnexal masses
The management of women with asymptomatic adnexal masses should aim to balance potential benefit with potential harm. While masses with highly worrisome features or other signs of malignancy should be referred for surgery, the vast majority of masses have an indeterminate or benign appearance and are candidates for observation. Evidence supports the use of initial short-term serial ultrasound in distinguishing between benign and malignant masses. However, benefit from prolonged, potentially life-long monitoring of stable masses has not been demonstrated. Since the goal of monitoring an adnexal mass is to observe for worrisome growth or increasing complexity as an indicator of malignancy, if the mass remains stable, the likelihood of malignancy and therefore, the potential benefit of observation wanes with time. The recognition that Type 2 high grade serous cancers, which are responsible for the majority of deaths from ovarian cancer, arise from fallopian tube rather than ovarian precursors, further diminishes the likelihood that monitoring a stable ovarian mass will lead to early diagnosis of high grade disease. While some Type 1 cancers may develop from ovarian precursors, the available data suggest that any measurable benefit of monitoring known lesions for detection of these cancers is realized within the first year of observation. The argument in favor of indefinite, potentially life-long monitoring of stable masses also fails to adequately account for the risks of perpetual imaging, which include the risk of incidental findings, an increased likelihood of unnecessary surgery, patient anxiety and cost. It is not always better to order a test than not order a test. Given the absence of evidence of benefit, observation of stable small adnexal masses should be limited in duration in order to minimize potential harms.
Authors: Suh-Burgmann E; Kinney W
Am J Obstet Gynecol. 2015 Dec;213(6):816.e1-4. Epub 2015-09-09.
Risk of Sensorineural Hearing Loss and Bilirubin Exchange Transfusion Thresholds
High bilirubin levels are associated with sensorineural hearing loss (SNHL). However, few large studies of relative and excess risk exist. We sought to quantify the risk of SNHL in newborns who had bilirubin levels at or above American Academy of Pediatrics exchange transfusion thresholds (ETT). Infants born at ?35 weeks gestation in 15 Kaiser Permanente Northern California hospitals from 1995-2011 were eligible (N = 525?409). We used a nested double cohort design. The exposed cohort included subjects with ?1 bilirubin level at or above ETT. The unexposed cohort was a 3.6% random sample of subjects with all bilirubin levels below ETT (10 unexposed per exposed). An audiologist, blinded to bilirubin levels, reviewed the charts of children in whom SNHL had been diagnosed before age 8 years to confirm the diagnosis. We calculated Cox proportional hazard ratios for time to diagnosis of SNHL. SNHL was confirmed in 11 (0.60%) of the 1834 exposed subjects and in 43 (0.23%) of the 19?004 unexposed. Only bilirubin levels ?10 mg/dL above ETT were associated with a statistically significant increased risk of SNHL (hazard ratio: 36 [95% confidence interval (CI): 13 to 101]). Likewise, only bilirubin levels ?35 mg/dL were associated with a statistically significant increased risk of SNHL (hazard ratio: 91 [95% CI: 32 to 255]). For subjects with total serum bilirubin levels 0 to 4.9 mg/dL above ETT, the upper limit of the 95% CI for excess risk was 0.5%. Only bilirubin levels well above ETT were associated with SNHL. At lower bilirubin levels, the excess risk of SNHL was low.
Authors: Wickremasinghe AC; Risley RJ; Kuzniewicz MW; Wu YW; Walsh EM; Wi S; McCulloch CE; Newman TB
Pediatrics. 2015 Sep;136(3):505-12. Epub 2015-08-17.
Prevalence and Predictors of Complementary and Alternative Medicine Use in a Large Insured Sample of Children with Autism Spectrum Disorders
The purpose of the present study was to examine the prevalence and predictors of complementary and alternative medicine (CAM) use as well as parental perceptions of CAM efficacy in a large, geographically diverse sample of children with Autism Spectrum Disorders (ASD). Data were obtained from a web-based survey administered to parents of children with ASD at four sites participating in the Mental Health Research Network (MHRN). The web survey obtained information about services and treatments received by children with ASD as well as the caregivers’ experiences with having a child with ASD. Approximately 88% of the sample had either used CAM in the past or had recently used some type of CAM. The following characteristics were associated with CAM use: greater parental education, younger child age, a mix of regular and special classroom settings and prescription drug use in the past three months. The use of CAM was very prevalent in this large, geographically diverse sample of children with ASD. It is critical that providers be prepared to discuss the advantages and potential side effects with families to help them make well-informed health care decisions and prevent possible CAM-drug interactions.
Authors: Owen-Smith AA; Bent S; Lynch FL; Coleman KJ; Yau VM; Pearson KA; Massolo ML; Quinn V; Croen LA
Res Autism Spectr Disord. 2015 Sep 01;17:40-51.
Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication
This cohort study examines medication use in term neonates with hypoxic-ischemic encephalopathy and seizures before and after implementation of a Neonatal Neurocritical Care Service (N = 108), which included increased seizure monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post-Neonatal Neurocritical Care Service) and total loading dose did not vary among groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment for seizure burden, neonates managed during the Neonatal Neurocritical Care Service era, on average, received 30 mg/kg less cumulative phenobarbital (95% confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95% confidence interval 3-8 days) than those who were treated prior to implementation of the service. In spite of the enhanced ability to detect seizures because of improved monitoring and increased vigilance by bedside practitioners, implementation of the Neonatal Neurocritical Care Service was associated with decreased use of potentially harmful phenobarbital treatment among neonates with hypoxic-ischemic encephalopathy.
Authors: Wietstock SO; Bonifacio SL; McCulloch CE; Kuzniewicz MW; Glass HC
J Child Neurol. 2015 Aug;30(9):1135-41. Epub 2014-11-07.
Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort
Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (?485 000 CpG sites). We also examined associated regions in an independent sample of post-mortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)] <0.05 associated with performance on the Autism Observational Scale for Infants (AOSI) at 12 months of age in offspring. The DMRs clustered near genes involved in developmental processes, including many genes in the SNORD family, within the Prader-Willi syndrome gene cluster. These results were consistent among the 75 probes on the Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75 (24%) 450K array probes showed consistent differences in the cerebellums of autistic individuals compared with controls. These data suggest that epigenetic differences in paternal sperm may contribute to autism risk in offspring, and provide evidence that directionally consistent, potentially related epigenetic mechanisms may be operating in the cerebellum of individuals with autism.
Authors: Feinberg JI; Bakulski KM; Jaffe AE; Tryggvadottir R; Brown SC; Goldman LR; Croen LA; Hertz-Picciotto I; Newschaffer CJ; Fallin MD; Feinberg AP
Int J Epidemiol. 2015 Aug;44(4):1199-210. Epub 2015-04-14.
Pooled Analysis of Six Pharmacologic and Nonpharmacologic Interventions for Vasomotor Symptoms
To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials. An analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time. The 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements. These analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), and NCT01418209 (MsFLASH 03).
Authors: Guthrie KA; Caan B; Anderson GL; et al.
Obstet Gynecol. 2015 Aug;126(2):413-22.
Validation of Autism Spectrum Disorder Diagnoses in Large Healthcare Systems with Electronic Medical Records
To identify factors associated with valid Autism Spectrum Disorder (ASD) diagnoses from electronic sources in large healthcare systems. We examined 1,272 charts from ASD diagnosed youth <18 years old. Expert reviewers classified diagnoses as confirmed, probable, possible, ruled out, or not enough information. A total of 845 were classified with 81% as a confirmed, probable, or possible ASD diagnosis. The predictors of valid ASD diagnoses were >2 diagnoses in the medical record (OR 2.94; 95% CI 2.03-4.25; p < 0.001) and being male (OR 1.51; 95% CI 1.05-2.17; p = 0.03). In large integrated healthcare settings, at least two diagnoses can be used to identify ASD patients for population-based research.
Authors: Coleman KJ; Croen LA; et al.
J Autism Dev Disord. 2015 Jul;45(7):1989-96.
Effects of estrogen and venlafaxine on menopause-related quality of life in healthy postmenopausal women with hot flashes: a placebo-controlled randomized trial
This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind, placebo-controlled, randomized trial of low-dose oral 17?-E2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical placebo, was conducted among 339 women (aged 40-62 y) experiencing two or more vasomotor symptoms (VMS) per day (mean [SD], 8.07 [5.29]) who were recruited at three clinical sites from November 2011 to October 2012. The primary trial outcome, as reported previously, was frequency of VMS at 8 weeks. Here, we report on secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and from measures of pain (Pain, Enjoyment in life, and General activity scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and perceived stress (Perceived Stress Scale). Treatment with both E2 and venlafaxine resulted in significantly greater improvement in quality of life, as measured by total MENQOL scores, compared with placebo (E2: mean difference at 8 wk, -0.4; 95% CI, -0.7 to -0.2; P < 0.001; venlafaxine: mean difference at 8 wk, -0.2; 95% CI, -0.5 to 0.0; P = 0.04). Quality-of-life domain analyses revealed that E2 had beneficial treatment effects on all domains of the MENQOL except for the psychosocial domain, whereas venlafaxine benefits were observed only in the psychosocial domain. Neither E2 nor venlafaxine improved pain, anxiety, or depressive symptoms, although baseline symptom levels were low. Modest benefits were observed for perceived stress with venlafaxine. Both low-dose E2 and venlafaxine are effective pharmacologic agents for improving menopause-related quality of life in healthy women with VMS.
Authors: Caan B; Sternfeld B; Ensrud K; et al.
Menopause. 2015 Jun;22(6):607-15.
The Association Between Influenza Vaccination and Other Preventative Health Behaviors in a Cohort of Pregnant Women
Although pregnant women are a high-priority group for seasonal influenza vaccination, vaccination rates in this population remain below target levels. Previous studies have identified sociodemographic predictors of vaccine choice, but relationships between preconception heath behaviors and seasonal influenza vaccination are poorly understood. This prospective cohort study followed pregnant women during the 2010-2011 influenza season to determine if certain health behaviors were associated with vaccination status. Participants were pregnant women receiving prenatal care from Kaiser Permanente Northwest and Kaiser Permanente Northern California. Women were surveyed about preconception smoking, alcohol consumption, and vitamin/supplement use. Vaccination data were obtained from health plan databases and state immunization records. Data from 1,204 women were included in this analysis. Most participants (1,204; 66.4%) received a seasonal influenza vaccine during the study period. Women vaccinated prior to pregnancy were more likely to use a supplement containing folic acid (80%) or vitamin D (30%) compared with women who were vaccinated during pregnancy (72% and 15%, respectively) or unvaccinated women (62% and 12%, respectively, p < .001). Women vaccinated prior to or during pregnancy were more likely (75%) to have never smoked compared with women who were not vaccinated (70%, p = .005). There were no significant differences in alcohol use or household cigarette smoke exposure by vaccination group. Women who engaged in specific preconception health behaviors were more likely to receive seasonal influenza vaccination. Failure to participate in these health behaviors could alert health care practitioners to patients' increased risk of remaining unvaccinated during pregnancy.
Authors: Scheminske M; Henninger M; Irving SA; Thompson M; Williams J; Shifflett P; Ball SW; Avalos LA; Naleway AL; Pregnancy and Influenza Project Workgroup
Health Educ Behav. 2015 Jun;42(3):402-8. Epub 2014-12-12.
Asthma Treatments and Mental Health Visits After a Food and Drug Administration Label Change for Leukotriene Inhibitors
In 2009, the US Food and Drug Administration (FDA) mandated a label change for leukotriene inhibitors (LTIs) to include neuropsychiatric adverse events (eg, depression and suicidality) as a precaution. This study investigated how this label change affected the use of LTIs and other asthma controller medications, mental health visits, and suicide attempts. We analyzed data (2005-2010) from 5 large health plans in the US Population-Based Effectiveness in Asthma and Lung Diseases (PEAL) Network. The study cohort included children and adolescents (n = 30,000), young adults (n = 20,000), and adults (n = 90,000) with asthma. We used interrupted time series to examine changes in rates of LTI dispensings, non-LTI dispensings, mental health visits, and suicide attempts (using a validated algorithm based on a combination of diagnoses of injury or poisoning and psychiatric conditions). The label change was associated with abrupt reductions in LTI use among all age groups (relative reductions of 8.3%, 15.1%, and 6.0% among adolescents, young adults, and adults, respectively, compared with expected rates at 1 year after the warnings). Although we detected immediate offset increases in non-LTI asthma medication use, these increases were not sustained among adolescents and young adults. There were small increases in mental health visits among LTI users. The FDA label change for LTIs communicated possible risk of neuropsychiatric events. Communication and enhanced awareness may have increased reporting of mental health symptoms among young adults and adults. It is important to assess intended and unintended consequences of FDA warnings and label changes.
Authors: Lu CY; Zhang F; Lakoma MD; Butler MG; Fung V; Larkin EK; Kharbanda EO; Vollmer WM; Lieu T; Soumerai SB; Chen Wu A
Clin Ther. 2015 Jun 1;37(6):1280-91. Epub 2015-04-25.
Factors Associated with Seasonal Influenza Vaccination in Pregnant Women
This observational study followed a cohort of pregnant women during the 2010-2011 influenza season to determine factors associated with vaccination. Participants were 1105 pregnant women who completed a survey assessing health beliefs related to vaccination upon enrollment and were then followed to determine vaccination status by the end of the 2010-2011 influenza season. We conducted univariate and multivariate analyses to explore factors associated with vaccination status and a factor analysis of survey items to identify health beliefs associated with vaccination. Sixty-three percent (n=701) of the participants were vaccinated. In the univariate analyses, multiple factors were associated with vaccination status, including maternal age, race, marital status, educational level, and gravidity. Factor analysis identified two health belief factors associated with vaccination: participant’s positive views (factor 1) and negative views (factor 2) of influenza vaccination. In a multivariate logistic regression model, factor 1 was associated with increased likelihood of vaccination (adjusted odds ratio [aOR]=2.18; 95% confidence interval [CI]=1.72-2.78), whereas factor 2 was associated with decreased likelihood of vaccination (aOR=0.36; 95% CI=0.28-0.46). After controlling for the two health belief factors in multivariate analyses, demographic factors significant in univariate analyses were no longer significant. Women who received a provider recommendation were about three times more likely to be vaccinated (aOR=3.14; 95% CI=1.99-4.96). Pregnant women’s health beliefs about vaccination appear to be more important than demographic and maternal factors previously associated with vaccination status. Provider recommendation remains one of the most critical factors influencing vaccination during pregnancy.
Authors: Henninger ML; Irving SA; Thompson M; Avalos LA; Ball SW; Shifflett P; Naleway AL; Influenza Project (PIP) Working Group
J Womens Health (Larchmt). 2015 May;24(5):394-402. Epub 2015-04-15.
Immune mediated conditions in autism spectrum disorders
We conducted a case-control study among members of Kaiser Permanente Northern California (KPNC) born between 1980 and 2003 to determine the prevalence of immune-mediated conditions in individuals with autism, investigate whether these conditions occur more often than expected, and explore the timing of onset relative to autism diagnosis. Cases were children and young adults with at least two autism diagnoses recorded in outpatient records (n=5565). Controls were children without autism randomly sampled at a ratio of 5 to 1, matched to cases on birth year, sex, and length of KPNC membership (n=27,825). The main outcomes – asthma, allergies, and autoimmune diseases – were identified from KPNC inpatient and outpatient databases. Chi-square tests were used to evaluate case-control differences. Allergies and autoimmune diseases were diagnosed significantly more often among children with autism than among controls (allergy: 20.6% vs. 17.7%, Crude odds ratio (OR)=1.22, 95% confidence interval (CI) 1.13-1.31; autoimmune disease: 1% vs. 0.76%, OR=1.36, 95% CI 1.01-1.83), and asthma was diagnosed significantly less often (13.7% vs. 15.9%; OR=0.83, 95% CI 0.76-0.90). Psoriasis occurred more than twice as often in cases than in controls (0.34% vs. 0.15%; OR=2.35, 95% CI 1.36-4.08). Our results support previous observations that children with autism have elevated prevalence of specific immune-related comorbidities.
Authors: Zerbo O; Leong A; Barcellos L; Bernal P; Fireman B; Croen LA
Brain Behav Immun. 2015 May;46:232-6. Epub 2015-02-11.
Results of a Pilot Study using Self-Collected Mid-Turbinate Nasal Swabs for Detection of Influenza Virus Infection among Pregnant Women
We evaluated the feasibility of asking pregnant women to self-collect and ship respiratory specimens. In a preliminary laboratory study, we compared the RT-PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4 to 35°C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30 days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (-20°C) (baseline condition). In a subsequent pilot study, during January-February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods. CT values were stable after storage at temperatures <27°C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26.5, 95% confidence interval [CI] = 26.0-27.1) and for the 8 influenza A virus positives in our pilot (32.2, 95% CI = 28.9-35.5) were significantly higher than the CTs observed in our 2010-2012 study using staff-collected nasal pharyngeal swabs (P-values < 0.01). Self-collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach.
Authors: Thompson MG; Ferber JR; Odouli R; David D; Shifflett P; Meece JK; Naleway AL; Bozeman S; Spencer SM; Fry AM; Li DK
Influenza Other Respir Viruses. 2015 May;9(3):155-60.
Early weight loss nomograms for formula fed newborns
To develop nomograms depicting percentiles of weight loss by hour of age for both vaginal and cesarean-delivered newborns who are exclusively formula fed. Data regarding delivery mode, race/ethnicity, feeding type, and weights were extracted from electronic medical records of the birth hospitalization at 14 Kaiser Permanente Northern California hospitals between 2009 and 2013. Newborns whose first feeding was formula from a cohort of 161 471 healthy, term, singleton neonates born at ?36 weeks’ gestation between 2009 and 2013 were identified. Quantile regression was used to create nomograms stratified according to delivery mode; percentiles of weight loss were estimated as a function of time among formula-fed neonates. Weights measured subsequent to any breast milk feeding were excluded. Percentiles were determined through 48 and 72 hours of age for those born vaginally and via cesarean delivery, respectively. A total of 7075 formula-fed newborns had weights recorded; 4525 were delivered vaginally, and 2550 were born via cesarean delivery. The median weight loss was 2.9% at 48 hours after vaginal delivery; weight loss>7% was rare. For cesarean-delivered neonates, median weight losses at 48 and 72 hours were 3.7% and 3.5%, respectively; weight loss>8% was rare. For newborns who are formula fed, these results provide nomograms depicting percentiles of weight loss according to mode of delivery. These plots can be used to classify early weight loss according to percentile and may enable early identification of feeding difficulties or other neonatal morbidities.
Authors: Miller JR; Flaherman VJ; Schaefer EW; Kuzniewicz MW; Li SX; Walsh EM; Paul IM
Hosp Pediatr. 2015 May;5(5):263-8.
A Vaccine Study Design Selection Framework for the Postlicensure Rapid Immunization Safety Monitoring Program
The Postlicensure Rapid Immunization Safety Monitoring Program, the vaccination safety monitoring component of the US Food and Drug Administration’s Mini-Sentinel project, is currently the largest cohort in the US general population for vaccine safety surveillance. We developed a study design selection framework to provide a roadmap and description of methods that may be utilized to evaluate potential associations between vaccines and health outcomes of interest in the Postlicensure Rapid Immunization Safety Monitoring Program and other systems using administrative data. The strengths and weaknesses of designs for vaccine safety monitoring, including the cohort design, the case-centered design, the risk interval design, the case-control design, the self-controlled risk interval design, the self-controlled case series method, and the case-crossover design, are described and summarized in tabular form. A structured decision table is provided to aid in planning of future vaccine safety monitoring activities, and the data components comprising the structured decision table are delineated. The study design selection framework provides a starting point for planning vaccine safety evaluations using claims-based data sources.
Authors: Baker MA; Lieu TA; Li L; Hua W; Qiang Y; Kawai AT; Fireman BH; Martin DB; Nguyen MD
Am J Epidemiol. 2015 Apr 15;181(8):608-18. Epub 2015-03-13.
Maternal caffeine intake during pregnancy and risk of obesity in offspring: a prospective cohort study
In-utero exposures through adverse fetal programming are emerging as an important contributing factor to the epidemic of childhood obesity. This study examines the impact of in-utero exposure to caffeine on the risk of childhood obesity in offspring. A prospective study of pregnant women with 15 years follow-up of their offspring was conducted to examine the impact of in-utero exposure to caffeine on the risk of childhood obesity. Maternal caffeine intake was prospectively ascertained during pregnancy and outcome measures (body mass index (BMI)) were ascertained from medical charts, with 17 BMI measurements per child, on average, during the follow-up period. Potential confounders including known perinatal risk factors for childhood obesity were adjusted for using the generalized estimating equations model with repeated measurements. After controlling for potential confounders, compared with those without caffeine exposure, in-utero exposure to caffeine overall is associated with 87% increased risk of childhood obesity: odds ratio (OR) =1.87, 95% confidence interval (CI): 1.12-3.12. This association demonstrated a dose-response relationship: OR=1.77 (1.05-3.00) for maternal daily caffeine intake <150?mg per day, OR=2.37 (1.24-4.52) for caffeine intake ?150?mg per day during pregnancy, respectively. We also observed a linear relationship: every one unit increase (log10 scale) in the amount of maternal caffeine intake was associated with 23% increased risk of obesity in offspring. The dose-response relationship appears stronger for persistent obesity than for transitory obesity (occasional high BMI), and for girls than for boys. We observed an association of in-utero exposure to caffeine with increased risk of childhood obesity. If this observation is further replicated in other studies, the finding will contribute to the understanding of fetal programming of childhood diseases and development of intervention strategy to prevent childhood obesity.
Authors: Li DK; Ferber JR; Odouli R
Int J Obes (Lond). 2015 Apr;39(4):658-64. Epub 2014-11-12.
A Randomized Clinical Trial of Therapeutic Hypothermia Mode during Transport for Neonatal Encephalopathy
To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.
Authors: Akula VP; Kuzniewicz M; Van Meurs K; et al.
J Pediatr. 2015 Apr;166(4):856-61.e1-2. Epub 2015-02-12.
Reproductive health outcomes of insured adolescent and adult women who access oral levonorgestrel emergency contraception
To assess the level of risk for adolescents and women who seek emergency contraception through various clinical routes and the opportunities for improved care provision. This study looked at a retrospective cohort to assess contraception and other reproductive health outcomes among adolescents and women aged 15-44 years who accessed oral levonorgestrel emergency contraception through an office visit or the call center at Kaiser Permanente Northern California from 2010 to 2011. Of 21,421 prescriptions, 14,531 (67.8%) were accessed through the call center. In the subsequent 12 months, 12,127 (56.6%) adolescents and women had short-acting contraception (pills, patches, rings, depot medroxyprogesterone) dispensed and 2,264 (10.6%) initiated very effective contraception (intrauterine contraception, implants, sterilization). Initiation of very effective contraception was similar for adolescents and women who accessed it through the call center-1,569 (10.8%) and office visits-695 (10.1%) (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.93-1.13). In the subsequent 6 months, 2,056 (9.6%) adolescents and women became pregnant. Adolescents and women who accessed emergency contraception through the call center were less likely to become pregnant within 3 months of accessing emergency contraception than woman who accessed it through office visits (adjusted OR 0.82, 95% CI 0.72-0.94); however, they were more likely to become pregnant within 4-6 months (adjusted OR 1.37, 95% CI 1.16-1.60). Among adolescents and women who were tested for chlamydia and gonorrhea, 689 (7.8%) and 928 (7.9%) were positive in the 12 months before and after accessing emergency contraception, respectively. Protocols to routinely address unmet needs for contraception at every call for emergency contraception and all office visits, including visits with primary care providers, should be investigated.
Authors: Raine-Bennett T; Merchant M; Sinclair F; Lee JW; Goler N
Obstet Gynecol. 2015 Apr;125(4):904-11.
Follow-up of extreme neonatal hyperbilirubinemia: more reassuring results from Denmark
Authors: Newman TB; Kuzniewicz MW
Dev Med Child Neurol. 2015 Apr;57(4):314-5. Epub 2014-10-28.
Topiramate use during pregnancy and major congenital malformations in multiple populations
We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk. Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3. MCMs were a code for any major congenital malformation dated within 30 days of the delivery date on the mother’s claims or within 365 days after infant birth date, excluding a genetic or syndromic basis, and with procedure or healthcare usage consistent with the MCM diagnosis code in the 365 days after infant birth. Of the 10 specific common MCMs evaluated, 1 (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both primary comparisons, and 4 (ventricular septal defect, atrial septal defect, hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5 for one of the two comparisons. Following screening of organ systems with elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus arteriosus in both comparisons and for obstructive genitourinary defects in one comparison. To evaluate a large number of MCMs across many pregnancies, we used crude methods for detecting potential signals. Therefore, these results should be seen as potential signals, not causal.
Authors: Tennis P; Li DK; Esposito DB; et al.
Birth Defects Res Part A Clin Mol Teratol. 2015 Apr;103(4):269-75. Epub 2015-03-16.
Simple physical performance measures and vascular health in late midlife women: the Study of Women’s Health across the nation
Physical performance measures have been shown to predict mortality and incident cardiovascular disease (CVD) mainly in elderly populations. We evaluated whether physical performance measures are associated with vascular health indices (carotid intima-media thickness (cIMT), adventitial diameter (cAD) and carotid plaque) in a large sample of multi-ethnic, late midlife women. Participants from the Study of Women’s Health Across the Nation free of CVD and who had carotid ultrasound assessed at the 12th annual visit were evaluated. Physical function (PF) measures at visit 12 included: average 40-foot walking speed and average time needed for sit-to-stand assessment. A total of 1103 women (53.7% White, 30.5% Black, 15.9% Chinese) aged 59.6±2.7years at visit 12, were included. In models adjusted for study site, race, current age, menopausal status and systolic blood pressure, slower walking speed and longer time needed for sit-to-stand were significantly associated with wider cAD, thicker cIMT and a higher probability of a high level of carotid plaque burden (all P-values<0.05). Associations between walking speed and cAD, and between time needed for sit-to-stand and cAD, remained significant (P=0.04) or marginally significant (P=0.07), respectively, after additional adjustment for CVD risk factors, medications and physical activity. However, the associations between PF measures and cIMT and plaque burden were largely explained by traditional CVD risk factors. The current study suggests that worse performance in simple objective PF tests may be an early indicator of vascular structural changes that precede vascular disease among women at late midlife.
Authors: El Khoudary SR; Chen HY; Barinas-Mitchell E; McClure C; Selzer F; Karvonen-Gutierrez C; Jackson EA; Ylitalo KR; Sternfeld B
Int J Cardiol. 2015 Mar 1;182:115-20. Epub 2014-12-23.
Parents’ Choices and Rationales for Alternative Vaccination Schedules: A Qualitative Study
A growing number of parents adopt alternative vaccination schedules for their children. A better understanding of parents’ rationales for these choices is needed to guide vaccine decision making. We conducted 24 semistructured telephone interviews with parents of 12- to 36-month-olds and analyzed data using an inductive approach. We identified 5 alternative vaccination approaches: “Dr Sears” schedule, shot-limiting approach, selective delay or decline, visit-by-visit decisions, and refusal of all vaccines. Parents who adopted alternative approaches expressed a desire for more control of exposure to vaccine ingredients; vaccine safety, immune system burden, and perceived disease risk were articulated as concerns. Parents who adopt alternative vaccination schedules can be classified in defined subgroups based on their decision-making approaches, and many describe considered reasons to support their actions. Communications that acknowledge and address those reasons may be better able to engage parents and ultimately enhance the process of decision making about vaccines.
Authors: Saada A; Lieu TA; Morain SR; Zikmund-Fisher BJ; Wittenberg E
Clin Pediatr (Phila). 2015 Mar;54(3):236-43. Epub 2014-09-07.
Risk for Cerebral Palsy in Infants With Total Serum Bilirubin Levels at or Above the Exchange Transfusion Threshold: A Population-Based Study
Exchange transfusion is recommended for newborns with total serum bilirubin (TSB) levels thought to place them at risk for cerebral palsy (CP). However, the excess risk for CP among these infants is unknown. To quantify the risks for CP and CP consistent with kernicterus that are associated with high TSB levels based on the 2004 American Academy of Pediatrics exchange transfusion threshold (ETT) guidelines. We enrolled 2 cohorts from a population of 525,409 infants in the Late Impact of Getting Hyperbilirubinemia or Phototherapy (LIGHT) birth cohort. Eligible infants were born at a gestational age of at least 35 weeks at 15 hospitals within the Kaiser Permanente Northern California integrated medical care delivery system from January 1, 1995, through December 31, 2011. The exposed cohort included all 1833 infants with at least 1 TSB measurement at or above the ETT based on age at testing, gestational age, and results of direct antiglobulin testing. The unexposed cohort was a 20% random sample of 104 716 infants with TSB levels below the ETT. A pediatric neurologist blinded to the TSB levels reviewed medical records to determine the presence of CP, defined as a nonprogressive congenital motor dysfunction with hypertonia or dyskinesia. Cerebral palsy was judged to be consistent with kernicterus if magnetic resonance imaging of the brain revealed bilateral globus pallidus injury in the setting of dyskinetic CP. We identified CP in 7 of 1833 exposed (0.4%) vs 86 of 104 716 unexposed (0.1%) infants (relative risk, 4.7 [95% CI, 2.2-10.0]). Absolute risk differences were 0.2% (95% CI, 0%-0.5%) for a TSB level 0 to 4.9 mg/dL above the ETT (n = 1705), 0.9% (95% CI, 0.1%-5.3%) for a TSB level 5.0 to 9.9 mg/dL above the ETT (n = 102), and 7.6% (95% CI, 2.1%-24.1%) for a TSB level 10 mg/dL or more above the ETT (n = 26). Cerebral palsy consistent with kernicterus occurred in 3 infants (incidence, 0.57 per 100,000 births); all 3 had TSB levels of more than 5.0 mg/dL above the ETT and at least 2 risk factors for neurotoxicity, such as prematurity, glucose-6-phosphate dehydrogenase deficiency, or hypoxia-ischemia. Cerebral palsy consistent with kernicterus occurred only in infants with 2 or more risk factors for neurotoxicity and TSB levels of more than 5 mg/dL above the ETT. Among infants with lower degrees of TSB level elevation, the excess risk for CP is minimal.
Authors: Wu YW; Kuzniewicz MW; Wickremasinghe AC; Walsh EM; Wi S; McCulloch CE; Newman TB
JAMA Pediatr. 2015 Mar;169(3):239-46.
Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders
Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay (n = 45), and general population controls (GP) (n = 149). Samples were retrieved from prenatal and newborn screening specimen archives. Adjusted logistic regression models showed inverse associations between ASD and log transformed TSH levels in maternal serum samples (ASD vs. GP: OR [95 % CI] 0.33 [0.12-0.91], Early Onset ASD vs. GP: 0.31 [0.10-0.98]). Results for thyroid levels in newborn blood samples were similar though not significant (ASD vs. GP: 0.61 [0.18-2.04]).
Authors: Yau VM; Lutsky M; Yoshida CK; Lasley B; Kharrazi M; Windham G; Gee N; Croen LA
J Autism Dev Disord. 2015 Mar;45(3):719-30.
Exposure to bisphenol-A and reproductive hormones among male adults
Bisphenol A (BPA) is a suspected human endocrine disruptor which is widely used. In order to determine whether urine BPA level is associated with serum reproductive hormone levels among male adults, we carried out a cross-sectional study in China. We recruited 592 male workers and collected their urine samples for BPA measurement. We also collected blood samples and examined serum reproductive hormones. We used multiple linear regression and log-binomial model to examine associations between urine BPA level and hormone levels after controlling for age and smoking status. An increased urine BPA level was associated with increased prolactin (p<0.001), estradiol (p<0.001), sex hormone-binding globulin level (p=0.001), and a reduced androstenedione (p<0.001) and free androgen index level (p=0.021). Males, whose urine BPA level was in the 2nd, 3rd and highest quartiles, had respectively 1.58, 1.33 and 3.09-fold increased prevalence of having a high prolactin level (>P75 level). The highest quartile of BPA level was associated with 1.63 and 1.50-fold increased prevalence of having a high estradiol and elevated sex hormone-binding globulin level. Males with higher quartile of BPA level had a lower inhibin B level. High BPA exposure is associated with increased prolactin, estradiol and sex hormone-binding globulin level in males, and may contribute to male infertility.
Authors: Liu X; Miao M; Zhou Z; Gao E; Chen J; Wang J; Sun F; Yuan W; Li DK
Environ Toxicol Pharmacol. 2015 Mar;39(2):934-41. Epub 2015-03-14.
Increased female autosomal burden of rare copy number variants in human populations and in autism families
Autosomal genetic variation is presumed equivalent in males and females and makes a major contribution to disease risk. We set out to identify whether maternal copy number variants (CNVs) contribute to autism spectrum disorders (ASDs). Surprisingly, we observed a higher autosomal burden of large, rare CNVs in females in the population, reflected in, but not unique to, ASD families. Meta-analysis across control data sets confirms female excess in CNV number (P=2.1 × 10(-5)) and gene content (P=4.1 × 10(-3)). We additionally observed CNV enrichment in ASD mothers compared with control mothers (P=0.03). We speculate that tolerance for CNV burden contributes to decreased female fetal loss in the population and that ASD-specific maternal CNV burden may contribute to high sibling recurrence. These data emphasize the need for study of familial CNV risk factors in ASDs and the requirement of sex-matched comparisons.
Authors: Desachy G; Croen LA; Torres AR; Kharrazi M; Delorenze GN; Windham GC; Yoshida CK; Weiss LA
Mol Psychiatry. 2015 Feb;20(2):170-5. Epub 2015-01-13.
Primary Adherence to Controller Medications for Asthma is Poor
Few previous studies have evaluated primary adherence (whether a new prescription is filled within 30 d) to controller medications in individuals with persistent asthma. To compare adherence to the major controller medication regimens for asthma. This was a retrospective cohort study of enrollees from five large health plans. We used electronic medical data on patients of all ages with asthma who had experienced an asthma-related exacerbation in the prior 12 months. We studied adherence measures including proportion of days covered and primary adherence (first prescription filled within 30 d). Our population included 69,652 subjects who had probable persistent asthma and were prescribed inhaled corticosteroids (ICSs), leukotriene antagonists (LTRAs), or ICS/long-acting ?-agonists (ICS/LABAs). The mean age was 37 years and 58% were female. We found that 14-20% of subjects who were prescribed controller medicines for the first time did not fill their prescriptions. The mean proportion of days covered was 19% for ICS, 30% for LTRA, and 25% for ICS/LABA over 12 months. Using multivariate logistic regression, subjects prescribed LTRA were less likely to be primary adherent than subjects prescribed ICS (odds ratio, 0.82; 95% confidence interval, 0.74-0.92) or ICS/LABA (odds ratio, 0.88; 95% confidence interval, 0.80-0.97). Black and Latino patients were less likely to fill the prescription compared with white patients. Adherence to controller medications for asthma is poor. In this insured population, primary adherence to ICSs was better than to LTRAs and ICS/LABAs. Adherence as measured by proportion of days covered was better for LTRAs and ICS/LABAs than for ICSs.
Authors: Wu AC; Butler MG; Li L; Fung V; Kharbanda EO; Larkin EK; Vollmer WM; Miroshnik I; Davis RL; Lieu TA; Soumerai SB
Ann Am Thorac Soc. 2015 Feb;12(2):161-6.
Geographic Clusters in Underimmunization and Vaccine Refusal
Parental refusal and delay of childhood vaccines has increased in recent years and is believed to cluster in some communities. Such clusters could pose public health risks and barriers to achieving immunization quality benchmarks. Our aims were to (1) describe geographic clusters of underimmunization and vaccine refusal, (2) compare clusters of underimmunization with different vaccines, and (3) evaluate whether vaccine refusal clusters may pose barriers to achieving high immunization rates. We analyzed electronic health records among children born between 2000 and 2011 with membership in Kaiser Permanente Northern California. The study population included 154,424 children in 13 counties with continuous membership from birth to 36 months of age. We used spatial scan statistics to identify clusters of underimmunization (having missed 1 or more vaccines by 36 months of age) and vaccine refusal (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes). We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010-2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P < .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them. Underimmunization and vaccine refusal cluster geographically. Spatial scan statistics may be a useful tool to identify locations with challenges to achieving high immunization rates, which deserve focused intervention.
Authors: Lieu TA; Ray GT; Klein NP; Chung C; Kulldorff M
Pediatrics. 2015 Feb;135(2):280-9. Epub 2015-01-19.
Severity of influenza and non-influenza acute respiratory illness among pregnant women, 2010-12
The objective of the study was to identify characteristics of influenza illness contrasted with noninfluenza acute respiratory illness (ARI) in pregnant women. ARI among pregnant women was identified through daily surveillance during 2 influenza seasons (2010-2012). Within 8 days of illness onset, nasopharyngeal swabs were collected, and an interview was conducted for symptoms and other characteristics. A follow-up telephone interview was conducted 1-2 weeks later, and medical records were extracted. Severity of illness was evaluated by self-assessment of 12 illness symptoms, subjective ratings of overall impairment, highest reported temperature, illness duration, and medical utilization. Of 292 pregnant women with ARI, 100 tested positive for influenza viruses. Women with influenza illnesses reported higher symptom severity than those with noninfluenza ARI (median score, 18 vs 16 of 36; P < .05) and were more likely to report severe subjective feverishness (18% vs 5%; P < .001), myalgia (28% vs 14%; P < .005), cough (46% vs 30%; P < .01), and chills (25% vs 13%; P < .01). More influenza illnesses were associated with fever greater than 38.9°C (20% vs 5%; P < .001) and higher subjective impairment (mean score, 5.9 vs 4.8; P < .001). Differences in overall symptom severity, fever, cough, chills, early health care-seeking behavior, and impairment remained significant in multivariate models after adjusting for study site, season, age, vaccination status, and number of days since illness onset. Influenza had a greater negative impact on pregnant women than noninfluenza ARIs, as indicated by symptom severity and greater likelihood of elevated temperature. These results highlight the importance of preventing and treating influenza illnesses in pregnant women.
Authors: Sokolow LZ; Naleway AL; Li DK; Shifflett P; Reynolds S; Henninger ML; Ferber JR; Odouli R; Irving SA; Thompson MG; Pregnancy and Influenza Project Workgroup
Am J Obstet Gynecol. 2015 Feb;212(2):202.e1-11. Epub 2014-08-08.
Antidepressant medication use, depression, and the risk of preeclampsia
To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser Permanente Northern California members between 2010 and 2012. The overall risk of preeclampsia was 4.5%. The timing of antidepressant medication exposure was an important factor. A significant increase in the risk of preeclampsia emerged for women with a depression diagnosis who took antidepressant medications during the second trimester compared to women with untreated depression (adjusted relative risk [aRR]: 1.6, 95% CI: 1.06, 2.39) and to women without depression (aRR: 1.70, 95% CI: 1.30, 2.23). Similar associations existed for women who took antidepressant medications, but without depression. In contrast, depressed women with psychotherapy showed no increased risk of preeclampsia compared to women with untreated depression or no depression. There was also a statistically significant relationship between the duration of antidepressant medication use and preeclampsia. The observed association appeared stronger for selective serotonin reuptake inhibitor (SSRI) use, although a nonsignificant trend was also noted for use of norepinephrine-dopamine reuptake inhibitors (NDRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Study findings suggest that antidepressant use during pregnancy may increase the risk of preeclampsia, especially use during the second trimester.
Authors: Avalos LA; Chen H; Li DK
CNS Spectr. 2015 Feb;20(1):39-47.
Recent evidence exploring the associations between physical activity and menopausal symptoms in midlife women: perceived risks and possible health benefits
Although the health benefits of physical activity are well established, the prevalence of midlife women accumulating sufficient physical activity to meet current physical activity guidelines is strikingly low, as shown in United States (U.S.) based surveillance systems that utilize either (or both) participant-reported and device-based (i.e., accelerometers) measures of activity. For midlife women, these low prevalence estimates may be due, in part, to a general lack of time given more pressing work commitments and family obligations. Further, the benefits or “reward” of allocating limited time to physical activity may be perceived, by some, as too distant for immediate action or attention. However, shifting the health promotion message from the long term benefits of physical activity to the more short-term, acute benefits may encourage midlife women to engage in more regular physical activity. In this article, we review the latest evidence (i.e., past 5 years) regarding the impact of physical activity on menopausal symptoms. Recent studies provide strong support for the absence of an effect of physical activity on vasomotor symptoms; evidence is still inconclusive regarding the role of physical activity on urogenital symptoms (vaginal dryness, urinary incontinence) and sleep, but consistently suggestive of a positive impact on mood and weight control. To further advance this field, we also propose additional considerations and future research directions.
Authors: Pettee Gabriel K; Mason JM; Sternfeld B
Womens Midlife Health. 2015;1:1. Epub 2015-08-11.
A STUDY OF GENOTYPING FOR THE MANAGEMENT OF HUMAN PAPILLOMAVIRUS-POSITIVE, CYTOLOGY-NEGATIVE CERVICAL SCREENING RESULTS
The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. This study included 18,810 women with Hybrid Capture 2 (HC2)-positive, cytology-negative results and who were age ?30 years from Kaiser Permanente Northern California. The median follow-up was 475 days (interquartile range [IQR], 0 to 1,077 days; maximum, 2,217 days). The baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive noncases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, the 3-year cumulative risks of CIN3+ were calculated for each individual high-risk HPV type. The 3-year cumulative risk of CIN3+ among all women with HC2-positive, cytology-negative results was 4.6%. HPV16 status conferred the greatest type-specific risk stratification; women with HC2-positive/HPV16-positive results had a 10.6% risk of CIN3+, while women with HC-2 positive/HPV16-negative results had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were HPV33 (5.9%) and HPV18 (5.9%). With regard to the etiologic fraction, 20 of 71 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma in the cohort were positive for HPV18. HPV16 genotyping provides risk stratification useful for guiding clinical management; the risk among HPV16-positive women clearly exceeds the U.S. consensus risk threshold for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is a less clear clinical value of distinguishing the other high-risk HPV types.
Authors: Schiffman M; Burk RD; Boyle S; Raine-Bennett T; Katki HA; Gage JC; Wentzensen N; Kornegay JR; Aldrich C; Tam T; Erlich H; Apple R; Befano B; Castle PE
J Clin Microbiol. 2015 Jan;53(1):52-9. Epub 2014-10-22.
Early weight loss nomograms for exclusively breastfed newborns
The majority of newborns are exclusively breastfed during the birth hospitalization, and weight loss is nearly universal for these neonates. The amount of weight lost varies substantially among newborns with higher amounts of weight loss increasing risk for morbidity. No hour-by-hour newborn weight loss nomogram exists to assist in early identification of those on a trajectory for adverse outcomes. For 161?471 term, singleton neonates born at ?36 weeks’ gestation at Northern California Kaiser Permanente hospitals in 2009-2013, data were extracted from the birth hospitalization regarding delivery mode, race/ethnicity, feeding type, and weights from electronic records. Quantile regression was used to create nomograms stratified by delivery mode that estimated percentiles of weight loss as a function of time among exclusively breastfed neonates. Weights measured subsequent to any nonbreastmilk feeding were excluded. Among this sample, 108?907 newborns had weights recorded while exclusively breastfeeding with 83?433 delivered vaginally and 25?474 delivered by cesarean. Differential weight loss by delivery mode was evident 6 hours after delivery and persisted over time. Almost 5% of vaginally delivered newborns and >10% of those delivered by cesarean had lost ?10% of their birth weight 48 hours after delivery. By 72 hours, >25% of newborns delivered by cesarean had lost ?10% of their birth weight. These newborn weight loss nomograms demonstrate percentiles for weight loss by delivery mode for those who are exclusively breastfed. The nomograms can be used for early identification of neonates on a trajectory for greater weight loss and related morbidities.
Authors: Flaherman VJ; Schaefer EW; Kuzniewicz MW; Li SX; Walsh EM; Paul IM
Pediatrics. 2015 Jan;135(1):e16-23. Epub 2014-12-01.
The burden of nocturia among middle-aged and older women
To examine the prevalence, predictors, and effects of nocturia in women and evaluate overlaps with established urinary tract disorders. This was a cross-sectional analysis of 2,016 women, aged 40 years and older, recruited from Kaiser Permanente Northern California from 2008 to 2012. Nocturia and other urinary symptoms were assessed using structured interviewer-administered questionnaires. Nocturia was defined as patient-reported nocturnal voiding of two or more times per night over a typical week. Thirty-four percent (n=692) reported nocturia, and 40% of women with nocturia reported no other urinary tract symptom. Women with nocturia were older (mean age 58 compared with 55 years) (odds ratio [OR] per 5-year increase 1.21, 95% confidence interval [CI] 1.12-1.31), more likely black (45%) (OR 1.75, 95% CI 1.30-2.35) or Latina (37%) (OR 1.36, 95% CI 1.02-1.83) compared with non-Latina white (30%), have worse depression (mean Hospital Anxiety and Depression Scale score 3.8 compared with 2.8) (OR per 1-point increase in Hospital Anxiety and Depression Scale score 1.08, 95% CI 1.04-1.12), and worse mobility (mean Timed Up-and-Go 11.3 compared with 10 seconds) (OR per 5-second increase in Timed Up-and-Go 1.29, 95% CI 1.05-1.58). Nocturia occurred more among women with hysterectomy (53% compared with 33%) (OR 1.78, 95% CI 1.08-2.94), hot flushes (38% compared with 32%) (OR 1.49, 95% CI 1.19-1.87), and vaginal estrogen use (42% compared with 34%) (OR 1.50, 95% CI 1.04-2.18). Nocturia is common in women and not necessarily attributable to other urinary tract disorders. Factors not linked to bladder function may contribute to nocturia risk, underlining the need for multiorgan prevention and treatment strategies. II.
Authors: Hsu A; Nakagawa S; Walter LC; Van Den Eeden SK; Brown JS; Thom DH; Lee SJ; Huang AJ
Obstet Gynecol. 2015 Jan;125(1):35-43.
Response to Comment on Hedderson et al. Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus. Diabetes Care 2014;37:1296-1303
Authors: Hedderson MM; Ferrara A
Diabetes Care. 2014 Dec;37(12):e280.
Outcomes from ultrasound follow-up of small complex adnexal masses in women over 50
The discovery of a complex adnexal mass in an older woman often raises concern for cancer. We evaluate outcomes for a large population-based cohort of women older than age 50 years with a small complex adnexal mass reported on ultrasound, without elevated CA125 or other evidence of malignancy, including time to detection of malignancy and stage at diagnosis for those initially observed. Women older than age 50 years who had an ultrasound during 2007-2011 reporting a complex adnexal mass 1-6 cm in size were identified. Previous or subsequent pelvic ultrasounds were reviewed to determine when the mass was first identified and whether there was change over time. Women with concurrent elevated CA125, evidence of metastatic disease, or less than 24 months of clinical follow-up were excluded. Surgical pathology from removal and diagnoses of ovarian cancer within 24 months of follow-up were identified. Among 1363 complex masses identified, 18 cancers or borderline tumors (1.3%; 95% confidence interval, 0.8-2.1%) were found. Six cases were diagnosed among 204 women who had immediate surgery after initial ultrasound (15%), and 12 additional cases were found among 994 women with at least 1 repeat ultrasound (73%). Growth was apparent on ultrasound by 7 months for all borderline and epithelial ovarian cancers. Of the 12 cases diagnosed during follow-up, 10 were found to be stage 1 at surgery. Among isolated adnexal masses reported as complex and 1-6 cm on pelvic ultrasound in women older than 50 years, the overall risk of malignancy is low. All cases of epithelial cancer and borderline tumor demonstrated growth by 7 months of observation.
Authors: Suh-Burgmann E; Hung YY; Kinney W
Am J Obstet Gynecol. 2014 Dec;211(6):623.e1-7. Epub 2014-07-25.
Genital herpes and its treatment in relation to preterm delivery
To examine the risks of genital herpes and antiherpes treatment during pregnancy in relation to preterm delivery (PTD), we conducted a multicenter, member-based cohort study within 4 Kaiser Permanente regions: northern and southern California, Colorado, and Georgia. The study included 662,913 mother-newborn pairs from 1997 to 2010. Pregnant women were classified into 3 groups based on genital herpes diagnosis and treatment: genital herpes without treatment, genital herpes with antiherpes treatment, and no herpes diagnosis or treatment (unexposed controls). After controlling for potential confounders, we found that compared with being unexposed, having untreated genital herpes during first or second trimester was associated with more than double the risk of PTD (odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.80, 2.76). The association was stronger for PTD due to premature rupture of membrane (OR = 3.57, 95% CI: 2.53, 5.06) and for early PTD (?35 weeks gestation) (OR = 2.87, 95% CI: 2.22, 3.71). In contrast, undergoing antiherpes treatment during pregnancy was associated with a lower risk of PTD compared with not being treated, and the PTD risk was similar to that observed in the unexposed controls (OR = 1.11, 95% CI: 0.89, 1.38). The present study revealed increased risk of PTD associated with genital herpes infection if left untreated and a potential benefit of antiherpes medications in mitigating the effect of genital herpes infection on the risk of PTD.
Authors: Li DK; Raebel MA; Cheetham TC; Hansen C; Avalos L; Chen H; Davis R
Am J Epidemiol. 2014 Dec 1;180(11):1109-17. Epub 2014-11-12.
Familial Recurrence of Autism Spectrum Disorder: Evaluating Genetic and Environmental Contributions
This study was designed to examine the pattern of familial recurrence of autism spectrum disorder (ASD) in terms of genetic and environmental contributions related to timing of birth. The authors linked California Department of Developmental Services records with state birth certificates to identify all siblings and half siblings of individuals affected with ASD born between 1990 and 2003. A total of 6,616 full siblings, 644 maternal half siblings, and 299 paternal half siblings born after ASD index cases were used to calculate recurrence risks. Control families, identified through matching to cases, were included for comparison (a total of 29,384 siblings). The overall sibling recurrence risk was 10.1%, compared with a prevalence of 0.52% in siblings of controls. The recurrence risk in second-born children was higher (11.5%) than in later-born siblings (7.3%); a similar pattern was observed for maternal half siblings (6.5% for second-born compared with 3.0% for later-born siblings; 4.8% overall). The recurrence risk was significantly higher for siblings who immediately followed the index case in birth order compared with those later in birth order. The recurrence risk for paternal half siblings (2.3%) was half the overall recurrence risk for maternal half siblings but was similar to that for later-born maternal half siblings. An exponential effect of short interbirth interval was observed, with the recurrence risk reaching 14.4% for an interbirth interval of 18 months or less, compared with 6.8% for an interval of 4 years or more. An identical phenomenon was observed in maternal half siblings. The results support genetic susceptibility in the familial recurrence of ASD along with factors related to timing of birth.
Authors: Risch N; Hoffmann TJ; Anderson M; Croen LA; Grether JK; Windham GC
Am J Psychiatry. 2014 Nov 1;171(11):1206-13.
Trends in Elective Labor Induction for Six United States Health Plans, 2001-2007
To describe trends in labor induction, including elective induction, from 2001 to 2007 for six U.S. health plans and to examine the validity of induction measures derived from birth certificate and health plan data. This retrospective cohort study included 339,123 deliveries at 35 weeks’ gestation or greater. Linked health plan and birth certificate data provided information about induction, maternal medical conditions, and pregnancy complications. Induction was defined from diagnosis and procedure codes and birth certificate data and considered elective if no accepted indication was coded. We calculated induction prevalence across health plans and years. At four health plans, we reviewed medical records to validate induction measures. Based on electronic data, induction prevalence rose from 28% in 2001 to 32% in 2005, then declined to 29% in 2007. The trend was driven by changes in the prevalence of apparent elective induction, which rose from 11% in 2001 to 14% in 2005 and then declined to 11% in 2007. The trend was similar for subgroups by parity and gestational age. Elective induction prevalence varied considerably across plans. On review of 86 records, 36% of apparent elective inductions identified from electronic data were confirmed as valid. Elective induction appeared to peak in 2005 and then decline. The decrease may reflect quality improvement initiatives or changes in policies, patient or provider attitudes, or coding practices. The low validation rate for measures of elective induction defined from electronic data has important implications for existing quality measures and for research studies examining induction’s outcomes.
Authors: Dublin S; Avalos LA; Caughey AB; et al.
J Womens Health (Larchmt). 2014 Nov;23(11):904-11. Epub 2014-10-20.
Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring
To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity. We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls’ adiposity, measured annually: (1) ?85th age-specific percentile for BMI; (2) percent body fat (%BF); and (3) waist-to-height ratio (WHR). Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl’s age, and girl’s age at onset of puberty, having a mother with GDM increased a girl’s risk of having a BMI ?85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28-9.92]; OR 3.13 [95% CI 1.08-9.09]; and OR 2.80 [95% CI 1.00-7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ?85th percentile (OR 5.56 [95%CI 1.70-18.2]; Q4 %BF, OR 6.04 [95% CI 1.76-20.7]; and Q4 WHR, OR 3.60 [95% CI 1.35-9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity. Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.
Authors: Kubo A; Ferrara A; Windham GC; Greenspan LC; Deardorff J; Hiatt RA; Quesenberry CP; Laurent C; Mirabedi AS; Kushi LH
Diabetes Care. 2014 Nov;37(11):2996-3002. Epub 2014-08-22.
The Impact of Multimorbidity on Sexual Function in Middle-Aged and Older Women: Beyond the Single Disease Perspective
Little is known about sexual activity and function in women with multiple chronic health conditions. To examine the impact of multimorbidity on sexual activity and function in middle-aged and older women. Multiethnic cross-sectional cohort of 1,997 community-dwelling women (mean age of 60.2 [±9.5] years) in California. Structured questionnaires assessed prior diagnoses of common cardiometabolic, colorectal, neuropsychiatric, respiratory, musculoskeletal, and genitourinary conditions. Sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (i.e., difficulty with arousal, lubrication, orgasm, and pain) were assessed by structured questionnaires. Seventy-one percent of women had two or more diagnosed chronic conditions. Fifty-nine percent reported low sexual desire, 53% reported less than monthly sexual activity, and 47% reported low overall sexual satisfaction. Multimorbidity was associated with increased odds of reporting low sexual desire (OR?=?1.11, 95% CI?=?1.06-1.17, per each additional chronic condition), less than monthly sexual activity (OR?=?1.11, 95% CI?=?1.05-1.17 per each additional condition), and low sexual satisfaction (OR?=?1.10, 95% CI?=?1.04-1.16 per each additional condition), adjusting for age, race/ethnicity, and partner status. Depression and urinary incontinence were each independently associated with low desire (OR?=?1.53, 95% CI?=?1.19-1.97, and OR?=?1.23, 95% CI?=?1.00-1.52, respectively), less than monthly sexual activity (OR?=?1.39, 95% CI?=?1.06-1.83, and OR?=?1.29, 95% CI?=?1.02-1.62, respectively), and low sexual satisfaction (OR?=?1.49, 95% CI?=?1.14-1.93, and OR?=?1.38, 95% CI?=?1.11-1.73, respectively), adjusting for other types of conditions. After adjustment for total number of chronic conditions, age remained a significant predictor of low desire and less than monthly sexual activity, but not sexual satisfaction. Women with multiple chronic health conditions are at increased risk for decreased sexual function. Depression and incontinence may have particularly strong effects on sexual desire, frequency of activity, and satisfaction in women, independent of other comorbid conditions. Women’s overall sexual satisfaction may be more strongly influenced by multimorbidity than age.
Authors: Appa AA; Creasman J; Brown JS; Van Den Eeden SK; Thom DH; Subak LL; Huang AJ
J Sex Med. 2014 Nov;11(11):2744-55. Epub 2014-08-22.
Topiramate use in pregnancy and the birth prevalence of oral clefts
First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC. This retrospective cohort study used 1997-2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims), Truven Health (Medicaid claims), and Kaiser Permanente Northern California Region (electronic medical records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester (TPM cohort) with the prevalence in infants of women formerly exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort) and infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort). To control for confounding, we used stratification and standardization for individual variables and propensity score deciles. The birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13?512) in the FE cohort, and 0.07% (9/13?614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results. Consistent with other recent epidemiologic research, first-trimester TPM exposure was associated with an elevated birth prevalence of OC.
Authors: Mines D; Li DK; Chan KA; et al.
Pharmacoepidemiol Drug Saf. 2014 Oct;23(10):1017-25. Epub 2014-04-01.
Volume and Type of Alcohol During Early Pregnancy and the Risk of Miscarriage
Research on alcohol consumption during pregnancy and miscarriage spans over three decades, yet the relationship is still not well-understood. To assess the relationship between volume and type of alcohol consumed during pregnancy in relation to miscarriage. We utilized data from a population-based cohort study of pregnant women (n = 1061) of which 172 (16%) women had a miscarriage. Upon study entry, participants were asked about their alcohol consumption during pregnancy. Based on the average number of drinks per week, women were categorized into one of three categories: four or more drinks per week (n = 32, 3%), less than four drinks per week (n = 403, 38%), and no alcohol intake (n = 626, 59%). In addition, women were categorized by the type of alcohol beverage they consumed: beer only (n = 47, 4%), spirits only (n = 56, 5%), wine only (n = 160, 15%), or a combination of two or more types of alcohol (n = 172, 16%). A significant increased risk of miscarriage (adjusted hazard ratio (aHR): 2.65; 95% confidence interval (CI): 1.38, 5.10) was found for women who drank four or more drinks a week. Our findings also suggest the relationship between alcohol intake during pregnancy and miscarriage is strongest for miscarriage occurring prior to 10 weeks of gestation. In addition, women who drank only spirits had more than a two-fold increased risk of miscarriage compared to women who abstained (aHR: 2.24; 95% CI: 1.32, 3.81). Conclusions/Importance: Future research assessing the factors that may contribute to an increased risk of miscarriage should consider the type of alcohol consumed.
Authors: Avalos LA; Roberts SC; Kaskutas LA; Block G; Li DK
Subst Use Misuse. 2014 Sep;49(11):1437-45. Epub 2014-05-08.
Use of leukotriene receptor antagonists are associated with a similar risk of asthma exacerbations as inhaled corticosteroids
Based on results of clinical trials, inhaled corticosteroids (ICS) are the most-effective controller medications for preventing asthma-related exacerbations, yet few studies in real-life populations have evaluated the comparative effectiveness of ICS. To determine the likelihood of asthma exacerbations among children with asthma after initiation of controller medications: ICS, leukotriene antagonists (LTRA), and ICS-long-acting ?-agonist (LABA) combination therapy. This was a retrospective cohort study of subjects who were part of the Population-Based Effectiveness in Asthma and Lung Diseases Network. We conducted Cox regression analyses by adjusting for baseline covariates, adherence by using proportion of days covered, and high-dimensional propensity scores. The main outcome measurements were emergency department visits, hospitalizations, or oral corticosteroid use. Our population included 15,567 health plan subjects and 10,624 TennCare Medicaid subjects with uncontrolled asthma. Overall adherence to controller medications was low, with no more than 50% of the subjects refilling the medication after the initial fill. For subjects with allergic rhinitis, the subjects in TennCare Medicaid treated with LTRAs were less likely to experience ED visits (hazard ratio 0.44 [95% CI, 0.21-0.93]) compared with the subjects treated with ICS. For all other groups, the subjects treated with LTRA or ICS-LABA were just as likely to experience ED visits or hospitalizations, or need oral corticosteroids as the subjects treated with ICS. Risks of asthma-related exacerbations did not differ between children who initiated LTRA and ICS. These findings may be explainable by LTRA, which has similar effectiveness as ICS in real-life usage by residual confounding by indication or other unmeasured factors.
Authors: Wu AC; Lieu TA; et al.
J Allergy Clin Immunol Pract. 2014 Sep-Oct;2(5):607-13. Epub 2014-07-25.
Incidence, Etiology, and Outcomes of Hazardous Hyperbilirubinemia in Newborns
Total serum bilirubin (TSB) levels ? 30 mg/dL are rare but potentially hazardous. A better understanding of their incidence, causes, and outcomes could help inform preventive efforts. We identified infants born ? 35 weeks’ gestational age from 1995-2011 in Kaiser Permanente Northern California (n = 525409) and examined the medical records of infants with a TSB ? 30 mg/dL to determine etiology and the occurrence of acute bilirubin encephalopathy. We reviewed inpatient and outpatient encounters through 2013 for evidence of sensorineural hearing loss (SNHL) or cerebral palsy (CP). We identified 47 infants with TSB ? 30 mg/dL (8.6 per 100000 births). In 44 infants (94%), the hyperbilirubinemia occurred after the initial birth hospitalization. The etiology was not identified in 33 (70%). Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in only 25 (53%) of whom 10 (40%) were deficient. Four children had acute bilirubin encephalopathy of whom 2 developed both CP and SNHL, and 1 developed isolated SNHL. These 3 infants all had G6PD deficiency and TSB >40 mg/dL. One additional 35-week infant with TSB 38.2 mg/dL had SNHL. Hazardous (? 30 mg/dL) hyperbilirubinemia is a rare event. No etiology could be identified from the clinical record in most cases. G6PD deficiency was the leading cause of hazardous hyperbilirubinemia when an etiology was identified, but many were not tested. Chronic, bilirubin-induced neurotoxicity was uncommon and occurred only in the setting of additional risk factors and TSB values well over (>15 mg/dL) the American Academy of Pediatrics exchange transfusion thresholds.
Authors: Kuzniewicz MW; Wickremasinghe AC; Wu YW; McCulloch CE; Walsh EM; Wi S; Newman TB
Pediatrics. 2014 Sep;134(3):504-9. Epub 2014-08-04.
Maternal gestational weight gain and offspring risk for childhood overweight or obesity
The objective of the study was to evaluate the association between gestational weight gain, per the 2009 Institute of Medicine (IOM) recommendations, and offspring overweight/obesity at 2-5 years of age. This was a prospective cohort study of 4145 women who completed a health survey (2007-2009) and subsequently delivered a singleton at Kaiser Permanente Northern California (2007-2010). Childhood overweight/obesity was defined as a body mass index (BMI) z-score of the 85th percentile or greater of the Centers for Disease Control and Prevention child growth standards. Gestational weight gain was categorized according to the 2009 IOM recommendations. Logistic regression was used; meeting the IOM recommendations was the referent. Exceeding the IOM recommendations was associated with a 46% increase in odds of having an overweight/obese child (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.17-1.83), after adjusting for maternal prepregnancy BMI, race/ethnicity, age at delivery, education, child age, birthweight, gestational age at delivery, gestational diabetes, parity, infant sex, total metabolic equivalents, and dietary pattern. The OR (95% CI) for childhood overweight/obesity among women gaining below the IOM recommendations was 1.23 (0.88-1.71). The associations between gaining outside the IOM recommendations and childhood obesity were stronger among women with a normal prepregnancy BMI (OR, 1.63; 95% CI, 1.03-2.57) (below); OR, 1.79; 95% CI, 1.32-2.43) (exceeded). Gestational weight gain outside the IOM recommendations is associated with increased odds of childhood overweight/obesity, independent of several potential confounders and mediators. Gestational weight gain had a greater impact on childhood overweight/obesity among normal-weight women, suggesting that the effect may be independent of genetic predictors of obesity.
Authors: Sridhar SB; Darbinian J; Ehrlich SF; Markman MA; Gunderson EP; Ferrara A; Hedderson MM
Am J Obstet Gynecol. 2014 Sep;211(3):259.e1-8. Epub 2014-04-13.
Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin
One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator-activated receptor-? and hepatocyte nuclear factor 4-?, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response.
Authors: Goswami S; Hedderson MM; Savic RM; et al.
Clin Pharmacol Ther. 2014 Sep;96(3):370-9. Epub 2014-05-22.
Genetic risk score for prediction of newborn adiposity and large-for-gestational-age birth
CONTEXT: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.
OBJECTIVE: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.
SETTING AND DESIGN: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association with newborn size. GRS’s for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.
PARTICIPANTS: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).
OUTCOME MEASURES: Birth weight >90th percentile (LGA) and newborn SSF>90th percentile were primary outcomes.
RESULTS: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, body mass index, height, blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P ≤ 1.6 × 10(-19)) and improved prediction of birth weight and SSF >90th percentile when added to a baseline model incorporating the covariates listed above.
CONCLUSIONS: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.
Authors: Chawla R; Badon SE; Rangarajan J; Reisetter AC; Armstrong LL; Lowe LP; Urbanek M; Metzger BE; Hayes MG; Scholtens DM; Lowe WL Jr
J Clin Endocrinol Metab. 2014 Nov;99(11):E2377-86. doi: 10.1210/jc.2013-4221. Epub 2014 Aug 19.
Evidence of Reproductive Stoppage in Families With Autism Spectrum Disorder: A Large, Population-Based Cohort Study
Few studies have examined the curtailment of reproduction (ie, stoppage) after the diagnosis of a child with autism spectrum disorder (ASD). To examine stoppage in a large, population-based cohort of families in which a child has received a diagnosis of ASD. Individuals with ASD born from January 1, 1990, through December 31, 2003, were identified in the California Department of Developmental Services records, which were then linked to state birth certificates to identify full sibs and half-sibs and to obtain information on birth order and demographics. A total of 19,710 case families in which the first birth occurred within the study period was identified. These families included 39,361 individuals (sibs and half-sibs). Control individuals were randomly sampled from birth certificates and matched 2:1 to cases by sex, birth year, and maternal age, self-reported race/ethnicity, and county of birth after removal of children receiving services from the California Department of Developmental Services. Using similar linkage methods as for case families, 36,215 pure control families (including 75,724 total individuals) were identified that had no individuals with an ASD diagnosis. History of affected children. Stoppage was investigated by comparing the reproductive behaviors of parents after the birth of a child with ASD vs an unaffected child using a survival analysis framework for time to next birth and adjusting for demographic variables. For the first few years after the birth of a child with ASD, the parents’ reproductive behavior was similar to that of control parents. However, birth rates differed in subsequent years; overall, families whose first child had ASD had a second child at a rate of 0.668 (95% CI, 0.635-0.701) that of control families, adjusted for birth year, birth weight, maternal age, and self-reported maternal race/ethnicity. Results were similar when a later-born child was the first affected child in the family. Reproductive curtailment was slightly stronger among women who changed partners (relative rate for second-born children, 0.553 [95% CI, 0.498-0.614]). These results provide the first quantitative assessment and convincing statistical evidence of reproductive stoppage related to ASD. These findings have implications for recurrence risk estimation and genetic counseling.
Authors: Hoffmann TJ; Windham GC; Anderson M; Croen LA; Grether JK; Risch N
JAMA Psychiatry. 2014 Aug;71(8):943-51.
Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders
Prenatal and early-life exposures to mercury have been hypothesized to be associated with increased risk of autism spectrum disorders (ASDs). This study investigated the association between ASDs and levels of total mercury measured in maternal serum from mid-pregnancy and infant blood shortly after birth. The study sample was drawn from the Early Markers for Autism (EMA) Study. Three groups of children who were born in Orange County, CA in 2000-2001 were identified: children with ASD (n=84), children with intellectual disability or developmental delay (DD) (n=49), and general population controls (GP) (n=159). Maternal serum specimens and newborn bloodspots were retrieved from the California Department of Public Health prenatal and newborn screening specimen archives. Blood mercury levels were measured in maternal serum samples using mass spectrometer and in infant bloodspots with a 213 nm laser. Maternal serum and infant blood mercury levels were significantly correlated among all study groups (all correlations >0.38, p<0.01). Adjusted logistic regression models showed no significant associations between ASD and log transformed mercury levels in maternal serum samples (ASD vs. GP: OR [95% CI]=0.96 [0.49-1.90]; ASD vs. DD: OR [95% CI]=2.56 [0.89-7.39]). Results for mercury levels in newborn blood samples were similar (ASD vs. GP: OR [95% CI]=1.18 [0.71-1.95]; ASD vs. DD: OR [95% CI]=1.96 [0.75-5.14]). Results indicate that levels of total mercury in serum collected from mothers during mid-pregnancy and from newborn bloodspots were not significantly associated with risk of ASD, though additional studies with greater sample size and covariate measurement are needed.
Authors: Yau VM; Green PG; Alaimo CP; Yoshida CK; Lutsky M; Windham GC; Delorenze G; Kharrazi M; Grether JK; Croen LA
Environ Res. 2014 Aug;133:294-303. Epub 2014-06-28.
Lactation intensity and fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin in postpartum women with recent gestational diabetes mellitus: The SWIFT cohort
Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance. The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6-9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models. Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%-28% lower fasting triglycerides, 15%-21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04). Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.
Authors: Gunderson EP; Quesenberry CP; Lo JC; Dewey KG; et al.
Metab Clin Exp. 2014 Jul;63(7):941-50. Epub 2014-04-13.
Prenatal and perinatal risk factors in a twin study of autism spectrum disorders
Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently. Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed. Shared factors including parental age, prenatal use of medications, uterine bleeding, and prematurity did not increase concordance risks for ASDs in twins. Among the individual factors, respiratory distress demonstrated the strongest association with increased risk for ASDs in the group as a whole (OR 2.11, 95% CI 1.27-3.51). Furthermore, respiratory distress (OR 2.29, 95% CI 1.12-4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04-3.80) were associated with increased risks for ASDs in males, while jaundice was associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28-6.74). Perinatal factors associated with respiratory distress and other markers of hypoxia appear to increase risk for autism in a subgroup of twins. Future studies examining potential gender differences and additional prenatal, perinatal and postnatal environmental factors are required for elucidating the etiology of ASDs and suggesting new methods for treatment and prevention.
Authors: Froehlich-Santino W; Croen LA; Hallmayer J; et al.
J Psychiatr Res. 2014 Jul;54:100-8. Epub 2014-03-29.
Post-partum weight loss and glucose metabolism in women with gestational diabetes: the DEBI Study
Women with gestational diabetes are at high risk for developing diabetes; post-partum weight loss may reduce the risk of diabetes. We evaluated the association of post-partum weight change with changes in glucose, insulin and homeostasis model assessment of insulin resistance in a subsample (n = 72) of participants from Diet Exercise and Breastfeeding Intervention (DEBI), a randomized pilot trial of lifestyle intervention for women with gestational diabetes. Glucose and insulin were measured fasting and 2 h after an oral glucose tolerance test at 6 weeks and 12 months post-partum. Women were categorized by weight change (lost > 2 kg vs. maintained/gained) between 6 weeks and 12 months post-partum. Compared with women who maintained or gained weight, women who lost > 2 kg experienced significantly lower increases in fasting glucose [age-adjusted means: 0.1 mmol/l (95% CI -0.03 to 0.3) vs. 0.4 mmol/l (95% CI 0.3-0.6); P < 0.01] and 2-h insulin [10.0 pmol/l (95% CI -56.9 to 76.9) vs. 181.2 pmol/l (95% CI 108.3-506.9); P < 0.01] and a significant reduction in 2-h glucose [-0.9 mmol/l (95% CI -1.4 to -0.3) vs. 0.3 mmol/l (95% CI -0.3 to 0.9); P < 0.01]. In multiple linear regression models adjusted for age, Hispanic ethnicity, medication use, meeting the Institute of Medicine's recommendations for gestational weight gain, breastfeeding and randomized group, a 1-kg increase in weight was significantly associated with increases in fasting and 2-h glucose (P < 0.05), but was not associated with insulin or homeostasis model assessment of insulin resistance. In women with gestational diabetes, modest post-partum weight loss may be associated with improvements in glucose metabolism.
Authors: Ehrlich SF; Hedderson MM; Quesenberry CP; Feng J; Brown SD; Crites Y; Ferrara A
Diabet Med. 2014 Jul;31(7):862-7. Epub 2014-03-25.
Pregravid Liver Enzyme Levels and Risk of Gestational Diabetes During a Subsequent Pregnancy
Liver enzymes are independent predictors of type 2 diabetes. Although liver fat content correlates with features of insulin resistance, a risk factor for developing gestational diabetes mellitus (GDM), the relationship between liver enzymes and GDM is unclear. The objective of this study was to assess whether pregravid liver enzyme levels are associated with subsequent risk of GDM. A nested case-control study was conducted among women who participated in the Kaiser Permanente Northern California multiphasic health checkup (1984-1996) and had a subsequent pregnancy (1984-2009). Case patients were 256 women who developed GDM. Two control subjects were selected for each case patient and matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies. Being in the highest quartile versus the lowest quartile of ?-glutamyl transferase (GGT) levels was associated with a twofold increased risk of subsequent GDM (odds ratio 1.97 [95% CI 1.14-3.42]), after adjusting for race/ethnicity, prepregnancy BMI, family history of diabetes, and alcohol use. This result was attenuated after adjusting for homeostasis model assessment of insulin resistance (HOMA-IR), fasting status, and rate of gestational weight gain. There was significant interaction between GGT and HOMA-IR; the association with GGT was found among women in the highest tertile of HOMA-IR. Aspartate aminotransferase and alanine aminotransferase were not associated with increased GDM risk. Pregravid GGT level, but not alanine aminotransferase or aspartate aminotransferase level, predicted the subsequent risk of GDM. Markers of liver fat accumulation, such as GGT level, are present years before pregnancy and may help to identify women at increased risk for subsequent GDM.
Authors: Sridhar SB; Xu F; Darbinian J; Quesenberry CP; Ferrara A; Hedderson MM
Diabetes Care. 2014 Jul;37(7):1878-84. Epub 2014-05-02.
A Call to Increase Physical Activity Among Women of Reproductive Age: Is It Possible?
Authors: Hedderson M; Ferrara A
JAMA Intern Med. 2014 Jul;174(7):1056-7.
Low-Dose Estradiol and the Serotonin-Norepinephrine Reuptake Inhibitor Venlafaxine for Vasomotor Symptoms: A Randomized Clinical Trial
Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date. To determine the efficacy and tolerability of low-dose oral 17?-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS). In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012. Participants were randomized to double-blind treatment with low-dose oral 17?-estradiol (0.5 mg/d) (n?=?97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n?=?96), or placebo (n?=?146) for 8 weeks. The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments. Compared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P?
Authors: Joffe H; Caan B; Sternfeld B; Cohen L; et al.
JAMA Intern Med. 2014 Jul;174(7):1058-66.
Prevention of Vertical Transmission of Hepatitis B: An Observational Study
For mothers with chronic hepatitis B virus (HBV) infection, the Centers for Disease Control and Prevention recommends immunoprophylaxis to decrease perinatal transmission. However, its effectiveness and risk factors for failure have not been well-studied in community practice. To investigate the effectiveness of a contemporary immunoprophylaxis protocol. Observational study. An HBV perinatal immunoprophylaxis program within Kaiser Permanente Northern California. 4446 infants born to 3253 HBV-positive mothers between 1997 and 2010. Adherence to immunoprophylaxis, follow-up testing rates, maternal risk factors for HBV transmission, and transmission rates. The infant infection rate was 0.75 per 100 births from 1997 to 2010 (Poisson 95% CI, 0.48 to 1.10). Rates per 100 births were 3.37 (CI, 2.08 to 5.14) for e antigen-positive mothers and 0.04 (CI, 0.001 to 0.24) for e antigen-negative mothers. Among mothers with viral load testing, the lowest level associated with transmission was 6.32 × 107 IU/mL. Infection rates per 100 births were 3.61 (CI, 0.75 to 10.56) among the 83 births to mothers with viral loads of 5 × 107 IU/mL or greater and 0 among the 831 births to mothers with viral loads less than 5 × 107 IU/mL, regardless of e antigen status. Testing for HBV immunity and infection was less complete in earlier years. Viral load testing was only consistently available starting in 2007. Prenatal HBV screening followed by postnatal prophylaxis is highly effective in preventing vertical transmission of HBV. A negative e antigen status or a viral load less than 5 × 107 IU/mL (90.9% of women tested) identifies women at extremely low risk for transmission after immunoprophylaxis who are unlikely to benefit from further interventions. Kaiser Permanente Community Benefit and National Institutes of Health.
Authors: Kubo A; Shlager L; Marks AR; Lakritz D; Beaumont C; Gabellini K; Corley DA
Ann Intern Med. 2014 Jun 17;160(12):828-35.
Proteinuria testing among patients with diabetes mellitus is associated with bladder cancer diagnosis: potential for unmeasured confounding in studies of pioglitazone and bladder cancer
The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a full urinalysis. We reanalyzed patients with diabetes mellitus within Kaiser Permanente Northern California. Logistic and Cox regression adjusted for age, sex, race, and smoking were used to assess the association of proteinuria testing with pioglitazone use, subsequent full urinalysis, and diagnosis with bladder cancer. Patients treated with pioglitazone were more likely than others with diabetes to undergo testing for proteinuria (p?4?years exposure HR: from 1.38 to 1.28). Proteinuria testing may be a confounder in studies of pioglitazone and bladder cancer but does not fully explain the association between pioglitazone and bladder cancer in this cohort. Optimal adjustment for proteinuria testing likely requires knowledge of the test result.
Authors: Lewis JD; Habel L; Quesenberry C; Mamtani R; Peng T; Bilker WB; Hedderson M; Nessel L; Vaughn DJ; Strom BL; Ferrara A
Pharmacoepidemiol Drug Saf. 2014 Jun;23(6):636-45. Epub 2014-04-25.
Determining Source Strength of Semivolatile Organic Compounds using Measured Concentrations in Indoor Dust
Consumer products and building materials emit a number of semivolatile organic compounds (SVOCs) in the indoor environment. Because indoor SVOCs accumulate in dust, we explore the use of dust to determine source strength and report here on analysis of dust samples collected in 30 US homes for six phthalates, four personal care product ingredients, and five flame retardants. We then use a fugacity-based indoor mass balance model to estimate the whole-house emission rates of SVOCs that would account for the measured dust concentrations. Di-2-ethylhexyl phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were the most abundant compounds in these dust samples. On the other hand, the estimated emission rate of diethyl phthalate is the largest among phthalates, although its dust concentration is over two orders of magnitude smaller than DEHP and DiNP. The magnitude of the estimated emission rate that corresponds to the measured dust concentration is found to be inversely correlated with the vapor pressure of the compound, indicating that dust concentrations alone cannot be used to determine which compounds have the greatest emission rates. The combined dust-assay modeling approach shows promise for estimating indoor emission rates for SVOCs. The combined dust-assay modeling approach in this study can be used to predict the source strength of indoor released compounds, integrating emissions from consumer products, building materials, and other home furnishings. Our findings show that estimated emission rates are closely related to not only the level of compounds on dust, but also the vapor pressure of the compound. Thus, a fugacity-based indoor mass balance model and measured dust concentrations can be used to estimate the whole-house emission rates from all sources in actual indoor settings, when individual sources of emissions are unknown.
Authors: Shin HM; McKone TE; Nishioka MG; Fallin MD; Croen LA; Hertz-Picciotto I; Newschaffer CJ; Bennett DH
Indoor Air. 2014 Jun;24(3):260-71. Epub 2013-10-31.
Safety of influenza vaccination during pregnancy: A review of subsequent maternal obstetric events and findings from two recent cohort studies
Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as a barrier to vaccination. This review describes the safety of inactivated influenza vaccination during pregnancy with a focus on maternal obstetric events, including hypertensive disorders, gestational diabetes, and chorioamnionitis. Included in the review are new findings from two studies which examined the safety of seasonal inactivated influenza vaccination during pregnancy. The first study enrolled 641 pregnant women during the 2010-2011 season and prospectively followed them until delivery or pregnancy termination. The second study enrolled 1616 pregnant women during the 2010-2011 influenza season, and followed the women and their infants for six months after delivery. No associations between inactivated influenza vaccination and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or chorioamnionitis were observed in either cohort. When considered as a whole, these studies should further reassure women and clinicians that influenza vaccination during pregnancy is safe for mothers.
Authors: Naleway AL; Irving SA; Henninger ML; Li DK; Shifflett P; Ball S; Williams JL; Cragan J; Gee J; Thompson MG; Vaccine Safety Datalink and Pregnancy and Influenza Project
Vaccine. 2014 May 30;32(26):3122-7. Epub 2014-04-14.
Adaptation of the ‘ten questions’ to screen for autism and other neuro-developmental disorders in Uganda
Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors. We then conducted household screening of 1169 children, 2-9 years of age, followed by clinical assessment of children who screened positive and a sample of those who screened negative to evaluate the validity of the screener. We found that 320 children (27% of the total) screened positive and 68 children received a clinical diagnosis of one or more moderate to severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy; epilepsy; cognitive, speech and language, hearing, or vision impairment), including 8 children with autism spectrum disorders. Prevalence and validity of the screener were evaluated under different statistical assumptions. Sensitivity of the 23Q ranged from 0.55 to 0.80 and prevalence for ?1 neurodevelopmental disorders from 7.7/100 children to 12.8/100 children depending on which assumptions were used. The combination of screening positive on both autism spectrum disorders and Ten Questions items was modestly successful in identifying a subgroup of children at especially high risk of autism spectrum disorders. We recommend that autism spectrum disorders and related behavioral disorders be included in studies of neurodevelopmental disorders in low-resource settings to obtain essential data for planning local and global public health responses.
Authors: Kakooza-Mwesige A; Ssebyala K; Karamagi C; Kiguli S; Smith K; Anderson MC; Croen LA; Trevathan E; Hansen R; Smith D; Grether JK
Autism. 2014 May;18(4):447-57. Epub 2013-03-27.
Does antidepressant exposure in pregnancy affect maternal serum markers for aneuploidy?
The objective of this study was to examine the effect of maternal antidepressant exposure on first- and second-trimester maternal serum markers for aneuploidy. We conducted a 10-year retrospective cohort study within a large health care organization. Pregnant women diagnosed with depression who underwent serum screening for aneuploidy were identified. Antidepressant exposure was defined by a filled prescription. Levels of pregnancy-associated plasma protein-A, alpha-fetoprotein, estriol, inhibin, and second-trimester human chorionic gonadotropin (hCG) were obtained, expressed as multiples of the mean. We compared levels of serum analytes between women who were and were not exposed to antidepressants. Using recorded Patient Health Questionnaire scores, we assessed depression severity as a confounder. Antidepressant exposure occurred in 52% of 19,186 pregnancies. Mean inhibin levels were significantly higher in the unexposed group (1.124 multiples of the median compared with 1.084 multiples of the median, P=.003) as were mean hCG levels (1.188 multiples of the median compared with 1.165 multiples of the median, P=.007). Mean estriol levels were lower in the unexposed group (1.005 multiples of the median compared with 1.015 multiples of the median, P=.030). There were no statistically significant differences in the mean values of pregnancy-associated plasma protein-A or alpha-fetoprotein. In bivariate analyses, there were no interactions between analyte values and depression severity. There were no significant differences in the proportion of patients with one or more abnormal level of serum analytes between exposed and unexposed groups. Antidepressant exposure affects mean levels of inhibin, hCG, and estriol. As a result of our large number of participants, small differences could be detected. Further research is necessary to determine if such differences are of clinical significance.
Authors: Schroeder C; Wu D; Merchant M; Ferber J; Currier R; Li DK
Obstet Gynecol. 2014 May;123 Suppl 1:77S-8S.
Challenges conducting comparative effectiveness research: The Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE) experience
The Clinical and Health Outcomes Initiative in Comparative Effectiveness (CHOICE) program, which includes 12 ongoing comparative effectiveness research (CER) trials funded by the Agency for Healthcare Research and Quality under the American Recovery and Reinvestment Act of 2009, has had firsthand experience in dealing with the unique challenges of conducting CER since the trials started in the fall of 2010. This paper will explore the collective experience of the CHOICE program and discuss common challenges and successes the CHOICE investigators have experienced conducting CER research in the United States. The specific aims of this paper are to describe the common features of the CHOICE award studies (observational studies and trials), to summarize the strategies undertaken to address the challenges in conducting comparative effectiveness pragmatic trials and observational studies from the patient, physician, and administrative perspective, and to provide recommendations for improving the efficiency and feasibility of conducting prospective CER studies in the future.
Authors: Friedly JL; Bauer Z; Comstock BA; DiMangoE; Ferrara A; Huang SS; Israel E; Jarvik JG; Nierenberg AA; Ong MK; Penson DF; Smith-Bindman R; Stillman AE; Vollmer WM; Warren SM; Zhan C; Hsia DC; Trontell A
Comp Eff Res (Auckl). 2014 May;4:1-12.
Efficacy of yoga for vasomotor symptoms: a randomized controlled trial
This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother. This study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of ?-3 fatty acid (n = 177) or placebo (n = 178) capsules. Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6 weeks, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks. Among 249 randomized women, 237 (95%) completed 12-week assessments. The mean baseline VMS frequency was 7.4 per day (95% CI, 6.6 to 8.1) in the yoga group and 8.0 per day (95% CI, 7.3 to 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n = 237). There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks (mean difference [yoga–usual activity] from baseline at 6 wk, -0.3 [95% CI, -1.1 to 0.5]; mean difference [yoga–usual activity] from baseline at 12 wk, -0.3 [95% CI, -1.2 to 0.6]; P = 0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga – usual activity] in the change in Insomnia Severity Index, 1.3 [95% CI, -2.5 to -0.1]; P = 0.007). Among healthy women, 12 weeks of yoga class plus home practice, compared with usual activity, do not improve VMS frequency or bother but reduce insomnia symptoms.
Authors: Newton KM; Caan B; LaCroix AZ; et al.
Menopause. 2014 Apr;21(4):339-46.
Efficacy of omega-3 for vasomotor symptoms treatment: a randomized controlled trial
This study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women. This study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules, and simultaneously to yoga (n = 107), aerobic exercise (n = 106), or their usual physical activity (n = 142). Participants received 1.8 g of omega-3 daily for 12 weeks. Each capsule contained ethyl eicosapentaenoic acid (425 mg), docosahexaenoic acid (100 mg), and other omega-3s (90 mg). Primary outcomes were VMS frequency and bother. Secondary outcomes included sleep quality (Pittsburgh Sleep Quality Index), insomnia symptoms (Insomnia Severity Index), depressive symptoms (Physician’s Health Questionnaire-8), and anxiety (Generalized Anxiety Disorder-7). The mean baseline frequency of VMS per day was 7.6 (95% CI, 7.0 to 8.2). After 12 weeks, the reduction in VMS frequency with omega-3 (-2.5; 95% CI, -3.0 to -1.9) did not differ significantly from that with placebo (-2.7; 95% CI, -3.3 to -2.2), with a relative difference of 0.3 fewer hot flashes per day (95% CI, -0.5 to 1.0; P = 0.28). Changes in VMS bother at 12 weeks were also similar between groups, with no relative difference on a four-point scale (95% CI, -0.1 to 0.2; P = 0.36). Omega-3s compared with placebo showed no improvement in self-reported sleep or mood (P > 0.09 for all comparisons). Among healthy, sedentary perimenopausal and postmenopausal women, a 12-week treatment with omega-3 does not improve VMS frequency, VMS bother, sleep, or mood compared with placebo.
Authors: Cohen LS; Joffe H; Guthrie KA; Ensrud KE; Freeman M; Carpenter JS; Learman LA; Newton KM; Reed SD; Manson JE; Sternfeld B; Caan B; Freeman EW; LaCroix AZ; Tinker LF; Booth-Laforce C; Larson JC; Anderson GL
Menopause. 2014 Apr;21(4):347-54.
Efficacy of exercise for menopausal symptoms: a randomized controlled trial
This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms. Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usual activity. The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12. Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index and Pittsburgh Sleep Quality Index), and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire). At the end of week 12, changes in VMS frequency in the exercise group (mean change, -2.4 VMS/d; 95% CI, -3.0 to -1.7) and VMS bother (mean change on a four-point scale, -0.5; 95% CI, -0.6 to -0.4) were not significantly different from those in the control group (-2.6 VMS/d; 95% CI, -3.2 to -2.0; P = 0.43; -0.5 points; 95% CI, -0.6 to -0.4; P = 0.75). The exercise group reported greater improvement in insomnia symptoms (P = 0.03), subjective sleep quality (P = 0.01), and depressive symptoms (P = 0.04), but differences were small and not statistically significant when P values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only. These findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality, insomnia, and depression in midlife sedentary women.
Authors: Sternfeld B; Caan BJ; et al.
Menopause. 2014 Apr;21(4):330-8.
Gestational weight gain and neonatal adiposity in the Hyperglycemia and Adverse Pregnancy Outcome study-North American region
OBJECTIVE: To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.METHODS: GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as >90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.RESULTS: Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds >90th percentile (OR = 1.75 and 4.77, respectively) and percentage body fat >90th percentile (OR = 2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight >90th percentile (OR = 2.80 and 1.93, respectively) compared to women who gained within the recommendation.CONCLUSIONS: This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.
Authors: Badon SE; Dyer AR; Josefson JL
Obesity (Silver Spring). 2014 Jul;22(7):1731-8. doi: 10.1002/oby.20742. Epub 2014 Mar 27.
Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription
Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor, released from plastics is associated with ED in occupationally exposed workers. However, in rats, despite the induction of hypogonadism, apoptosis of the penile corporal smooth muscle (SM), fat infiltration into the cavernosal tissue and changes in global gene expression with the intraperitoneal administration of high dose BPA, ED was not observed. We investigated whether BPA administered orally rather than intraperitoneally to rats for longer periods and lower doses will lead to ED. Main outcome measures are ED, histological, and biochemical markers in rat penile tissues. In all, 2.5-month-old rats were given drinking water daily without and with BPA at 1 and 0.1 mg kg(-1) per day. Two months later, erectile function was determined by cavernosometry and electrical field stimulation (EFS) and serum levels of testosterone (T), estradiol (E2) and BPA were measured. Penile tissue sections were assayed by Masson (SM/collagen), Oil Red O (fat), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) (apoptosis), immunohistochemistry for Oct4 (stem cells), and ?-SM actin/calponin (SM and myofibroblasts), applying quantitative image analysis. Other markers were assayed by western blotting. DNA microarrays/microRNA (miR) assays defined transcription profiles. Orally administered BPA did not affect body weight, but (1) decreased serum T and E2; (2) reduced the EFS response and increased the drop rate; (3) increased within the corporal tissue the presence of fat, myofibroblasts and apoptosis; (4) lowered the contents of SM and stem cells, but not nerve terminals; and (5) caused alterations in the transcriptional profiles for both mRNA and miRs within the penile shaft. Long-term exposure of rats to oral BPA caused a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to alterations within the corporal tissue that pose gene transcriptional changes related to inflammation, fibrosis and epithelial/mesenchymal transition (EMT).
Authors: Kovanecz I; Gelfand R; Masouminia M; Gharib S; Segura D; Vernet D; Rajfer J; Li DK; Kannan K; Gonzalez-Cadavid NF
Int J Impot Res. 2014 Mar-Apr;26(2):67-75. Epub 2013-12-05.
Menopausal Quality of Life: A RCT of Yoga, Exercise and Omega-3 Supplements
The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect.
Authors: Reed SD; Caan B; Sternfeld BS; LaCroix AZ; et al.
Am J Obstet Gynecol. 2014 Mar;210(3):244.e1-11. Epub 2013-11-08.
Intussusception Risk after Rotavirus Vaccination in U.S. Infants
International postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States. The study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time. The analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2. RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.).
Authors: Yih WK; Lieu TA; Kulldorff M; Martin D; McMahill-Walraven CN; Platt R; Selvam N; Selvan M; Lee GM; Nguyen M
N Engl J Med. 2014 Feb 6;370(6):503-12. Epub 2014-01-14.
Brief report: risk of adverse fetal outcomes associated with immunosuppressive medications for chronic immune-mediated diseases in pregnancy
To assess the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune-mediated diseases. Health plan data were obtained from the Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases, with linkage to both vital records and medical records. Women with inflammatory arthropathies, those with systemic lupus erythematosus, and those with inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from the electronic data and validated with medical record review. The cohort included 608 infants, including 437 with exposure to immunosuppressive drugs during the mother’s pregnancy (402 during the first trimester, and 35 during the second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressive treatments before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, and 10 fetal deaths (1.6% of the cohort). Among 113 preterm infants with exposures during pregnancy, 23 (20.4%) had life-threatening neonatal complications, and among 485 term infants, 10 (2.1%) had life-threatening complications. Compared to the reference group (treatment before, but not during, pregnancy), the risk ratios (RRs) for adverse fetal outcomes associated with immunosuppressive treatments (by exposure category) during pregnancy included the following: methotrexate (RR 1.39, 95% confidence interval [95% CI] 0.43-4.53), tumor necrosis factor inhibitors (RR 0.98, 95% CI 0.38-2.55), hydroxychloroquine (RR 1.33, 95% CI 0.69-2.55), and other immunosuppressive medications (RR 0.98, 95% CI 0.48-1.98). In this study, there was no evidence of a large increase in risk of adverse fetal outcomes from first-trimester exposure to immunosuppressive medications, although the confidence intervals for the risk ratios were wide. Further studies will be needed as use of these medications increases over time.
Authors: Cooper WO; Cheetham TC; Li DK; Stein CM; Callahan ST; Morgan TM; Shintani AK; Chen N; Griffin MR; Ray WA
Arthritis Rheumatol. 2014 Feb;66(2):444-50.
Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010-2011 and 2011-2012 influenza seasons
Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. We conducted a case-control study over 2 influenza seasons (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%-67%) using the influenza-negative controls and 53% (95% CI, 24%-72%) using the ARI-negative controls. Receipt of the prior season’s vaccine, however, had an effect similar to receipt of the current season’s vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%-76%) and ARI-negative controls (48%-76%). Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons.
Authors: Thompson MG; Li DK; Avalos LA; Pregnancy and Influenza Project Workgroup; et al.
Clin Infect Dis. 2014 Feb;58(4):449-57. Epub 2013-11-26.
A pragmatic cluster randomized clinical trial of diabetes prevention strategies for women with gestational diabetes: design and rationale of the Gestational Diabetes’ Effects on Moms (GEM) study
Women with gestational diabetes (GDM) are at high risk of developing diabetes later in life. After a GDM diagnosis, women receive prenatal care to control their blood glucose levels via diet, physical activity and medications. Continuing such lifestyle skills into early motherhood may reduce the risk of diabetes in this high risk population. In the Gestational Diabetes’ Effects on Moms (GEM) study, we are evaluating the comparative effectiveness of diabetes prevention strategies for weight management designed for pregnant/postpartum women with GDM and delivered at the health system level. The GEM study is a pragmatic cluster randomized clinical trial of 44 medical facilities at Kaiser Permanente Northern California randomly assigned to either the intervention or usual care conditions, that includes 2,320 women with a GDM diagnosis between March 27, 2011 and March 30, 2012. A Diabetes Prevention Program-derived print/telephone lifestyle intervention of 13 telephonic sessions tailored to pregnant/postpartum women was developed. The effectiveness of this intervention added to usual care is to be compared to usual care practices alone, which includes two pages of printed lifestyle recommendations sent to postpartum women via mail. Primary outcomes include the proportion of women who reach a postpartum weight goal and total weight change. Secondary outcomes include postpartum glycemia, blood pressure, depression, percent of calories from fat, total caloric intake and physical activity levels. Data were collected through electronic medical records and surveys at baseline (soon after GDM diagnosis), 6 weeks (range 2 to 11 weeks), 6 months (range 12 to 34 weeks) and 12 months postpartum (range 35 to 64 weeks). There is a need for evidence regarding the effectiveness of lifestyle modification for the prevention of diabetes in women with GDM, as well as confirmation that a diabetes prevention program delivered at the health system level is able to successfully reach this population. Given the use of a telephonic case management model, our Diabetes Prevention Program-derived print/telephone intervention has the potential to be adopted in other settings and to inform policies to promote the prevention of diabetes among women with GDM.
Authors: Ferrara A; Hedderson MM; Brown SD; Ehrlich SF; Caan BJ; Sternfeld B; Gordon NP; Schmittdiel JA; Gunderson EP; Quesenberry CP; et al.
BMC Pregnancy Childbirth. 2014;14:21. Epub 2014-01-15.
Correlation between Exposure to Magnetic Fields and Embryonic Development in the First Trimester
To explore the correlation between maternal magnetic field (MF) exposure in daily life and embryonic development. A cross-sectional study was conducted among 149 pregnant women who were seeking induced abortion of unwanted pregnancies. Participating women were asked to wear an EMDEX Lite magnetic field meter for a 24-h period to obtain MF exposure level within 4 weeks following the abortion. Embryonic bud and sac lengths were measured through B-mode ultrasound before the surgical abortion. Embryo sections were prepared and examined for histological changes, and the apoptosis status of the deciduas was examined using the TUNEL apoptosis assay. Embryonic bud length was inversely associated with maternal daily MF exposure level; the association was statistically significant at the time-weighted-average and 75th percentile of MF exposure levels, with coefficients of -3.09 (P?=?0.0479) and -3.07 (P?=?0.0228), respectively. Logistic regression for examining the risk of higher MF exposure indicated that women with her 75th percentile of daily MF measurements ?0.82 mG had a 3.95-fold risk of having a fetus with a shorter embryonic bud length than those whose daily MF exposure were <0.82 mG. MF exposure was associated with a higher degree of apoptosis, but the association was not statistically significant. We failed to find a statistical correlation between MF exposure and embryonic sac length and histological changes in the first trimester. Prenatal MF exposure may have an adverse effect on embryonic development.
Authors: Su XJ; Yuan W; Tan H; Liu XY; Li D; Li DK; Huang GY; Zhang LW; Miao MH
PLoS ONE. 2014;9(6):e101050. Epub 2014-06-30.
Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study
Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.
Authors: Maro JC; Fryback DG; Lieu TA; Lee GM; Martin DB
PLoS ONE. 2014;9(12):e115553. Epub 2014-12-23.
Feasibility and acceptability of a novel, computerized screening and brief intervention (SBI) for alcohol and sweetened beverage use in pregnancy
Recommended screening and brief intervention (SBI) for alcohol use during pregnancy is impeded by high patient loads and limited resources in public health settings. We evaluated the feasibility, acceptability and validity of a new self-administered, single-session, bilingual, computerized Screening and Brief Intervention (SBI) program for alcohol and sugar sweetened beverage (SSB) use in pregnancy. We developed and tested the computerized SBI program at a public health clinic with 290 pregnant women. Feasibility, acceptability, and validity measures were included in the program which had several modules, including those on demographics, health and beverage use. Time to complete the program and user experience items were used to determine program feasibility and acceptability. Validity analyses compared proportions of prenatal alcohol use identified by the program versus in-person screening by clinic staff. Most program users (87%, n?=?251) completed the entire program; 91% (n?=?263) completed the key screening and brief intervention modules. Most users also completed the program in ten to fifteen minutes. Program users reported that the program was easy to use (97%), they learned something new (88%), and that they would share what they learned with others (83%) and with their doctors or clinic staff (76%). Program acceptability did not differ by age, education, or type of beverage intervention received. The program identified alcohol use in pregnancy among 21% of users, a higher rate than the 13% (p?
Authors: Nayak MB; Korcha RA; Kaskustas LA; Avalos LA
BMC Pregnancy Childbirth. 2014;14:379. Epub 2014-11-25.
Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus
Lower levels of sex hormone-binding globulin (SHBG) have been associated with increased risk of diabetes among postmenopausal women; however, it is unclear whether they are associated with glucose intolerance in younger women. We examined whether SHBG concentrations, measured before pregnancy, are associated with risk of gestational diabetes mellitus (GDM). This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up examination (1984-1996) and had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case patients were 256 women in whom GDM developed. Two control subjects were selected for each case patient and were matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies. Compared with the highest quartile of SHBG concentrations, the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44-2.52]; 2.33 [1.07-5.09]; 4.06 [1.90-8.65]; P for trend < 0.001), after adjusting for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use, prepregnancy weight changes, and homeostasis model assessment of insulin resistance. Having SHBG levels below the median (<64.5 nmol/L) and a BMI ?25.0 kg/m(2) was associated with fivefold increased odds of GDM compared with normal-weight women with SHBG levels at or above the median (5.34 [3.00-9.49]). Low prepregnancy SHBG concentrations were associated with increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.
Authors: Hedderson MM; Xu F; Darbinian JA; Quesenberry CP; Sridhar S; Kim C; Gunderson EP; Ferrara A
Diabetes Care. 2014;37(5):1296-303. Epub 2014-02-21.
Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study
Biologic markers of infection and inflammation have been associated with Autism Spectrum Disorders (ASD) but prior studies have largely relied on specimens taken after clinical diagnosis. Research on potential biologic markers early in neurodevelopment is required to evaluate possible causal pathways and screening profiles. To investigate levels of cytokines and chemokines in newborn blood specimens as possible early biologic markers for autism. We conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, California, USA. The study population included children ascertained from the California Department of Developmental Services with Autism Spectrum Disorder (ASD, n?=?84), or developmental delay but not ASD (DD, n?=?49), and general population controls randomly sampled from the birth certificate files and frequency matched to ASD cases on sex, birth month and birth year (GP, n?=?159). Cytokine and chemokine concentrations were measured in archived neonatal blood specimens collected for routine newborn screening. Cytokines were not detected in the vast majority of newborn samples regardless of case or control status. However, the chemokine monocyte chemotactic protein-1 (MCP-1) was elevated and the chemokine Regulated upon Activation Normal T-Cell Expressed and Secreted (RANTES) was decreased in ASD cases compared to GP controls. The chemokines macrophage inflammatory protein-1alpha (MIP-1?) and RANTES were decreased in children with DD compared to GP controls. Measurement of immune system function in the first few days of life may aid in the early identification of abnormal neurodevelopment and shed light on the biologic mechanisms underlying normal neurodevelopment.
Authors: Zerbo O; Yoshida C; Grether JK; Van de Water J; Ashwood P; Delorenze GN; Hansen RL; Kharrazi M; Croen LA
J Neuroinflammation. 2014;11:113. Epub 2014-06-20.
LINE-1 hypomethylation in spermatozoa is associated with Bisphenol A exposure
Bisphenol A (BPA) is an endocrine disruptor with potentially harmful effects on humans. However, epigenetic mechanisms that modulate the effects of BPA remain unclear. Methylation of long interspersed nucleotide elements (LINE-1) is a marker of genome-wide methylation status. This study aims to examine whether BPA exposure was associated with LINE-1 methylation changes in men. Male factory workers in Hunan, China (N = 149) were studied, 77 with BPA exposure in workplace (BPA-exposed group) and 72 without BPA exposure in workplace (control group). Pre-shift and post-shift urine samples were collected from the BPA-exposed group and spot urine samples were collected from the control group. Urine samples were assessed for BPA. In addition, blood and semen samples were collected from both groups for LINE-1 methylation analysis. In multivariate analysis adjusted for age, education, smoking habits and alcohol consumption, sperm LINE-1 methylation level was significantly lower in BPA exposed workers (p < 0.001) compared to that in the unexposed workers. Linear regression analysis also showed that log-transformed urine BPA levels were inversely associated with sperm LINE-1 methylation (p < 0.0001), but not peripheral blood cell LINE-1 methylation. Moreover, the association between urine BPA level and semen quality was not attenuated after adjustments for LINE-1 level. In summary, the observed independent relationship between BPA exposure and LINE-1 methylation may have public health implications on reproductive health in men because of ubiquitous exposure to BPA.
Authors: Miao M; Zhou X; Li Y; Zhang O; Zhou Z; Li T; Yuan W; Li R; Li DK
Andrology. 2014 Jan;2(1):138-44. Epub 2013-12-01.
Prevalence and Neonatal Factors Associated with Autism Spectrum Disorders in Preterm Infants
To determine the prevalence of autism spectrum disorders (ASD) across gestational age, examine the risk of ASD by gestational age controlling for other risk factors, and identify potential risk factors in the neonatal intensive care unit. A retrospective cohort of infants born at ? 24 weeks between January 1, 2000, and December 31, 2007 at 11 Kaiser Permanente Northern California hospitals (n = 195,021). ASD cases were defined by a diagnosis made at a Kaiser Permanente ASD evaluation center, by a clinical specialist, or by a pediatrician. Cox proportional hazards regression models were used to evaluate the association between gestational age and ASD as well as potential risk factors in the neonatal intensive care unit and ASD. The prevalence of ASD in infants <37 weeks was 1.78% compared with 1.22% in infants born ? 37 weeks (P < .001). Compared with term infants, infants born at 24-26 weeks had an adjusted hazard ratio (HR) for a diagnosis of ASD of 2.7 (95% CI 1.5-5.0). Infants born at 27-33 weeks (adjusted HR 1.4, 95% CI 1.1-1.8) and 34-36 weeks (adjusted HR 1.3, 95% CI 1.1-1.4) were also at increased risk. High frequency ventilation and intracranial hemorrhage were associated with ASD in infants < 34 weeks. ASD was ~ 3 times more prevalent in infants <27 weeks compared with term infants. Each week of shorter gestation was associated with an increased risk of ASD. High frequency ventilation and intracranial hemorrhage were associated with ASD among infants <34 weeks.
Authors: Kuzniewicz MW; Wi S; Qian Y; Walsh EM; Armstrong MA; Croen LA
J Pediatr. 2014 Jan;164(1):20-5. Epub 2013-10-22.
The Multigroup Ethnic Identity Measure-Revised: Measurement Invariance Across Racial and Ethnic Groups
The Multigroup Ethnic Identity Measure-Revised (MEIM-R), a brief instrument assessing affiliation with one’s ethnic group, is a promising advance in the ethnic identity literature. However, equivalency of its measurement properties across specific racial and ethnic groups should be confirmed before using it in diverse samples. We examined (a) the psychometric properties of the MEIM-R, including factor structure, measurement invariance, and internal consistency reliability, and (b) levels of and differences in ethnic identity across multiple racial and ethnic groups and subgroups. Asian (n = 630), Black/African American (n = 58), Hispanic (n = 240), multiethnic (n = 160), and White (n = 375) women completed the MEIM-R as part of the “Gestational diabetes’ Effect on Moms” diabetes prevention trial in the Kaiser Permanente Northern California health care setting (N = 1,463; M age = 32.5 years, SD = 4.9). Multiple-groups confirmatory factor analyses provided provisional evidence of measurement invariance, i.e., an equal, correlated 2-factor structure, equal factor loadings, and equal item intercepts across racial and ethnic groups. Latent factor means for the 2 MEIM-R subscales, exploration and commitment, differed across groups; effect sizes ranging from small to large generally supported the notion of ethnic identity as more salient among people of color. Pending replication, good psychometric properties in this large and diverse sample of women support the future use of the MEIM-R. Preliminary evidence of measurement invariance suggests that the MEIM-R could be used to measure and compare ethnic identity across multiple racial and ethnic groups.
Authors: Brown SD; Unger Hu KA; Mevi AA; Hedderson MM; Shan J; Quesenberry CP; Ferrara A
J Couns Psychol. 2014 Jan;61(1):154-61. Epub 2013-11-04.
The Prevalence and Trends of Antiviral Medication Use During Pregnancy in the US: A Population-Based Study of 664,297 Deliveries in 2001-2007
To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Live-born deliveries between 2001 and 2007, to women aged 15-45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program, a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4 % (n = 25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5 to 5 %. The most commonly used antiviral medication was acyclovir, with 3 % of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2 % of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy.
Authors: Avalos LA; Li DK; et al.
Matern Child Health J. 2014 Jan;18(1):64-72.
Post-licensure rapid immunization safety monitoring program (PRISM) data characterization
The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA’s Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data. We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates. The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data. Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM’s computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases. PRISM program’s data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring.
Authors: Baker MA; Nguyen M; Cole DV; Lee GM; Lieu TA
Vaccine. 2013 Dec 30;31 Suppl 10:K98-112.
Invited Commentary: Does Neonatal Hyperbilirubinemia Cause Asthma?
In an analysis of data from the US Collaborative Perinatal Project, Huang et al. (Am J Epidemiol. 2013;178(12):1691-1697) report an association between neonatal total serum bilirubin levels and childhood asthma. To consider the implications of this finding, we need to evaluate whether the association is causal. The results do not appear to be due to chance or any obvious biases. It is likely that the observed association is the result of a common cause of both hyperbilirubinemia and asthma (confounding). Polymorphisms in the glutathione S-transferase gene are a potential genetic confounder. The glutathione S-transferase M1-null phenotype has been linked to both neonatal hyperbilirubinemia and asthma in several studies. Before making any changes in practice aimed at lowering peak bilirubin levels to reduce asthma risk, it is vital to determine not only whether the association between higher bilirubin levels and asthma risk is causal, but also whether interventions to reduce peak bilirubin levels (or their duration) are associated with decreased risk of asthma (without evidence of other adverse effects). The study by Huang et al. should encourage further investigation of these questions.
Authors: Kuzniewicz MW; Wickremasinghe AC; Newman TB
Am J Epidemiol. 2013 Dec 15;178(12):1698-701. Epub 2013-10-31.
Levels of Cotinine in Dried Blood Specimens from Newborns as a Biomarker of Maternal Smoking Close to the Time of Delivery
The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001-2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35–mm punches by using liquid chromatography–tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R(2) = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (? = 0.95, R(2) = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery.
Authors: Yang J; Pearl M; Jacob P; DeLorenze GN; Benowitz NL; Yu L; Havel C; Kharrazi M
Am J Epidemiol. 2013 Dec 1;178(11):1648-54. Epub 2013-09-25.
Low Prepregnancy Adiponectin Concentrations Are Associated With a Marked Increase in Risk for Development of Gestational Diabetes Mellitus
To examine whether circulating total and high-molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM). This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984-1996) with a serum sample obtained and who had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies. Compared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7-2.9], 3.7 [1.9-7.2], and 5.2 [2.6-10.1]; P(trend) <0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P(trend) <0.001). The combined effects of having total adiponectin levels below the median (<10.29 mg/mL) and being overweight or obese (BMI ?25.0 kg/m(2)) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6-12.5]). Prepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention.
Authors: Hedderson MM; Darbinian J; Havel PJ; Quesenberry CP; Sridhar S; Ehrlich S; Ferrara A
Diabetes Care. 2013 Dec;36(12):3930-7. Epub 2013-08-29.
Cohort Study of Insulin Glargine and Risk of Breast, Prostate, and Colorectal Cancer Among Patients With Diabetes
To examine whether use of insulin glargine, compared with another long-acting insulin, is associated with risk of breast, prostate, colorectal cancer, or all cancers combined. Computerized health records from Kaiser Permanente Northern and Southern California regions starting in 2001 and ending in 2009 were used to conduct a population-based cohort study among patients with diabetes aged ?18 years. With use of Cox regression modeling, cancer risk in users of insulin glargine (n = 27,418) was compared with cancer risk in users of NPH (n = 100,757). The cohort had a median follow-up of 3.3 years during which there was a median of 1.2 years of glargine use and 1.4 years of NPH use. Among users of NPH at baseline, there was no clear increase in risk of breast, prostate, colorectal, or all cancers combined associated with switching to glargine. Among those initiating insulin, ever use or ?2 years of glargine was not associated with increased risk of prostate or colorectal cancer or all cancers combined. Among initiators, the hazard ratio (HR) for breast cancer associated with ever use of glargine was 1.3 (95% CI 1.0-1.8); the HR for breast cancer associated with use of glargine for ?2 years was 1.6 or 1.7 depending on whether glargine users had also used NPH. Results of this study should be viewed cautiously, given the relatively short duration of glargine use to date and the large number of potential associations examined.
Authors: Habel LA; Danforth KN; Quesenberry CP; Capra A; Van Den Eeden SK; Weiss NS; Ferrara A
Diabetes Care. 2013 Dec;36(12):3953-60. Epub 2013-10-29.
Chronic High Dose Intraperitoneal Bisphenol A (BPA) Induces Substantial Histological and Gene Expression Alterations in Rat Penile Tissue Without Impairing Erectile Function
Bisphenol A (BPA), released from plastics and dental sealants, is a suspected endocrine disruptor and reproductive toxicant. In occupationally exposed workers, BPA has been associated with erectile dysfunction (ED). To determine whether long-term exposure to high doses of BPA in the rat affects serum levels of testosterone (T) and estradiol (E2), and induces corporal histopathology and resultant ED. Young rats were injected intraperitoneal (IP) injection daily with BPA at 25 mg/kg/day or vehicle (n = 8/group). Erectile function was measured at 3 months by cavernosometry and electrical field stimulation (EFS). BPA was assayed in serum, urine, and penile tissue, and serum T and E2 were determined. Quantitative Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling, Oil Red O, immunohistochemistry for calponin, ?-smooth muscle actin, and Oct 4 were applied to penile tissue sections. Protein markers were assessed by Western blots and 2-D minigels, and RNA by DNA microarrays. Erectile function, histological, and biochemical markers in corporal tissue. In the BPA-treated rats, total and free BPA levels were increased in the serum, urine, and penile tissue while serum T and E2 levels were reduced. In addition, the corpora cavernosa demonstrated a reduction in smooth muscle (SM) content, SM/collagen ratio, together with an increase in myofibroblasts, fat deposits, and apoptosis, but no significant change in collagen content or stem cells (nuclear/perinuclear Oct 4). In the penile shaft, BPA induced a downregulation of Nanog (stem cells), neuronal nitric oxide synthase (nitrergic terminals), and vascular endothelial growth factor (angiogenesis), with genes related to SM tone and cytoskeleton upregulated 5- to 50-fold, accompanied by changes in the multiple protein profile. However, both cavernosometry and EFS were unaltered by BPA. While rats treated chronically with a high IP dose of BPA developed hypogonadism and a corporal histo- and molecular-pathology usually associated with ED, no changes were detected in erectile function as measured by EFS and cavernosometry. Further studies using alternate routes of BPA administration with various doses and length of exposure are needed to expand these findings.
Authors: Kovanecz I; Gelfand R; Masouminia M; Gharib S; Segura D; Vernet D; Rajfer J; Li DK; Liao CY; Kannan K; Gonzalez-Cadavid NF
J Sex Med. 2013 Dec;10(12):2952-66. Epub 2013-10-17.
Counseling and provision of long-acting reversible contraception in the US: National survey of nurse practitioners
Nurse practitioners (NPs) provide frontline care in women’s health, including contraception, an essential preventive service. Their importance for contraceptive care will grow, with healthcare reforms focused on affordable primary care. This study assessed practice and training needs to prepare NPs to offer high-efficacy contraceptives – intrauterine devices (IUDs) and implants. A US nationally representative sample of nurse practitioners in primary care and women’s health was surveyed in 2009 (response rate 69%, n=586) to assess clinician knowledge and practices, guided by the CDC US Medical Eligibility Criteria for Contraceptive Use. Two-thirds of women’s health NPs (66%) were trained in IUD insertions, compared to 12% of primary care NPs. Contraceptive counseling that routinely included IUDs was low overall (43%). Nurse practitioners used overly restrictive patient eligibility criteria, inconsistent with CDC guidelines. Insertion training (aOR=2.4, 95%CI: 1.10 5.33) and knowledge of patient eligibility (aOR=2.9, 95%CI: 1.91 4.32) were associated with IUD provision. Contraceptive implant provision was low: 42% of NPs in women’s health and 10% in primary care. Half of NPs desired training in these methods. Nurse practitioners have an increasingly important position in addressing high unintended pregnancy in the US, but require specific training in long-acting reversible contraceptives.
Authors: Harper CC; Stratton L; Raine TR; Thompson K; Henderson JT; Blum M; Postlethwaite D; Speidel JJ
Prev Med. 2013 Dec;57(6):883-8. Epub 2013-10-12.
Medication Exposure in Pregnancy Risk Evaluation Program: The Prevalence of Asthma Medication Use During Pregnancy
Asthma is one of the most common chronic diseases in women of reproductive age, occurring in up to 8 % of pregnancies. The objective of this study is to assess the prevalence of asthma medication use during pregnancy in a large diverse cohort. We identified women aged 15-45 years who delivered a live born infant between 2001 and 2007 across 11 U.S. health plans within the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). Using health plans’ administrative and claims data, and birth certificate data, we identified deliveries for which women filled asthma medications from 90 days before pregnancy through delivery. Prevalence (%) was calculated for asthma diagnosis and medication dispensing. There were 586,276 infants from 575,632 eligible deliveries in the MEPREP cohort. Asthma prevalence among mothers was 6.7 %, increasing from 5.5 % in 2001 to 7.8 % in 2007. A total of 9.7 % (n = 55,914) of women were dispensed asthma medications during pregnancy. The overall prevalence of maintenance-only medication, rescue-only medication, and combined maintenance and rescue medication was 0.6, 6.7, and 2.4 % respectively. The prevalence of maintenance-only use doubled during the study period from 0.4 to 0.8 %, while rescue-only use decreased from 7.4 to 5.8 %. In this large population-based pregnancy cohort, the prevalence of asthma diagnoses increased over time. The dispensing of maintenance-only medication increased over time, while rescue-only medication dispensing decreased over time.
Authors: Hansen C; Li DK; Davis R; et al.
Matern Child Health J. 2013 Nov;17(9):1611-21.
Childbirth and female sexual function later in life
To examine relationships among parity, mode of delivery, and other parturition-related factors with women’s sexual function later in life. Self-administered questionnaires examined sexual desire, activity, satisfaction, and problems in a multiethnic cohort of women aged 40 years and older with at least one past childbirth event. Trained abstractors obtained information on parity, mode of delivery, and other parturition-related factors from archived records. Multivariable regression models examined associations with sexual function controlling for age, race or ethnicity, partner status, diabetes, and general health. Among 1,094 participants, mean (standard deviation) age was 56.3 (±8.7) years, 568 (43%) were racial or ethnic minorities (214 African American, 171 Asian, and 183 Latina), and 963 (88%) were multiparous. Fifty-six percent (n=601) reported low sexual desire; 53% (n=577) reported less than monthly sexual activity, and 43% (n=399) reported low overall sexual satisfaction. Greater parity was not associated with increased risk of reporting low sexual desire (adjusted odds ratio [OR] 1.08, confidence interval [CI] 0.96-1.21 per each birth), less than monthly sexual activity (adjusted OR 1.05, CI 0.93-1.20 per each birth), or low sexual satisfaction (adjusted OR 0.96, CI 0.85-1.09 per each birth). Compared with vaginal delivery alone, women with a history of cesarean delivery were not significantly more likely to report low desire (adjusted OR 0.71, CI 0.34-1.47), less than monthly sexual activity (adjusted OR 1.03, CI 0.46-2.32), or low sexual satisfaction (adjusted OR 0.57, CI 0.26-1.22). Women with a history of operative-assisted delivery were more likely to report low desire (adjusted OR 1.38, CI 1.04-1.83). Among women with at least one childbirth event, parity and mode of delivery are not major determinants of sexual desire, activity, or satisfaction later in life. II.
Authors: Fehniger JE; Brown JS; Creasman JM; Van Den Eeden SK; Thom DH; Subak LL; Huang AJ
Obstet Gynecol. 2013 Nov;122(5):988-97.
Statin Exposure is Associated with Decreased Asthma-Related Emergency Department Visits and Oral Corticosteroid Use
Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects. To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort. Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non-statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression. Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04). There were no differences in asthma-related hospitalizations (OR, 0.91; 95% CI, 0.66-1.24; P = 0.52). Among statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings.
Authors: Tse SM; Lieu T; Wu AC; et al.
Am J Respir Crit Care Med. 2013 Nov;188(9):1076-82.
Head Circumferences in Twins With and Without Autism Spectrum Disorders
To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20 % of males and 27 % of females with an ASD had macrocephaly. Unaffected co-twins showed similar rates (16 % of males and 22 % of females). Statistical analysis revealed no significant difference in HCs between affected and unaffected twins. Twins with ASDs and unaffected co-twins have similar HCs and increased rates of macrocephaly. Correlations demonstrated partial inheritance of HCs. Thus, macrocephaly may represent an endophenotype in ASDs.
Authors: Froehlich W; Croen LA; Hallmayer J; et al.
J Autism Dev Disord. 2013 Sep;43(9):2026-37.
Abnormal vaginal bleeding after epidural steroid injection: a paired observation cohort study
OBJECTIVE: The use of epidural steroid injections has increased dramatically, but knowledge of potential adverse effects is lacking. An association between steroid injection and subsequent abnormal vaginal bleeding has been suspected clinically, but evidence has been limited to anecdotal reports. STUDY DESIGN: Paired observational retrospective cohort study using electronic medical records from a large integrated health care system. Participants were all nonhysterectomized women who underwent epidural steroid injections in 2011. For each steroid injection, encounters for abnormal vaginal bleeding during the 60 days preceding and 60 days after the injection were compared as paired observations. For women found to have bleeding, medical records review was performed to examine menopausal status and bleeding evaluation outcomes. RESULTS: Among 8166 epidural steroid injection procedures performed on 6926 nonhysterectomized women, 201 (2.5%) procedures were followed by at least 1 outpatient visit for abnormal vaginal bleeding. Women were 2.8 times more likely to present with abnormal vaginal bleeding during the postinjection period compared with the preinjection period (P < .0001). Of the 197 women with postinjection bleeding, 137 (70%) were premenopausal and 60 (30%) were postmenopausal. Postinjection bleeding prompted endometrial biopsy evaluation in 103 (52%) cases, with benign findings for 100% of premenopausal women (59/59) and 95% of postmenopausal women (42/44). CONCLUSION: Epidural steroid injections are associated with subsequent abnormal vaginal bleeding for both premenopausal and postmenopausal women. Women undergoing epidural steroid injection should be advised of abnormal bleeding as a potential adverse effect and providers should be aware of this association when evaluating abnormal bleeding.
Authors: Suh-Burgmann E; Hung YY; Mura J
Am J Obstet Gynecol. 2013 Sep;209(3):206.e1-6. Epub 2013 Jun 28.
Clinical predictors and significance of postvoid residual volume in women with diabetes
To identify women with diabetes at risk of increased postvoid residual volume (PVR) and investigate the relationship of increased PVR to urinary symptoms in women with diabetes. PVR was measured by bladder ultrasonography in a cross-sectional cohort of 427 middle-aged and older women with diabetes. Participants completed questionnaires assessing urgency incontinence, stress incontinence, daytime frequency, nocturia, obstructive voiding, and diabetes-related end-organ complications: heart disease, stroke, neuropathy. Serum HbA1c and creatinine were recorded. 75% of participants had a PVR of 0-49, 13% had a PVR of 50-99, and 12% had a PVR ? 100 mL. Approximately 59% of women with a PVR < 50 mL reported at least one lower urinary tract symptom. Women with diabetes and a PVR ? 100 mL were more likely to report urgency incontinence (OR 2.18, CI 1.08-4.41) and obstructive voiding symptoms (OR 2.47, CI 1.18-5.17) than women with PVR < 50 mL. In multivariable models, poorer glycemic control was associated with an increased likelihood of PVR ? 100 mL (OR 1.30, CI 1.06-1.59 per 1.0-U increase in HbA1c). PVR volumes ? 100 mL may indicate increased risk of urgency incontinence and obstructive voiding. Glycemic control may play a role in preventing increased PVR in women with diabetes.
Authors: Appa AA; Brown JS; Creasman J; Van Den Eeden SK; Subak LL; Thom DH; Ferrara A; Huang AJ
Diabetes Res Clin Pract. 2013 Aug;101(2):164-9. Epub 2013-06-14.
Methods of linking mothers and infants using health plan data for studies of pregnancy outcomes
Research on medication safety in pregnancy often utilizes health plan and birth certificate records. This study discusses methods used to link mothers with infants, a crucial step in such research. We describe how eight sites participating in the Medication Exposure in Pregnancy Risk Evaluation Program created linkages between deliveries, infants and birth certificates for the 2001-2007 birth cohorts. We describe linkage rates across sites, and for two sites, we compare the characteristics of populations linked using different methods. Of 299,260 deliveries, 256,563 (86%; range by site, 74-99%) could be linked to infants using a deterministic algorithm. At two sites, using birth certificate data to augment mother-infant linkage increased the representation of mothers who were Hispanic or non-White, younger, Medicaid recipients, or had low educational level. A total of 236,460 (92%; range by site, 82-100%) deliveries could be linked to a birth certificate. Tailored approaches enabled linking most deliveries to infants and to birth certificates, even when data systems differed. The methods used may affect the composition of the population identified. Linkages established with such methods can support sound pharmacoepidemiology studies of maternal drug exposure outside the context of a formal registry.
Authors: Johnson KE; Li DK; Dublin S; et al.
Pharmacoepidemiol Drug Saf. 2013 Jul;22(7):776-82. Epub 2013-04-18.
Evaluation of e-mail contact to conduct follow-up among adolescent women participating in a longitudinal cohort study of contraceptive use
The purpose of this study was to determine whether e-mail contact is a viable method for gathering information from adolescent women about contraceptive use. Adolescent women initiating contraception followed in a prospective longitudinal cohort study and who had access to the Internet were randomized to the control or intervention arm and were contacted at 3, 6 and 12 months after enrollment. The control arm completed follow-up surveys in-person or by telephone. The intervention arm received Web-based surveys via e-mail. There were 46 women in each group. Women in both groups were approximately 20 years old, were sexually active minority women, and were in school or employed. While participants in the intervention group initially had lower response rates than those in the control group (59% vs. 91%, respectively), with the addition of traditional follow-up methods, the overall response rates were comparable (94% vs. 91%, respectively). E-mail follow-up with Web-based surveys was effective amongst adolescent women at risk for unintended pregnancy. This indicates that e-mail contact could be used as a preliminary follow-up strategy to capture a substantial proportion of participants and that standard follow-up can be used as a second-line approach. A two-pronged approach with initial e-mail contact and traditional follow-up for participants who do not respond may be a viable method when evaluating sensitive areas such as contraceptive use.
Authors: Haider S; Dodge LE; Brown BA; Hacker MR; Raine TR
Contraception. 2013 Jul;88(1):18-23. Epub 2013-01-03.
Risk of Large-for-Gestational-Age Newborns in Women With Gestational Diabetes by Race and Ethnicity and Body Mass Index Categories
OBJECTIVE: To compare the prevalence of large-for-gestational-age (LGA) newborns across categories of body mass index (BMI) in five racial and ethnic groups. METHODS: This cohort study examined 7,468 women with gestational diabetes mellitus (GDM) who delivered a live newborn between 1995 and 2006 at Kaiser Permanente Northern California. The racial and ethnic groups were non-Hispanic white, African American, Hispanic, Asian, and Filipina. The BMI was classified using the World Health Organization International guidelines (normal, 18.50-24.99; overweight, 25.00-29.99; obese, 30.00-34.99; obese class II, 35.00 or higher). Having an LGA newborn was defined as birth weight more than 90th percentile for the study population’s race or ethnicity and gestational age–specific birth weight distribution. Logistic regression was used to estimate odds of having an LGA newborn by BMI and race and ethnicity. RESULTS: Overall prevalence of LGA newborns was highest in African American women (25.1%), lowest in Asians (13.9%), and intermediate among Hispanic (17.3%), white (16.4%), and Filipina women (15.3%). The highest increased risk of LGA newborns was observed among women with class II obesity in most racial and ethnic groups, and African American and Asian women with class II obesity had a four-fold increased risk of LGA newborns compared with women of normal weight in the same racial and ethnic group. CONCLUSIONS: African American women with GDM have a greater risk of LGA newborns at a lower BMI than other racial and ethnic groups. Clinicians should be aware that among women with GDM, there may be significant racial and ethnic differences in the risk of LGA newborns by BMI threshold.
Authors: Sridhar SB; Ferrara A; Ehrlich SF; Brown SD; Hedderson MM
Obstet Gynecol. 2013 Jun;121(6):1255-62.
Black Race Is Not Protective Against Hazardous Bilirubin Levels
Although black race is considered protective against hyperbilirubinemia, black infants appear at increased risk of kernicterus. We found that although black infants have a lower risk of developing total serum bilirubin levels >/= 20 mg/dL than white infants, they appear at greater risk of developing levels >/= 30 mg/dL.
Authors: Wickremasinghe AC; Kuzniewicz MW; Newman TB
J Pediatr. 2013 May;162(5):1068-9. Epub 2013 Feb 10.
Pregnancy Glycemia in Mexican-American Women Without Diabetes or Gestational Diabetes and Programming for Childhood Obesity
In the present study, we estimated the association between pregnancy glucose levels and offspring body mass index (BMI) z scores at 2, 3.5, 5, and 7 years of age, as well as z score trajectories across this age range, among Mexican-American women without diabetes or gestational diabetes. Beginning in 1999-2000, the Center for the Health Assessment of Mothers and Children of Salinas prospectively followed women from Monterey County, California (52 obese and 214 nonobese women) and their children. Plasma glucose values obtained 1 hour after a 50-g oral glucose load comprised the exposure. Offspring BMIs were compared with national data to calculate z scores. Increasing pregnancy glucose levels were associated with increased offspring BMI z scores at 7 years of age; a 1-mmol/L increase in glucose corresponded to an increase of 0.11 (standard deviation = 0.044) z-score units (P < 0.05). In nonobese women only, the mean z score over this age range increased with increasing glucose levels. The average BMI z score at 4.5 years of age increased by 0.12 (standard error, 0.059) units for each 1-mmol/L increase in glucose (P = 0.04). In obese women only, increasing glucose was associated with increases in BMI z score over time (P = 0.07). Whether interventions to reduce glucose values in women free of disease could mitigate childhood obesity remains unknown.
Authors: Ehrlich SF; Rosas LG; Ferrara A; King JC; Abrams B; Harley KG; Hedderson MM; Eskenazi B
Am J Epidemiol. 2013 Apr 15;177(8):768-75. Epub 2013 Mar 15.
Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001-2007: a population-based study of 585,615 deliveries
This study aims to estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. We identified live born deliveries to women aged 15-45 years in 2001-2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program. We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Among 585,615 qualifying deliveries, 4,223 (0.72%) were to women who received an atypical antipsychotic and 548 (0.09%) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33% (95% confidence interval: 0.29%, 0.37%) in 2001 to 0.82% (0.76%, 0.88%) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63%), followed by bipolar disorder (43%) and schizophrenia (13%). The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy.
Authors: Toh S; Li DK; Avalos LA; Andrade SE; et al.
Arch Womens Ment Health. 2013 Apr;16(2):149-57. Epub 2013 Feb 7.
Five-year risk of recurrence after treatment of CIN 2, CIN 3, or AIS: performance of HPV and Pap cotesting in posttreatment management
After excisional treatment, cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) can recur. It is not clear how many negative posttreatment Pap or cotest results are needed to ensure adequate safety against CIN 2+ before returning to extended retesting intervals. We observed 5-year risks of CIN 2+ for 3 follow-up management strategies after treatment (Pap-alone, human papillomavirus [HPV]-alone, and HPV/Pap cotesting) for 3,273 women aged 25 years and older who were treated for CIN 2, CIN 3, or adenocarcinoma in situ (AIS) between 2003 and 2010 at Kaiser Permanente Northern California. Five-year risks of recurrent CIN 2+ after treatment varied both by antecedent screening test result and the histology of the treated lesion. The risk ranged from 5% for CIN 2 preceded by HPV-positive/atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion to 16% for CIN 3/AIS preceded by atypical glandular cells (AGC)/atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (ASC-H)/high-grade squamous intraepithelial lesion or worse (HSIL+) (p < .0001). However, after posttreatment negative tests, risks were lowered and similar regardless of antecedent screening test and histology of treated disease. The 5-year recurrent CIN 2+ risk after a negative posttreatment cotest (2.4%) was lower than that following a negative HPV test (3.7%, p = .3) or negative Pap result (4.2%, p = .1). Two negative posttreatment tests of each kind conferred slightly lower 5-year CIN 2+ risk than one (2 negative Pap tests vs. 1, 2.7% vs 4.2%, p = .2; 2 negative HPV tests vs. 1, 2.7% vs 3.7%, p = .7; 2 negative cotests vs. 1, 1.5% vs 2.4%, p = .8). The 5-year CIN 2+ risk after 2 negative cotests of 1.5% (95% confidence interval = 0.3%-7.2%) approached the 0.68% risk after a negative Pap test during routine screening. Women with antecedent AGC/ASC-H/HSIL+ Pap results or those treated for CIN 3/AIS had a substantial risk of developing CIN 2+ posttreatment. On the basis of the principle of "equal management of equal risks," after negative test results posttreatment, no subgroup of women achieved risk sufficiently low to return to 5-year routine screening. However, negative cotests after treatment provided more reassurance against recurrent CIN 2+ than either negative Pap tests or HPV tests alone.
Authors: Katki HA; Schiffman M; Castle PE; Fetterman B; Poitras NE; Lorey T; Cheung LC; Raine-Bennett T; Gage JC; Kinney WK
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S78-84.
Five-year risk of CIN 3+ to guide the management of women aged 21 to 24 years
Current US national guidelines recommend beginning screening at age 21 using Pap tests only, with cotesting starting at age 30. To inform the management of Pap test abnormalities among women aged 21 to 24 years, who have extremely low cancer risks, we compared risks of CIN 3+ among women aged 21 to 24 versus 25 to 29 years or 30 to 64 years. We estimated 5-year risks of CIN 3+ given different Pap test results, with human papillomavirus (HPV) triage of atypical squamous cells of undetermined significance (ASC-US), among 133,947 women aged 21 to 24 years, compared with 135,382 women aged 25 to 29 years and 965,360 women aged 30 to 64 years, between 2003 and 2010 at Kaiser Permanente Northern California. There were 3 cancers diagnosed during follow-up in women aged 21 to 24 years. After high-grade Pap results (0.6% of Pap results), the 5-year CIN 3+ risks among women aged 21 to 24 years were comparable to those aged 25 to 29 and 30 to 64 years (atypical glandular cells, 6.9% vs 14% vs 8.5%, p = .8; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion, 16% vs 24% vs 18%, p = .8; high-grade squamous intraepithelial lesion, 28% vs 28% vs 47%, p = .4). After low-grade squamous intraepithelial lesion, the 5-year CIN 3+ risk was lower among women aged 21 to 24 years (3.0%) than that among women aged 25 to 29 years (5.0%, p = .01) or aged 30 to 64 years (5.2%, p = .0002). Although the 5-year CIN 3+ risk after HPV-negative/ASC-US was similar across all 3 groups (0.57% vs 0.59% vs 0.43%, p = 1), risk after HPV-positive/ASC-US was lower among women aged 21 to 24 years (4.4%) than that among women aged 25 to 29 years (7.1%, p < .0001) or 30 to 64 years (6.8%, p < .0001). Women aged 21 to 24 years had almost zero cancer risk, and positive Pap test results predicted low CIN 3+ risk except for the 0.6% of women with high-grade Pap results. The generally low risk supports conservative management of women aged 21 to 24 years.
Authors: Katki HA; Schiffman M; Castle PE; Fetterman B; Poitras NE; Lorey T; Cheung LC; Raine-Bennett T; Gage JC; Kinney WK
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S64-8.
Five-year risks of CIN 3+ and cervical cancer among women with HPV testing of ASC-US Pap results
New screening guidelines recommend that human papillomavirus (HPV)-negative/atypical squamous cells of undetermined significance (ASC-US) results be considered as equivalent to HPV-negative/Pap-negative results, leading to rescreening in 5 years. However, despite ample data, the routine clinical performance of HPV testing of women with ASC-US has not been adequately documented. We estimated 5-year risks of cervical intraepithelial neoplasia (CIN) 3+ and of cancer among 2 groups of women between 2003 and 2010 at Kaiser Permanente Northern California: 27,050 aged 30 to 64 years who underwent HPV and Pap cotesting and had an ASC-US Pap result and 12,209 aged 25 to 29 years who underwent HPV triage of ASC-US. Five-year risks of CIN 3+ and of cancer among women aged 30 to 64 years testing HPV-negative/ASC-US and among 923,152 women testing Pap-negative alone were similar although statistically distinguishable (CIN 3+, 0.43% vs 0.26%, p = .001; cancer, 0.050% vs 0.025%, p = .1). The increased risk of cancer after HPV-negative/ASC-US versus Pap-negative alone was confined to women aged 60 to 64 years (0.26% vs 0.035%, p = .3). Five-year risks of CIN 3+ and cancer among women with HPV-negative/ASC-US results were substantially higher than those among women testing HPV-negative/Pap-negative (CIN 3+, 0.43% vs 0.08%, p < .0001; cancer, 0.050% vs 0.011%, p = .003). For women aged 30 to 64 years testing HPV-positive/ASC-US, 5-year risks of CIN 3+ and cancer were slightly higher than those among 9,374 women with low-grade squamous intraepithelial lesion (LSIL) (CIN 3+, 6.8% vs 5.2%, p = .0007; cancer, 0.41% vs 0.16%, p = .04). Similar patterns were seen for women aged 25 to 29 years. Women with HPV-negative/ASC-US had a similar risk as women testing Pap-negative alone but had a higher risk than women testing HPV-negative/Pap-negative. Based upon the principle of "equal management of equal risks," our findings support the equal management of women with HPV-negative/ASC-US and those with Pap-negative alone, except for exiting women from screening because cancer risks at ages 60 to 64 years may be higher for women testing HPV-negative/ASC-US. Our findings also support managing HPV-positive/ASC-US and LSIL similarly.
Authors: Katki HA; Schiffman M; Castle PE; Fetterman B; Poitras NE; Lorey T; Cheung LC; Raine-Bennett T; Gage JC; Kinney WK
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S36-42.
Benchmarking CIN 3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines
In 2012, the US Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and human papillomavirus (HPV) testing ("cotesting") for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by Pap-alone, without consideration of HPV test results. To promote management that is consistent with accepted practice, new guidelines incorporating cotesting should aim to achieve equal management of women at equal risk of cervical intraepithelial neoplasia grade 3 and cancer (CIN 3+). We estimated cumulative 5-year risks of CIN 3+ for 965,360 women aged 30 to 64 years undergoing cotesting at Kaiser Permanente Northern California over 2003 to 2010. We calculated the implicit risk thresholds for Pap-alone and applied them for new management guidance on HPV and Pap cotesting, citing 2 examples: HPV-positive/atypical squamous cells of undetermined significance (ASC-US) and HPV-negative/Pap-negative. We call this guidance process "benchmarking." A low-grade squamous intraepithelial lesion result, for which immediate colposcopy is prescribed, carries a 5-year CIN 3+ risk of 5.2%, suggesting that test results with similar risks should be managed with colposcopy. Similarly, ASC-US (2.6% risk) is managed with a 6- to 12-month follow-up visit and Pap-negative (0.26% risk) is managed with a 3-year follow-up visit. The 5-year CIN 3+ risk for women with HPV-positive/ASC-US was 6.8% (95% confidence interval = 6.2%-7.6%). This is greater than the 5.2% risk implicitly leading to referral to colposcopy, consistent with current management recommendations that HPV-positive/ASC-US should be referred for immediate colposcopy. The 5-year CIN 3+ risk for women with HPV-negative/Pap-negative was 0.08% (95% confidence interval = 0.07%-0.09%), far below the 0.26% implicitly required for a 3-year return and justifying a longer (e.g., 5-year) return. Using the principle of "equal management of equal risks," benchmarking to implicit risk thresholds based on Pap-alone can be used to achieve safe and consistent incorporation of cotesting.
Authors: Katki HA; Schiffman M; Castle PE; Fetterman B; Poitras NE; Lorey T; Cheung LC; Raine-Bennett T; Gage JC; Kinney WK
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S28-35.
Five-year risks of CIN 2+ and CIN 3+ among women with HPV-positive and HPV-negative LSIL Pap results
Low-grade squamous intraepithelial lesion (LSIL) Pap results do not typically lead to human papillomavirus (HPV) testing. HPV triage is not cost-effective because most cases are HPV-positive. However, under new national guidelines recommending cotesting for women aged 30 to 64 years, clinicians will increasingly receive the HPV test result with LSIL Pap results. Some authors have suggested that HPV triage might be effective at older ages, when the percentage of HPV positivity among women with LSIL declines. We estimated 5-year risks of CIN 2+ and CIN 3+ among 9,033 women aged 30 to 64 years who had both an HPV test and an LSIL Pap result. HPV positivity among women with LSIL decreased only slightly with age (30 to 34 vs 60 to 64 years, 88% vs 72%, p < .0001). The 5-year risks of CIN 2+ and CIN 3+ of women aged 30 to 64 years testing HPV-positive/LSIL were larger than those among women testing HPV-negative/LSIL (CIN 2+, 19% vs 5.1%, p < .0001; CIN 3+, 6.1% vs 2.0%, p<.0001). The 5-year risk of CIN 3+ in HPV-negative/LSIL women was similar to that for women with atypical squamous cells of undetermined significance (ASC-US) Pap test result without knowledge of HPV test results (2.0% vs 2.6%, p = .4). HPV-negative/LSIL posed lower risk than other Pap results that guidelines currently recommend for referral to immediate colposcopy. By the principle of "equal management of equal risks," women with HPV-negative/LSIL might reasonably be managed similarly to those with ASC-US Pap results without knowledge of HPV testing, that is, retesting at 6 to 12 months, rather than immediate colposcopy. Although the HPV test result for LSIL Pap results provides actionable information to clinicians who screen with cotesting, the high HPV positivity of LSIL at even the oldest ages suggests the lack of cost-effectiveness of HPV triage of LSIL for clinicians who do not use routine cotesting.
Authors: Katki HA; Schiffman M; Castle PE; Fetterman B; Poitras NE; Lorey T; Cheung LC; Raine-Bennett T; Gage JC; Kinney WK
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S43-9.
Surgical outcomes of total knee replacement according to diabetes status and glycemic control, 2001 to 2009
BACKGROUND: Poor glycemic control in patients with diabetes may be associated with adverse surgical outcomes. We sought to determine the association of diabetes status and preoperative glycemic control with several surgical outcomes, including revision arthroplasty and deep infection. METHODS: We conducted a retrospective cohort study in five regions of a large integrated health-care organization. Eligible subjects, identified from the Kaiser Permanente Total Joint Replacement Registry, underwent an elective first primary total knee arthroplasty during 2001 through 2009. Data on demographics, diabetes status, preoperative hemoglobin A1c (HbA1c) level, and comorbid conditions were obtained from electronic medical records. Subjects were classified as nondiabetic, diabetic with HbA1c < 7% (controlled diabetes), or diabetic with HbA1c >/= 7% (uncontrolled diabetes). Outcomes were deep venous thrombosis or pulmonary embolism within ninety days after surgery and revision surgery, deep infection, incident myocardial infarction, and all-cause rehospitalization within one year after surgery. Patients without diabetes were the reference group in all analyses. All models were adjusted for age, sex, body mass index, and Charlson Comorbidity Index. RESULTS: Of 40,491 patients who underwent total knee arthroplasty, 7567 (18.7%) had diabetes, 464 (1.1%) underwent revision arthroplasty, and 287 (0.7%) developed a deep infection. Compared with the patients without diabetes, no association between controlled diabetes (HbA1c < 7%) and the risk of revision (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.99 to 1.76), risk of deep infection (OR, 1.31; 95% CI, 0.92 to 1.86), or risk of deep venous thrombosis or pulmonary embolism (OR, 0.84; 95% CI, 0.60 to 1.17) was observed. Similarly, compared with patients without diabetes, no association between uncontrolled diabetes (HbA1c >/= 7%) and the risk of revision (OR, 1.03; 95% CI, 0.68 to 1.54), risk of deep infection (OR, 0.55; 95% CI 0.29 to 1.06), or risk of deep venous thrombosis or pulmonary embolism (OR, 0.70; 95% CI, 0.43 to 1.13) was observed. CONCLUSIONS: No significantly increased risk of revision arthroplasty, deep infection, or deep venous thrombosis was found in patients with diabetes (as defined on the basis of preoperative HbA1c levels and other criteria) compared with patients without diabetes in the study population of patients who underwent elective total knee arthroplasty.
Authors: Adams AL; Paxton EW; Wang JQ; Johnson ES; Bayliss EA; Ferrara A; Nakasato C; Bini SA; Namba RS
J Bone Joint Surg Am. 2013 Mar 20;95(6):481-7.
Is Infertility Associated with Childhood Autism?
Concerns persist about a possible link between infertility and risk of autism spectrum disorders (ASD). Interpretation of existing studies is limited by racial/ethnic homogeneity of study populations and other factors. Using a case-control design, we evaluated infertility history and treatment documented in medical records of members of Kaiser Permanente Northern California. Among singletons (349 cases, 1,847 controls), we found no evidence to support an increase in risk of ASD associated with infertility. Among multiple births (21 cases, 54 controls), we found an increased risk associated with infertility history and with infertility evaluations and treatment around the time of index pregnancy conception; however, small sample size and lack of detailed data on treatments preclude firm interpretation of results for multiple births.
Authors: Grether JK; Qian Y; Croughan MS; Wu YW; Schembri M; Camarano L; Croen LA
J Autism Dev Disord. 2013 Mar;43(3):663-72.
‘Do ask, do provide’ contraception for women in the u.s. Military
Authors: Raine-Bennett T
Obstet Gynecol. 2013 Feb;121(2 Pt 1):229-30.
Use of Birth Certificates to Examine Maternal Occupational Exposures and Autism Spectrum Disorders in Offspring
The continuing rise in the prevalence of autism spectrum disorders has led to heightened interest in the role of nongenetic factors, including exogenous exposures, but little research has been conducted. To explore a possible role in autism etiology, we used data available from our prior studies to examine potential occupational exposures, as these may occur at higher levels than environmental exposures. Parental occupation was obtained from birth certificates for 284 children with autism and 659 controls, born in 1994 in the San Francisco Bay Area. Self-reported occupation and industry were coded into eight exposure/chemical groups based on potential neurotoxicity or reprotoxicity by a board-certified physician in occupational medicine and an industrial hygienist blinded to case-control status. Mothers of autistic children were twice as likely to work in occupations considered exposed (14.4%) as mothers of controls (7.2%) (adjusted odds ratio [AOR] 2.3 [95% confidence interval {CI} 1.3-4.2]). The exposure categories of the greatest frequency among case mothers were exhaust and combustion products (AOR = 12.0 [95% CI 1.4-104.6]) and disinfectants (AOR = 4.0 [95% CI 1.4-12.0]). Paternal occupational exposure was not associated with autism, potentially consistent with a direct in-utero exposure effect. There are several limitations of this hypothesis-generating study, including lack of detail on workplace and job duties, leading to possible misclassification and low proportion exposed. However, this misclassification would not be biased by case-control status and is unlikely to explain the associations we did find, suggesting that further research on exogenous exposures may yield useful etiologic clues.
Authors: Windham GC; Sumner A; Li SX; Anderson M; Katz E; Croen LA; Grether JK
Autism Res. 2013 Feb;6(1):57-63. Epub 2013 Jan 29.
Impact of type 2 diabetes on lower urinary tract symptoms in men: a cohort study
BACKGROUND: Studies of the impact of type 2 diabetes on the prevalence and incidence of lower urinary tract symptoms (LUTS) among men have provided divergent results. We sought to examine this issue using two large and diverse cohorts. METHODS: This study used questionnaire and clinical data from two large multiethnic cohorts, the California Men’s Health Study (CMHS) and Research Program in Genes, Environment and Health (RPGEH). Diabetes characteristics data were derived from questionnaire and Diabetes Registry data. LUTS were measured using a standardized scale. Socioeconomic and comorbidity data were obtained by self-report. Multivariable logistic regression analysis was used to examine the association between baseline DM status and prevalence and incidence of LUTS, with adjustment for potential confounding variables. RESULTS: We found type 2 diabetes to be associated with prevalent LUTS (odds ratio (OR) = 1.32, 95% confidence interval (CI) 1.26, 1.38). The association was stronger among men with type 2 diabetes who were on active pharmaceutical treatment and had it for a longer duration. No association was observed between type 2 diabetes and new onset LUTS. CONCLUSIONS: Type 2 diabetes increases the risk of LUTS.
Authors: Van Den Eeden SK; Ferrara A; Shan J; Jacobsen SJ; Quinn VP; Haque R; Quesenberry CP
BMC Urol. 2013 Feb 20;13:12.
Validity of health plan and birth certificate data for pregnancy research
PURPOSE: To evaluate the validity of health plan and birth certificate data for pregnancy research. METHODS: A retrospective study was conducted using administrative and claims data from 11 U.S. health plans and corresponding birth certificate data from state health departments. Diagnoses, drug dispensings, and procedure codes were used to identify infant outcomes (cardiac defects, anencephaly, preterm birth, and neonatal intensive care unit [NICU] admission) and maternal diagnoses (asthma and systemic lupus erythematosus [SLE]) recorded in the health plan data for live born deliveries between January 2001 and December 2007. A random sample of medical charts (n = 802) was abstracted for infants and mothers identified with the specified outcomes. Information on newborn, maternal, and paternal characteristics (gestational age at birth, birth weight, previous pregnancies and live births, race/ethnicity) was also abstracted and compared to birth certificate data. Positive predictive values (PPVs) were calculated with documentation in the medical chart serving as the gold standard. RESULTS: PPVs were 71% for cardiac defects, 37% for anencephaly, 87% for preterm birth, and 92% for NICU admission. PPVs for algorithms to identify maternal diagnoses of asthma and SLE were >/= 93%. Our findings indicated considerable agreement (PPVs > 90%) between birth certificate and medical record data for measures related to birth weight, gestational age, prior obstetrical history, and race/ethnicity. CONCLUSIONS: Health plan and birth certificate data can be useful to accurately identify some infant outcomes, maternal diagnoses, and newborn, maternal, and paternal characteristics. Other outcomes and variables may require medical record review for validation.
Authors: Andrade SE; Li DK; Cooper WO; et al.
Pharmacoepidemiol Drug Saf. 2013 Jan;22(1):7-15. Epub 2012 Jul 3.
Prevalence, Trends, and Patterns of Use of Antidiabetic Medications Among Pregnant Women, 2001-2007
OBJECTIVE:: To describe the prevalence, trends, and patterns in use of antidiabetic medications to treat hyperglycemia and insulin resistance before and during pregnancy in a large U.S. cohort of insured pregnant women. METHODS:: Pregnancies resulting in live births were identified (N=437,950) from 2001 to 2007 among 372,543 females 12-50 years of age at delivery from 10 health maintenance organizations participating in the Medication Exposure in Pregnancy Risk Evaluation Program. Information for these descriptive analyses, including all antidiabetic medications dispensed during this period, was extracted from electronic health records and newborn birth certificates. RESULTS:: A little more than 1% (1.21%) of deliveries were to women dispensed antidiabetic medication in the 120 days before pregnancy. Use of antidiabetic medications before pregnancy increased from 0.66% of deliveries in 2001 to 1.66% of deliveries in 2007 (P<.001) because of an increase in metformin use. Most women using metformin before pregnancy had a diagnosis code for polycystic ovaries or female infertility (67.2%), whereas only 13.6% had a diagnosis code for diabetes. The use of antidiabetic medications during the second or third trimester of pregnancy increased from 2.8% of deliveries in 2001 to 3.6% in 2007 (P<.001). Approximately two thirds (68%) of women using metformin before pregnancy did not use any antidiabetic medications during pregnancy. CONCLUSIONS:: Antidiabetic medication use before and during pregnancy increased from 2001 to 2007, possibly because of increasing prevalence of gestational diabetes mellitus, type 1 and type 2 diabetes, and other conditions associated with insulin resistance. LEVEL OF EVIDENCE:: III.
Authors: Lawrence JM; Avalos LA; Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) Study Group; et al.
Obstet Gynecol. 2013 Jan;121(1):106-14.
A genome-wide survey of transgenerational genetic effects in autism
Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4)) that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.
Authors: Tsang KM; Croen LA; Torres AR; Kharrazi M; Delorenze GN; Windham GC; Yoshida CK; Zerbo O; Weiss LA
PLoS ONE. 2013;8(10):e76978. Epub 2013-10-24.
Sequencing of the IL6 gene in a case–control study of cerebral palsy in children
Cerebral palsy (CP) is a group of nonprogressive disorders of movement and posture caused by abnormal development of, or damage to, motor control centers of the brain. A single nucleotide polymorphism (SNP), rs1800795, in the promoter region of the interleukin-6 (IL6) gene has been implicated in the pathogenesis of CP by mediating IL-6 protein levels in amniotic fluid and cord plasma and within brain lesions. This SNP has been associated with other neurological, vascular, and malignant processes as well, often as part of a haplotype block. To refine the regional genetic association with CP, we sequenced (Sanger) the IL6 gene and part of the promoter region in 250 infants with CP and 305 controls. We identified a haplotype of 7 SNPs that includes rs1800795. In a recessive model of inheritance, the variant haplotype conferred greater risk (OR?=?4.3, CI?=?[2.0-10.1], p?=?0.00007) than did the lone variant at rs1800795 (OR?=?2.5, CI?=?[1.4-4.6], p?=?0.002). The risk haplotype contains one SNP (rs2069845, CI?=?[1.2-4.3], OR?=?2.3, p?=?0.009) that disrupts a methylation site. The risk haplotype identified in this study overlaps with previously identified haplotypes that include additional promoter SNPs. A risk haplotype at the IL6 gene likely confers risk to CP, and perhaps other diseases, via a multi-factorial mechanism.
Authors: Khankhanian P; Baranzini SE; Johnson BA; Madireddy L; Nickles D; Croen LA; Wu YW
BMC Med Genet. 2013;14:126. Epub 2013-12-07.
Urine bisphenol-a level in relation to obesity and overweight in school-age children
Bisphenol-A (BPA) is a potential endocrine disruptor impacting metabolic processes and increasing the risk of obesity. To determine whether urine BPA level is associated with overweight/obesity in school-age children, we examined 1,326 students in grades 4-12 from three schools (one elementary, one middle, and one high school) in Shanghai. More than 98% of eligible students participated. Total urine BPA concentration was measured and anthropometric measures were taken by trained research staff. Information on risk factors for childhood obesity was collected for potential confounders. Age- and gender-specific weight greater than 90(th) percentile of the underlying population was the outcome measure. After adjustment for potential confounders, a higher urine BPA level (?2 µg/L), at the level corresponding to the median urine BPA level in the U.S. population, was associated with more than two-fold increased risk of having weight >90(th) percentile among girls aged 9-12 (adjusted odds ratio (aOR)?=?2.32, 95% confidence interval: 1.15-4.65). The association showed a dose-response relationship with increasing urine BPA level associated with further increased risk of overweight (p?=?0.006 for trend test). Other anthropometric measures of obesity showed similar results. The same association was not observed among boys. This gender difference of BPA effect was consistent with findings from experimental studies and previous epidemiological studies. Our study suggests that BPA could be a potential new environmental obesogen. Widespread exposure to BPA in the human population may also be contributing to the worldwide obesity epidemic.
Authors: Li DK; Miao M; Zhou Z; Wu C; Shi H; Liu X; Wang S; Yuan W
PLoS ONE. 2013;8(6):e65399. Epub 2013-06-12.
With pills, patches, rings, and shots: who still uses condoms? A longitudinal cohort study
PURPOSE: To describe women’s condom use patterns over time and assess predictors of dual method use 12 months after initiating hormonal contraceptives. METHODS: We conducted a prospective cohort study among women aged 15-24 years initiating oral contraceptive pills, patch, ring, or depot medroxyprogesterone and attending public family planning clinics. Participants completed questionnaires at baseline and 3, 6, and 12 months after enrollment. We used multivariable logistic regression to assess baseline factors associated with dual method use at 12 months among 1,194 women who were sexually active in the past 30 days. RESULTS: At baseline, 36% were condom users, and only 5% were dual method users. After initiation of a hormonal method, condom use decreased to 27% and remained relatively unchanged thereafter. Dual method use increased to a peak of 20% at 3 months but decreased over time. Women who were condom users at baseline had nearly twice the odds of being a dual method user at 12 months compared with nonusers (adjusted odds ratio [AOR] = 2.01, 95% CI: 1.28-3.14). Women who believed their main partner thought condoms were ‘very important,’ regardless of perceived sexually transmitted infection risk or participant’s own views of condoms, had higher odds of dual method use (AOR = 2.89, 95% CI: 1.47-5.71). CONCLUSIONS: These results highlight a potential missed opportunity for family planning providers. Providers focus on helping women initiate hormonal methods, however, they may improve outcomes by giving greater attention to method continuation and contingency planning in the event of method discontinuation and to the role of the partner in family planning.
Authors: Goldstein RL; Upadhyay UD; Raine TR
J Adolesc Health. 2013 Jan;52(1):77-82. Epub 2012 Oct 8.
Genetic risk factors for perinatal arterial ischemic stroke
The cause of perinatal arterial ischemic stroke is unknown in most cases. We explored whether genetic polymorphisms modify the risk of perinatal arterial ischemic stroke. In a population-based case-control study of 1997-2002 births at Kaiser Permanente Northern California, we identified 13 white infants with perinatal arterial ischemic stroke. Control subjects included 86 randomly selected white infants. We genotyped polymorphisms in nine genes involved in inflammation, thrombosis, or lipid metabolism previously linked with stroke, and compared genotype frequencies in case and control individuals. We tested several polymorphisms: tumor necrosis factor-alpha -308, interleukin-6, lymphotoxin A, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and apolipoprotein E epsilon2 and epsilon4 alleles. Patients with perinatal arterial ischemic stroke were more likely than control subjects to demonstrate at least one apolipoprotein E epsilon4 allele (54% vs 25%, P = 0.03). More patients with perinatal arterial ischemic stroke carried two epsilon4 alleles than did control subjects (15% vs 2%, P = 0.09), although this finding lacked statistical significance. Proinflammatory and prothrombotic polymorphisms were not associated with perinatal arterial ischemic stroke. The apolipoprotein E polymorphism may confer genetic susceptibility for perinatal arterial ischemic stroke. Larger population-based studies are required to confirm this finding.
Authors: Gelfand AA; Croen LA; Torres AR; Wu YW
Pediatr Neurol. 2013 Jan;48(1):36-41.
Pregnancy Glucose Levels in Women without Diabetes or Gestational Diabetes and Childhood Cardiometabolic Risk at 7 Years of Age
OBJECTIVE: To estimate the association between pregnancy glucose values in women without recognized pregestational diabetes or gestational diabetes and cardiometabolic risk in their children. STUDY DESIGN: This longitudinal cohort study of 211 Mexican American mother-child pairs participating in the Center for the Health Assessment of Mothers and Children of Salinas study used multiple logistic regression to estimate the children’s risk of nonfasting total cholesterol, nonfasting triglycerides, blood pressure (BP), and waist circumference (WC) >/=75th percentile at 7 years of age associated with a 1-mmol/L (18-mg/dL) increase in maternal pregnancy glucose level, measured 1 hour after a 50-g oral glucose load. RESULTS: The ORs for children in the upper quartile of diastolic BP, systolic BP, and WC associated with a 1-mmol/L increase in pregnancy glucose level were 1.39 (95% CI, 1.10-1.75), 1.38 (95% CI, 1.10-1.73), and 1.25 (95% CI, 1.02-1.54), respectively. Prepregnancy obesity was independently associated with increased odds of children belonging to the upper quartile of WC; maternal sugar-sweetened beverage consumption and gestational weight gain prior to the glucose test were not independently associated with any of the cardiometabolic outcomes. CONCLUSION: In Mexican American women without recognized pregestational diabetes or gestational diabetes, we found an association between increasing pregnancy glucose values and the children’s diastolic and systolic BPs and WC at 7 years of age. Whether interventions to reduce pregnancy glucose values, even if below levels diagnostic of overt disease, will mitigate high BP and abdominal obesity in late childhood remains to be determined.
Authors: Ehrlich SF; Rosas LG; Ferrara A; King JC; Abrams B; Harley KG; Hedderson MM; Eskenazi B
J Pediatr. 2012 Dec;161(6):1016-21. Epub 2012 Jul 11.
Trends in the Use of Antiepileptic Drugs among Pregnant Women in the US, 2001-2007: A Medication Exposure in Pregnancy Risk Evaluation Program Study
BACKGROUND: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. RESULTS: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. CONCLUSIONS: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.
Authors: Bobo WV; Li DK; Avalos LA; Cooper WO; et al.
Paediatr Perinat Epidemiol. 2012 Nov;26(6):578-88.
Alcohol, tobacco and drug use as reasons for abortion
AIMS: Concern about the effects of alcohol and drug use during pregnancy is intertwined with debates about abortion. There is concern that alcohol abstinence recommendations lead women using low levels of alcohol to terminate otherwise wanted pregnancies. This study examines how women describe alcohol, tobacco and/or drug use (ATOD) as reasons for deciding to have abortions and assesses the differences between women reporting and not reporting ATOD as reasons for deciding to have an abortion. METHODS: Data come from the UCSF Turnaway Study which recruited 956 women seeking an abortion at one of 30 US clinics between 2008 and 2010. Mixed methods were used and data were analyzed through thematic coding and logistic regression. RESULTS: Nearly 5% reported ATOD as a reason for abortion. Women worried that their ATOD had affected their baby’s health and that their or their partner’s ATOD would influence parenting. Most women (84%) who reported alcohol as a reason binge drank or had an alcohol-problem symptom in the month before discovering their pregnancy. Sixty-one percent who reported drugs as a reason used drugs, with 88% using more than once/week. Although two-thirds smoked tobacco, no woman reported tobacco alone as a reason. Ninety-eight percent of women reporting ATOD as a reason had unintended pregnancies. CONCLUSION: Women reporting ATOD as a reason drink at levels exceeding a low threshold and do not appear to be terminating otherwise wanted pregnancies. Thus, findings are inconsistent with hypotheses that abstinence recommendations and punitive policies lead women using low levels of alcohol or using drugs to terminate otherwise wanted pregnancies.
Authors: Roberts SC; Avalos LA; Sinkford D; Foster DG
Alcohol Alcohol. 2012 Nov-Dec;47(6):640-8. Epub 2012 Aug 22.
Success Of Program Linking Data Sources To Monitor H1N1 Vaccine Safety Points To Potential For Even Broader Safety Surveillance
In response to the 2009 H1N1 pandemic and subsequent vaccination program, the Department of Health and Human Services and collaborators developed the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration project to detect rare adverse events rapidly. The program monitored three million people who had received the H1N1 vaccine by linking data from large private health plans and from public immunization registries that had originally not been designed to share data, and on a larger scale than had been previously attempted. The program generated safety data in two weeks rather than three to six monty 10ths-the standard time frame achievable using health plan data. PRISM substantially contributed to the understanding of the safety of H1N1 vaccines. Its use in the case of H1N1 highlights the necessity of proactive planning, scalable infrastructure, and public-private partnerships in tracking adverse events after vaccination in epidemics. It also illustrates how data could be integrated to produce policy-relevant information for other medical products.
Authors: Salmon D; Lieu T; PRISM Program Group; et al.
Health Aff (Millwood). 2012 Nov;31(11):2518-27.
The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network
The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal, gastrointestinal, and sociodemographic characteristics. SEED uses a case-control design with population-based ascertainment of children aged 2-5 years with an autism spectrum disorder (ASD) and children in two control groups-one from the general population and one with non-ASD developmental problems. Data from parent-completed questionnaires, interviews, clinical evaluations, biospecimen sampling, and medical record abstraction focus on the prenatal and early postnatal periods. SEED is a valuable resource for testing hypotheses regarding ASD characteristics and causes.
Authors: Schendel DE; Croen LA; Yeargin-Allsopp M; et al.
J Autism Dev Disord. 2012 Oct;42(10):2121-40.
A Large, Population-Based Study of 2009 Pandemic Influenza A Virus Subtype H1N1 Infection Diagnosis During Pregnancy and Outcomes for Mothers and Neonates
BACKGROUND: Pregnant women were at increased risk for serious outcomes of 2009 pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but little is known about the overall impact of the pandemic on neonatal and maternal outcomes. METHODS: We identified live births that occurred from 1 July 2008 through 31 May 2010 in 5 Kaiser Permanente regions. Pregnant women were considered to have influenza if they had a positive result of a laboratory test for influenza virus or if they received a diagnosis of influenza during a period in which seasonal influenza virus or A(H1N1)pdm09 was the predominant circulating virus. RESULTS: There were 111 158 births from 109 015 pregnancies involving 107 889 mothers; 368 pregnant women (0.3%) received a diagnosis of influenza due to seasonal virus, and 959 (0.9%) received a diagnosis of influenza due to A(H1N1)pdm09; 107 688 did not receive an influenza diagnosis. Pregnant women with influenza due to A(H1N1)pdm09 were more likely than women with seasonal influenza infection to be hospitalized within 30 days of the diagnosis (27% vs 12%; odds ratio [OR], 2.84 [95% confidence interval {CI}, 2.01-4.02]). Pregnant women with A(H1N1)pdm09 who started antiviral treatment >/=2 days after the diagnosis were significantly more likely to be hospitalized than those who started antiviral treatment <2 days after diagnosis (OR, 3.43 [95% CI, 1.55-7.56]). Mothers with seasonal influenza virus infection had an increased risk for having a small-for-gestational-age infant (OR, 1.59 [95% CI, 1.15-2.20]). CONCLUSIONS: In this large, geographically diverse population, A(H1N1)pdm09 infection increased the risk for hospitalization during pregnancy. Late initiation of antiviral treatment was also associated with an increased risk for hospitalization.
Authors: Hansen C; Desai S; Bredfeldt C; Cheetham C; Gallagher M; Li DK; Raebel MA; Riedlinger K; Shay DK; Thompson M; Davis RL
J Infect Dis. 2012 Oct;206(8):1260-8. Epub 2012 Aug 2.
Fecal Incontinence Decreases Sexual Quality of Life, But Does Not Prevent Sexual Activity in Women
BACKGROUND: The impact of anal incontinence on women’s sexual function is poorly understood. OBJECTIVE: The aim of this study was to investigate the relationship between anal incontinence and sexual activity and functioning in women. DESIGN: This is a cross-sectional study. SETTINGS: This investigation was conducted in a community-based integrated health care delivery system. PATIENTS: Included were 2269 ethnically diverse women aged 40 to 80 years. MAIN OUTCOME MEASURES: Self-administered questionnaires assessed accidental leakage of gas (flatal incontinence) and fluid/mucus/stool (fecal incontinence) in the past 3 months. Additional questionnaires assessed sexual activity, desire and satisfaction, as well as specific sexual problems (difficulty with arousal, lubrication, orgasm, or pain). Multivariable logistic regression models compared sexual function in women with 1) isolated flatal incontinence, 2) fecal incontinence (with or without flatal incontinence), and 3) no fecal/flatal incontinence, controlling for potential confounders. RESULTS: Twenty-four percent of women reported fecal incontinence and 43% reported isolated flatal incontinence in the previous 3 months. The majority were sexually active (62% of women without fecal/flatal incontinence, 66% with isolated flatal incontinence, and 60% with fecal incontinence; p = 0.06). In comparison with women without fecal/flatal incontinence, women with fecal incontinence were more likely to report low sexual desire (OR: 1.41 (CI: 1.10-1.82)), low sexual satisfaction (OR: 1.56 (CI: 1.14-2.12)), and limitation of sexual activity by physical health (OR: 1.65 (CI: 1.19-2.28)) after adjustment for confounders. Among sexually active women, women with fecal incontinence were more likely than women without fecal/flatal incontinence to report difficulties with lubrication (OR: 2.66 (CI: 1.76-4.00)), pain (OR: 2.44 (CI: 1.52-3.91)), and orgasm (OR: 1.68 (CI: 1.12-2.51)). Women with isolated flatal incontinence reported sexual functioning similar to women without fecal/flatal incontinence. LIMITATIONS: The cross-sectional design prevented evaluation of causality. CONCLUSIONS: Although most women with fecal incontinence are at high risk for several aspects of sexual dysfunction, the presence of fecal incontinence does not prevent women from engaging in sexual activity. This indicates that sexual function is important to women with anal incontinence and should be prioritized during therapeutic management.
Authors: Imhoff LR; Brown JS; Creasman JM; Subak LL; Thom DH; Varma MG; Huang AJ; Van den Eeden SK
Dis Colon Rectum. 2012 Oct;55(10):1059-65.
Increased risk for respiratory distress among white, male, late preterm and term infants
OBJECTIVE: To determine whether race/ethnicity and sex independently increase risk of respiratory distress syndrome (RDS) in late preterm and term infants. STUDY DESIGN: Using a cohort design, we studied the risk of RDS associated with race/ethnicity and sex in infants with gestational age (GA) 34 to 42 weeks born between 1 January 2000 and 31 December 2009 (n=286 454) within 12 hospitals in the Northern California Kaiser Permanente Medical Care Program. RESULT: Male sex (adjusted odds ratio (aOR) 1.68; 95% confidence interval 1.45 to 1.93) and White race/ethnicity (vs Asians (aOR 0.57; 95% confidence interval 0.47 to 0.70), Blacks (aOR 0.66; 95% confidence interval 0.50 to 0.87), and Hispanics (aOR 0.76; 95% confidence interval 0.64 to 0.90)) independently increase risk for RDS regardless of GA. A GA <39 weeks, operative delivery, maternal diabetes, and chorioamnionitis also increased RDS risk in this cohort. CONCLUSION: Male sex and White race/ethnicity independently increase risk for RDS in late preterm and term infants. Timing of elective delivery should acknowledge these risks.
Authors: Anadkat JS; Kuzniewicz MW; Chaudhari BP; Cole FS; Hamvas A
J Perinatol. 2012 Oct;32(10):780-5. Epub 2012 Jan 5.
Risk of preterm delivery in non-diabetic women with polycystic ovarian syndrome
OBJECTIVE: To examine the risk and etiology of preterm delivery in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Retrospective cohort study comparing preterm delivery rate among non-diabetic PCOS and non-PCOS women with singleton pregnancy. Multivariable logistic regression was used to identify predictors of preterm delivery among PCOS women. RESULT: Among 908 PCOS women with singleton pregnancy, 12.9% delivered preterm compared with 7.4% among non-PCOS women (P<0.01). Causes of preterm delivery among PCOS women included preterm labor (41%), cervical insufficiency (11%), hypertensive complications (20%), preterm premature rupture of membranes (15%), fetal-placental concerns (9%) and intrauterine fetal demise (5%). Maternal age, race/ethnicity and nulliparity were significant predictors of preterm delivery in PCOS, whereas body mass index and fertility medications were not. CONCLUSION: A higher proportion of PCOS women delivered preterm (12.9%) compared with non-PCOS women, with the majority of cases due to spontaneous preterm birth. Future studies should explore etiologies and strategies to improve pregnancy outcomes in PCOS.
Authors: Yamamoto M; Feigenbaum SL; Crites Y; Escobar GJ; Yang J; Ferrara A; Lo JC
J Perinatol. 2012 Oct;32(10):770-6. Epub 2012 Jan 19.
Sex ratio variations among the offspring of women with diabetes in pregnancy
AIMS: It has long been hypothesized that natural selection would favour a reproductive strategy biased towards females under adverse circumstances in order to maximize the number of surviving grandchildren. An excess of daughters in women with Type 1 diabetes and a greater likelihood of gestational diabetes in women carrying male fetuses have also been reported. This study aims to compare the sex ratio across categories of maternal glycaemia. METHODS: Among 288,009 mother-infant pairs delivering at Kaiser Permanente Northern California in 1996-2008, sex ratios were calculated for the following categories: pregravid diabetes, gestational diabetes, mild pregnancy hyperglycaemia (defined as an abnormal screening but normal diagnostic test for gestational diabetes) and normoglycaemia. Odds ratios for delivering a male were estimated with logistic regression; normoglycaemic pregnancies comprised the reference. RESULTS: Women with pregravid diabetes delivered the fewest males (ratio male/female = 1.01), followed by women with normoglycaemic pregnancies and those with an abnormal screening only (both sex ratios = 1.05); women with gestational diabetes delivered the most males (sex ratio = 1.07). Odds ratio estimates suggested the same pattern, but none attained statistical significance. CONCLUSIONS: The crude sex ratios in this cohort suggest a possible gradient by category of maternal glycaemia. Women with gestational diabetes, a condition characterized by excessive fuel substrates, appear to deliver more males. Women with pregravid diabetes delivered the fewest males, possibly reflecting the unfavourable state of chronic disease.
Authors: Ehrlich SF; Eskenazi B; Hedderson MM; Ferrara A
Diabet Med. 2012 Sep;29(9):e273-8.
Prenatal and Perinatal Characteristics Associated with Pediatric-Onset Inflammatory Bowel Disease
BACKGROUND: The majority of studies that report early life risk factors for pediatric-onset inflammatory bowel disease (IBD) do not account for potential confounding, which can lead to spurious associations and incorrect inferences. AIMS: To assess the relationship between prenatal and perinatal characteristics and the risk of pediatric-onset IBD accounting for potential confounding. METHODS: We conducted a nested case-control study of 189 cases aged
Authors: Hutfless S; Li DK; Heyman MB; Bayless TM; Abramson O; Herrinton LJ
Dig Dis Sci. 2012 Aug;57(8):2149-56. Epub 2012 Mar 24.
Diabetes mellitus and sexual function in middle-aged and older women
Diabetes mellitus is an established risk factor for sexual dysfunction in men, but its effect on female sexual function is poorly understood. We examined the relationship of diabetes to sexual function in middle-aged and older women. Sexual function was examined in a cross-sectional cohort of ethnically diverse women aged 40-80 years using self-administered questionnaires. Multivariable regression models compared self-reported sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (difficulty with lubrication, arousal, orgasm, or pain) among insulin-treated diabetic, non-insulin-treated diabetic, and nondiabetic women. Additional models assessed relationships between diabetic end-organ complications (heart disease, stroke, renal dysfunction, and peripheral neuropathy) and sexual function. Among the 2,270 participants, mean±standard deviation age was 55±9.2 years, 1,006 (44.4%) were non-Latina white, 486 (21.4%) had diabetes, and 139 (6.1%) were taking insulin. Compared with 19.3% of nondiabetic women, 34.9% of insulin-treated diabetic women (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.32-3.15) and 26.0% of non-insulin-treated diabetic women (adjusted OR 1.42, 95% CI 1.03-1.94) reported low overall sexual satisfaction. Among sexually active women, insulin-treated diabetic women were more likely to report problems with lubrication (OR 2.37, 95% CI 1.35-4.16) and orgasm (OR 1.80, 95% CI 1.01-3.20) than nondiabetic women. Among all diabetic women, end-organ complications such as heart disease, stroke, renal dysfunction, and peripheral neuropathy were associated with decreased sexual function in at least one domain. Compared with nondiabetic women, diabetic women are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women. II.
Authors: Copeland KL; Brown JS; Creasman JM; Van Den Eeden SK; Subak LL; Thom DH; Ferrara A; Huang AJ
Obstet Gynecol. 2012 Aug;120(2 Pt 1):331-40.
Influence of breastfeeding during the postpartum oral glucose tolerance test on plasma glucose and insulin
OBJECTIVE: To examine the effect of breastfeeding during the postpartum oral glucose tolerance test (OGTT) on maternal blood glucose and insulin among women with recent gestational diabetes mellitus. METHODS: Participants were enrolled in the Study of Women, Infant Feeding, and Type 2 Diabetes, a prospective observational cohort study of 1,035 Kaiser Permanente Northern California members who had been diagnosed with GDM and subsequently underwent a 2-hour 75-g OGTT at 6-9 weeks postpartum for the study enrollment examinations from 2008 to 2011. For this analysis, we selected 835 study participants who reported any intensity of lactation and were observed either breastfeeding their infants (ie, putting the infant to the breast) or not breastfeeding during the OGTT. RESULTS: Of 835 lactating women, 205 (25%) breastfed their infants during the 2-hour 75-g OGTT at 6-9 weeks postpartum. Mean (standard deviation) duration of breastfeeding during the OGTT was 15.3 (8.1) minutes. Compared with not having breastfed during the OGTT, having breastfed during the test was associated with lower adjusted mean (95% confidence interval) 2-hour glucose (mg/dL) by -6.2 (-11.5 to -1.0; P=.02), 2-hour insulin (microunits/mL) by -15.1 (-26.8 to -3.5; P=.01), and natural log 2-hour insulin by -0.15 (-0.25 to -0.06; P<.01), and with higher insulin sensitivity index0,120 by 0.08 (0.02-0.15; P=.02), but no differences in plasma fasting glucose or insulin concentrations. CONCLUSION: Among postpartum women with recent gestational diabetes mellitus, breastfeeding an infant during the 2-hour 75-g OGTT may modestly lower plasma 2-hour glucose (5% lower on average) as well as insulin concentrations in response to ingestion of glucose.
Authors: Gunderson EP; Hedderson MM; Quesenberry CP; Lo JC; Ferrara A; Sternfeld B; et al.
Obstet Gynecol. 2012 Jul;120(1):136-43.
Prepregnancy cardiometabolic and inflammatory risk factors and subsequent risk of hypertensive disorders of pregnancy
OBJECTIVE: The purpose of this study was to examine prepregnancy cardiometabolic and inflammatory markers and the subsequent risk of hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 3380 women who took part in a comprehensive multiphasic health checkup (MHC) examination between 1984 and 1996 and who subsequently delivered at Kaiser Permanente Northern California. RESULTS: Two hundred five women were diagnosed with a hypertensive disorder of pregnancy. Prepregnancy measurements of overweight/obesity (body mass index, >/=25.0 kg/m(2)), prehypertension, and inflammation (leukocytes, >/=7.2 10(3)/muL) were associated independently with hypertensive disorder of pregnancy risk (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.3; OR, 2.1; 95% CI, 1.5-2.8; and OR, 1.6; 95% CI, 1.1-2.3, respectively). Being overweight/obese and having prehypertension before pregnancy was associated with a 3.5-fold increased risk of hypertensive disorder of pregnancy compared with women with normal levels of both risk factors. CONCLUSION: A prepregnancy cardiometabolic and inflammation risk profile may help clinicians identify high-risk women to target for early intervention or management of hypertensive disorder of pregnancy.
Authors: Hedderson MM; Darbinian JA; Sridhar SB; Quesenberry CP
Am J Obstet Gynecol. 2012 Jul;207(1):68.e1-9. Epub 2012 May 23.
Racial/Ethnic Disparities in the Prevalence of Gestational Diabetes by BMI
OBJECTIVE: To examine whether the association between gestational diabetes mellitus (GDM) and BMI category varies by racial/ethnic group. RESEARCH DESIGN AND METHODS: In a cohort of 123,040 women without recognized pregravid diabetes who delivered babies between 1995 and 2006 at Kaiser Permanente of Northern California, we examined racial/ethnic disparities in the prevalence of GDM by BMI category and the population-attributable risk (PAR) associated with overweight/obesity. RESULTS: Among all racial/ethnic groups, the age-adjusted prevalence of GDM increased with increasing BMI (kg/m(2)) category. However, Asian and Filipina women had a prevalence of GDM of 9.9 and 8.5%, respectively, at a BMI of 22.0-24.9 kg/m(2), whereas in Hispanic, non-Hispanic white, and African American women, the prevalence of GDM was >8.0% at a higher BMI, such as 28-30, 34-36, and >/=37 kg/m(2), respectively. The estimated PARs suggest that the percentage of GDM that could be prevented if all pregnant women were of normal weight (BMI <25.0 kg/m(2)) ranging from 65% for African American women to only 23% among Asian women. CONCLUSIONS: Clinicians should be aware that the BMI thresholds for increased risk of GDM varies by racial/ethnic group and that the risk is high even at relatively low BMI cutoffs in Asian and Filipina women. Asian women may benefit from different prevention strategies in addition to weight management.
Authors: Hedderson M; Ehrlich S; Sridhar S; Darbinian J; Moore S; Ferrara A
Diabetes Care. 2012 Jul;35(7):1492-8. Epub 2012 May 22.
A systematic review to calculate background miscarriage rates using life table analysis
The objectives of the current study were to calculate: (1) the expected rates of miscarriage by gestational week; (2) the cumulative risk of miscarriage; and (3) the remaining risk of miscarriage for gestational weeks five through 20, through a systematic review of the literature. We searched MEDLINE for articles published in English through the end of 2009. References of articles were also searched. Four studies were identified to have the three necessary pieces of information for the proposed calculations: (1) gestational age at study entry, (2) pregnancy outcome; and (3) the gestational age at which the pregnancy outcome occurred. Data were extracted from each study and Life Table Analysis Methods were conducted. Weekly miscarriage rates varied in the early gestational weeks with the highest rate documented at >20 miscarriages per 1000 women-weeks at each week of gestation prior to week 13. By week 14, the rate for all studies became relatively comparable and fell below 10 miscarriages per 1000 woman-weeks at risk and fell even lower through week 20. The cumulative risk of miscarriage for weeks 5 through 20 of gestation ranged from 11 miscarriages per 100 women to 22 miscarriages per 100 women (11-22%). Based on data from comparable study populations, a range of background miscarriage rates by week of gestation for weeks 5 through 20, the cumulative risk of miscarriage, and the remaining risk of miscarriage are presented. Wider variation of miscarriage rates and risks occurred early in gestation (<14 weeks).
Authors: Ammon Avalos L; Galindo C; Li DK
Birth Defects Res A Clin Mol Teratol. 2012 Jun;94(6):417-23. Epub 2012 Apr 18.
Referral to telephonic nurse management improves outcomes in women with gestational diabetes
OBJECTIVE: We sought to determine whether, among women with gestational diabetes mellitus, referral to a telephonic nurse management program was associated with lower risk of macrosomia and increased postpartum glucose testing. STUDY DESIGN: There was medical center-level variation in the percent of patients referred to a telephonic nurse management program at 12 Kaiser Permanente medical centers, allowing us to examine in a quasi-experimental design the associations between referral and outcomes. RESULTS: Compared with women from centers where the annual proportion of referral nurse management was <30%, women who delivered from centers with an annual referral proportion >70% were less likely to have a macrosomic infant and more likely to have postpartum glucose testing (multiple-adjusted odds ratio, 0.75; 95% confidence interval, 0.57-0.98 and multiple-adjusted odds ratio, 22.96; 95% confidence interval, 2.56-3.42, respectively). CONCLUSION: Receiving care at the centers with higher referral frequency to telephonic nurse management for gestational diabetes mellitus was associated with decreased risk of macrosomic infant and increased postpartum glucose testing.
Authors: Ferrara A; Hedderson MM; Ching J; Kim C; Peng T; Crites YM
Am J Obstet Gynecol. 2012 Jun;206(6):491.e1-5. Epub 2012 Apr 24.
The value of additional pathology comments indicating suspicion of adenocarcinoma among women diagnosed preoperatively with complex atypical endometrial hyperplasia
Over 40% of women with a preoperative diagnosis of complex atypical hyperplasia (CAH) will have endometrial cancer at hysterectomy. CAH diagnoses are often qualified by comments indicating suspicion of cancer. We examine whether these comments correlate with cancer found at hysterectomy. Pathology reports for 824 women with CAH diagnoses who underwent hysterectomy were reviewed to identify those qualified by comments indicating concern for cancer. The rate of cancer, severity of disease, and effects of endometrial sampling method and age were determined. Comments indicating suspicion of cancer qualified 219 of 824 (27%) CAH diagnoses and were associated with a significantly higher cancer rate at hysterectomy (69% versus 40%; P<0.0001), regardless of whether sampling consisted of curettage or biopsy. Cancer severity correlated independently with age. Comments indicating concern for underlying cancer frequently qualify CAH diagnoses and are associated with a high likelihood of cancer and with more extensive disease, especially for older women.
Authors: Suh-Burgmann E; Hung YY; Armstrong MA
Int J Gynecol Pathol. 2012 May;31(3):222-6.
California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case-control study
Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases and 796 control mother-infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.
Authors: Kharrazi M; Pearl M; Yang J; Delorenze GN; Bean CJ; Callaghan WM; Grant A; Lackritz E; Romero R; Satten GA; Simhan H; Torres AR; Westover JB; Yolken R; Williamson DM
Paediatr Perinat Epidemiol. 2012 May;26(3):250-63. Epub 2012 Jan 31.
Social support for healthy behaviors: scale psychometrics and prediction of weight loss among women in a behavioral program
Social support could be a powerful weight-loss treatment moderator or mediator but is rarely assessed. We assessed the psychometric properties, initial levels, and predictive validity of a measure of perceived social support and sabotage from friends and family for healthy eating and physical activity (eight subscales). Overweight/obese women randomized to one of two 6-month, group-based behavioral weight-loss programs (N = 267; mean BMI 32.1 ± 3.5; 66.3% White) completed subscales at baseline, and weight loss was assessed at 6 months. Internal consistency, discriminant validity, and content validity were excellent for support subscales and adequate for sabotage subscales; qualitative responses revealed novel deliberate instances not reflected in current sabotage items. Most women (>75%) "never" or "rarely" experienced support from friends or family. Using nonparametric classification methods, we identified two subscales-support from friends for healthy eating and support from family for physical activity-that predicted three clinically meaningful subgroups who ranged in likelihood of losing ≥5% of initial weight at 6 months. Women who "never" experienced family support were least likely to lose weight (45.7% lost weight) whereas women who experienced both frequent friend and family support were more likely to lose weight (71.6% lost weight). Paradoxically, women who "never" experienced friend support were most likely to lose weight (80.0% lost weight), perhaps because the group-based programs provided support lacking from friendships. Psychometrics for support subscales were excellent; initial support was rare; and the differential roles of friend vs. family support could inform future targeted weight-loss interventions to subgroups at risk.
Authors: Kiernan M; Moore SD; Schoffman DE; Lee K; King AC; Taylor CB; Kiernan NE; Perri MG
Obesity (Silver Spring). 2012 Apr;20(4):756-64. doi: 10.1038/oby.2011.293. Epub 2011 Oct 13.
An Over-the-Counter Simulation Study of a Single-Tablet Emergency Contraceptive in Young Females
OBJECTIVES: To evaluate use of a single-tablet (levonorgestrel 1.5 mg) emergency contraceptive administered to young females under simulated over-the-counter conditions. Secondary objectives were to assess repeat use, pregnancy, and adverse events. METHODS: Females aged 11-17 years requesting emergency contraception at teen reproductive health clinics in five cities were eligible to participate. Participants read the study product label and determined whether and how to use the product without interacting with providers. Study product was dispensed to participants who appropriately selected to use it; participants were contacted 1, 4, and 8 weeks later to assess use, pregnancy, and adverse events. The incidences of outcomes were calculated and regression analysis was used to assess the effect of age and use status (ever used or no previous use) on primary outcomes. RESULTS: Of the 345 females enrolled, 279 were younger than age 17 years. Among the 340 participants included in the selection analysis, 311 (91.5%) (97.5% confidence interval 87.5- 94.5%) participants appropriately selected to use or not use product. Among the 298 participants who used product, 274 (92.9%) (97.5% confidence interval 88.8-95.8%) correctly used it as labeled. Selection and correct use were not associated with age. Fifty-seven participants (18.8%) used additional emergency contraception over the study period and seven (2.3%) participants who used product became pregnant; there were no unusual adverse events. CONCLUSION: Restricting young females’ use of a single-tablet emergency contraceptive by prescription only is not warranted, because females younger than 17 years can use it in a manner consistent with over-the-counter access. LEVEL OF EVIDENCE: II.
Authors: Raine TR; Ricciotti N; Sokoloff A; Brown BA; Hummel A; Harper CC
Obstet Gynecol. 2012 Apr;119(4):772-9.
Lactation Intensity and Postpartum Maternal Glucose Tolerance and Insulin Resistance in Women With Recent GDM: The SWIFT cohort
OBJECTIVE: To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6-9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS: Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (
Authors: Gunderson EP; Hedderson MM; Quesenberry CP; Lo JC; Sternfeld B; Ferrara A; Selby JV; et al.
Diabetes Care. 2012 Jan;35(1):50-6. Epub 2011 Oct 19.
Evaluating Changes in the Prevalence of the Autism Spectrum Disorders (ASDs)
Autism spectrum disorders (ASDs) are estimated to occur among about one percent of children in the United States. This estimate is in line with estimates from other industrialized countries. However, the identified prevalence of ASDs has increased significantly in a short time period based on data from multiple studies including the U.S. Centers for Disease Control and Prevention’s (CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network. Whether increases in ASD prevalence are partly attributable to a true increase in the risk of developing ASD or solely to changes in community awareness and identification patterns is not known. It is clear that more children are identified with an ASD now than in the past and the impact on individuals, families, and communities is significant. However, disentangling the many potential reasons for ASD prevalence increases has been challenging. Understanding the relative contribution of multiple factors such as variation in study methods, changes in diagnostic and community identification, and potential changes in risk factors is an important priority for the ADDM Network and for CDC. This article summarizes the discussion from a workshop that was co-sponsored by CDC and Autism Speaks as a forum for sharing knowledge and opinions of a diverse range of stakeholders about changes in ASD prevalence. Panelists discussed recommendations for building on existing infrastructure and developing new initiatives to better understand ASD trends. The information, research, and opinions shared during this workshop add to the knowledge base about ASD prevalence in an effort to stimulate further work to understand the multiple reasons behind increasing ASD prevalence.
Authors: Rice CE; Rosanoff M; Dawson G; Durkin MS; Croen LA; Singer A; Yeargin-Allsopp M
Public Health Rev. 2012;34(2):1-22.
A genome-wide association search for type 2 diabetes genes in african americans
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5x10(-8)). SNP rs7560163 (P = 7.0x10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5x10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
Authors: Palmer ND; Ferrara A; Bowden DW; et al.
PLoS One. 2012;7(1):e29202. Epub 2012 Jan 4.
Infant siblings and the investigation of autism risk factors
ABSTRACT: Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI).
Authors: Newschaffer CJ; Croen LA; Shedd-Wise KM; et al.
J Neurodev Disord. 2012 Apr 18;4(1):7.
A Prospective Study of In-utero Exposure to Magnetic Fields and the Risk of Childhood Obesity
We conducted a prospective study to examine whether in-utero exposure to magnetic fields (MFs) increases the risk of childhood obesity. Participating women carried a meter measuring MF levels during pregnancy and 733 of their children were followed up to 13 years to collect clinically recorded information on growth patterns with 33 weight measurements per child on average. Prenatal exposure to high MF level was associated with increased risk of being obese in offspring than those with lower MF level (odds ratio = 1.69, 95% confidence interval: 1.01-2.84). The association demonstrated a dose-response relationship and was stronger (more than 2.3 fold increased risk) among children who were followed up to the end of the study. The association existed only for persistent obesity, but not for transitory (unlikely) obesity. Maternal exposure to high MF during pregnancy may be a new and previously unknown factor contributing to the world-wide epidemic of childhood obesity/overweight.
Authors: Li DK; Ferber JR; Odouli R; Quesenberry CP Jr
Sci Rep. 2012;2:540. Epub 2012 Jul 27.
Candidate Genes and Risk for Cerebral Palsy: a Population-Based Study
Studies suggest that genetic polymorphisms may increase an individual’s susceptibility to CP. Most findings have yet to be corroborated in an independent cohort. This case-control study is nested within all 334,333 infants >/=36 wk gestation born at Kaiser Permanente Medical Care Program, 1991-2002. We included only non-Hispanic whites who had a neonatal blood sample available. Case patients (n = 138) were identified from medical records to have spastic or dyskinetic CP. Controls (n = 165) were randomly selected from the population. We genotyped polymorphisms previously associated with CP: inducible NOS (iNOS)-231, apolipoprotein E (apoE) epsilon2 and epsilon4 alleles, TNF-alpha-308, IL-8 -251, lymphotoxin 60, endothelial NOS -922, endothelial protein C receptor 219, mannose-binding lectin 54 and 52, factor V Leiden, methyltetrahydrofolate reductase 1298 and 667, prothrombin 20210, and platelet activator inhibitor 11053. Similar to previous reports, the iNOS-231 T allele (25.7 versus 18.9%, p = 0.04) and the apoE epsilon4 allele (19.3 versus 13.2%, p = 0.04) were more common in patients with CP than in controls. However, there was no statistically significant association between any genetic polymorphism and CP after correction for multiple comparisons.
Authors: Wu YW; Croen LA; Vanderwerf A; Gelfand AA; Torres AR
Pediatr Res. 2011 Dec;70(6):642-6.
Urinary incontinence self-report questions: reproducibility and agreement with bladder diary
INTRODUCTION AND HYPOTHESIS: This study aims to measure self-report urinary incontinence questions’ reproducibility and agreement with bladder diary. METHODS: Data were analyzed from the Reproductive Risk of Incontinence Study at Kaiser. Participating women reporting at least weekly incontinence completed self-report incontinence questions and a 7-day bladder diary. Self-report question reproducibility was assessed and agreement between self-reported and diary-recorded voiding and incontinence frequency was measured. Test characteristics and area under the curve were calculated for self-reported incontinence types using diary as the gold standard. RESULTS: Five hundred ninety-one women were included and 425 completed a diary. The self-report questions had moderate reproducibility and self-reported and diary-recorded incontinence and voiding frequencies had moderate to good agreement. Self-reported incontinence types identified stress and urgency incontinence more accurately than mixed incontinence. CONCLUSIONS: Self-report incontinence questions have moderate reproducibility and agreement with diary, and considering their minimal burden, are acceptable research tools in epidemiologic studies.
Authors: Bradley CS; Brown JS; Van den Eeden SK; Schembri M; Ragins A; Thom DH
Int Urogynecol J. 2011 Dec;22(12):1565-71. Epub 2011 Jul 28.
Prenatal exposure to beta2-adrenergic receptor agonists and risk of autism spectrum disorders
This study aims to investigate the association between prenatal exposure to terbutaline and other beta2 adrenergic receptor (B2AR) agonists and autism spectrum disorders (ASDs). The methodology used is a case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n = 291) were children with an ASD diagnosis; controls (n = 284) were children without ASDs, randomly sampled and frequency-matched to cases on sex, birth year, and delivery hospital. Exposure to B2AR agonists during 30 days prior to conception and each trimester of pregnancy was ascertained from prenatal medical records and health plan databases. The frequency of exposure to any B2AR agonist during pregnancy was similar for mothers of children with ASD and mothers of controls (18.9% vs. 14.8%, P = 0.19). Exposure to B2AR agonists other than terbutaline was not associated with an increased risk for ASDs. However, terbutaline exposure for >2 days during the third trimester was associated with more than a fourfold increased risk for ASDs independent of indication although the limited sample size resulted in an imprecise and nonsignificant effect estimate (OR(adj) = 4.4; 95% confidence interval, 0.8-24.6). This analysis does not offer evidence linking B2AR exposure in pregnancy with autism risk. However, exposure to terbutaline during the third trimester for >2 days may be associated with an increased risk of autism. Should this result be confirmed in larger samples, it would point to late pregnancy as an etiologic window of interest in autism risk factor research.
Authors: Croen LA; Connors SL; Matevia M; Qian Y; Newschaffer C; Zimmerman AW
J Neurodev Disord. 2011 Dec;3(4):307-15. Epub 2011 Aug 27.
ADHD drugs and serious cardiovascular events in children and young adults
BACKGROUND: Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS: We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models. RESULTS: Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point. CONCLUSIONS: This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.).
Authors: Cooper WO; Habel LA; Fireman BH; Ray WA; et al.
N Engl J Med. 2011 Nov 17;365(20):1896-904. Epub 2011 Nov 1.
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. Design, Setting, and PARTICIPANTS: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services. MAIN OUTCOME MEASURES: Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD). CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.
Authors: Hallmayer J; Croen LA; Risch N; et al.
Arch Gen Psychiatry. 2011 Nov;68(11):1095-102. Epub 2011 Jul 4.
Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders
CONTEXT: The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD. OBJECTIVE: To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD. DESIGN: Population-based case-control study. Medical records were used to ascertain case children and control children and to derive prospectively recorded information on mothers’ use of antidepressant medications, mental health history of mothers, and demographic and medical covariates. SETTING: The Kaiser Permanente Medical Care Program in Northern California. PARTICIPANTS: A total of 298 case children with ASD (and their mothers) and 1507 randomly selected control children (and their mothers) drawn from the membership of the Kaiser Permanente Medical Care Program in Northern California. MAIN OUTCOME MEASURES: ASDs. RESULTS: Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]). No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors. CONCLUSION: Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders. Further studies are needed to replicate and extend these findings.
Authors: Croen LA; Grether JK; Yoshida CK; Odouli R; Hendrick V
Arch Gen Psychiatry. 2011 Nov;68(11):1104-12. Epub 2011 Jul 4.
Parturition events and risk of urinary incontinence in later life
AIMS: To examine the association between specific events during vaginal deliveries and urinary incontinence later in life. METHODS: A retrospective cohort study of 1,521 middle-aged and older women with at least one vaginal delivery who were long-term members of an integrated health delivery system. Age, race/ethnicity, current incontinence status, medical, surgical history, pregnancy and parturition history, menopausal status, hormone replacement, health habits, and general health were obtained by questionnaire. Labor and delivery records, archived since 1948, were abstracted by professional medical record abstractors to obtain parturition events including induction, length of labor stages, type of anesthesia, episiotomy, instrumental delivery, and birth weight. The primary dependent variable was current weekly urinary incontinence (once per week or more often) versus urinary incontinence less than monthly (including no incontinence) in past 12 months. Associations of parturition events and later incontinence were assessed in multivariate analysis with logistic regression. RESULTS: The mean age of participants was 56 years. After adjustment for multiple risk factors, weekly urinary incontinence significantly associated with age at first birth (P = 0.036), greatest birth weight (P = 0.005), and ever having been induced for labor (OR = 1.51; 95%CI = 1.06-2.16, P = 0.02). Risk of incontinence increased from OR = 1.35 (95%CI = 0.92-1.97, P = 0.12) for women with one induction to OR = 2.67 (95%CI = 1.25-5.71, P = 0.01) for women with two or more inductions (P = 0.01 for trend). No other parturition factors were associated with incontinence. CONCLUSIONS: Younger age at first birth, greatest birth weight, and induction of labor were associated with an increased risk of incontinence in later life. Neurourol. Urodynam. (c) 2011 Wiley-Liss, Inc.
Authors: Thom DH; Brown JS; Schembri M; Ragins AI; Creasman JM; Van den Eeden SK
Neurourol Urodyn. 2011 Nov;30(8):1456-61. Epub 2011 Jul 20.
Does Lack of Multinutrient Supplementation During Early Pregnancy Increase Vulnerability to Alcohol-Related Preterm or Small-for-Gestational-Age Births?
The objective of this study was to assess whether women who do not take multinutrient supplements during early pregnancy are more susceptible to the effects of low-to-moderate alcohol consumption on preterm birth and small-for-gestational-age birth (SGA) compared to women who do take multinutrients. This analysis included 800 singleton live births to mothers from a cohort of pregnant women recruited for a population-based cohort study conducted in the Kaiser Permanente Medical Care Program in Northern California. Participants were recruited in their first trimester of pregnancy and information about their alcohol use and supplement intake during pregnancy was collected. Preterm birth (n = 53, 7%) was defined as a delivery prior to 37 completed weeks of gestation and SGA birth (n = 124, 16%) was defined as birth weight less than the 10th percentile for the infant’s gestational age and sex compared to US singleton live births. A twofold increase in the odds of SGA birth attributed to low-to-moderate alcohol intake was found among multinutrient supplement non-users (95% CI: 1.1, 5.3). Yet, among multinutrient supplement users, there was no increased risk of an SGA birth for women who drank low-to-moderately compared to women who abstained (aOR: 0.97, 95% CI: 0.6, 1.6). Similar results emerged for preterm birth. Our findings provide marginal evidence that multinutrient supplementation during early pregnancy may modify the risk of SGA births and preterm birth associated with alcohol consumption during pregnancy and may have important implications for pregnant women and women of child-bearing age. However, future research needs to be conducted.
Authors: Avalos LA; Kaskutas L; Block G; Abrams B; Li DK
Matern Child Health J. 2011 Nov;15(8):1324-32.
Birth Prevalence of Autism Spectrum Disorders in the San Francisco Bay Area by Demographic and Ascertainment Source Characteristics
Using standardized methods for multi-source surveillance, we calculated the prevalence of autism spectrum disorders (ASD) among children born in a racially diverse region in 1994 or 1996 as 4.7/1000 live births. Children with ASD before age 9 were identified through chart abstraction at health-related sources; three-quarters were being served by the state-wide Department of Developmental Services. In adjusted models, we found a male:female ratio of 6:1, a doubling of ASD prevalence among children of older mothers (40+), and lower prevalence with lower paternal education. Children of Black or Hispanic mothers had lower prevalence than those of White, non-Hispanic mothers, but these differences were attenuated after adjustment. Prevalence in children of Asian mothers was similar to Whites. Potential under-counting is discussed.
Authors: Windham GC; Anderson MC; Croen LA; Smith KS; Collins J; Grether JK
J Autism Dev Disord. 2011 Oct;41(10):1362-72.
In utero exposure to bisphenol-A and anogenital distance of male offspring
BACKGROUND: Bisphenol-A (BPA) is an endocrine disruptor with widespread human exposure. The effect of in utero BPA exposure on human offspring remains largely unknown. METHODS: Anogenital distance (AGD) of sons of workers who did or did not have occupational BPA exposure during pregnancy were compared in an occupational cohort study. Parental BPA exposure level during the index pregnancy was estimated through a job-exposure matrix based on personal air sampling measurement. Maternal exposure was considered direct in utero exposure to the fetus, whereas paternal exposure was considered indirect in utero exposure. RESULTS: A total of 153 boys were included in the final analysis, among them 56 with parental occupational exposure during pregnancy and 97 without. After controlling for the boys’ ages and weights using linear regression, parental occupational exposure to BPA during pregnancy was associated with shortened AGD in male offspring. The association was stronger for maternal exposure (p < 0.01). There was also a dose-response relationship with increased BPA exposure levels in pregnancy associated with greater magnitude of shortened AGD in male offspring, with a statistically significant trend for the association (p = 0.008). CONCLUSION: Our findings provide the first epidemiologic evidence that in utero BPA exposure may adversely affect male genital development. Birth Defects Research (Part A) 91:867-872, 2011. (c) 2011 Wiley-Liss, Inc.
Authors: Miao M; Yuan W; He Y; Zhou Z; Wang J; Gao E; Li G; Li DK
Birth Defects Res A Clin Mol Teratol. 2011 Oct;91(10):867-72. Epub 2011 Aug 26.
Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring
OBJECTIVE: To determine whether maternal exposure to high levels of magnetic fields (MFs) during pregnancy is associated with the risk of asthma in offspring. DESIGN: A prospective cohort study. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Pregnant Kaiser Permanente Northern California members in the San Francisco area. MAIN OUTCOME MEASURES: Asthma was clinically diagnosed among 626 children who were followed up for as long as 13 years. All participants carried a meter to measure their MF levels during pregnancy. RESULTS: After adjustment for potential confounders, a statistically significant linear dose-response relationship was observed between increasing maternal median daily MF exposure level in pregnancy and an increased risk of asthma in offspring: every 1-mG increase of maternal MF level during pregnancy was associated with a 15% increased rate of asthma in offspring (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04-1.27). Using the categorical MF level, the results showed a similar dose-response relationship: compared with the children whose mothers had a low MF level (median 24-hour MF level, 2.0 mG) had more than a 3.5-fold increased rate of asthma (aHR, 3.52; 95% CI, 1.68-7.35), while children whose mothers had a medium MF level (>0.3-2.0 mG) had a 74% increased rate of asthma (aHR, 1.74; 95% CI, 0.93-3.25). A statistically significant synergistic interaction was observed between the MF effect and a maternal history of asthma and birth order (firstborn). CONCLUSION: Our findings provide new epidemiological evidence that high maternal MF levels in pregnancy may increase the risk of asthma in offspring.
Authors: Li DK; Chen H; Odouli R
Arch Pediatr Adolesc Med. 2011 Oct;165(10):945-50. Epub 2011 Aug 1.
Epidemiology of peripartum cardiomyopathy: incidence, predictors, and outcomes
OBJECTIVES: To estimate the incidence, describe the mortality, and identify independent predictors of peripartum cardiomyopathy, a very serious cardiovascular complication of pregnancy associated with maternal morbidity and mortality among otherwise healthy women without prior heart disease. METHODS: We identified all cases of diagnosed heart failure that occurred among women within 1 month before to 5 months after delivery of a liveborn neonate in Kaiser Permanente Northern California delivery hospitals between 1995 and 2004. Incident peripartum cardiomyopathy was confirmed from medical records documenting dilated cardiomyopathy with reduced left ventricular systolic function after excluding women with prior heart failure or valvular disease. Data sources included medical records, electronic clinical databases, and state birth and death files. RESULTS: Among 227,224 eligible women, we confirmed 110 recognized peripartum cardiomyopathy cases (incidence: 4.84 per 10,000 live births, 95% confidence interval 3.98-5.83). Independent predictors included maternal age of 25 years or older, non-Hispanic African American and Filipino groups, parity of 4 or greater, multiple gestation, severe anemia, pre-existing and pregnancy-related hypertensive disorders, and hemolysis, elevated liver enzymes, low platelets syndrome. Maternal death rate (per 1,000 person-years) was higher among cases (6.12) than noncases (0.23; P<.001). Neonates whose mothers developed peripartum cardiomyopathy experienced poorer clinical outcomes. CONCLUSION: Within a large, diverse northern California population, 1 of every 2,066 women delivering a liveborn neonate had recognized, confirmed peripartum cardiomyopathy, which was associated with higher maternal and neonatal death rates and worse neonatal outcomes. Several readily available patient characteristics can be used to identify women at risk for this severe pregnancy complication. LEVEL OF EVIDENCE: II.
Authors: Gunderson EP; Croen LA; Chiang V; Yoshida CK; Walton D; Go AS
Obstet Gynecol. 2011 Sep;118(3):583-91.
Increased midgestational IFN-gamma, IL-4 and IL-5 in women bearing a child with autism: A case-control study
ABSTRACT: BACKGROUND: Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders. METHODS: Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis. RESULTS: Elevated concentrations of IFN-gamma, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism. CONCLUSION: The profile of elevated serum IFN-gamma, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.
Authors: Goines PE; Croen LA; Braunschweig D; Yoshida CK; Grether J; Hansen R; Kharrazi M; Ashwood P; Van de Water J
Mol Autism. 2011 Aug 2;2:13.
Preservation of fertility after partial resection of bilateral ovarian cystadenofibromas: a case report
BACKGROUND: Benign cystadenofibromas and adenofibromas may represent precursors to malignant lesions. CASE: A 20-year-old woman undergoing infertility treatment was found to have cystadenofibromas involving both ovaries, with no separable normal ovarian tissue visible. Because complete resection of the tumors would have required bilateral oophorectomy, the tumors were only partially resected using a shave technique. This patient subsequently had 3 normal-term deliveries over 7 years and did not have any clinically significant regrowth of her tumors during this time. CONCLUSION: It may be reasonable to delay removing benign tumors in a young woman who has not completed her childbearing.
Authors: Ewing TL; Suh-Burgmann B
J Reprod Med. 2011 Jul-Aug;56(7-8):364-5.
Pregravid cardiometabolic risk profile and risk for gestational diabetes mellitus
OBJECTIVE: The purpose of this study was to examine pregravid cardiometabolic profile and subsequent risk of gestational diabetes mellitus (GDM). STUDY DESIGN: GDM cases (n = 199) and control subjects (n = 381) were selected from a cohort of women who took part in a multiphasic health checkup examination at Kaiser Permanente from 1984-1996 and who had a subsequent pregnancy and were matched by year and age at multiphasic health checkup examination and age at delivery. RESULTS: Pregravid measurements of serum glucose levels of 100-140 mg/dL, body mass index of >/=25.0 kg/m(2), and prehypertension/hypertension level were associated independently with GDM risk (odds ratios [OR], 4.8; 95% confidence interval [CI], 1.7-13.9; OR, 2.7; 95% CI, 1.6-4.3; and OR, 1.5; 95% CI, 1.0-2.3, respectively). The risk of GDM increased with the number of cardiometabolic risk factors (P < .001); adverse levels of both body mass index and glucose were associated with a 4.6-fold increased risk of GDM, compared with women with normal levels (P = .0001). CONCLUSION: Pregravid cardiometabolic risk profile may help clinicians to identify high-risk women to target for primary prevention or early management of GDM.
Authors: Hedderson MM; Darbinian JA; Quesenberry CP; Ferrara A
Am J Obstet Gynecol. 2011 Jul;205(1):55.e1-7. Epub 2011 May 28.
In utero exposure to bisphenol-A and its effect on birth weight of offspring
To examine the effect of in utero BPA exposure on the birth weight of offspring, a total of 587 children from families in which parent(s) did or did not have occupational exposure to BPA were examined. Their birth weights were obtained by an in-person interview of the mother. Parental BPA exposure level during the index pregnancy was determined through personal air sampling measurements and exposure history. After controlling for potential confounders, parental exposure to BPA in the workplace during pregnancy was associated with decreased birth weight. The association was stronger for maternal exposure which is statistically significant (P=0.02). A dose-response relationship was observed with increased BPA exposure levels in pregnancy associated with greater magnitude of decrease of birth weight in offspring (P=0.003). Our findings provide the new epidemiologic evidence suggesting that in utero exposure to BPA during pregnancy may be associated with decreased birth weight in offspring.
Authors: Miao M; Yuan W; Zhu G; He X; Li DK
Reprod Toxicol. 2011 Jul;32(1):64-8. Epub 2011 Mar 31.
A pregnancy and postpartum lifestyle intervention in women with gestational diabetes mellitus reduces diabetes risk factors: a feasibility randomized control trial
OBJECTIVE: To pilot, among women with gestational diabetes mellitus (GDM), the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program. The intervention was delivered by telephone, and support for breastfeeding was addressed. RESEARCH DESIGN AND METHODS: The goal was to help women return to their prepregnancy weight, if it was normal, or achieve a 5% reduction from prepregnancy weight if overweight. Eligible participants were identified shortly after a GDM diagnosis; 83.8% consented to be randomly assigned to intervention or usual medical care (96 and 101 women, respectively). The retention was 85.2% at 12 months postpartum. RESULTS: The proportion of women who reached the postpartum weight goal was higher, although not statistically significant, in the intervention condition than among usual care (37.5 vs. 21.4%, absolute difference 16.1%, P=0.07). The intervention was more effective among women who did not exceed the recommended gestational weight gain (difference in the proportion of women meeting the weight goals: 22.5%, P=0.04). The intervention condition decreased dietary fat intake more than the usual care (condition difference in the mean change in percent of calories from fat: -3.6%, P=0.002) and increased breastfeeding, although not significantly (condition difference in proportion: 15.0%, P=0.09). No differences in postpartum physical activity were observed between conditions. CONCLUSIONS: This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight. Strategies to help postpartum women overcome barriers to increasing physical activity are needed.
Authors: Ferrara A; Hedderson MM; Albright CL; Ehrlich SF; Quesenberry CP Jr; Peng T; Feng J; Ching J; Crites Y
Diabetes Care. 2011 Jul;34(7):1519-25. Epub 2011 May 3.
The Pregnancy and Influenza Project: design of an observational case-cohort study to evaluate influenza burden and vaccine effectiveness among pregnant women and their infants
The US Centers for Disease Control and Prevention is conducting an observational study of 300-500 women infected with influenza during pregnancy. Women are being recruited from members of the Kaiser Permanente health plan in 2 metropolitan areas before and during the 2010 through 2011 influenza season either following routine prenatal care visits or presentation with an acute respiratory infection. All enrolled mothers and their infants will be followed up through 1 month after delivery. Infants of mothers who had influenza during pregnancy and 1000 infants of mothers who were not diagnosed with influenza during pregnancy will be followed up for an additional 5 months. The Pregnancy and Influenza Project is focused on better understanding the burden of influenza during and after pregnancy and estimating the effectiveness of maternal influenza vaccination against influenza among women and their infants confirmed by real-time reverse transcription polymerase chain reaction assays.
Authors: Thompson M; Williams J; Naleway A; Li DK; Chu S; Bozeman S; Hill HA; Cragan J; Shay DK; Pregnancy and Influenza Project Workgroup
Am J Obstet Gynecol. 2011 Jun;204(6 Suppl 1):S69-76. Epub 2011 Mar 16.
Change in body mass index between pregnancies and the risk of gestational diabetes in a second pregnancy
OBJECTIVE: To estimate the association between interpregnancy change in body mass index (BMI) and the risk of gestational diabetes mellitus (GDM) in a second pregnancy. METHODS: In a retrospective cohort analysis of 22,351 women, logistic regression models provided adjusted estimates of the risk of GDM in women gaining 3.0 or more 2.0-2.9, and 1.0-1.9 BMI units, or losing 1.0-2.0 and more than 2.0 units between pregnancies (one BMI unit corresponds to 5.9 pounds for the average height [5 feet 4 inches] of the study population). Women with stable BMIs (+/-1.0 BMI unit) comprised the reference. RESULTS: For those with GDM in the first pregnancy, the age-adjusted risk of GDM in the second pregnancy was 38.19% (95% confidence interval [CI] 34.96-41.42); for those whose first pregnancy was not complicated by GDM, the risk was 3.52% (95% CI 3.27-3.76). Compared with women who remained stable, interpregnancy BMI gains were associated with an increased risk of GDM in the second pregnancy (odds ratio [OR] 1.71 [95% CI 1.42-2.07] for gaining 1.0-1.9 BMI units; OR 2.46 [95% CI 2.00-3.02] for 2.0-2.9 BMI units; and OR 3.40 [95% CI 2.81-4.12] for 3.0 or more BMI units). The loss of BMI units was associated with a lower risk of GDM only among women who were overweight or obese in the first pregnancy (OR 0.26 [95% CI 0.14-0.47] for the loss of at least 2.0 BMI units). In overweight and obese women, those with GDM in the first pregnancy that did not develop the condition again gained fewer BMI units than those experiencing recurrent GDM (mean change 0.66 [95% CI 0.25-1.07] compared with 2.00 [95% CI 1.56-2.43] BMI units, respectively). CONCLUSION: Interpregnancy increases in BMI between the first and second pregnancy increases a woman’s risk of GDM pregnancy.
Authors: Ehrlich SF; Hedderson MM; Feng J; Davenport ER; Gunderson EP; Ferrara A
Obstet Gynecol. 2011 Jun;117(6):1323-30.
Population-based ectopic pregnancy trends, 1993-2007
BACKGROUND: The accuracy of ectopic pregnancy rates based on nationally representative data has been compromised for many years, impairing surveillance and evaluation of the continued public health importance of this condition. PURPOSE: To estimate long-term population-based ectopic pregnancy rates and trends within a defined population over a largely unevaluated time period, including the evaluation of trends in outpatient versus inpatient management and medical versus surgical treatment modalities. METHODS: Using computerized Group Health Cooperative inpatient and outpatient data, age-adjusted and age-specific ectopic pregnancy rates were calculated from 1993 to 2007 among enrollees aged 15-44 years. Overall trends and trends for care setting (inpatient versus outpatient) and treatment modality (medical versus surgical) were also evaluated. Analyses were conducted in 2009. RESULTS: Between 1993 and 2007, a total of 2114 ectopic pregnancy cases (726 inpatient; 1388 outpatient) were identified among 1,180,070 woman-years, an annual age-adjusted ectopic pregnancy rate of 17.9 per 10,000 woman-years. Rates were stable from 1993 to 2004 and increased in the most recent 3 years (2005-2007, rate=21.1 per 10,000 woman-years). Rates per 1000 pregnancies increased over the 15-year period from 19.2 to 26.2 per 1000 pregnancies (p-value=0.001). Inpatient-diagnosed cases decreased from 45.4% in 1993-1995 to 26.9% in 2005-2007 (p-value<0.0001) and the percentage with surgical treatment decreased from 48.1% to 30.7% (p-value<0.0001). CONCLUSIONS: The results suggest a trend toward increasing ectopic pregnancy rates over a recent 15-year period. Rates are similar to the last available national estimate, suggesting that the significance of ectopic pregnancy as a public health problem has not diminished in these intervening years.
Authors: Trabert B; Holt VL; Yu O; Van den Eeden SK; Scholes D
Am J Prev Med. 2011 May;40(5):556-60.
Polychlorinated biphenyl (PCB) exposure in mothers and time to pregnancy in daughters
Developmental exposure to polychlorinated biphenyls (PCBs) disrupts reproduction in animals. Human data are lacking. We measured PCBs in preserved mothers’ serum samples collected during 1960-1963, 1-3 days after their daughters’ birth. We recorded time to pregnancy (TTP) in 289 daughters 28-31 years later. PCB congeners 187, 156, and 99 in mother’s serum were associated with longer TTP in their daughters while PCB congeners 105, 138 and 183 were associated shorter TTP. Probability of pregnancy fell by 38% (95% CI 17-53%) and infertility was higher (30% not pregnant after 13 cycles versus 11% not pregnant after 13 cycles) among women whose mothers had a higher proportion of PCB congeners associated with longer TTP (75th percentile versus 25th percentile). This study demonstrates, for the first time, that developmental exposure to PCBs may disrupt pregnancy in humans.
Authors: Cohn BA; Cirillo PM; Sholtz RI; Ferrara A; Park JS; Schwingl PJ
Reprod Toxicol. 2011 Apr;31(3):290-6. Epub 2011 Feb 3.
Diabetes and risk of bladder cancer: evidence from a case-control study in New England
BACKGROUND: Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long-term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta-analysis found that bladder cancer incidence was approximately 40% higher in individuals with diabetes; however, few studies considered duration or type of therapy and had limited adjustment for potentially confounding factors. METHODS: To further investigate the potential role of diabetes in risk of bladder cancer, the authors analyzed data from a case-control study conducted in New Hampshire in which patients with bladder cancer, and controls sampled from the population, completed an interview regarding history of diabetes, cigarette smoking history, height, weight, and history of urinary tract infections. RESULTS: The study consisted of 331 cases and 263 controls on whom information regarding diabetes was ascertained. History of diabetes was related to an increased bladder cancer risk (adjusted odds ratio = 2.2, 95% CI, 1.3 to 3.8). The association was strongest in those who had diabetes for the longest duration (OR for 16 or more years = 3.6, 1.1 to 11.2) and in those taking oral hypoglycemic medications (OR = 3.3, 1.5 to 7.1). CONCLUSIONS: Our findings support an association between bladder cancer incidence and diabetes, and further suggest that the risk may be greater among patients taking oral hypoglycemics and those with diabetes of longer duration.
Authors: MacKenzie T; Zens MS; Ferrara A; Schned A; Karagas MR
Cancer. 2011 Apr 1;117(7):1552-6. Epub 2010 Nov 8.
Vitamin D, pregnancy, breastfeeding, and postpartum multiple sclerosis relapses
OBJECTIVE: To determine whether low levels of 25-hydroxyvitamin D (25[OH]D) contribute to the increased risk of postpartum multiple sclerosis (MS) relapses. DESIGN: Prospective cohort study. SETTING: Outpatients identified through membership records of Kaiser Permanente Northern California or Stanford University outpatient neurology clinics. PATIENTS: Twenty-eight pregnant women with MS. INTERVENTIONS: We prospectively followed up patients through the postpartum year and assessed exposures and symptoms through structured interviews. Total serum 25(OH)D levels were measured using the DiaSorin Liaison Assay during the third trimester and 2, 4, and 6 months after giving birth. The data were analyzed using longitudinal multivariable methods. MAIN OUTCOME MEASURES: Levels of 25(OH)D and relapse rate. RESULTS: Fourteen (50%) women breastfed exclusively, and 12 women (43%) relapsed within 6 months after giving birth. During pregnancy, the average 25(OH)D levels were 25.4 ng/mL (range, 13.7-42.6) and were affected only by season (P=.009). In contrast, in the postpartum period, 25(OH)D levels were significantly affected by breastfeeding and relapse status. Levels of 25(OH)D remained low in the exclusive breastfeeding group, yet rose significantly in the nonexclusive breastfeeding group regardless of season (P=.007, unadjusted; P=.02, adjusted for season). By 4 and 6 months after childbirth, 25(OH)D levels were, on average, 5 ng/mL lower in the women who breastfed exclusively compared with the nonbreastfeeding group (P=.001). CONCLUSIONS: Pregnancy and exclusive breastfeeding are strongly associated with low 25(OH)D levels in women with MS. However, these lower vitamin D levels were not associated with an increased risk of postpartum MS relapses. These data suggest that low vitamin D in isolation is not an important risk factor for postpartum MS relapses.
Authors: Langer-Gould A; Huang S; Van Den Eeden SK; Gupta R; Leimpeter AD; Albers KB; Horst R; Hollis B; Steinman L; Nelson LM
Arch Neurol. 2011 Mar;68(3):310-3. Epub 2010 Nov 8.
The risk of large for gestational age across increasing categories of pregnancy glycemia
OBJECTIVE: We sought to estimate the risk of large for gestational age (LGA) across categories of glucose tolerance. STUDY DESIGN: In a cohort of 89,141 participants, women without gestational diabetes mellitus (GDM) were categorized by their screening and diagnostic test results; those with GDM were categorized as meeting the National Diabetes Data Group or only the American Diabetes Association (ADA) criteria. Multivariable logistic regression models estimated the risk of LGA; screening values 5.5-6.0 mmol/L comprised the referent. RESULTS: In women without GDM, the odds ratio for LGA was 1.89 (95% confidence interval [CI], 1.45-2.45) for fasting, 1.57 (95% CI, 1.31-1.89) for 1-hour, 1.60 (95% CI, 1.33-1.93) for 2-hour, and 1.62 (95% CI, 1.23-2.14) for 3-hour values meeting the ADA time point-specific thresholds. CONCLUSION: For GDM identified in a 2-step procedure, our findings support the use of isolated abnormal fasting values according to the ADA threshold in identifying women who could benefit from treatment.
Authors: Ehrlich SF; Crites YM; Hedderson MM; Darbinian JA; Ferrara A
Am J Obstet Gynecol. 2011 Mar;204(3):240.e1-6. Epub 2011 Jan 17.
Jaundice-autism link unconvincing
Authors: Newman TB; Croen LA
Pediatrics. 2011 Mar;127(3):e858-9.
Strategies for diabetes prevention before and after pregnancy in women with GDM
Interventions for lifestyle modification promoting weight loss and pharmacotherapy interventions for improving insulin sensitivity have been shown to be effective in preventing or delaying the onset of type 2 diabetes (T2DM) in high risk populations. Women with gestational diabetes mellitus (GDM) are at high risk for T2DM, but only two trials have assessed the feasibility of diabetes prevention in this population. We present evidence supporting an intervention with lifestyle modification for women with GDM that would begin during pregnancy and continue through the postpartum period, as pharmacotherapy interventions may not be appropriate for pregnant women or women of reproductive age who could again become pregnant. Young women with GDM may not be aware of their diabetes risk and may perceive difficulty in changing behaviors. Thus, novel approaches will be necessary to translate the lifestyle modification programs previously proven effective among older women with impaired glucose tolerance to younger women with a recent history of GDM, particularly those with normal glucose tolerance postpartum. Understanding barriers to increasing physical activity and adopting a healthy diet and finding strategies for the successful integration of lifestyle modification programs into the busy schedules of women with young children remain priorities for future research.
Authors: Ferrara A; Ehrlich SF
Curr Diabetes Rev. 2011 Mar;7(2):75-83.
Does antiviral medication for treating herpes simplex during pregnancy increase the risk of birth defects in offspring?
Authors: Li DK
Evid Based Med. 2011 Feb;16(1):30. Epub 2010 Nov 25.
Urine bisphenol-A (BPA) level in relation to semen quality
OBJECTIVE: To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. DESIGN: Cohort study. SETTING: Four regions in China where high exposure to BPA in the workplace existed. PATIENT(S): 218 men with and without BPA exposure in the workplace. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen parameters. RESULT(S): After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. CONCLUSION(S): These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.
Authors: Li DK; Zhou Z; Miao M; He Y; Wang J; Ferber J; Herrinton LJ; Gao E; Yuan W
Fertil Steril. 2011 Feb;95(2):625-30.e1-4. Epub 2010 Oct 29.
Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial
CONTEXT: Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes. OBJECTIVE: To determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes. DESIGN, SETTING, AND PATIENTS: A multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010. INTERVENTION: Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks. MAIN OUTCOME MEASURES: Primary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency >/=50% decrease from baseline). RESULTS: Mean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (-0.52; 95% CI, -0.64 to -0.40 vs -0.30; 95% CI, -0.42 to -0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group. CONCLUSION: Among healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00894543.
Authors: Freeman EW; Caan B; Sternfeld B; Lacroix AZ; et al.
JAMA. 2011 Jan 19;305(3):267-74.
Outcome expectations and realizations as predictors of weight regain among dieters
This prospective study tested whether (a) baseline outcome expectations regarding the benefits of a weight-loss diet, (b) 6-month outcome realizations regarding perceived benefits actually experienced, and/or (c) the interaction between them predicted 6-12-month weight regain among overweight/obese women randomized to one of four popular weight-loss diets (N=311). Positive 6-month realizations regarding improvements in physical shape and appearance predicted less 6-12-month weight regain among Atkins diet participants only (n=70), controlling for baseline expectations, the expectations-realization interaction, and initial weight loss. Atkins participants displayed three distinct patterns of regain based on levels of 6-month realizations and initial weight loss. Experimental research should investigate whether improving realizations leads to reduced weight regain in response to this popular diet.
Authors: Moore SD; King AC; Kiernan M; Gardner CD
Eat Behav. 2011 Jan;12(1):60-3. doi: 10.1016/j.eatbeh.2010.08.007. Epub 2010 Sep 21.
Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study
OBJECTIVE: To examine a reported association between use of angiotensin converting enzyme (ACE) inhibitors during the first trimester and risk of malformations in offspring. DESIGN: A population based, retrospective cohort study linking automated clinical and pharmacy databases including comprehensive electronic medical records. PARTICIPANTS: Pregnant women and their live born offspring (465 754 mother-infant pairs) in the Kaiser Permanente Northern California region from 1995 to 2008. MAIN OUTCOME MEASURE: Congenital malformation in live births. RESULTS: The prevalence of ACE inhibitor use in the first trimester only was 0.9/1000, and the use of other antihypertensive medications was 2.4/1000. After adjustment for maternal age, ethnicity, parity, and obesity, use of ACE inhibitors during the first trimester only seemed to be associated with increased risk of congenital heart defects in offspring compared with normal controls (those with neither hypertension nor use of any antihypertensives during pregnancy) (15/381 (3.9%) v 6232/400 021 (1.6%) cases, odds ratio 1.54 (95% confidence interval 0.90 to 2.62)). A similar association was observed for use of other antihypertensives (28/1090 (2.6%) cases of congenital heart defects, odds ratio 1.52 (1.04 to 2.21)). However, compared with hypertension controls (those with a diagnosis of hypertension but without use of antihypertensives) (708/29 735 (2.4%) cases of congenital heart defects), neither use of ACE inhibitors or of other antihypertensives in the first trimester was associated with increased congenital heart defects risk (odds ratios 1.14 (0.65 to 1.98) and1.12 (0.76 to 1.64) respectively). CONCLUSIONS: Maternal use of ACE inhibitors in the first trimester has a risk profile similar to the use of other antihypertensives regarding malformations in live born offspring. The apparent increased risk of malformations associated with use of ACE inhibitors (and other antihypertensives) in the first trimester is likely due to the underlying hypertension rather than the medications.
Authors: Li DK; Yang C; Andrade S; Tavares V; Ferber JR
BMJ. 2011 Oct 18;343:d5931.
Neonatally measured immunoglobulins and risk of autism
Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N = 213 cases and N = 265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P = 0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted.
Authors: Grether JK; Croen LA; Anderson MC; Nelson KB; Yolken RH
Autism Res. 2010 Dec;3(6):323-32. Epub 2010 Dec 9.
Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism
OBJECTIVE: Exposure to thimerosal, a mercury-containing preservative that is used in vaccines and immunoglobulin preparations, has been hypothesized to be associated with increased risk of autism spectrum disorder (ASD). This study was designed to examine relationships between prenatal and infant ethylmercury exposure from thimerosal-containing vaccines and/or immunoglobulin preparations and ASD and 2 ASD subcategories: autistic disorder (AD) and ASD with regression. METHODS: A case-control study was conducted in 3 managed care organizations (MCOs) of 256 children with ASD and 752 controls matched by birth year, gender, and MCO. ASD diagnoses were validated through standardized in-person evaluations. Exposure to thimerosal in vaccines and immunoglobulin preparations was determined from electronic immunization registries, medical charts, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We used conditional logistic regression to assess associations between ASD, AD, and ASD with regression and exposure to ethylmercury during prenatal, birth-to-1 month, birth-to-7-month, and birth-to-20-month periods. RESULTS: There were no findings of increased risk for any of the 3 ASD outcomes. The adjusted odds ratios (95% confidence intervals) for ASD associated with a 2-SD increase in ethylmercury exposure were 1.12 (0.83-1.51) for prenatal exposure, 0.88 (0.62-1.26) for exposure from birth to 1 month, 0.60 (0.36-0.99) for exposure from birth to 7 months, and 0.60 (0.32-0.97) for exposure from birth to 20 months. CONCLUSIONS: In our study of MCO members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to increased risk of ASDs.
Authors: Price CS; Croen LA; DeStefano F; et al.
Pediatrics. 2010 Oct;126(4):656-64. Epub 2010 Sep 13.
Incidence of and risk factors for change in urinary incontinence status in a prospective cohort of middle-aged and older women: the reproductive risk of incontinence study in Kaiser
PURPOSE: Urinary incontinence is a dynamic condition that can progress and regress but few groups have examined risk factors for change in incontinence status. MATERIAL AND METHODS: We used stratified random sampling to construct a racially and ethnically diverse, population based cohort of 2,109 women 40 to 69 years old. Data were collected by questionnaires and medical record review. A second survey approximately 5 years later was completed by 1,413 women (67%) from the original cohort. The frequency of urinary incontinence was categorized as less than weekly, weekly and daily. Change in incontinence status was defined as new onset incontinence, incontinence progression or regression between frequency categories and resolution of incontinence. Predictor variables were demographics, body mass index and other medical conditions. We used logistic regression to estimate the adjusted OR and 95% CI. RESULTS: Compared to white nonHispanic women, black women were less likely to have incontinence progression (OR 0.46, 95% CI 0.24-0.88). New onset incontinence was more common in women with a higher body mass index at baseline (p = 0.006) and those who experienced increased body mass index (p = 0.03) or decreased general health (p = 0.007) during the study. Participants with chronic obstructive pulmonary disorder at baseline were more likely to report incontinence progression (OR 2.64, 95% CI 1.22-5.70). Baseline incontinence type was not significantly associated with the risk of change in continence status independent of frequency. CONCLUSIONS: Identifying risk factors for change in incontinence status may be important to develop interventions to decrease the burden of incontinence in the general population.
Authors: Thom DH; Brown JS; Schembri M; Ragins AI; Subak LL; Van Den Eeden SK
J Urol. 2010 Oct;184(4):1394-401. Epub 2010 Aug 19.
Disparities in the risk of gestational diabetes by race-ethnicity and country of birth
Little information exists on the association between maternal country of birth and risk of gestational diabetes (GDM). We examined within each race-ethnicity group whether the risk of GDM differs between women born inside and outside the US. The study was a cohort study of 216 089 women who delivered an infant between 1995 and 2004 with plasma glucose data from the screening 50-g glucose challenge test and the diagnostic 100-g, 3-h oral glucose tolerance test. The age-adjusted prevalence of GDM varied by race-ethnicity and was lowest for non-Hispanic white (4.1%) and highest among Asian Indians (11.1%). In multivariable models, being born outside of the US was associated with an increased risk of GDM among black, Asian Indian, Filipina, Pacific Islanders, Chinese, Mexicans and non-Hispanic white women, whereas, Japanese and Korean foreign-born women had a decreased risk of GDM. Clinicians should be aware that among certain race-ethnicity groups women born outside the US may be at increased risk of GDM and may warrant special preventive and culturally sensitive care.
Authors: Hedderson MM; Darbinian JA; Ferrara A
Paediatr Perinat Epidemiol. 2010 Sep;24(5):441-8.
Lactation and maternal risk of type 2 diabetes: a population-based study
BACKGROUND: Lactation has been associated with improvements in maternal glucose metabolism. METHODS: We explored the relationships between lactation and risk of type 2 diabetes in a well-characterized, population-representative cohort of women, aged 40-78 years, who were members of a large integrated health care delivery organization in California and enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008. Multivariable logistic regression was used to control for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index while examining the impact of duration, exclusivity, and consistency of lactation on risk of having developed type 2 diabetes. RESULTS: Of 2233 women studied, 1828 were mothers; 56% had breastfed an infant for > or =1 month. In fully adjusted models, the risk of type 2 diabetes among women who consistently breastfed all of their children for > or =1 month remained similar to that of women who had never given birth (odds ratio [OR] 1.01; 95% confidence interval [CI], 0.56-1.81). In contrast, mothers who had never breastfed an infant were more likely to have developed type 2 diabetes than nulliparous women (OR 1.92; 95% CI, 1.14-3.27). Mothers who never exclusively breastfed were more likely to have developed type 2 diabetes than mothers who exclusively breastfed for 1-3 months (OR 1.52; 95% CI, 1.11-2.10). CONCLUSIONS: Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life. Mothers should be encouraged to exclusively breastfeed all of their infants for at least 1 month.
Authors: Schwarz EB; Brown JS; Creasman JM; Stuebe A; McClure CK; Van Den Eeden SK; Thom D
Am J Med. 2010 Sep;123(9):863.e1-6.
Urinary incontinence, fecal incontinence and pelvic organ prolapse in a population-based, racially diverse cohort: prevalence and risk factors
OBJECTIVES: : We investigated the prevalence of and risk factors for combinations of urinary incontinence (UI), fecal incontinence (FI) and pelvic organ prolapse (POP) in racially diverse women older than 40 years. METHODS: : The Reproductive Risks for Incontinence Study at Kaiser is a population-based study with data from 2106 women older than 40 years. Pelvic floor conditions were determined by self-report. Risk factors were assessed by self-report, interview and record review. Independent risk factors were identified by multinomial logistic regression analysis. RESULTS: : At least one pelvic floor condition was reported by 714 (34%) women. Of these, 494 (69%) had only UI, 60 (8%) only POP, and 46 (6%) only FI. Both UI and FI were reported by 64 (9%) and both UI and POP by 51 (7%). Among women with FI, 60% reported more than one condition. Corresponding figures for POP and UI were 49% and 18%. Estrogen use and constipation were shared risk factors for UI, FI and POP. Body mass index was a unique risk factor UI only, diabetes FI only and parity POP only. No clear pattern could be found to support the hypothesis that risk factors for single conditions are more strongly associated with combined conditions. CONCLUSIONS: : Patients with FI or POP often have concomitant UI. These diseases both share and have unique risk factors in a complex pattern.
Authors: Rortveit G; Subak LL; Thom DH; Creasman JM; Vittinghoff E; Brown JS; Van den Eeden SK
Female Pelvic Med Reconstr Surg. 2010 Sep;16(5):278-83.
International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy
Authors: International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Persson B; Schmidt MI; et al.
Diabetes Care. 2010 Mar;33(3):676-82.
Gestational weight gain and risk of gestational diabetes mellitus
OBJECTIVE: To estimate the relationship between the rate of gestational weight gain before the 50-g, 1-hour oral glucose challenge test screening for gestational diabetes mellitus (GDM) and subsequent risk of GDM. METHODS: We conducted a nested case-control study (345 women with GDM and 800 women in the control group) within a multiethnic cohort of women delivering between 1996 and 1998 who were screened for GDM at 24-28 weeks of gestation. GDM was diagnosed according to the National Diabetes Data Group plasma glucose cut-offs for the 100-g, 3-hour oral glucose tolerance test. Women’s plasma glucose levels, weights, and covariate data were obtained by medical record chart review. RESULTS: After adjusting for age at delivery, race/ethnicity, parity, and prepregnancy body mass index, the risk of GDM increased with increasing rates of gestational weight gain. Compared with the lowest tertile of rate of gestational weight gain (less than 0.27 kg/week [less than 0.60 lb/wk]), a rate of weight gain from 0.27-0.40 kg/wk (0.60-0.88 lb/wk) and 0.41 kg/wk (0.89 lb/wk) or more, were associated with increased risks of GDM (odds ratio 1.43, 95% confidence interval 0.96-2.14; and odds ratio 1.74, 95% confidence interval 1.16-2.60, respectively). The association between the rate of gestational weight gain and GDM was primarily attributed to increased weight gain in the first trimester. The association was stronger in overweight [corrected] and nonwhite women. CONCLUSION: High rates of gestational weight gain, especially early in pregnancy, may increase a woman’s risk of GDM. Gestational weight gain during early pregnancy may represent a modifiable risk factor for GDM and needs more attention from health care providers.
Authors: Hedderson MM; Gunderson EP; Ferrara A
Obstet Gynecol. 2010 Mar;115(3):597-604.
Pelvic floor disorders and quality of life in women with self-reported irritable bowel syndrome
BACKGROUND: Quality of life among women with irritable bowel syndrome may be affected by pelvic floor disorders. AIM: To assess the association of self-reported irritable bowel syndrome with urinary incontinence, pelvic organ prolapse, sexual function and quality of life. METHODS: We analysed data from the Reproductive Risks for Incontinence Study at Kaiser Permanente, a random population-based study of 2109 racially diverse women (mean age = 56). Multivariate analyses assessed the association of irritable bowel syndrome with pelvic floor disorders and quality of life. RESULTS: The prevalence of irritable bowel syndrome was 9.7% (n = 204). Women with irritable bowel had higher adjusted odds of reporting symptomatic pelvic organ prolapse (OR 2.4; 95% CI, 1.4-4.1) and urinary urgency (OR 1.4; 95% CI, 1.0-1.9); greater bother from pelvic organ prolapse (OR 4.3; 95% CI, 1.5-11.9) and faecal incontinence (OR 2.0; 95% CI, 1.3-3.2); greater lifestyle impact from urinary incontinence (OR 2.2; 95% CI, 1.3-3.8); and worse quality of life (P < 0.01). Women with irritable bowel reported more inability to relax and enjoy sexual activity (OR 1.8; 95% CI, 1.3-2.6) and lower ratings for sexual satisfaction (OR 1.8; 95% CI, 1.3-2.5), but no difference in sexual frequency, interest or ability to have an orgasm. CONCLUSIONS: Women with irritable bowel are more likely to report symptomatic pelvic organ prolapse and sexual dysfunction, and report lower quality of life.
Authors: Wang J; Varma MG; Creasman JM; Subak LL; Brown JS; Thom DH; Van Den Eeden SK
Aliment Pharmacol Ther. 2010 Feb 1;31(3):424-31. Epub 2009 Oct 23.
Antenatal ultrasound and risk of autism spectrum disorders
We evaluated antenatal ultrasound (U/S) exposure as a risk factor for autism spectrum disorders (ASD), comparing affected singleton children and control children born 1995-1999 and enrolled in the Kaiser Permanente health care system. Among children with ASD (n = 362) and controls (n = 393), 13% had no antenatal exposure to U/S examinations; case-control differences in number of exposures during the entire gestation or by trimester were small and not statistically significant. In analyses adjusted for covariates, cases were generally similar to controls with regard to the number of U/S scans throughout gestation and during each trimester. This study indicates that antenatal U/S is unlikely to increase the risk of ASD, although studies examining ASD subgroups remain to be conducted.
Authors: Grether JK; Li SX; Yoshida CK; Croen LA
J Autism Dev Disord. 2010 Feb;40(2):238-45. Epub 2009 Sep 1.
Interferon-gamma-producing T cells, pregnancy, and postpartum relapses of multiple sclerosis
OBJECTIVE: To determine whether fluctuations in functional T-cell subsets can explain why multiple sclerosis (MS) relapses decline during pregnancy and increase in the postpartum period. DESIGN: Case-control study. SETTING: Kaiser Permanente Northern California and Stanford University. PARTICIPANTS: Twenty-six pregnant women with MS and 24 age-matched, pregnant controls. Intervention We prospectively followed up the pregnant women with MS and the age-matched, pregnant controls; conducted structured interviews; and collected peripheral blood mononuclear cells during each trimester and 2, 4, 6, 9, and 12 months post partum. MAIN OUTCOME MEASURES: Sixteen functional cell types, including interferon-gamma (IFN-gamma)- and tumor necrosis factor-producing T-cell subsets, were measured using multicolor flow cytometry. Since these cell types may also fluctuate with pregnancy, lactational amenorrhea, or MS treatment, the data were analyzed taking into account these factors. RESULTS: Fifteen women with MS (58%) had relapses during the postpartum year. CD4(+)IFN-gamma-producing cells fluctuated with MS relapses, declining during pregnancy in women with MS (P < .001) and continuing to decline after parturition in women with relapses (P = .001), yet rising or remaining stable in women with nonrelapsing MS or healthy pregnant women. Lactational amenorrhea was associated with a rise in CD4(+)IFN-gamma-producing cells in women with MS (P = .009). In contrast, CD4(+) tumor necrosis factor-producing cells decreased during lactational amenorrhea in all groups of women and, once this was taken into account, obscured any relationship to MS relapses. CD8(+)IFN-gamma-producing cells were elevated in women with MS throughout the study (P < .001) but did not fluctuate with relapses. CONCLUSIONS: Our findings suggest that a decline in circulating CD4(+)IFN-gamma-producing cells leads to postpartum MS relapses. Our findings also suggest that the decline in these cells may begin during late pregnancy and that lactational amenorrhea induced by exclusive breastfeeding may be able to interrupt this process.
Authors: Langer-Gould A; Gupta R; Huang S; Hagan A; Atkuri K; Leimpeter AD; Albers KB; Greenwood E; Van Den Eeden SK; Steinman L; Nelson LM
Arch Neurol. 2010 Jan;67(1):51-7.
Contraception before and after GDM
Authors: Hedderson M
In: Kim C, Ferrara A, editors. Gestational diabetes during and after pregnancy. London: Springer; 2010.
Gestational diabetes during and after pregnancy
Gestational Diabetes Mellitus is becoming an increasingly prevalent disease as obesity and other chronic diseases are on the rise. It requires careful and informed clinical management as the care received during pregnancy affects not only perinatal health but the risk of developing type 2 diabetes even decades into the future, in both the mother and the child. From epidemiology and pathophysiology to diagnosis and management, covering recent breakthroughs in research and up-to-date developments in clinical practice, "Gestational Diabetes During and After Pregnancy" offers the reader.
Authors: Kim C; Ferrara A
New York; London: Springer: 2010.
Diabetes prevention interventions for women with a history of GDM
Authors: Ferrara A; Ehrlich SF
In: Kim C, Ferrara A, editors. Gestational diabetes during and after pregnancy. London: Springer; 2010.
Exposure to magnetic fields and the risk of poor sperm quality
We conducted a population-based case-control study among healthy sperm donors to study exposure to magnetic fields (MFs) and poor sperm quality. All participants wore a meter to capture daily MF exposure. After controlling for confounders, compared to those with lower MF exposure, those whose 90th percentile MF level > or = 1.6mG had a two-fold increased risk of abnormal sperm motility and morphology (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.0-3.9). Increasing duration of MF exposure above 1.6 mG further increased the risk (p=0.03 for trend test). Importantly, the association and dose-response relationship were strengthened when restricted to those whose measurement day reflected their typical day of the previous 3 months (a likely period of spermatogenesis). Age-adjusted Spearman Rank Order Correlations showed an inverse correlation between MF exposure and all semen parameters. Our study provides some evidence for the first time that MF exposure may have an adverse effect on sperm quality.
Authors: Li DK; Yan B; Li Z; Gao E; Miao M; Gong D; Weng X; Ferber JR; Yuan W
Reprod Toxicol. 2010 Jan;29(1):86-92. Epub 2009 Nov 6.
Racial differences in pelvic organ prolapse
OBJECTIVE: To compare the estimated prevalence of, risk factors for, and level of bother associated with subjectively reported and objectively measured pelvic organ prolapse in a racially diverse cohort. METHODS: The Reproductive Risks for Incontinence Study at Kaiser 2 is a population-based cohort study of 2,270 middle-aged and older women. Symptomatic prolapse was self-reported, and bother was assessed on a five-point scale. In 1,137 women, prolapse was measured with the Pelvic Organ Prolapse Quantification (POP-Q) system. Multivariable logistic regression analysis was used to identify the independent association of prolapse and race while controlling for risk factors. RESULTS: The participants’ mean (standard deviation) age was 55 (9) years, and 44% were white, 20% were African American, 18% were Asian American, and 18% were Latina or other race. Seventy-four women (3%) reported symptomatic prolapse. In multivariable analysis, the risk of symptomatic prolapse was higher in white (prevalence ratio 5.35, 95% confidence interval [CI] 1.89-15.12) and Latina (prevalence ratio 4.89, 95% CI 1.64-14.58) compared with African-American women. Race was not associated with report of moderate to severe bother. Degree of prolapse by POP-Q stage was similar across all racial groups; however, the risk of the leading edge of prolapse at or beyond the hymen was higher in white (prevalence ratio 1.40, 95% CI 1.02-1.92) compared with African-American women. CONCLUSION: Compared with African-American women, Latina and white women had four to five times higher risk of symptomatic prolapse, and white women had 1.4-fold higher risk of objective prolapse with leading edge of prolapse at or beyond the hymen. LEVEL OF EVIDENCE: II.
Authors: Whitcomb EL; Rortveit G; Brown JS; Creasman JM; Thom DH; Van Den Eeden SK; Subak LL
Obstet Gynecol. 2009 Dec;114(6):1271-7.
Do multivitamin supplements modify the relationship between prenatal alcohol intake and miscarriage?
OBJECTIVE: To determine whether multivitamin supplements modify the relationship between alcohol consumption during pregnancy and the risk of miscarriage. STUDY DESIGN: We used data from a population-based cohort study of pregnant women (n=1061; response rate=39%). Participants were asked about their alcohol consumption and vitamin intake during pregnancy. RESULTS: Among multivitamin nonusers, women who drank alcohol during their pregnancy were more likely to have a miscarriage compared with women who abstained (adjusted hazard ratio, 1.67; 95% confidence interval, 1.04-2.69). However, among multivitamin users, there was no difference in the risk of miscarriage between alcohol consumers and abstainers. Results suggest the volume of alcohol as well as the timing of multivitamin supplementation may also be important. CONCLUSION: Our findings suggest that a woman of childbearing years might decrease her risk of miscarriage associated with alcohol intake by taking multivitamin supplements. However, our findings should be interpreted with caution and future research replicating these findings is necessary.
Authors: Ammon Avalos L; Kaskutas LA; Block G; Li DK
Am J Obstet Gynecol. 2009 Dec;201(6):563.e1-9. Epub 2009 Oct 20.
Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants
OBJECTIVE: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6 -174 G/C polymorphism confers increased risk for CP in term infants. METHODS: This population-based case-control study included 334,333 live-born infants born at >or=36 weeks gestation within Kaiser Permanente Medical Care Program from 1991 to 2002. Case patients (n = 250) were identified from electronic records and confirmed by chart review, and comprised all infants with spastic or dyskinetic CP not caused by developmental abnormalities who had a neonatal blood specimen available for study. Control patients (n = 305) were randomly selected from the study population. RESULTS: Compared with genotype GG, the less common CC genotype was associated with increased risk for overall CP (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.6), quadriparetic CP (OR, 4.1; 95% CI, 1.8-9.3), and hemiparetic CP (OR, 2.7; 95% CI, 1.3-5.7), after controlling for race. The C allele conferred increased risk for CP in both recessive and additive genetic models. In multivariate analysis controlling for race, independent risk factors for CP included CC genotype compared with GG (OR, 2.4; 95% CI, 1.3-4.4), clinical chorioamnionitis (OR, 4.6; 95% CI, 2.1-10.4), maternal age >or= 35 (OR, 2.6; 95% CI, 1.6-4.1), and male sex (OR, 1.6; 95% CI, 1.1-2.4). INTERPRETATION: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.
Authors: Wu YW; Croen LA; Torres AR; Van De Water J; Grether JK; Hsu NN
Ann Neurol. 2009 Nov;66(5):663-70.
Risk of autism and increasing maternal and paternal age in a large north American population
Previous studies are inconsistent regarding whether there are independent effects of maternal and paternal age on the risk of autism. Different biologic mechanisms are suggested by maternal and paternal age effects. The study population included all California singletons born in 1989-2002 (n = 7,550,026). Children with autism (n = 23,311) were identified through the California Department of Developmental Services and compared with the remainder of the study population, with parental ages and covariates obtained from birth certificates. Adjusted odds ratios and 95% confidence intervals were used to evaluate the risk of autism associated with increasing maternal and paternal age. In adjusted models that included age of the other parent and demographic covariates, a 10-year increase in maternal age was associated with a 38% increase in the odds ratio for autism (odds ratio = 1.38, 95% confidence interval: 1.32, 1.44), and a 10-year increase in paternal age was associated with a 22% increase (odds ratio = 1.22, 95% confidence interval: 1.18, 1.26). Maternal and paternal age effects were seen in subgroups defined by race/ethnicity and other covariates and were of greater magnitude among first-born compared with later-born children. Further studies are needed to help clarify the biologic mechanisms involved in the independent association of autism risk with increasing maternal and paternal age.
Authors: Grether JK; Anderson MC; Croen LA; Smith D; Windham GC
Am J Epidemiol. 2009 Nov 1;170(9):1118-26. Epub 2009 Sep 25.
Investigation of shifts in autism reporting in the California Department of Developmental Services
We investigated if shifts in the coding of qualifying conditions in the California Department of Developmental Services (DDS) have contributed to the increase in California children with autism observed in recent years. Qualifying condition codes for mental retardation (MR) and autism in DDS electronic files were compared to hard-copy records for samples of children born 1987, 1990, 1994, and 1997. Contrary to expectations, we did not find evidence of a coding shift from ‘MR only’ to ‘both MR and autism’ or an increase in the proportion of children with coded autism who lacked supportive diagnostic documentation in records (possible ‘misclassifications’). These results indicate that changes in DDS coding practices are unlikely to explain the increase in DDS clients with autism.
Authors: Grether JK; Rosen NJ; Smith KS; Croen LA
J Autism Dev Disord. 2009 Oct;39(10):1412-9. Epub 2009 May 29.
Complex atypical endometrial hyperplasia: the risk of unrecognized adenocarcinoma and value of preoperative dilation and curettage
OBJECTIVE: To evaluate whether preoperative dilation and curettage (D&C) lowers the risk of unexpected cancer at hysterectomy. METHODS: Women with complex atypical endometrial hyperplasia on sampling from January 2000 to May 2008 who underwent hysterectomy within 6 months were identified using a pathology database. Patient age, sampling procedures, and hysterectomy pathology were recorded. Women were categorized as having either an office biopsy-based evaluation or a curettage-based evaluation. The proportion of women with cancer at surgery was estimated and compared for the two groups. RESULTS: Of 824 women with complex atypical endometrial hyperplasia on initial sampling, 48% were found to have cancer. For 100 women, cancer was diagnosed preoperatively by additional sampling before hysterectomy. For the remaining 724, 298 (41%) had unexpected cancer at hysterectomy. The diagnosis of complex atypical endometrial hyperplasia was biopsy-based for 531 (73%) and curettage-based for 193 (27%). The risk of cancer for women who had a D&C was significantly lower than for those who had biopsy, but still of concern (30% compared with 45%, P<.001), as was the risk of myometrial invasion (18% compared with 25%, P=.05). Age was strongly correlated to risk of cancer, invasive cancer, and deeply invasive or grade 3 disease. CONCLUSION: Dilation and curettage lowered the risk of unexpected cancer compared with biopsy, but 18% of women still had invasive cancer found at hysterectomy. The risk of unexpected cancer is strongly related to age. Dilation and curettage can help detect cancer preoperatively but is not reliable for excluding cancer. LEVEL OF EVIDENCE: II.
Authors: Suh-Burgmann E; Hung YY; Armstrong MA
Obstet Gynecol. 2009 Sep;114(3):523-9.
Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis
OBJECTIVE: To determine if exclusive breastfeeding protects against postpartum relapses of multiple sclerosis (MS) and, if so, whether this protection is related to prolonged lactational amenorrhea. DESIGN: We conducted structured interviews to assess clinical, menstrual, and breastfeeding history during each trimester and 2, 4, 6, 9, and 12 months postpartum and collected neurological examination findings from the treating physicians of women with MS. Hazards ratios (HRs) were adjusted for measures of disease severity and age. SETTING: Kaiser Permanente Northern California and Stanford University. PARTICIPANTS: We prospectively enrolled 32 pregnant women with MS and 29 age-matched, pregnant controls. Main Outcome Measure Postpartum relapse. RESULTS: Of the 52% of women with MS who did not breastfeed or began regular supplemental feedings within 2 months postpartum, 87% had a postpartum relapse, compared with 36% of the women with MS who breastfed exclusively for at least 2 months postpartum (unadjusted HR, 5.0; 95% confidence interval, 1.7-14.2; P = .003; adjusted HR, 7.1; 95% confidence interval, 2.1-24.3; P = .002). Sixty percent reported that the primary reason for foregoing exclusive breastfeeding was to resume MS therapies. Women who breastfed exclusively had a later return of menses (P = .001) than women who did not, and lactational amenorrhea was associated with a reduced risk of postpartum relapses (P = .01). CONCLUSIONS: Our findings suggest that exclusive breastfeeding and concomitant suppression of menses significantly reduce the risk of postpartum relapses in MS. Our findings call into question the benefit of foregoing breastfeeding to start MS therapies and should be confirmed in a larger study.
Authors: Langer-Gould A; Huang SM; Gupta R; Leimpeter AD; Greenwood E; Albers KB; Van Den Eeden SK; Nelson LM
Arch Neurol. 2009 Aug;66(8):958-63. Epub 2009 Jun 8.
Sexual function and aging in racially and ethnically diverse women
OBJECTIVES: To examine factors influencing sexual activity and functioning in racially and ethnically diverse middle-aged and older women. DESIGN: Cross-sectional cohort study. SETTING: Integrated healthcare delivery system. PARTICIPANTS: One thousand nine hundred seventy-seven women aged 45 to 80. MEASUREMENTS: Self-administered questionnaires assessed sexual desire, activity, satisfaction, and problems. RESULTS: Of the 1,977 participants (876 white, 388 African American, 347 Latina, and 351 Asian women), 43% reported at least moderate sexual desire, and 60% had been sexually active in the previous 3 months. Half of sexually active participants (n=969) described their overall sexual satisfaction as moderate to high. Among sexually inactive women, the most common reason for inactivity was lack of interest in sex (39%), followed by lack of a partner (36%), physical problem of partner (23%), and lack of interest by partner (11%); only 9% were inactive because of personal physical problems. In multivariable analysis, African-American women were more likely than white women to report at least moderate desire (odds ratio (OR)=1.65, 95% confidence interval (CI)=1.25-2.17) but less likely to report weekly sexual activity (OR=0.68, 95% CI=0.48-0.96); sexually active Latina women were more likely than white women to report at least moderate sexual satisfaction (OR=1.75, 95% CI=1.20-2.55). CONCLUSION: A substantial proportion of community-dwelling women remain interested and engaged in sexual activity into older age. Lack of a partner capable of or interested in sex may contribute more to sexual inactivity than personal health problems in this population. Racial and ethnic differences in self-reported sexual desire, activity, and satisfaction may influence discussions about sexual difficulties in middle-aged and older women.
Authors: Huang AJ; Subak LL; Thom DH; Van Den Eeden SK; Ragins AI; Kuppermann M; Shen H; Brown JS
J Am Geriatr Soc. 2009 Aug;57(8):1362-8. Epub 2009 Jun 24.
Mixed urinary incontinence: greater impact on quality of life
PURPOSE: We compared the impact of mixed, stress and urge urinary incontinence on quality of life in middle-aged or older women. MATERIALS AND METHODS: We analyzed cross-sectional data from a population based cohort of 2,109 ethnically diverse middle-aged or older women. Among participants reporting weekly incontinence, clinical type of incontinence was assessed by self-reported questionnaires and disease specific quality of life impact was evaluated using the Incontinence Impact Questionnaire. Multivariable logistic regression was used to compare the odds of greater quality of life impact from incontinence, defined as an Incontinence Impact Questionnaire score in the 75th percentile or greater in women with stress, urge and mixed incontinence. RESULTS: More than 28% (598) of women reported weekly incontinence, including 37% with stress, 31% with urge and 21% with mixed incontinence. Unadjusted Incontinence Impact Questionnaire scores were higher for women with mixed vs urge or stress incontinence (median score 29 vs 17 and 13, respectively, p <0.01). Adjusting for age, race/ethnicity, health status and clinical incontinence severity, women with mixed incontinence were more likely to report a greater overall quality of life impact compared to those with stress incontinence (OR 2.5, 95% CI 1.4-4.3), as well as a greater specific impact on travel (OR 2.2, 95% CI 1.3-3.7) and emotional (OR 1.8, 95% CI 1.0-3.4) Incontinence Impact Questionnaire domains. The overall impact of urge incontinence did not differ significantly from that of stress (urge vs stress OR 1.6, 95% CI 0.9-2.7) or mixed incontinence (mixed vs urge OR 1.6, 95% CI 0.9-2.8) in adjusted models. CONCLUSIONS: In middle-aged or older women mixed incontinence is associated with a greater quality of life impact than stress incontinence independent of age, race, health or incontinence severity. Identification of women with mixed incontinence symptoms may be helpful in discovering which women are most likely to experience functional limitations and decreased well-being from incontinence.
Authors: Frick AC; Huang AJ; Van Den Eeden SK; Knight SK; Creasman JM; Yang J; Ragins AI; Thom DH; Brown JS
J Urol. 2009 Aug;182(2):596-600. Epub 2009 Jun 17.
Gestational diabetes mellitus: Diagnosis, maternal and fetal outcomes, and management
Authors: Ferrara A; Kim, Catherine
In: Tsatsoulis A,Wyckoff JA,Brown FM, editors. Diabetes in women: Pathophysiology and therapy. Totowa (NJ): Humana; 2008.
Bisphenol A levels in blood and urine in a Chinese population and the personal factors affecting the levels
The objective of the study was to describe the background bisphenol A (BPA) levels in urine and serum of a Chinese population without occupational exposure and to examine the personal characteristics influencing these levels. Workers from 10 factories and their family members were recruited and their peripheral blood and spot urine samples were collected. The conjugated and free BPA of the samples was assayed with high-performance liquid chromatography. The exposure levels were checked with 2-independent-samples test, and the potential personal factors influencing exposure levels were analyzed using nonlinear correlation. Of the total of 952 subjects participating in the study, urine and blood samples were taken from 97% and 93% of them, respectively. The detectable rates were 50% for urine samples and 17% for serum samples, given the detection limit of 0.31 microg/L for urine and 0.39 microg/L for serum. The arithmetic mean (AM) and geometric mean (GM) of non-creatinine-adjusted urinary BPA level were 10.45 and 0.87 microg/L, which became 24.93 and 0.38 microg/g Cr after the creatinine level was adjusted; serum BPA levels were 2.84 microg/L (AM) and 0.18 microg/L (GM). Males and those with smoking habit had higher biological burden of BPA. The results indicated that half of the study subjects had detectable BPA in their urine samples. BPA levels were influenced by gender and smoking status. The sources of non-occupational BPA exposures should be explored.
Authors: He Y; Miao M; Herrinton LJ; Wu C; Yuan W; Zhou Z; Li DK
Environ Res. 2009 Jul;109(5):629-33. Epub 2009 May 8.
New vaccines against otitis media: projected benefits and cost-effectiveness
OBJECTIVE: New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. METHODS: We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. RESULTS: With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not result in savings compared with pneumococcal-nontypeable H influenzae vaccine use, but would cost $48 000 more per quality-adjusted life-year saved. The results were sensitive to variations in assumptions on vaccine effectiveness and vaccine dose costs but not to variations in other assumptions. CONCLUSIONS: New candidate vaccines against otitis media have the potential to prevent millions of disease episodes in the United States annually. If priced comparably with other recently introduced vaccines, these new otitis vaccines could achieve cost-effectiveness comparable with or more favorable than that of the 7-valent pneumococcal conjugate vaccine.
Authors: O'Brien MA; Prosser LA; Paradise JL; Ray GT; Kulldorff M; Kurs-Lasky M; Hinrichsen VL; Mehta J; Colborn DK; Lieu TA
Pediatrics. 2009 Jun;123(6):1452-63.
Trends in postpartum diabetes screening and subsequent diabetes and impaired fasting glucose among women with histories of gestational diabetes mellitus: A report from the Translating Research Into Action for Diabetes (TRIAD) Study
OBJECTIVE: The purpose of this study was to examine trends in postpartum glucose screening for women with gestational diabetes mellitus (GDM), predictors of screening, trends in postpartum impaired fasting glucose (IFG) and diabetes, and diabetes and pre-diabetes detected by postpartum fasting plasma glucose (FPG) versus a 75-g oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS: This was a cohort study of 14,448 GDM pregnancies delivered between 1995 and 2006. Postpartum screening was defined as performance of either an FPG or OGTT at least 6 weeks after delivery and within 1 year of delivery. RESULTS: Between 1995 and 2006, the age- and race/ethnicity-adjusted proportion of women who were screened postpartum rose from 20.7% (95% CI 17.8-23.5) to 53.8% (51.3-56.3). Older age, Asian or Hispanic race/ethnicity, higher education, earlier GDM diagnosis, use of diabetes medications during pregnancy, and more provider contacts after delivery were independent predictors of postpartum screening. Obesity and higher parity were independently associated with lower screening performance. Among women who had postpartum screening, the age- and race/ethnicity-adjusted proportion of IFG did not change over time (24.2 [95% CI 20.0-27.8] in 1995-1997 to 24.3 [22.6-26.0] in 2004-2006), but the proportion of women with diabetes decreased from 6.1 (95% CI 4.2-8.1) in 1995-1997 to 3.3 (2.6-4.0) in 2004-2006. Among women who received an OGTT in 2006, 38% of the 204 women with either diabetes or pre-diabetes were identified only by the 2-h glucose measurements. CONCLUSIONS: Postpartum screening has increased over the last decade, but it is still suboptimal. Compared with FPGs alone, the 2-h values identify a higher proportion of women with diabetes or pre-diabetes amenable to intervention.
Authors: Ferrara A; Peng T; Kim C
Diabetes Care. 2009 Feb;32(2):269-74. Epub 2008 Nov 4.
Presence of depressive symptoms during early pregnancy and the risk of preterm delivery: a prospective cohort study
BACKGROUND: The impact of prenatal depression on pregnancy outcomes is largely unknown. METHODS: We conducted a population-based prospective cohort study among pregnant women of the Kaiser Permanente Medical Care Program to examine the impact of prenatal depression on the risk of preterm delivery. We interviewed pregnant women in their early pregnancy. Women’s depressive symptoms were ascertained using the standard Center for Epidemiological Studies Depression Scale (CESD). The presence of significant prenatal depressive symptoms and severe depressive symptoms was determined by CESD scores > or =16 and > or =22, respectively. RESULTS: Among the 791 participants who answered CESD questions and delivered a live birth, after controlling for potential confounders using the Cox proportional hazard regression, women with CESD scores > or =16 had almost twice the risk of preterm delivery compared with women without depressive symptoms: adjusted hazard ratio (aHR) = 1.9, 95% confidence interval (CI) 1.0-3.7. The risk of preterm delivery increased with increasing severity of depression: aHR = 1.6 (CI 0.7-3.6) for CESD 16-21 and aHR = 2.2 (CI 1.1-4.7) for CESD > or =22. The risk of preterm delivery associated with prenatal depression appears to be exacerbated by low educational level, a history of fertility problems and the presence of obesity and stressful events. The observed associations were not confounded by the use of antidepressants, although some of the associations did not reach statistical significance. CONCLUSIONS: Our findings show that pregnant women with depressive symptoms are at increased risk of preterm delivery and, in addition, provide preliminary evidence that social and reproductive risk factors as well as obesity and stressful events may exacerbate the effect.
Authors: Li D; Liu L; Odouli R
Hum Reprod. 2009 Jan;24(1):146-53. Epub 2008 Oct 23.
Mothers of children diagnosed with attention-deficit/hyperactivity disorder: health conditions and medical care utilization in periods before and after birth of the child
BACKGROUND: Analyzing health conditions and medical utilization of mothers of children with attention-deficit/hyperactivity disorder (ADHD) can shed light on biologic, environmental, and psychosocial factors relating to ADHD. OBJECTIVE: To examine health conditions, health care utilization, and costs of mothers of children with ADHD in periods before the child was diagnosed. METHODS: Using automated data from Northern California Kaiser Permanente we identified mothers of children with ADHD, mothers of children without ADHD, and mothers of children with asthma. Mothers’ diagnostic clusters, health care utilization, and costs were compared. Mothers of children with ADHD were compared with mothers of children without ADHD and, separately, to mothers of children with asthma. RESULTS: Compared with mothers of children without ADHD, mothers of children with ADHD were more likely to be diagnosed with numerous medical and mental health problems in the 2 years after birth of their child, including depression [odds ratio (OR): 1.88], anxiety neuroses (OR: 1.64), obesity (OR: 1.70), and musculoskeletal symptoms (OR: 1.51). Results were similar for the year before delivery. Mothers of children with ADHD also had higher total health care costs per person in the year before ($1,003) and the 2 years after ($953) the birth of their child. Mothers of children with ADHD also were diagnosed with more health conditions and had higher health care costs than mothers of children with asthma. CONCLUSIONS: Our findings suggest that the likelihood of being diagnosed with ADHD is related to maternal conditions and use of health services that precede the child’s diagnosis. Future studies are needed to clarify whether this is due to biologic, psychosocial, or environmental factors, or a combination.
Authors: Ray GT; Croen LA; Habel LA
Med Care. 2009 Jan;47(1):105-14.
High blood pressure before and during early pregnancy is associated with an increased risk of gestational diabetes mellitus
OBJECTIVE: While women with prior gestational diabetes mellitus (GDM) are more likely to display features of the metabolic syndrome, including hypertension, in the years after delivery, it is unclear whether these components are also present before pregnancy. We examined the relationship between blood pressure (BP) measured before and during early pregnancy (<20 weeks) and the risk of GDM in a nested case-control study. RESEARCH DESIGN AND METHODS: Case (n = 381) and control (n = 942) subjects were selected from a cohort of women delivering between 1996 and 1998 and screened for GDM between 24 and 28 weeks' gestation. GDM was defined by the National Diabetes Data Group criteria. BP and covariates data were obtained by review of the medical records. Women were categorized according to BP levels recommended by the American Heart Association outside of pregnancy: <120/80 mmHg (normal), 120-139/80-89 mmHg (prehypertension), and >or=140 and/or >or=90 mmHg or use of antihypertensive medications (hypertension). RESULTS: During early pregnancy, women with prehypertension had a small increased risk of GDM (odds ratio [OR] 1.56 [95% CI 1.16-2.10]), and women with hypertension had a twofold increased risk of GDM (2.04 [1.14-3.65]) compared with women with normal BP after adjusting for age, race/ethnicity, gestational week of BP, BMI, and parity. Similar results were seen among the subset of women with BP levels measured before pregnancy (1.44 [0.95-2.19] for prehypertension and 2.01 [1.01-3.99] for hypertension). CONCLUSIONS: Clinicians should be aware that women presenting with hypertension may warrant early screening or intervention to prevent GDM.
Authors: Hedderson MM; Ferrara A
Diabetes Care. 2008 Dec;31(12):2362-7. Epub 2008 Sep 22.
Factors influencing women’s acceptance of prenatal screening tests
OBJECTIVE: To determine the factors influencing a woman’s acceptance of the expanded alpha-fetoprotein (AFP) test. METHODS: A population-based case-control study. All women (age < 35) who declined the expanded AFP test were identified as eligible cases. Controls were randomly selected from all women (age < 35) who accepted the test. RESULTS: We interviewed 199 cases and 229 controls before 30 weeks of gestation. While 47% of cases reported opposition to abortion as one of their reasons for declining the test (Group A), the remaining 53% of cases had a variety of other reasons for declining (Group B). After controlling for potential confounders, factors significantly associated with declining the test included: skepticism of the usefulness of the test results (odds ratio (OR) = 33.0), influence from family members (OR = 11.4), low educational level (OR = 7.1), willingness to keep a malformed fetus (OR = 6.2), failure to use providers as useful sources of information (OR = 5.0), and misunderstanding of the purpose of the test (OR = 2.0). Polytomous logistic regression revealed that Groups A and B had different determining factors as well as common factors. CONCLUSION: While many influential factors for participating in prenatal screening remain unmodifiable, some of them may be addressed to improve women's acceptance of prenatal screening tests.
Authors: Li DK; Karlberg K; Wi S; Norem C
Prenat Diagn. 2008 Dec;28(12):1136-43.
Decreased transforming growth factor beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes
Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. There is evidence of both immune dysregulation and autoimmune phenomena in autism. We examined the regulatory cytokine transforming growth factor beta-1 (TGF beta 1) because of its role in controlling immune responses. Plasma levels of active TGF beta 1 were evaluated in 75 children with ASD compared with 68 controls. Children with ASD had significantly lower plasma TGF beta 1 levels compared with typically developing controls (p=0.0017) and compared with children with developmental disabilities other than ASD (p=0.0037), after adjusting for age and gender. In addition, there were significant correlations between psychological measures and TGF beta 1 levels, such that lower TGF beta 1 levels were associated with lower adaptive behaviors and worse behavioral symptoms. The data suggest that immune responses in autism may be inappropriately regulated due to reductions in TGF beta 1. Such immune dysregulation may predispose to the development of possible autoimmune responses and/or adverse neuroimmune interactions during critical windows in development.
Authors: Ashwood P; Enstrom A; Krakowiak P; Hertz-Picciotto I; Hansen RL; Croen LA; Ozonoff S; Pessah IN; Van de Water J
J Neuroimmunol. 2008 Nov 15;204(1-2):149-53.
Use of a fan during sleep and the risk of sudden infant death syndrome
OBJECTIVE: To examine the relation between room ventilation during sleep and risk of sudden infant death syndrome (SIDS). DESIGN: Population-based case-control study. SETTING: Eleven California counties. PARTICIPANTS: Mothers of 185 infants with a confirmed SIDS diagnosis and 312 randomly selected infants matched on county of residence, maternal race/ethnicity, and age. Intervention Fan use and open window during sleep. Main Outcome Measure Risk of SIDS. RESULTS: Fan use during sleep was associated with a 72% reduction in SIDS risk (adjusted odds ratio [AOR], 0.28; 95% confidence interval [CI], 0.10-0.77). The reduction in SIDS risk seemed more pronounced in adverse sleep environments. For example, fan use in warmer room temperatures was associated with a greater reduction in SIDS risk (AOR, 0.06; 95% CI, 0.01-0.52) compared with cooler room temperatures (0.77; 0.22-2.73). Similarly, the reduction associated with fan use was greater in infants placed in the prone or side sleep position (AOR, 0.14; 95% CI, 0.03-0.55) vs supine (0.84; 0.21-3.39). Fan use was associated with a greater reduction in SIDS risk in infants who shared a bed with an individual other than their parents (AOR, 0.15; 95% CI, 0.01-1.85) vs with a parent (0.40; 0.03-4.68). Finally, fan use was associated with reduced SIDS risk in infants not using pacifiers (AOR, 0.22; 95% CI, 0.07-0.69) but not in pacifier users (1.99; 0.16-24.4). Some differences in the effect of fan use on SIDS risk did not reach statistical significance. CONCLUSION: Fan use may be an effective intervention for further decreasing SIDS risk in infants in adverse sleep environments.
Authors: Coleman-Phox K; Odouli R; Li DK
Arch Pediatr Adolesc Med. 2008 Oct;162(10):963-8.
Obstructive defecation in middle-aged women
Obstructive defecation, a significant contributor to constipation, is frequently reported in middle-aged women, yet few population-based studies have established prevalence in this group. We analyzed data from the Reproductive Risks for Incontinence Study at Kaiser, a population-based cohort of racially diverse women, 40-69 years old, to describe the prevalence of obstructive defecation and identify associated risk factors. The Reproductive Risks for Incontinence Study at Kaiser is a randomly selected cohort of 2,109 women in the Kaiser Medical System. Obstructive defecation, determined by self-report, was defined as difficulty in passing stool, hard stool, straining for more than 15 min, or incomplete evacuation, occurring at least weekly. Age, race, income, education, drinking, health status, parity, pelvic organ prolapse, urinary incontinence, number of medications, hysterectomy, surgery for pelvic organ prolapse, colectomy, irritable bowel syndrome, and body mass index were assessed for both their univariate and multivariate association with obstructive defecation. Multivariate logistic regression was used to determine the independent association between associated factors and the primary outcome of obstructive defecation. Obstructive defecation that occurred at least weekly was reported by 12.3% of women. Significant independent risk factors included irritable bowel syndrome [odds ratio 1.78, (95% confidence interval 1.21-2.60)], vaginal or laparoscopic hysterectomy [2.01 (1.15-3.54)], unemployment [2.33 (1.39-3.92)], using three or more medications [1.81 (1.36-2.42)], symptomatic pelvic organ prolapse [2.34 (1.47-3.71)], urinary incontinence surgery [2.52 (1.29-4.90)], and other pelvic surgery [1.35 (1.03-1.78)]. We concluded that obstructive defecation is common in middle-aged women, especially those with a history of treatment for pelvic floor conditions. Women who had undergone laparoscopic/vaginal hysterectomies or surgery for pelvic organ prolapse or urinary incontinence had a nearly two times greater risk of weekly obstructive defecation. Demographic factors, with the exception of employment status, were not significant, indicating that obstructive defecation, although widespread, does not affect any particular group of women.
Authors: Varma MG; Hart SL; Brown JS; Creasman JM; Van Den Eeden SK; Thom DH
Dig Dis Sci. 2008 Oct;53(10):2702-9. Epub 2008 Mar 14.
Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study
BACKGROUND: Immune dysfunction has been associated with autism, yet whether maternal immune status during pregnancy plays a causal role remains to be clarified. METHODS: We conducted a population-based case-control study nested within the cohort of infants born July 2000-September 2001 to women who participated in the prenatal screening program in Orange County, California. Cases (AU; n = 84) were children receiving services for autism at the Regional Center of Orange County. Two control groups were included: children with mental retardation or developmental delay (MR; n = 49) receiving services at the same regional center; and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (GP; n = 160). Maternal autoantibody reactivity to fetal brain protein was measured by Western blot in archived mid-pregnancy blood specimens drawn during routine prenatal screening. Presence of specific bands and band patterns were compared between the three study groups. RESULTS: The pattern of maternal mid-gestation antibody reactivity to human fetal brain protein varied by study group and by autism onset type, although most differences did not reach statistical significance. Reactivity to a band at 39 kDa was more common among mothers of children with autism (7%) compared with mothers of MR (0%; p = .09) and GP control subjects (2%; p = .07), and simultaneous reactivity to bands at 39 kDa and 73 kDa was found only in mothers of children with early onset autism (n = 3). CONCLUSIONS: Our findings indicate that further studies of prenatal immune markers might be a productive area for etiologic and biologic marker discovery for autism.
Authors: Croen LA; Braunschweig D; Haapanen L; Yoshida CK; Fireman B; Grether JK; Kharrazi M; Hansen RL; Ashwood P; Van de Water J
Biol Psychiatry. 2008 Oct 1;64(7):583-8. Epub 2008 Jun 20.
Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders
OBJECTIVE: The objective of the study was to investigate the association between maternal Rh D status, prenatal exposure to anti-D immune globulin, and the risk of autism in the offspring. STUDY DESIGN: Case-control study among children born from 1995 to 1999 at Kaiser Permanente Northern California hospitals. Cases (n = 400) were children with an autism diagnosis; controls (n = 410) were children without autism, randomly sampled and frequency matched to cases on sex, birth year, and birth hospital. Maternal Rh D status and anti-D immune globulin exposure were ascertained from prenatal medical records. RESULTS: No case-control differences were observed for maternal Rh negative status (11.5% vs 10.0%, P = .5) or prenatal anti-D immune globulin exposure (10.0% vs. 9.3%, P = .7). Risk of autism remained unassociated with maternal Rh status or prenatal exposure to anti-D immune globulins after adjustment for covariates. CONCLUSION: These data support previous findings that prenatal exposure to thimerosal-containing anti-D immune globulins does not increase the risk of autism.
Authors: Croen LA; Matevia M; Yoshida CK; Grether JK
Am J Obstet Gynecol. 2008 Sep;199(3):234.e1-6. Epub 2008 Jun 13.
Predicting significant hyperbilirubinaemia using birth weight
BACKGROUND: A recent study proposed a risk factor scoring system for prediction of hyperbilirubinaemia that assigned increased risk to infants of higher birth weight. OBJECTIVE: To investigate this novel finding in a large, retrospective cohort analysis. METHODS: 105 384 newborns (> or =2000 g and > or =36 weeks) were analysed, and the effect of higher birth weight on total serum bilirubin (TSB) > or =342 micromol/l was reported using logistic regression to control for gestational age, scalp injury diagnosis, maternal diabetes, method of delivery and other confounders. RESULTS: The odds ratio for the effect of an additional 500 g of birth weight on TSB > or =342 micromol/l declined with increasing gestational age from 1.55 (95% CI 1.28 to 1.87) at 36 weeks to 1.30 (95% CI 1.12 to 1.50) at 37 weeks and 1.14 (95% CI 1.01 to 1.29) at 38 weeks. There was no association for infants > or =39 weeks. CONCLUSION: Higher birth weight predicts TSB > or =342 micromol/l in 36-38 week infants, but not in infants > or =39 weeks. Further research should explore the causal mechanism for the association in less-mature infants.
Authors: Flaherman VJ; Ferrara A; Newman TB
Arch Dis Child Fetal Neonatal Ed. 2008 Jul;93(4):F307-9. Epub 2008 Feb 19.
Detection of IL-17 and IL-23 in plasma samples of children with autism
Interleukin-23 (IL-23) is a survival factor for a newly described population of T lymphocytes, namely Th-17 cells, that secrete IL-17, tumor necrosis factor- alpha (TNF?) and IL-6. It has been shown that Th-17 cells are a pathogenic T cell subset involved in autoimmune and chronic inflammatory diseases. Based on the increasing evidence of immune dysfunction in autism, including possible autoimmune and inflammatory processes, we hypothesized that Th-17 cells, a T cell lineage that has not been previously examined in this disorder, may be altered in autism. To assess the potential role, if any, of Th-17 cells in autism, we analyzed plasma samples obtained from children ranging in age from 2-5 years with a diagnosis of autism and age-matched typically developing controls for the presence of IL-17 and IL-23 cytokines. Plasma samples from 40 children with autism including 20 children with a regressive form of autism, 20 with early onset and no regression and 20 typically developing age-matched control children were analyzed for IL-17 and IL-23, under the hypothesis that altered number and function of Th-17 cells would directly correlate with altered levels of IL-17 and IL-23 in the plasma. In this study, we were able to demonstrate that IL-23 cytokine levels were significantly different in children with autism compared with age-matched controls, a finding primarily driven by children with early onset autism. In contrast, there were no statistical differences in IL-17 levels autism compared with age-matched typically developing controls. This is the first study to report altered IL-23 production in autism. The decreased plasma IL-23 production observed in children with autism warrants further research as to its affect on the generation and survival of Th-17 cells, a subset important in neuroinflammatory conditions that may include autism.
Authors: Enstrom A; Onore C; Hertz-Piccioto I; Hansen R; Croen L; Van de Water J; Ashwood P
Am J Biochem Biotechnology. 2008 Jun;4(2):114-20.
Peripheral blood leukocyte production of BDNF following mitogen stimulation in early onset and regressive autism
Brain-derived neurotrophic factor (BDNF) is critical for neuronal differentiation and synaptic development. BDNF is also implicated in the development of psychological disorders including depression, bipolar disorder and schizophrenia. Previously, elevated BDNF levels were observed in neonatal blood samples from infants who were later diagnosed with autism when compared with children who developed normally, suggesting that BDNF may be involved in the development of autism. BDNF is produced by activated brain microglial cells, a cellular phenotype that shares several features with peripheral macrophages, suggesting an important role for the immune system in BDNF production. We hypothesized that under mitogenic stimulation, peripheral blood mononuclear cells obtained from children with autism may have altered BDNF production compared with age-matched typically developing control subjects. In addition, we examined the differences between the production of BDNF in classic/early-onset autism and children who had a regressive form of autism. We show here that plasma levels of BDNF levels are increased in children with autism, especially in early onset autism subjects. Furthermore, under mitogenic stimulation with PHA and LPS, BDNF production is significantly increased in children with autism compared with typically developing subjects. However, stimulation with tetanus toxoid results in a decreased response in children with autism. This data suggest that immune cell-derived production of BDNF could be an important source for the increased BDNF that is detected in some subjects with autism. As a neurotrophic factor produced by immune cells, BDNF could help elucidate the role of the immune system in neurodevelopment and neuronal maintenance, which may be dysregulated in autism.
Authors: Enstrom A; Onore C; Tarver A; Hertz-Picciotto I; Hansen R; Croen L; Van de Water J; Ashwood P
Am J Biochem Biotechnology. 2008 Jun;4(2):121-9.
Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study
This study compared parent-reported sleep characteristics in 2- to 5-year-old children with autism spectrum disorders (ASD) to children with other developmental delays (DD) and typical development (TD). We included 529 children (303 ASD [167 males], 63 DD [46 males], and 163 TD [134 males]) enrolled in the CHARGE study, an ongoing population-based case-control study. The mean age of participants was 3.6 years (standard deviation, 0.8 years). ASD diagnosis was confirmed with Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedules (ADOS). Cognitive and adaptive functioning was assessed using Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS), respectively. Demographic, medical and sleep history information were ascertained from California birth records, telephone interview, medical assessments at clinic visit, and parent-administered questionnaires. Fifty-three percent of children with ASD had at least one frequent sleep problem, followed by 46% of children with DD, and 32% of the TD group (P < 0.0001). Exploratory factor analyses of sleep history data yielded two factors: sleep onset problems and night waking. Children with ASD had marginally higher sleep onset factor scores and significantly higher night waking factor scores compared with the TD group. Factor scores for children with DD were intermediate between the ASD and TD groups. Cognitive or adaptive development did not predict severity of sleep problems in the ASD group.
Authors: Krakowiak P; Goodlin-Jones B; Hertz-Picciotto I; Croen LA; Hansen RL
J Sleep Res. 2008 Jun;17(2):197-206.
Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women’s Health Initiative
Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Women’s Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.
Authors: Neuhouser ML; Caan B; Prentice RL; et al.
Am J Epidemiol. 2008 May 15;167(10):1247-59. Epub 2008 Mar 15.
Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study
To investigate levels of brain-derived neurotrophic factor (BDNF) in mid-pregnancy and neonatal blood specimens as early biologic markers for autism, we conducted a population-based case-control study nested within the cohort of infants born from July 2000 to September 2001 to women who participated in the prenatal screening program in Orange County, CA. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid-pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead-based assay (Luminex, Biosource Human BDNF Antibody Bead Kit, Invitrogen-Biosource, Carlsbad, CA). The concentration of BDNF in maternal mid-pregnancy and neonatal specimens was similar across all three study groups. These data do not support previous findings of an association between BDNF and autism and suggest that the concentration of BDNF during critical periods of early neurodevelopment is not likely to be a useful biomarker for autism susceptibility.
Authors: Croen LA; Goines P; Braunschweig D; Yolken R; Yoshida CK; Grether JK; Fireman B; Kharrazi M; Hansen RL; Van de Water J
Autism Res. 2008 Apr;1(2):130-7.
Body mass index and weight gain prior to pregnancy and risk of gestational diabetes mellitus
OBJECTIVE: The objective of the study was to evaluate obesity and rate of weight change during the 5 years before pregnancy and risk of gestational diabetes mellitus (GDM) in a nested case-control study. STUDY DESIGN: GDM cases (n = 251) and controls (n = 204) were selected from a multiethnic cohort of 14,235 women who delivered a live birth between 1996 and 1998. Women who gained or lost weight were compared with those with a stable weight (+/- 1.0 kg/year). RESULTS: Women who gained weight at a rate of 1.1 to 2.2 kg/year had a small increased risk of GDM (odds ratio [OR] 1.63 [95% confidence interval (CI) 0.95 to 2.81]) and women who gained weight at a rate of 2.3 to 10.0 kg/year had a 2.5-fold increased risk of GDM (OR 2.61 [95% CI, 1.50 to 4.57]), compared with women with stable weight (after adjusting for age, race-ethnicity, parity, and baseline body mass index). CONCLUSION: Weight gain in the 5 years before pregnancy may increase the risk of GDM.
Authors: Hedderson MM; Williams MA; Holt VL; Weiss NS; Ferrara A
Am J Obstet Gynecol. 2008 Apr;198(4):409.e1-7. Epub 2008 Feb 20.
Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study
OBJECTIVE: The objective of the study was to examine whether the risk of miscarriage is associated with caffeine consumption during pregnancy after controlling for pregnancy-related symptoms. STUDY DESIGN: This was a population-based prospective cohort study. RESULTS: An increasing dose of daily caffeine intake during pregnancy was associated with an increased risk of miscarriage, compared with no caffeine intake, with an adjusted hazard ratio (aHR) of 1.42 (95% confidence interval 0.93 to 2.15) for caffeine intake of less than 200 mg/day, and aHR of 2.23 (1.34 to 3.69) for intake of 200 or more mg/day, respectively. Nausea or vomiting during pregnancy did not materially affect this observed association, nor did the change in intake pattern of caffeine during pregnancy. In addition, the magnitude of the association appeared to be stronger among women without a history of miscarriage (aHR 2.33, 1.48 to 3.67) than that among women with such a history (aHR 0.81, 0.34 to 1.94). CONCLUSION: Our results demonstrated that high doses of caffeine intake during pregnancy increase the risk of miscarriage, independent of pregnancy-related symptoms.
Authors: Weng X; Odouli R; Li DK
Am J Obstet Gynecol. 2008 Mar;198(3):279.e1-8. Epub 2008 Jan 25.
Autism: maternally derived antibodies specific for fetal brain proteins
Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies. To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73 and 37kDa in plasma from 7 of 61 (11.5%) mothers of children with autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of reactivity to these two bands was associated with parent report of behavioral regression in AU children when compared to the TD (p=0.0019) and DD (0.0089) groups. Individual reactivity to the 37kDa band was observed significantly more often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09-15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with autism, as well as the differential findings between mothers of children with early onset and regressive autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of autism in some children.
Authors: Braunschweig D; Ashwood P; Krakowiak P; Hertz-Picciotto I; Hansen R; Croen LA; Pessah IN; Van de Water J
Neurotoxicology. 2008 Mar;29(2):226-31. Epub 2007 Nov 6.
Effects of urinary incontinence, comorbidity and race on quality of life outcomes in women
PURPOSE: We investigated the effects of comorbidity and urinary incontinence on both generic and incontinence specific quality of life outcome measures, and investigated whether the association between urinary incontinence and quality of life varies by race. MATERIALS AND METHODS: Study participants were 2,109 women 40 to 69 years old randomly selected from an urban health maintenance organization and interviewed in person for a study of risk factors for urinary incontinence. The sample was racially diverse consisting of 48% white, 18% black, 17% Hispanic and 16% Asian-American women. In addition to incontinence, reproductive and medical history questionnaires, all participants completed the Medical Outcomes Study Short Form 36, a measure of health related quality of life. All participants with daily and weekly incontinence (29%) completed the Incontinence Impact Questionnaire, an incontinence specific quality of life measure. The health maintenance organization’s inpatient and outpatient electronic databases were used to calculate a Charlson comorbidity index score for each participant. ANCOVA was used to produce a model adjusting for sociodemographic variables, comorbidity and incontinence frequency. The same model was run for each of 4 racial groupings to examine differences by race/ethnicity. RESULTS: Urinary incontinence is significantly associated with a decreased quality of life and those with more frequent incontinence have significantly lower quality of life scores. In our model the Charlson score, an objective measure of comorbidity based on hospital and physician records, also has a significant negative impact on quality of life. When comorbidity is controlled, incontinence frequency continues to have a significant negative association with quality of life except among the sickest women. For women with the greatest extent of comorbidity, incontinence frequency is not significantly associated with negative quality of life outcomes. We did not find clear patterns of variation by race. CONCLUSIONS: Urinary incontinence and comorbidity each have an independent and significant role in reducing quality of life outcomes for all but the sickest women.
Authors: Ragins AI; Shan J; Thom DH; Subak LL; Brown JS; Van Den Eeden SK
J Urol. 2008 Feb;179(2):651-5; discussion 655. Epub 2007 Dec 21.
Detection of IL-17 and IL-23 in plasma samples of children with autism
Interleukin-23 (IL-23) is a survival factor for a newly described population of T lymphocytes, namely Th-17 cells, that secrete IL-17, tumor necrosis factor- alpha (TNF?) and IL-6. It has been shown that Th-17 cells are a pathogenic T cell subset involved in autoimmune and chronic inflammatory diseases. Based on the increasing evidence of immune dysfunction in autism, including possible autoimmune and inflammatory processes, we hypothesized that Th-17 cells, a T cell lineage that has not been previously examined in this disorder, may be altered in autism. To assess the potential role, if any, of Th-17 cells in autism, we analyzed plasma samples obtained from children ranging in age from 2-5 years with a diagnosis of autism and age-matched typically developing controls for the presence of IL-17 and IL-23 cytokines. Plasma samples from 40 children with autism including 20 children with a regressive form of autism, 20 with early onset and no regression and 20 typically developing age-matched control children were analyzed for IL-17 and IL-23, under the hypothesis that altered number and function of Th-17 cells would directly correlate with altered levels of IL-17 and IL-23 in the plasma. In this study, we were able to demonstrate that IL-23 cytokine levels were significantly different in children with autism compared with age-matched controls, a finding primarily driven by children with early onset autism. In contrast, there were no statistical differences in IL-17 levels autism compared with age-matched typically developing controls. This is the first study to report altered IL-23 production in autism. The decreased plasma IL-23 production observed in children with autism warrants further research as to its affect on the generation and survival of Th-17 cells, a subset important in neuroinflammatory conditions that may include autism.
Authors: Enstrom A; Onore C; Hertz-Piccioto I; Hansen R; Croen L; Van de Water J; Ashwood P
Am J Biochem Biotechnology. 2008 Jun;4(2):114-20.
Sex disparities in control and treatment of modifiable cardiovascular disease risk factors among patients with diabetes: Translating Research Into Action for Diabetes (TRIAD) Study
OBJECTIVE: Cardiovascular disease (CVD) mortality has decreased in men but not in women with diabetes. We investigated whether sex differences in control and treatment of CVD risk factors might underlie this disparity. RESEARCH DESIGN AND METHODS: We performed cross-sectional analyses from a cohort of patients with diabetes sampled from 10 U.S. managed care health plans. Study end points included not being in control for CVD risk factors (>or=140 mmHg for systolic blood pressure [SBP], >or=3.35 mmol/l for LDL cholesterol, and >or=8.0% for A1C) and the intensity of medication management (number of medication classes) for patients not in control. Logistic regression models with random intercepts were used to adjust probabilities of control and management for demographics, clinical characteristics, and clustering within health plans. RESULTS: There were 1,315 women and 1,575 men with a history of CVD and 3,415 women and 2,516 men without a history of CVD. Among patients with CVD, adjusted estimated probabilities for not being in control and risk differences varied significantly between men and women for SBP (men 41.2%, women 46.6%; risk difference -5.4% [95% CI -9.5 to -1.3]) and LDL cholesterol (men 22.4%, women 28.3%; risk difference -5.9% [-9.9 to -1.8]). There were no significant sex differences in intensity of medication management for patients not in control. In patients without CVD there were no significant differences in control or intensity of medication management. CONCLUSIONS: In diabetic patients with CVD, poorer control of SBP and LDL cholesterol for women may contribute to the sex disparity in CVD mortality trends.
Authors: Ferrara A; Mangione CM; Kim C; Marrero DG; Curb D; Stevens M; Selby JV; Translating Research Into Action for Diabetes Study Group
Diabetes Care. 2008 Jan;31(1):69-74. Epub 2007 Oct 12.
Regression in autism: prevalence and associated factors in the CHARGE Study
OBJECTIVE: The aim of this study was to examine the prevalence of regressive autism and associated demographic, medical, and developmental factors by using 2 different definitions of regression based on the Autism Diagnostic Interview, Revised. METHODS: Subjects were aged 2 to 5 years, with autism (AU) or autism spectrum disorder (ASD) confirmed by standardized measures. Children with regression, defined as a) loss of both language and social skills or b) loss of either language or social skills, were compared with each other and to children with AU or ASD with no reported loss of skills on developmental and adaptive functioning. Parents reported on seizure, gastrointestinal, and sleep concerns. RESULTS: Fifteen percent (50/333) of the combined AU-ASD group lost both language and social skills; 41% (138/333) lost either language or social skills. No differences were found between the 2 samples of children with regression. Few developmental, demographic, or medical differences were found between the combined regression group and children without loss of skills, in both the larger AU-ASD sample and the more homogeneous AU-only sample. Children with regression had significantly lower communication scores than children without regression. CONCLUSIONS: The prevalence of regression in a large sample of young children with AU and ASD varies depending on the definition used; requiring loss of language significantly underestimates the frequency of developmental regression. Children with regression performed significantly less well than those without regression on 2 measures of communication, but the clinical meaningfulness of these differences is uncertain because of the small effect sizes.
Authors: Hansen RL; Ozonoff S; Krakowiak P; Angkustsiri K; Jones C; Deprey LJ; Le DN; Croen LA; Hertz-Picciotto I
Ambul Pediatr. 2008 Jan-Feb;8(1):25-31.
Gene expression changes in children with autism
The objective of this study was to identify gene expression differences in blood differences in children with autism (AU) and autism spectrum disorder (ASD) compared to general population controls. Transcriptional profiles were compared with age- and gender-matched, typically developing children from the general population (GP). The AU group was subdivided based on a history of developmental regression (A-R) or a history of early onset (A-E without regression). Total RNA from blood was processed on human Affymetrix microarrays. Thirty-five children with AU (17 with early onset autism and 18 with autism with regression) and 14 ASD children (who did not meet criteria for AU) were compared to 12 GP children. Unpaired t tests (corrected for multiple comparisons with a false discovery rate of 0.05) detected a number of genes that were regulated more than 1.5-fold for AU versus GP (n=55 genes), for A-E versus GP (n=140 genes), for A-R versus GP (n=20 genes), and for A-R versus A-E (n=494 genes). No genes were significantly regulated for ASD versus GP. There were 11 genes shared between the comparisons of all autism subgroups to GP (AU, A-E, and A-R versus GP) and these genes were all expressed in natural killer cells and many belonged to the KEGG natural killer cytotoxicity pathway (p=0.02). A subset of these genes (n=7) was tested with qRT-PCR and all genes were found to be differentially expressed (p<0.05). We conclude that the gene expression data support emerging evidence for abnormalities in peripheral blood leukocytes in autism that could represent a genetic and/or environmental predisposition to the disorder.
Authors: Gregg JP; Lit L; Baron CA; Hertz-Picciotto I; Walker W; Davis RA; Croen LA; Ozonoff S; Hansen R; Pessah IN; Sharp FR
Genomics. 2008 Jan;91(1):22-9. Epub 2007 Nov 14.
Brief report: plasma leptin levels are elevated in autism: association with early onset phenotype?
There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p<.006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p<.042), TD controls (p<.0015), and DD controls (p<.004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group.
Authors: Ashwood P; Kwong C; Hansen R; Hertz-Picciotto I; Croen L; Krakowiak P; Walker W; Pessah IN; Van de Water J
J Autism Dev Disord. 2008 Jan;38(1):169-75. Epub 2007 Mar 9.
Urinary incontinence in women: Direct costs of routine care
OBJECTIVE: The purpose of this study was to estimate the direct costs of routine care for urinary incontinence (UI) in community-dwelling, racially diverse women. STUDY DESIGN: In the Reproductive Risks for Incontinence Study at Kaiser population-based study, 528 women with UI weekly or more quantified resources that were used for UI. Routine care costs were calculated with the use of national resource costs ($2005). Potential predictors of these outcomes were examined by multivariable linear regression. RESULTS: Mean age was 55 +/- 9 (SD) years. Among women with weekly UI, 69% reported incontinence-related costs. Median weekly cost was $1.83 (25%-75% interquartile range [IQR], $0.50, $5.23), increasing from $0.93 (IQR, $0, $3) for moderate to $7.82 (IQR, $5, $37) for very severe incontinence. Costs that increased with incontinence severity (P < .001) and body mass index (P < .001) were 2.2-fold higher for African American versus white women (P < .0001) and 42% higher for women with mixed versus stress incontinence (P < .05). CONCLUSION: Women pay a mean of >$250 per year out-of-pocket for UI routine care. Effective incontinence treatment may decrease costs.
Authors: Subak L; Van Den Eeden S; Thom D; Creasman JM; Brown JS; Reproductive Risks for Incontinence Study at Kaiser Research Group
Am J Obstet Gynecol. 2007 Dec;197(6):596.e1-9. Epub 2007 Sep 18.
Medical therapy for diabetes is associated with increased use of lower endoscopy
BACKGROUND: Diabetes mellitus is associated with an increased risk of colorectal neoplasia and diabetes medications may further influence the risk. Observational studies of the effect of diabetes medications on colonic neoplasia may be biased if use of diabetes medications is associated with undergoing lower endoscopy. This study examined the association between diabetes therapies and use of lower endoscopy. METHODS: This retrospective cohort study included patients with diabetes in an integrated, prepaid health plan. The primary exposure variables were use of sulfonylureas, metformin, thiazolidinediones (TZDs), and insulin. The outcome measure was completion of a flexible sigmoidoscopy or colonoscopy. Cox proportional hazards modeling, accounting for the time-varying nature of the medication exposures, was used to generate estimates of the relative hazard (HR) of lower endoscopy with different medications. RESULTS: The study included 44 169 patients followed for a mean duration of 4.2 years (SD = 2.5 years); 34% underwent at least one lower endoscopy. Patients who filled a diabetes medication prescription were more likely to undergo lower endoscopy (HR = 1.13, 95%CI 1.06-1.21). Compared to those taking only sulfonylureas, patients receiving sulfonylureas and metformin (HR = 1.12, 95%CI 1.06-1.18) or metformin alone (HR = 1.17, 95%CI 1.07-1.26) were more likely to undergo lower endoscopy. For all medications, new use was associated with undergoing lower endoscopy (p < 0.05 for all comparisons). CONCLUSIONS: Diabetic patients receiving medications are more likely to undergo lower endoscopy than those on diet control alone, particularly in the first year after initiating a new medication class and if taking metformin.
Authors: Lewis JD; Capra AM; Achacoso NS; Ferrara A; Levin TR; Quesenberry CP Jr; Habel LA
Pharmacoepidemiol Drug Saf. 2007 Nov;16(11):1195-202.
Preventive counseling among women with histories of gestational diabetes mellitus
OBJECTIVE: The purpose of this study was to examine the association between recall of recommendations for diabetes prevention and both health behaviors and screening among women with histories of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We surveyed 228 women with histories of GDM within the past 5 years who were enrolled in a university-affiliated managed care plan. In a cross-sectional analysis, we assessed the association between recall of health care provider advice and both postpartum lifestyle behaviors and reported performance of postpartum diabetes screening. Multivariate models were constructed that adjusted for correlates of counseling including postpartum diabetes, dyslipidemia, insulin use during pregnancy, and provider type. RESULTS: Participants were predominantly non-Hispanic white, college educated and affluent, and overweight or obese. The majority reported that they received counseling on lifestyle modification and postpartum diabetes screening. Postpartum physical activity levels, fruit and vegetable intake, and screening were suboptimal. No significant association existed between recall of advice and physical activity or between recall of advice and diet. Recall of advice along with distribution of laboratory slips for glucose testing was associated with performance of postpartum diabetes screening using self-report (adjusted odds ratio 2.07 [95% CI 1.51-2.84]) or claims data (1.64 [1.16-2.32]). CONCLUSIONS: Women with histories of GDM who recalled advice regarding postpartum glucose testing and received laboratory slips were significantly more likely to report having had postpartum diabetes screening. Although women’s recall of services may not reflect the actual services received, simple counseling may not be sufficient to optimize postpartum behaviors to reduce future risk of diabetes.
Authors: Kim C; McEwen LN; Kerr EA; Piette JD; Chames MC; Ferrara A; Herman WH
Diabetes Care. 2007 Oct;30(10):2489-95. Epub 2007 Jul 10.
Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California
BACKGROUND & AIMS: The aim of this study was to determine whether pregnancy outcomes differ between women with and without inflammatory bowel disease (IBD) and to determine what risk factors adversely affect outcomes. METHODS: We conducted a cohort study of all pregnant women within the Northern California Kaiser Permanente membership between the years 1995 and 2002. We abstracted the records of all pregnancies in women with IBD (exposed cohort) and a random sample of pregnancies from age-matched women without IBD (unexposed cohort) and evaluated risk factors for spontaneous abortion, complications of pregnancy, and adverse newborn events. RESULTS: A total of 461 pregnant women with IBD were matched to 493 unexposed pregnant women. Women with IBD were more likely to have an adverse conception outcome (odds ratio, 1.65; 95% confidence interval, 1.09-2.48), an adverse pregnancy outcome (odds ratio, 1.54; 95% confidence interval, 1.00-2.38), or a pregnancy complication (odds ratio, 1.78; 95% confidence interval, 1.13-2.81); however, the difference between the 2 groups in adverse newborn outcomes was not statistically significant (odds ratio, 1.89; 95% confidence interval, 0.98-3.69). Independent predictors of an adverse outcome included a diagnosis of IBD, a history of surgery for IBD, and non-Caucasian ethnicity. Severity of disease and medical treatments were not associated with an adverse outcome. CONCLUSIONS: Women with IBD are more likely to have an adverse outcome related to pregnancy. Disease activity and medical treatment did not predict adverse outcomes in a large, nonreferral population.
Authors: Mahadevan U; Sandborn WJ; Li DK; Hakimian S; Kane S; Corley DA
Gastroenterology. 2007 Oct;133(4):1106-12. Epub 2007 Jul 25.
Documentation of contraception and pregnancy when prescribing potentially teratogenic medications for reproductive-age women
BACKGROUND: Certain medications are identified by the U.S. Food and Drug Administration (FDA) as class D or X because they increase the risk for birth defects if used during pregnancy. OBJECTIVE: To assess pregnancy rates and the frequency of contraceptive counseling documented with prescriptions for class D or X drugs filled by women of reproductive age. DESIGN: Description of prescriptions filled in 2001. SETTING: A large health maintenance organization in northern California in 2001. PATIENTS: 488,175 women age 15 to 44 years who filled a total of 1,011,658 class A, B, D, or X prescriptions. MEASUREMENTS: Medications dispensed, contraceptive counseling, and pregnancy testing. RESULTS: A class D or X prescription was filled by 1 of every 6 women studied. Women who filled a prescription for class D or X medications were no more likely than women who filled prescriptions for safer, class A or B medications to have received contraceptive counseling, filled a contraceptive prescription, or been sterilized (48% vs. 51% of prescriptions). There was little variation by clinical indication in rates of contraceptive counseling with class D or X prescriptions, except for isotretinoin. Women who filled a class D or X prescription were only slightly less likely to have a pregnancy documented within 3 months than women filling a class A or B prescription (1.0% vs. 1.4% of prescriptions). LIMITATIONS: International Classification of Diseases, Ninth Revision, codes underestimate contraceptive counseling. Documentation of a positive pregnancy test after filling a prescription may overestimate medication use in early pregnancy. Women who filled several prescriptions are overrepresented in prescription analyses. CONCLUSION: Prescriptions for potentially teratogenic medications are frequently filled by women of childbearing age without documentation of contraceptive counseling.
Authors: Schwarz EB; Postlethwaite DA; Hung YY; Armstrong MA
Ann Intern Med. 2007 Sep 18;147(6):370-6.
Risk perception for diabetes among women with histories of gestational diabetes mellitus
OBJECTIVE: To examine risk perception for diabetes among women with histories of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We surveyed 217 women with histories of GDM who were enrolled in a managed-care plan and who did not currently have diabetes. In a cross-sectional design, we assessed the associations between risk perceptions and current lifestyle behavioral practices, plans to modify behaviors, and recent lifestyle behavior changes. Multivariable models included participant characteristics as well as potential modifiers of risk perception (knowledge of diabetes risk factors, optimistic bias, perceived personal control, and beliefs in the benefits and barriers of lifestyle modification). RESULTS: Ninety percent of women recognized that GDM was a risk factor for future diabetes, but only 16% believed that they themselves had a high chance of developing diabetes; perceived risk increased to 39% when women were asked to estimate their risk assuming they maintained their current lifestyle. Women who consumed three or more but less than five servings a day of fruits and vegetables reported lower odds of moderate/high risk perception (adjusted odds ratio [OR] 0.39 [95% CI 0.16-0.92]) than women who consumed less than three servings a day, although this association was not significant after further adjustment for income. Women who perceived themselves to be at moderate/high risk more often planned to modify their future lifestyle behaviors (9.1 [0.16-0.92]). CONCLUSIONS: Despite understanding the association between GDM and postpartum diabetes, women with histories of GDM usually do not perceive themselves to be at elevated risk.
Authors: Kim C; McEwen LN; Piette JD; Goewey J; Ferrara A; Walker EA
Diabetes Care. 2007 Sep;30(9):2281-6. Epub 2007 Jun 15.
Cytoreductive surgery for gynecologic malignancies–new standards of care
Studies on cytoreductive surgery for advanced ovarian and primary peritoneal cancer have consistently shown a strong correlation between cytoreduction and survival, with the best survival observed in patients who have no visible residual disease after successful cytoreductive surgery. Recent data that intraperitoneal chemotherapy further improves survival after optimal cytoreduction adds to the potential benefit of such surgery. More recently, significant survival benefit from optimal cytoreduction has also been shown for patients with recurrent disease and for women with advanced endometrial carcinoma. The selection criteria for patients and critical aspects of the operative technique and timing of cytoreductive surgery are discussed.
Authors: Suh-Burgmann E; Powell CB
Surg Oncol Clin N Am. 2007 Jul;16(3):667-82, x-xi.
Increasing prevalence of gestational diabetes mellitus: a public health perspective
Authors: Ferrara A
Diabetes Care. 2007 Jul;30 Suppl 2:S141-6.
Symptomatic pelvic organ prolapse: prevalence and risk factors in a population-based, racially diverse cohort
OBJECTIVE: To estimate the prevalence of and identify risk factors associated with symptomatic pelvic organ prolapse and level of distress in racially diverse women aged older than 40 years. METHODS: The Reproductive Risks for Incontinence Study at Kaiser is a population-based study of 2,001 randomly selected women. Symptomatic prolapse was determined by self-report of a feeling of bulge, pressure, or protrusion or a visible bulge from the vagina. Risk factors were assessed by self-report, interview, physical examination, and record review. Distress was assessed by self-report. Multivariable logistic regression analysis was used to identify independent risk factors. RESULTS: Symptomatic prolapse was reported by 118 (6%) women. Almost 50% of these women reported moderate or great distress, and 35% reported that the symptoms affected at least one physical, social or sexual activity. In multivariable analysis, the risk of prolapse was significantly increased in women with one (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.1-7.2), two (OR 4.1, 95% CI 1.8-9.5), and three or more (OR 5.3, 95% CI 2.3-12.3) vaginal deliveries compared with nulliparous women. Irritable bowel syndrome, constipation, and self-reported fair or poor health status were strongly associated with prolapse, with ORs of 2.8 (95% CI 1.7-4.6), 2.5 (95% CI 1.7-3.7), and 2.3 (95% CI 1.1-4.9), respectively. African-American women were significantly less likely to report symptomatic prolapse compared with white women (OR 0.4, 95% CI 0.2-0.8). CONCLUSION: Symptomatic prolapse is less common among African-American women and more common among women with a prior vaginal delivery, poor health status, constipation, or irritable bowel syndrome. Nearly one half of women with symptomatic prolapse are substantially bothered by their symptoms.
Authors: Rortveit G; Brown JS; Thom DH; Van Den Eeden SK; Creasman JM; Subak LL
Obstet Gynecol. 2007 Jun;109(6):1396-403.
Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain
BACKGROUND: Obesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial. METHODS: A randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women’s Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years. RESULTS: Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008). CONCLUSION: Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
Authors: Caan B; LaCroix A; et al.
Arch Intern Med. 2007 May 14;167(9):893-902.
Androgenicity of progestins in hormonal contraceptives and the risk of gestational diabetes mellitus
OBJECTIVE: There is some evidence that use of hormonal contraceptives, particularly the more androgenic formulations, can alter a woman’s glucose tolerance. We examined the association between hormonal contraceptive use, categorized by the androgenicity of the progestin component, and risk of gestational diabetes mellitus (GDM) in a nested case-control study. RESEARCH DESIGN AND METHODS: Case (n = 356) and control (n = 368) subjects were selected from a multiethnic cohort of 14,235 women who delivered a singleton live birth between 1 January 1996 and 30 June 1998, who were screened for GDM at 24-28 gestational weeks, and who were members of Kaiser Permanente for at least 5 years before pregnancy. GDM was defined using the National Diabetes Data Group plasma glucose cutoffs. Information concerning hormonal contraceptive use during the 5 years before pregnancy was obtained from medical charts and some pharmacy data. RESULTS: There was a suggestion that compared with no hormonal contraceptive use, use of a low-androgen hormonal contraceptive before pregnancy was associated with a slight reduction in risk of GDM (odds ratio 0.84 [95% CI 0.58-1.22]), whereas use of a high-androgen hormonal contraceptive was associated with a modest increase in GDM risk (1.43 [0.92-2.22]). CONCLUSIONS: The effects of hormonal contraceptive use on GDM risk may vary by the androgenicity of the progestin component.
Authors: Hedderson MM; Ferrara A; Williams MA; Holt VL; Weiss NS
Diabetes Care. 2007 May;30(5):1062-8. Epub 2007 Feb 15.
Maternal and paternal age and risk of autism spectrum disorders
OBJECTIVE: To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring. DESIGN: Historical birth cohort study. SETTING: Kaiser Permanente (KP) in Northern California. PARTICIPANTS: All singleton children born at KP from January 1, 1995, to December 31, 1999, were included in the study. We identified 593 children who had ASD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 299.0 or 299.8) recorded 2 or more times in KP outpatient databases before May 2005. These children were compared with all 132,251 remaining singleton KP births. Main Exposures Maternal and paternal age at birth of offspring. MAIN OUTCOME MEASURES: Relative risks (RRs) estimated from proportional hazards regression models. Risk of ASDs evaluated in relation to maternal and paternal age, adjusted for each other and for the sex, birth date, and birth order of the child, maternal and paternal educational level, and maternal and paternal race/ethnicity. RESULTS: Risk of ASDs increased significantly with each 10-year increase in maternal age (adjusted RR, 1.31; 95% confidence interval [CI], 1.07-1.62) and paternal age (RR, 1.28; 95% CI, 1.09-1.51). Adjusted RRs for both maternal and paternal age were elevated for children with autistic disorder (maternal age: RR, 1.18; 95% CI, 0.87-1.60; paternal age: RR, 1.34; 95% CI, 1.06-1.69) and children with Asperger disorder or pervasive developmental disorder not otherwise specified (maternal age: RR, 1.45; 95% CI, 1.09-1.93; paternal age: RR, 1.24; 95% CI, 0.99-1.55). Associations with parental age were somewhat stronger for girls than for boys, although sex differences were not statistically significant. CONCLUSION: Advanced maternal and paternal ages are independently associated with ASD risk.
Authors: Croen LA; Najjar DV; Fireman B; Grether JK
Arch Pediatr Adolesc Med. 2007 Apr;161(4):334-40.
Concordance of chart abstraction and patient recall of intrapartum variables up to 53 years later
OBJECTIVE: The purpose of this study was to determine the concordance of patient recall compared with chart abstraction for distant intrapartum variables and to evaluate predictors of concordance. STUDY DESIGN: A random sample from a cohort of diverse women aged 40-74 years. Intrapartum variables reported by participants were compared with the medical record. Outcomes were assessed for sensitivity, specificity, positive predictive value, and negative predictive value. Multivariate logistic regression was used to determine predictors of concordance of patient recall. RESULTS: Four hundred one births among 178 women were analyzed. Recall of cesarean delivery had the highest concordance (sensitivity, 0.98; specificity, 1.00; positive predictive value, 1.00; negative predictive value, 0.99). Laceration that required repair had the lowest concordance (sensitivity, 0.37; specificity, 0.68; positive predictive value, 0.34; negative predictive value, 0.81). No variables predicted concordance of recall for all variables. CONCLUSION: The concordance of patient recall to chart abstraction for intrapartum variables varies widely, although with a pattern of greater specificity and negative predictive value of recall. This should be kept in mind during patient interviews and in the performance of clinical research.
Authors: Hopkins LM; Caughey AB; Brown JS; Wassel Fyr CL; Creasman JM; Vittinghoff E; Van Den Eeden SK; Thom DH
Am J Obstet Gynecol. 2007 Mar;196(3):233.e1-6.
The epidemiology of autism spectrum disorders
Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. They are much more common than previously believed, second in frequency only to mental retardation among the serious developmental disorders. Although a heritable component has been demonstrated in ASD etiology, putative risk genes have yet to be identified. Environmental risk factors may also play a role, perhaps via complex gene-environment interactions, but no specific exposures with significant population effects are known. A number of endogenous biomarkers associated with autism risk have been investigated, and these may help identify significant biologic pathways that, in turn, will aid in the discovery of specific genes and exposures. Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes.
Authors: Newschaffer CJ; Croen LA; Windham GC; et al.
Annu Rev Public Health. 2007;28:235-58.
Using drink size to talk about drinking during pregnancy: Early start plus
Heavy drinking during pregnancy can cause birth defects and other alcohol-related effects. Because costs associated with fetal complications are high, health care organizations are invested in finding ways to intervene with pregnant drinkers. We describe a computerized intervention tested at prenatal clinics that uses drink size as a way of creating dialogue about pregnancy drinking. The intervention helps pregnant women screened as at-risk for alcohol use recognize how much they actually drink, using calibrated glassware and beverage containers along with computer graphics designed to define true volume for specific alcoholic beverage types. The intervention promotes abstinence; however, if that is not an obtainable goal, women are taught ways to cut down as much as possible during the rest of their pregnancy. Clinician feedback has been very positive, and the few women who continued to drink did not drink frequently or engage in binge drinking. Further, their average daily volume was 1 drink per day.
Authors: Witbrodt J; Armstrong MA; Diehl S; Kaskutas LA; Taillac C; Osejo VM; Escobar GJ
J Addict Nurs. 2007;18(4):199-206.
Infection in the first 2 years of life and autism spectrum disorders
OBJECTIVE: The purpose of this work was to investigate the association between infections in the first 2 years and subsequent diagnosis of autism spectrum disorders. METHODS: We conducted a case-control study among children born at Kaiser Permanente Northern California from 1995 to 1999. Case subjects (n = 403) were children with an autism diagnosis recorded in Kaiser Permanente databases. Control subjects (n = 2100) were randomly sampled from the remaining children without autism and frequency matched to case subjects on gender, birth year, and birth hospital. Information on infections and covariates were obtained from Kaiser Permanente and birth certificate databases. RESULTS: Overall, infection diagnoses in the first 2 years of life were recorded slightly less often for children with autism than control children (95.0% vs 97.5%). Among specific diagnoses, upper respiratory infections were significantly less frequently diagnosed and genitourinary infections more frequently diagnosed in children with autism. In the first 30 days of life, the frequency of having an infection was slightly higher among children with autism (22.6% vs 18.7%). CONCLUSIONS: Children with subsequent diagnoses of autism do not have more overall infections in the first 2 years of life than children without autism. Data suggest that children with autism may have modestly elevated rates of infection in the first 30 days and that, during the first 2 years, children with autism may be at higher risk for certain types of infections and lower risk for others. Additional studies that explore the associations between prenatal and early childhood infections and autism may help clarify the role of infection and the immune system in the etiology of autism spectrum disorder.
Authors: Rosen NJ; Yoshida CK; Croen LA
Pediatrics. 2007 Jan;119(1):e61-9.
Urinary incontinence and pelvic floor dysfunction in Asian-American women
OBJECTIVE: The objective of the study was to describe the prevalence, risk factors, and impact of urinary incontinence and other pelvic floor disorders among Asian-American women. STUDY DESIGN: This was a population-based cohort study of older women randomly selected from age and race strata. RESULTS: Weekly urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and urge incontinence being approximately equally common. In multivariate analysis, higher body mass index (greater than 25 kg/m2) was associated with both stress incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians. Hysterectomy was a significant risk factor for stress incontinence (odds ratio 2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly urinary incontinence reported ever having sought treatment. Pelvic floor exercises were the most common form of treatment, being used by 29% of Asian women with weekly incontinence. Asians were less likely then white women to report anal incontinence (21% versus 29%, P = .007), although this difference became nonsignificant after adjusting for differences in risk factors. CONCLUSION: Asian women share some risk factors for stress and urge urinary incontinence with white women. Urinary incontinence is associated with anal incontinence among Asian women.
Authors: Huang AJ; Thom DH; Kanaya AM; Wassel-Fyr CL; Van Den Eeden SK; Ragins AI; Subak LL; Brown JS
Am J Obstet Gynecol. 2006 Nov;195(5):1331-7. Epub 2006 Apr 27.
Pregnancy weight gain and risk of neonatal complications: macrosomia, hypoglycemia, and hyperbilirubinemia
OBJECTIVE: To examine whether pregnancy weight gains outside the Institute of Medicine (IOM) recommendations and rates of maternal weight gain are associated with neonatal complications. METHODS: In a cohort of 45,245 women who delivered singletons at Kaiser Permanente Medical Care Program Northern California in 1996-1998 and who did not have gestational diabetes as of 24-28 weeks of gestation, we conducted a nested case-control study with three case groups: macrosomia (birth weight more than 4,500 g, n=391), neonatal hypoglycemia (plasma glucose less than 40 mg/dL, n=328), and hyperbilirubinemia (serum bilirubin 20 mg/dL or more, n=432) and one control group (n=652). Medical records were reviewed to ascertain the woman’s prepregnancy and predelivery weight. RESULTS: Adjusting for age, race-ethnicity, parity, plasma glucose screening value, and difference in weeks between delivery and time when last weight was measured, women who gained more than recommended by the IOM were three times more likely to have an infant with macrosomia (odds ratio [OR] 3.05, 95% confidence interval [CI] 2.19-4.26), and nearly 1.5 times as likely to have an infant with hypoglycemia (OR 1.38, 95% CI 1.01-1.89), or hyperbilirubinemia (OR 1.43, 95% CI 1.06-1.93) than women whose weight gain was in the recommended range. Women who gained less than the IOM recommendations were less likely than women in the recommended range to have an infant with macrosomia (OR 0.38, 95% CI 0.20-0.70), but equally likely to have an infant with hypoglycemia or hyperbilirubinemia. Similar results were obtained using other means of categorizing weight gain during pregnancy. CONCLUSION: Maternal weight gain above the IOM recommendations was associated with an increased risk of the outcomes studied. LEVEL OF EVIDENCE: II-2.
Authors: Hedderson MM; Weiss NS; Sacks DA; Pettitt DJ; Selby JV; Quesenberry CP; Ferrara A
Obstet Gynecol. 2006 Nov;108(5):1153-61.
Quality-of-life impact and treatment of urinary incontinence in ethnically diverse older women
OBJECTIVE: To identify the factors associated with greater quality-of-life impact, treatment seeking, and use of treatments for urinary incontinence in ethnically diverse older women. METHODS: Cross-sectional analysis of a population-based cohort of 2109 middle-aged and older women who were randomly selected from age and race/ethnicity strata. Data were collected by self-report questionnaires and in-person interviews. Multivariable logistic regression was used to identify predictors of high quality-of-life impact (Incontinence Impact Questionnaire [IIQ] score > or =75th percentile), treatment seeking, and use of treatments for incontinence. RESULTS: More than one fourth (n = 603) of the study participants (including 96 black [16%], 123 Latina [20%], 65 Asian [11%], and 309 white [51%] women) reported weekly incontinence. After clinical severity and other factors were adjusted for, women were more likely to experience high quality-of-life impact if they had nighttime incontinence (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3-4.9), coital incontinence (OR, 1.9; 95% CI, 1.1-3.3), or comorbid fecal incontinence (OR, 2.2; 95% CI, 1.2-4.2). Predictors of treatment seeking included older age (OR, 1.6 per 10 years; 95% CI, 1.2-2.0); higher IIQ score (OR, 4.6 for highest IIQ quartile vs lowest IIQ quartile; 95% CI, 2.5-8.4), and higher household income (OR, 2.6 for income > or = US dollars 100 000/y vs < US dollars 20 000/y; 95% CI, 1.0-2.7). CONCLUSIONS: Clinicians seeking to evaluate the impact of incontinence on women's lives should assess not only the clinical severity of their symptoms but also the specific context in which symptoms occur. The prevalence of treatment seeking for incontinence is low across all ethnic groups, even when women have clinically severe symptoms and access to a health provider.
Authors: Huang AJ; Brown JS; Kanaya AM; Creasman JM; Ragins AI; Van Den Eeden SK; Thom DH
Arch Intern Med. 2006 Oct 9;166(18):2000-6.
Effect of hormone therapy on risk of hip and knee joint replacement in the Women’s Health Initiative
OBJECTIVE: To determine the effect of hormone therapy on arthroplasty rates. METHODS: We examined data from the Women’s Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n = 5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years. Participants reported hospitalizations, and arthroplasties were identified by procedure codes. Arthroplasties due to hip fracture were censored. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and outcome of time to first procedure. RESULTS: In the estrogen-alone trial, women receiving hormone therapy had significantly lower rates of any arthroplasty (HR 0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P = 0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P = 0.19). In the estrogen-plus-progestin trial, there was no association for total arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR 1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41) arthroplasties. CONCLUSION: These data suggest that hormone therapy may influence joint health, but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis.
Authors: Cirillo DJ; Wallace RB; Wu L; Yood RA
Arthritis Rheum. 2006 Oct;54(10):3194-204.
Potential association between infertility and spinal neural tube defects in offspring
BACKGROUND: We examined the possible association between infertility and spinal neural tube defects (NTDs). METHODS: This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). CONCLUSION: This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.
Authors: Wu YW; Croen LA; Henning L; Najjar DV; Schembri M; Croughan MS
Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):718-22.
Attention-deficit/hyperactivity disorder in children: excess costs before and after initial diagnosis and treatment cost differences by ethnicity
OBJECTIVES: To estimate the excess costs for children in the years surrounding initial diagnosis of attention-deficit/hyperactivity disorder (ADHD) and to estimate differences in treatment costs by ethnicity. DESIGN: We identified children diagnosed with ADHD and estimated their health service costs in the 2 years before and 2 years after initial diagnosis of ADHD. Costs were compared with those for children without ADHD. We adjusted for age, sex, ethnicity, pharmacy co-pay, estimated family income, coexisting mental health disorders, and chronic medical conditions. SETTING: Nonprofit, integrated health care delivery system in northern California from January 1, 1996, to December 31, 2004. PARTICIPANTS: Children aged 2 to 10 years with (n = 3122) and without (n = 15 899) ADHD. Main Exposure Attention-deficit/hyperactivity disorder. MAIN OUTCOME MEASURES: Health care costs and use in the years before and after initial ADHD diagnosis as well as costs of ADHD-related services. RESULTS: Compared with children without ADHD, children with ADHD had mean costs that were $488 more in the second year before their ADHD diagnosis, $678 more in the year before their diagnosis, $1328 more in the year after their diagnosis, and $1040 more in the second year after their diagnosis. Asian Americans diagnosed with ADHD had lower total ADHD-related mean costs per year than white Americans diagnosed with ADHD ($221 lower), and Asian Americans, African Americans, and Hispanic Americans all had lower ADHD-related pharmacy mean costs than white Americans ($95, $63, and $77 lower, respectively). CONCLUSIONS: Children with ADHD use significantly more health services before and after their diagnosis than children without ADHD. Among children diagnosed with ADHD, nonwhite Americans (especially Asian Americans) use fewer ADHD-related services than white Americans.
Authors: Ray GT; Levine P; Croen LA; Bokhari FA; Hu TW; Habel LA
Arch Pediatr Adolesc Med. 2006 Oct;160(10):1063-9.
A comparison of health care utilization and costs of children with and without autism spectrum disorders in a large group-model health plan
OBJECTIVE: Data on the current costs of medical services for children with autism spectrum disorders are lacking. Our purpose for this study was to compare health care utilization and costs of children with and without autism spectrum disorders in the same health plan. PATIENTS AND METHODS: Participants included all 2- to 18-year-old children with autism spectrum disorders (n = 3053) and a random sample of children without autism spectrum disorders (n = 30529) who were continuously enrolled in the Kaiser Permanente Medical Care Program in northern California between July 1, 2003, and June 30, 2004. Data on health care utilization and costs were derived from health plan administrative databases. MAIN OUTCOME MEASURES: Outcome measures included mean annual utilization and costs of health services per child. RESULTS: Children with autism spectrum disorders had a higher annual mean number of total clinic (5.6 vs 2.8), pediatric (2.3 vs 1.6), and psychiatric (2.2 vs 0.3) outpatient visits. A higher percentage of children with autism spectrum disorders experienced inpatient (3% vs 1%) and outpatient (5% vs 2%) hospitalizations. Children with autism spectrum disorders were nearly 9 times more likely to use psychotherapeutic medications and twice as likely to use gastrointestinal agents than children without autism spectrum disorders. Mean annual member costs for hospitalizations (550 dollars vs 208 dollars), clinic visits (1373 dollars vs 540 dollars), and prescription medications (724 dollars vs 96 dollars) were more than double for children with autism spectrum disorders compared with children without autism spectrum disorders. The mean annual age- and gender-adjusted total cost per member was more than threefold higher for children with autism spectrum disorders (2757 dollars vs 892 dollars). Among the subgroup of children with other psychiatric conditions, total mean annual costs were 45% higher for children with autism spectrum disorders compared with children without autism spectrum disorders; excess costs were largely explained by the increased use of psychotherapeutic medications. CONCLUSIONS: The utilization and costs of health care are substantially higher for children with autism spectrum disorders compared with children without autism spectrum disorders. Research is needed to evaluate the impact of improvements in the management of children with autism spectrum disorders on health care utilization and costs.
Authors: Croen LA; Najjar DV; Ray GT; Lotspeich L; Bernal P
Pediatrics. 2006 Oct;118(4):e1203-11.
Autism spectrum disorders in relation to distribution of hazardous air pollutants in the san francisco bay area
OBJECTIVE: To explore possible associations between autism spectrum disorders (ASD) and environmental exposures, we linked the California autism surveillance system to estimated hazardous air pollutant (HAP) concentrations compiled by the U.S. Environmental Protection Agency. METHODS: Subjects included 284 children with ASD and 657 controls, born in 1994 in the San Francisco Bay area. We assigned exposure level by census tract of birth residence for 19 chemicals we identified as potential neurotoxicants, developmental toxicants, and/or endocrine disruptors from the 1996 HAPs database. Because concentrations of many of these were highly correlated, we combined the chemicals into mechanistic and structural groups, calculating summary index scores. We calculated ASD risk in the upper quartiles of these group scores or individual chemical concentrations compared with below the median, adjusting for demographic factors. RESULTS: The adjusted odds ratios (AORs) were elevated by 50% in the top quartile of chlorinated solvents and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not for aromatic solvents. Adjusting for these three groups simultaneously led to decreased risks for the solvents and increased risk for metals (AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that contributed most to these associations included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results suggest a potential association between autism and estimated metal concentrations, and possibly solvents, in ambient air around the birth residence, requiring confirmation and more refined exposure assessment in future studies.
Authors: Windham GC; Zhang L; Gunier R; Croen LA; Grether JK
Environ Health Perspect. 2006 Sep;114(9):1438-44.
Neuroimaging abnormalities in infants with congenital hemiparesis
Clinical and neuroimaging characteristics of congenital hemiparesis were examined in a retrospective cohort study nested within 199,176 births within the Kaiser Permanente Medical Care Program, 1997-2002. Infants with a physician diagnosis of paresis or cerebral palsy were electronically identified, and charts were reviewed to confirm congenital hemiparesis. A neuroradiologist reviewed available head MRI and CT scans. Of 96 infants with congenital hemiparesis (population prevalence 4.8 per 10,000), 81% received either a head magnetic resonance imaging (n = 55) or head computed tomography only (n = 23). Perinatal arterial infarction was the most common (30%) neuroimaging finding in term infants. Infants with right-sided hemiparesis (relative risk 4.6, 95% confidence interval 1.4-14.4) or moderate to severe weakness (relative risk 4.4, 95% confidence interval 1.1-17.7) were more likely to have had a perinatal arterial infarction. Periventricular white matter lesions predominated in preterm infants (71%). Brain malformations observed in 14 (18%) patients included polymicrogyria, heterotopia, and schizencephaly. The 14 infants (18%) with a normal head imaging study were more likely to outgrow all signs of hemiparesis by age 3 than were infants with an abnormal brain image (29% vs 0%, P < 0.001). Neuroimaging studies provide useful diagnostic and prognostic information in infants with congenital hemiparesis.
Authors: Wu YW; Lindan CE; Henning LH; Yoshida CK; Fullerton HJ; Ferriero DM; Barkovich AJ; Croen LA
Pediatr Neurol. 2006 Sep;35(3):191-6.
Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS): ancillary study of the Women’s Health Initiative
OBJECTIVE: To evaluate the relationship between dietary lutein plus zeaxanthin and intermediate age-related macular degeneration (AMD). DESIGN: Women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intake of lutein plus zeaxanthin above the 78th (high) and below the 28th (low) percentiles at baseline in the Women’s Health Initiative Observational Study were recruited 4 to 7 years later into the Carotenoids in Age-Related Eye Disease Study (CAREDS), when the presence of AMD was determined by fundus photographs. Logistic regression analyses examined the prevalence of AMD in 1787 CAREDS participants, after accounting for potential covariates. RESULTS: The prevalence of intermediate AMD was not statistically different between the high and low lutein plus zeaxanthin intake recruitment groups after adjusting for age (odds ratio, 0.96; 95% confidence interval, 0.75-1.23). Limiting analyses to women younger than 75 years with stable intake of lutein plus zeaxanthin, without a history of chronic diseases that are often associated with diet changes, substantially lowered odds ratios (0.57; 95% confidence interval, 0.34-0.95). Exploratory analyses of advanced AMD in 34 participants resulted in protective, but statistically nonsignificant, associations in the overall sample and in women younger than 75 years. CONCLUSION: Diets rich in lutein plus zeaxanthin may protect against intermediate AMD in healthy women younger than 75 years.
Authors: Moeller SM; Parekh N; Tinker L; Ritenbaugh C; Blodi B; Wallace RB; Mares JA; CAREDS Research Study Group
Arch Ophthalmol. 2006 Aug;124(8):1151-62.
Cerebral palsy in a term population: risk factors and neuroimaging findings
OBJECTIVE: The purpose of this work was to study risk factors and neuroimaging characteristics of cerebral palsy in term and near-term infants. PATIENTS AND METHODS: Among a cohort of 334,339 infants > or = 36 weeks’ gestation born at Kaiser Permanente Medical Care Program in northern California in 1991-2003, we identified infants with cerebral palsy and obtained clinical data from electronic and medical charts. Risk factors for cerebral palsy among infants with different brain abnormalities were compared using polytomous logistic regression. RESULTS: Of 377 infants with cerebral palsy (prevalence: 1.1 per 1000), 273 (72%) received a head computed tomography or MRI. Abnormalities included focal arterial infarction (22%), brain malformation (14%), and periventricular white matter abnormalities (12%). Independent risk factors for cerebral palsy were maternal age > 35, black race, and intrauterine growth restriction. Intrauterine growth restriction was more strongly associated with periventricular white matter injury than with other neuroimaging findings. Nighttime delivery was associated with cerebral palsy accompanied by generalized brain atrophy but not with cerebral palsy accompanied by other brain lesions. CONCLUSIONS: Cerebral palsy is a heterogeneous syndrome with focal arterial infarction and brain malformation representing the most common neuroimaging abnormalities in term and near-term infants. Risk factors for cerebral palsy differ depending on the type of underlying brain abnormality.
Authors: Wu YW; Croen LA; Shah SJ; Newman TB; Najjar DV
Pediatrics. 2006 Aug;118(2):690-7.
Increased prevalence of gestational diabetes mellitus among women with diagnosed polycystic ovary syndrome: a population-based study
Authors: Lo JC; Feigenbaum SL; Escobar GJ; Yang J; Crites YM; Ferrara A
Diabetes Care. 2006 Aug;29(8):1915-7.
Conjugated equine estrogens and peripheral arterial disease risk: the Women’s Health Initiative
BACKGROUND: Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted. METHODS: The Estrogen Alone trial randomized 10739 postmenopausal women with prior hysterectomy, mean age 63.6 +/- 7.3 years, to conjugated equine estrogens (CEE 0.625 mg/d) or placebo and documented health outcomes over an average of 7.1 +/- 1.6 years. RESULTS: A trend toward increased risk of peripheral arterial events with CEE was observed (hazard ratio [HR] 1.32, 95% CI 0.99-1.77). Carotid arterial events (HR 1.19, 95% CI 0.82-1.74), lower extremity arterial events (HR 1.41, 95% CI 0.86-2.32), and abdominal aortic aneurysm (HR 2.40, 95% CI 0.92-6.23) were more frequent, but not individually significant, in the CEE group. However, the composite of lower extremity arterial disease/abdominal aortic aneurysm was significantly more frequent among women assigned to CEE (HR 1.63, 95 % CI 1.05-2.51). In subgroup analyses, no clear pattern of risk with CEE was apparent by age or by time since menopause. CONCLUSIONS: Unopposed CEE conferred no protection against peripheral arterial disease among generally healthy postmenopausal women; in fact, there was a suggestion of increased risk.
Authors: Hsia J; Criqui MH; Herrington DM; Manson JE; Wu L; Heckbert SR; Allison M; McDermott MM; Robinson J; Masaki K; Women's Health Initiative Research Group
Am Heart J. 2006 Jul;152(1):170-6.
Progress in pediatric asthma surveillance I: the application of health care use data in Alameda County, California
INTRODUCTION: The ability to conduct community-level asthma surveillance is increasingly crucial for public health programming and child health advocacy. We explored the potential and limitations of health care use records from both public and private sources for asthma surveillance in a California county. METHODS: We combined administrative patient record data from Kaiser Permanente of Northern California and Medi-Cal (the California Medicaid program) for Alameda County residents during 2001. We assessed the resulting data set for completeness, population representation, consistency with external data, and internal indicator consistency. RESULTS: Our resulting data set included records for 226,383 children younger than 18 years. Completeness of Medicaid data was affected by managed care market share, reducing our usable data set size to 176,789, approximately equal to one of every two children in the county or one of every 3 person-months. External data documenting hospitalization rates due to asthma were poorly correlated with hospitalization rates (r = 0.2120, P = .20) but highly correlated with emergency department visits (r = 0.8607, P <.001) in the resulting data set. High internal consistency of indicators suggested that the data set represented a broad spectrum of health care access and quality of care congruent with clinical aspects of the disease. CONCLUSION: The utility of these data is affected by logistical and administrative factors, including the health care payment structure and the market shares of care providers. These factors can be expected to similarly affect the utility of this approach in other counties. Our ability to generate county-level health statistics for comparison with other locations was limited, although the data set appeared well suited for within-county geographic analysis. In light of these findings, these data have the potential to expand the local health surveillance capacity of communities.
Authors: Roberts EM; English PB; Van Den Eeden SK; Ray GT
Prev Chronic Dis. 2006 Jul;3(3):A91. Epub 2006 Jun 15.
Dietary genistein intake and cognitive performance in a multiethnic cohort of midlife women
OBJECTIVE: To examine the relationship between food frequency questionnaire estimated isoflavone intakes and cognitive performance. DESIGN: The Study of Women’s Health Across the Nation (SWAN), is a multiethnic, community based, longitudinal study of women aged 42 to 52 years at entry. Dietary isoflavone intakes were estimated from an interviewer-administered food frequency questionnaire at baseline. Intakes of genistein and daidzein were highly correlated (r = 0.98); therefore, analyses were conducted using genistein only. The SWAN includes white, African American, Hispanic, Chinese, and Japanese women; this analysis was performed only in the latter two ethnic groups because the others had minimal genistein intake (median, <4 microg/day). Cognitive function tests were measured at the fourth annual follow-up visit using the East Boston Memory Test (Immediate and Delayed), Symbol Digit Modalities Test, and Digit Span Backward Test. Ethnicity-specific general linear models were used to examine the relationship between each of these cognitive tests and energy-adjusted genistein intake controlling for age, menopause stage, ever-use of any hormones, and current use of any hormones. RESULTS: Among 195 Japanese and women and 185 Chinese women, median intakes of genistein (mug/day) were 6,788 and 3,534, respectively. No associations between genistein intake and measures of cognitive performance were found in either ethnic group. CONCLUSIONS: Our results did not support the hypothesis that genistein intake, at the levels consumed by the study sample, benefits cognitive performance. It also possible that the bioavailability of genistein in food sources is insufficient to exert a neurophysiological effect or that the potential effect of genistein is only manifest in low-estrogen states; the current study is not able to address these possibilities.
Authors: Huang MH; Luetters C; Buckwalter GJ; Seeman TE; Gold EB; Sternfeld B; Greendale GA
Menopause. 2006 Jul-Aug;13(4):621-30.
The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism
Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children’s Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System.
Authors: Hertz-Picciotto I; Croen LA; Hansen R; Jones CR; van de Water J; Pessah IN
Environ Health Perspect. 2006 Jul;114(7):1119-25.
Progress in pediatric asthma surveillance II: geospatial patterns of asthma in Alameda County, California
INTRODUCTION: As with many diseases, the epidemic of asthma among children over the past few decades has been shaped by a social and environmental context that is becoming progressively more evident. Commonly used methods for asthma surveillance, however, are based on national rather than local data. The purpose of this study was to develop high-resolution asthma surveillance techniques responsive to the needs of health care professionals and local child health and social justice advocates. METHODS: We assembled a working data set of health care use records from 2001 from public and private sources covering 1.7 million person-months among children younger than 18 years in Alameda County, California. Health care use was categorized by type and analyzed by census tract demographic information. Images of the geographic distribution of health service events were created using density estimation mapping with overlapping 0.5-mile (805-m) radius spatial buffers, and statistical significance (two-tailed P & .05) was estimated using a Monte Carlo simulation algorithm. RESULTS: High-poverty communities had higher rates of emergency department visits due to asthma than low-poverty communities but had lower rates for indicators of quality primary asthma care. Geospatial analysis enabled visualization of this phenomenon; it further detected areas with elevated emergency department visit rates and potentially related environmental hazards in and around communities of concern. Areas of the county not previously considered to be deeply burdened by asthma were identified as having high emergency department visit rates. CONCLUSION: The assembly and high-resolution geospatial analysis of health care use data contributed to a more detailed depiction of pediatric asthma disparities than was previously available to community members, public health professionals, and clinicians. Information generated using these techniques facilitated discussion among stakeholders of the environmental and social contexts of asthma and health disparities in general. Proceedings of group evaluations suggested that the material aided in the translation of data describing spatial variations in health event risk to address specific community experiences and concerns.
Authors: Roberts EM; English PB; Wong M; Wolff C; Valdez S; Van den Eeden SK; Ray GT
Prev Chronic Dis. 2006 Jul;3(3):A92. Epub 2006 Jun 15.
Long-term outcomes following conservative surgery for borderline tumor of the ovary: a large population-based study
OBJECTIVES: To examine outcomes in women treated with conservative surgery for borderline ovarian tumor in a large population-based cohort with long-term follow-up. METHODS: Women treated by conservative surgery for borderline tumor of the ovary from 1982-2004 within a large HMO setting were identified using electronic and tumor registry data. Chart review was performed when electronic data were incomplete. The indications for and outcomes from any subsequent gynecologic surgery and the risk of recurrent ovarian borderline and malignant tumor were determined. Risk factors for recurrence were analyzed using multivariate regression. RESULTS: Among one hundred and ninety-three patients identified, the average age was 33 (12-95), with 97% having apparent Stage I disease. Patients were followed with remaining ovarian tissue in situ for a mean of 6.9 years, with 59 women having 10 or more years of such observation. There were 21 recurrences with borderline tumor (11%) with a median time to first recurrence of 4.7 years; women treated by cystectomy recurred three times more often compared to women treated by oophorectomy (23% versus 7%). Two patients (1%) recurred with malignant disease involving remaining ovarian tissue, both within the first 3 years after surgery, with one death due to recurrence. During long-term follow-up, 19% of patients eventually underwent complete removal of ovarian tissue: in 8%, the surgery was prophylactic, in 5%, surgery was done for benign pathology, and in 6% for recurrent disease. CONCLUSIONS: In this population-based HMO setting, 11% of women treated with conservative surgery for borderline tumor recurred; however, half of these recurrences were successfully managed by repeat conservative surgery, with only 6% of women overall needing eventual complete removal of ovaries for recurrent disease. Patients treated by cystectomy were three times more likely to recur than those treated by oophorectomy. Malignant recurrences were rare, and while borderline recurrences often occurred more than 3 years after initial surgery, late malignant recurrences were not observed. These favorable long-term outcomes provide support for conservative surgery for these women.
Authors: Suh-Burgmann E
Gynecol Oncol. 2006 Dec;103(3):841-7. Epub 2006 Jun 21.
Fecal incontinence in females older than aged 40 years: who is at risk?
PURPOSE: This study was designed to estimate the prevalence of, and identify risk factors associated with, fecal incontinence in racially diverse females older than aged 40 years. METHODS: The Reproductive Risks for Incontinence Study at Kaiser is a population-based study of 2,109 randomly selected middle-aged and older females (average age, 56 years). Fecal incontinence, determined by self-report, was categorized by frequency. Females reported the level of bother of fecal incontinence and their general quality of life. Potential risk factors were assessed by self-report, interview, physical examination, and record review. Multivariate logistic regression analysis was used to determine the independent association between selected risk factors and the primary outcome of any reported fecal incontinence in the past year. RESULTS: Fecal incontinence in the past year was reported by 24 percent of females (3.4 percent monthly, 1.9 percent weekly, and 0.2 percent daily). Greater frequency of fecal incontinence was associated with decreased quality of life (Medical Outcome Short Form-36 Mental Component Scale score, P = 0.01), and increased bother (P < 0.001) with 45 percent of females with fecal incontinence in the past year and 100 percent of females with daily fecal incontinence reporting moderate or great bother. In multivariate analysis, the prevalence of fecal incontinence in the past year increased significantly [odds ratio per 5 kg/m2 (95 percent confidence interval)] with obesity [1.2 (1.1-1.3)], chronic obstructive pulmonary disease [1.9 (1.3-2.9)], irritable bowel syndrome [2.4 (1.7-3.4)], urinary incontinence [2.1 (1.7-2.6)], and colectomy [1.9 (1.1-3.1)]. Latina females were less likely to report fecal incontinence than white females [0.6 (0.4-0.9)]. CONCLUSIONS: Fecal incontinence, a common problem for females, is associated with substantial adverse affects on quality of life. Several of the identified risk factors are preventable or modifiable, and may direct future research in fecal incontinence therapy.
Authors: Varma MG; Brown JS; Creasman JM; Thom DH; Van Den Eeden SK; Beattie MS; Subak LL; Reproductive Risks for Incontinence Study at Kaiser (RRISK) Research Group
Dis Colon Rectum. 2006 Jun;49(6):841-51.
Congenital anomalies associated with autism spectrum disorders
This study examined whether major congenital structural anomalies identified in infancy occurred more frequently in children later diagnosed with autism spectrum disorders (ASD; n=417; 341 males, 76 females) than in comparison children (n=2,067; 1,681 males, 386 females). Participants were sampled from infants born at Kaiser Permanente Northern California facilities between 1995 and 1999 who remained health plan members for at least 2 years (n=88,163). Comparison children were frequency-matched to children with ASD according to sex, birth year, and birth hospital. Congenital anomalies were diagnosed in 10.8% of children with ASD and 6.2% of comparison children (crude odds ratio [ORc] 1.8, 95% confidence interval [CI] 1.3-2.6). This association remained significant after adjustment for key maternal and infant covariates (adjusted OR [ORa] 1.7, 95% CI 1.1-2.4). Almost all organ-system anomaly categories were more prevalent in children with ASD, however only gastrointestinal anomalies were significantly associated with ASD in adjusted analyses (1.9 vs 0.4%, ORa 5.1, 95% CI 1.8-14.1).
Authors: Wier ML; Yoshida CK; Odouli R; Grether JK; Croen LA
Dev Med Child Neurol. 2006 Jun;48(6):500-7.
Effects of conjugated equine estrogen on stroke in the Women’s Health Initiative
BACKGROUND: The Women’s Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. METHODS AND RESULTS: The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin. CONCLUSIONS: CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.
Authors: Hendrix SL; Torner J; WHI Investigators; et al.
Circulation. 2006 May 23;113(20):2425-34. Epub 2006 May 15.
Combined analysis of Women’s Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease
Circumstances in which both randomized controlled trial and observational study data are available provide an important opportunity to identify biases and improve study design and analysis procedures. In addition, joint analyses of data from the two sources can extend clinical trial findings. The US Women’s Health Initiative includes randomized controlled trials of use of estrogen by posthysterectomy women and of estrogen plus progestin by women with a uterus, along with corresponding observational study components. In this paper, for coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin. These findings support certain combined analyses of the observational data on estrogen and the estrogen plus progestin clinical trial and observational study data to give adjusted observational study estimates of estrogen treatment effects. The resulting treatment effect estimates are compared with corresponding clinical trial estimates, and parallel analyses are also presented for estrogen plus progestin. An application to postmenopausal hormone treatment effects on coronary heart disease among younger women is also provided.
Authors: Prentice RL; Kotchen J; Women's Health Initiative Investigators; et al.
Am J Epidemiol. 2006 Apr 1;163(7):589-99. Epub 2006 Feb 16.
Childhood urinary symptoms predict adult overactive bladder symptoms
PURPOSE: A relationship between childhood urinary symptoms and adult lower urinary tract symptoms in women is often clinically suspected. In this analysis we investigated the relationship between childhood and adult urinary symptoms in middle-aged women. MATERIALS AND METHODS: A population based cohort of 2,109 women 40 to 69 years old who were members of a large health maintenance organization was randomly selected from age and race strata. Through self-reported questionnaires, women recalled a childhood history of and current urinary lower urinary tract symptoms, including frequent daytime urination, nocturia, urinary incontinence, nocturnal enuresis and UTIs. Current incontinence was also classified as urge or stress incontinence. Multivariate analysis was used to evaluate the association between childhood and current lower urinary tract symptoms controlling for age, race, hysterectomy status, parity, oral estrogen use, body mass index and diabetes. RESULTS: Women who reported childhood daytime frequency were more likely to report adult urgency (OR 1.9, 95% CI 1.3-2.6, p < 0.001). Frequent nocturia in childhood was strongly associated with adult nocturia (OR 2.3, 95% CI 1.5-3.5, p < 0.001). Childhood daytime incontinence was associated with adult urge incontinence (OR 2.6, 95% CI 1.1-5.9, p < 0.05), as was childhood nocturnal enuresis (OR 2.7, CI 1.3-5.5, p < 0.01). A history of more than 1 childhood UTI was associated with adult UTIs (OR 2.6, 95% CI 1.5-4.5, p < 0.001). CONCLUSIONS: Childhood urinary symptoms and UTIs were significantly associated with adult overactive bladder symptoms. There is a need to investigate the significance of childhood symptoms as predictors of eventual adult disorders to determine whether treatment of childhood symptoms will alter the prevalence of eventual adult disorders, and if such a history should alter clinical care of the older adult with OAB symptoms.
Authors: Fitzgerald MP; Thom DH; Wassel-Fyr C; Subak L; Brubaker L; Van Den Eeden SK; Brown JS; Reproductive Risks for Incontinence Study at Kaiser Research Group
J Urol. 2006 Mar;175(3 Pt 1):989-93.
Calcium plus vitamin D supplementation and the risk of fractures
BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women’s Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).
Authors: Jackson RD; Caan B; Women's Health Initiative Investigators; et al.
N Engl J Med. 2006 Feb 16;354(7):669-83.
Calcium plus vitamin D supplementation and the risk of colorectal cancer
BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).
Authors: Wactawski-Wende J; Caan B; Women's Health Initiative Investigators; et al.
N Engl J Med. 2006 Feb 16;354(7):684-96.
Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial
CONTEXT: Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed. OBJECTIVE: To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women’s Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years. INTERVENTION: Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials. MAIN OUTCOME MEASURES: Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke). RESULTS: By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits. CONCLUSIONS: Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Authors: Howard BV; Caan B; Kotchen JM; et al.
JAMA. 2006 Feb 8;295(6):655-66.
Use of a dummy (pacifier) during sleep and risk of sudden infant death syndrome (SIDS): population based case-control study
OBJECTIVES: To examine the association between use of a dummy (pacifier) during sleep and the risk of sudden infant death syndrome (SIDS) in relation to other risk factors. DESIGN: Population based case-control study. SETTING: Eleven counties in California. PARTICIPANTS: Mothers or carers of 185 infants whose deaths were attributed to SIDS and 312 randomly selected controls matched for race or ethnicity and age. MAIN OUTCOME MEASURE: Use of a dummy during sleep determined through interviews. RESULTS: The adjusted odds ratio for SIDS associated with using a dummy during the last sleep was 0.08 (95% confidence interval 0.03 to 0.21). Use was associated with a reduction in risk in every category of sociodemographic characteristics and risk factors examined. The reduced risk associated with use seemed to be greater with adverse sleep conditions (such as sleeping prone or on side and sleeping with a mother who smoked), although the observed interactions were not significant. In addition, use of a dummy may reduce the impact of other risk factors for SIDS, especially those related to adverse sleep environment. For example, infants who did not use a dummy and slept prone or on their sides (v on their back) had an increased risk of SIDS (2.61, 1.56 to 4.38). In infants who used dummies, there was no increased risk associated with sleeping position (0.66, 0.12 to 3.59). While cosleeping with a mother who smoked was also associated with increased risk of SIDS among infants who did not use a dummy (4.5, 1.3 to 15.1), there was no such association among those who did (1.1, 0.1 to 13.4). CONCLUSIONS: Use of a dummy seems to reduce the risk of SIDS and possibly reduces the influence of known risk factors in the sleep environment.
Authors: Li DK; Willinger M; Petitti DB; Odouli R; Liu L; Hoffman HJ
BMJ. 2006 Jan 7;332(7532):18-22. Epub 2005 Dec 9.
Low-fat dietary pattern and weight change over 7 years: the Women’s Health Initiative Dietary Modification Trial
CONTEXT: Obesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets. OBJECTIVES: To report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components. DESIGN, SETTING, AND PARTICIPANTS: Randomized intervention trial of 48,835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women’s Health Initiative Dietary Modification Trial; 40% (19,541) were randomized to the intervention and 60% (29,294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004). INTERVENTIONS: The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials. MAIN OUTCOME MEASURE: Change in body weight from baseline to follow-up. RESULTS: Women in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber. CONCLUSION: A low-fat eating pattern does not result in weight gain in postmenopausal women. Clinical Trial Registration ClinicalTrials.gov, NCT00000611.
Authors: Howard BV; Manson JE; Prentice R; et al.
JAMA. 2006 Jan 4;295(1):39-49.
Differences in prevalence of urinary incontinence by race/ethnicity
PURPOSE: We compared the prevalence of urinary incontinence by type among white, black, Hispanic and Asian-American women. MATERIALS AND METHODS: The RRISK is a population based cohort study of 2,109 randomly selected middle-aged and older women. Incontinence and other variables were assessed by self-report questionnaires and in person interviews. Labor and delivery and surgical data were abstracted from medical records archived since 1946. Logistic regression was used to estimate the OR with 95% CIs for incontinence while adjusting for covariates. RESULTS: The age adjusted prevalence of weekly incontinence was highest among Hispanic women, followed by white, black and Asian-American women (36%, 30%, 25% and 19%, respectively, p <0.001). Type of incontinence also differed among groups, with weekly stress incontinence prevalence being 18%, 15%, 8% and 8% (p <0.001), and weekly urge incontinence prevalence being 10%, 9%, 14% and 7% (p <0.001). After adjustment for age, parity, hysterectomy, estrogen use, body mass, menopausal status and diabetes, the risk of stress incontinence remained significantly lower in black (adjusted OR 0.36, 95% CI 0.23-0.57) and Asian-American (adjusted OR 0.54, 95% CI 0.34-0.86) women compared to white women. In contrast, the risk of urge incontinence was similar in black (adjusted OR 1.19, 95% CI 0.79-1.81) and Asian-American (adjusted OR 0.86, 95% CI 0.52-1.43) women compared to white women. CONCLUSIONS: Significant differences in the adjusted risk of stress incontinence among Hispanic, white, black and Asian-American women suggest the presence of additional, as yet unrecognized, risk or protective factors for stress incontinence.
Authors: Thom DH; Van Den Eeden SK; Ragins AI; Wassel-Fyr C; Vittinghof E; Subak LL; Brown JS
J Urol. 2006 Jan;175(1):259-64.
Effect of reproductive factors and postmenopausal hormone use on the risk of amyotrophic lateral sclerosis
OBJECTIVE: To examine the associations of reproductive factors and postmenopausal hormone use with the risk of amyotrophic lateral sclerosis (ALS) among women. METHODS: This case-control study was conducted within the Kaiser Permanente Medical Care Program (KPMCP) of Northern California during the years 1996-2000. Among the 193 postmenopausal women, 62 were incident ALS cases and 131 were controls randomly selected from KPMCP members and frequency matched by age and respondent type (self versus proxy) to the cases. Statistical analyses were carried out using logistic regression. RESULTS: Reproductive factors such as age at menarche, age at final menstrual period, parity, oral contraceptive use, and type of menopause (natural vs. hysterectomy with or without oophorectomy) were not associated with risk of ALS. Postmenopausal hormone use was positively, but not significantly, associated with the risk of ALS (adjusted OR 1.9, 95% CI 0.9-3.8). CONCLUSIONS: Reproductive factors were not associated with ALS risk. There is no evidence that suggests a protective effect of postmenopausal hormone use against the development of ALS. However, due to insufficient power, we cannot rule out a possible increase in ALS risk associated with postmenopausal hormone use.
Authors: Popat RA; Van Den Eeden SK; Tanner CM; Bernstein AL; Bloch DA; Leimpeter A; McGuire V; Nelson LM
Neuroepidemiology. 2006;27(3):117-21. Epub 2006 Aug 1.
Predictors of outcome in perinatal arterial stroke: a population-based study
Some infants with perinatal arterial ischemic stroke (PAS) experience development of cerebral palsy (CP), epilepsy, and cognitive impairment, whereas others have a normal outcome. Previous prognostic studies rarely have included all diagnosed cases of PAS within a population. Among 199,176 infants born within Kaiser Permanente from 1997 to 2002, we electronically identified head imaging reports and physician diagnoses suggesting stroke. The diagnosis of PAS was confirmed by review of brain imaging and medical records. Presentation of PAS was considered delayed if symptoms were only noted after 28 days. Outcomes were determined by chart review. Of 40 infants with PAS, 36 were observed over 12 months. Abnormal outcomes included CP (58%), epilepsy (39%), language delay (25%), and behavioral abnormalities (22%). A delayed presentation was associated with increased risk for CP (relative risk [RR], 2.2; 95% confidence interval [CI], 1.2-4.2). Radiological predictors of CP included large stroke size (RR, 2.0; 95% CI, 1.2-3.2) and injury to Broca’s area (RR, 2.5; 95% CI, 1.3-5.0), internal capsule (RR, 2.2; 95% CI, 1.1-4.4), Wernicke’s area (RR, 2.0; 95% CI, 1.1-3.8), or basal ganglia (RR, 1.9; 95% CI, 1.1-3.3). Among infants with PAS, specific radiological findings and a lack of symptoms in the newborn period are associated with increased risk for CP.
Authors: Lee J; Croen LA; Lindan C; Nash KB; Yoshida CK; Ferriero DM; Barkovich AJ; Wu YW
Ann Neurol. 2005 Aug;58(2):303-8.
Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization
OBJECTIVE: This study was undertaken to compare the use of glyburide with insulin for the treatment of gestational diabetes mellitus (GDM) unresponsive to diet therapy. STUDY DESIGN: A retrospective study was performed among women with singleton pregnancies who had GDM diagnosed, with fasting plasma glucose 140 mg/dL or less on glucose tolerance testing, between 12 and 34 weeks who failed diet therapy from 1999 to 2002. We identified 584 women and compared those treated with insulin between 1999 and 2000 with women treated with glyburide between 2001 and 2002. Maternal and neonatal outcomes and complications were assessed. Statistical methods included univariate analyses and multivariable logistic regression. RESULTS: In 1999 through 2000, 268 women had GDM diagnosed and were treated with insulin; in 2001 through 2002, 316 women had GDM diagnosed of which 236 (75%) received glyburide. The 2 groups were similar with regard to age, nulliparity, and historical GDM risk factors; however, women in the insulin group had a higher mean body mass index (31.9 vs 30.6 kg/m 2 , P=.04), a greater proportion identified themselves as white (43%, 28%, P<.001) and fewer as Asian (24%, 37%, P=.001), and they had a significantly higher mean fasting on glucose tolerance test (105.4 vs 102.4 mg/dL , P=.005) compared with the glyburide group. There were no significant differences in birth weight (3599+/-650 g vs 3661+/-629 g, P=.3), macrosomia (24%, 25%, P=.7), or cesarean delivery (35%, 39 %, P=.4). Women in the glyburide group had a higher incidence of preeclampsia (12%, 6%, P=.02), and neonates in the glyburide group were more likely to receive phototherapy (9%, 5%, P<.05), and less likely to be admitted to the neonatal intensive care unit (NICU) (15%, 24%, P=.008) though they had a longer NICU length of stay (4.3+/-9.6 vs 8.0+/-10.1, P=.002). Posttreatment glycemic control data were available for 122 women treated with insulin and 137 women treated with glyburide. More women in the glyburide group achieved mean fasting and postprandial goals (86%, 63%, P<.001). These findings remained significant in logistic regression analysis. CONCLUSION: In a large managed care organization, glyburide was at least as effective as insulin in achieving glycemic control and similar birth weights in women with GDM who failed diet therapy. The increased risk of preeclampsia and phototherapy in the glyburide group warrant further study.
Authors: Jacobson GF; Ramos GA; Ching JY; Kirby RS; Ferrara A; Field DR
Am J Obstet Gynecol. 2005 Jul;193(1):118-24.
Ectopic pregnancy rate and treatment utilization in a large managed care organization
OBJECTIVE: To estimate the ectopic pregnancy rate at Kaiser Permanente, Northern California, during 1997-2000. METHODS: Computerized data systems covering inpatient, outpatient, and pharmacy records were reviewed for evidence of ectopic pregnancies during the study period. Denominator data were calculated from computerized utilization and membership data for the same period. RESULTS: We identified 2,617 ectopic pregnancies that occurred between 1997 and 2000 among 126,451 reported pregnancies for an annual rate of 20.70 per 1,000 reported pregnancies and 1.03 per 1,000 women 15-44 years old. There was no evidence of a trend over time in these data. The rate increased with increasing age. Approximately 35% of these women were medically treated, and we observed an increase over time in the proportion of women who were medically treated. CONCLUSION: Using computerized data systems in a large integrated health delivery system, we found that the rate of ectopic pregnancy in 1997-2000 was similar to the national rate in 1990-1992, when national data were last available. These data suggest that the ectopic pregnancy rate is not increasing, although differences in the study populations need to be kept in mind. Medical treatment seems to be increasing over time.
Authors: Van Den Eeden SK; Shan J; Bruce C; Glasser M
Obstet Gynecol. 2005 May;105(5 Pt 1):1052-7.
Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002
OBJECTIVE: To examine temporal trends in the rates of severe bronchopulmonary dysplasia (BPD) between 1994 and 2002. STUDY DESIGN: In a retrospective cohort study, all infants with a gestational age (GA) <33 weeks in a large managed care organization were identified. Annual rates of BPD (defined as an oxygen requirement at 36 weeks corrected GA), severe BPD (defined as respiratory support at 36 weeks corrected GA), and death before 36 weeks corrected GA were examined. RESULTS: Of the 5115 infants in the study cohort, 603 (12%) had BPD, including 246 (4.9%) who had severe BPD. There were 481 (9.5%) deaths before 36 weeks corrected GA. Although the decline in BPD in this period was not significant, the rates of severe BPD declined from 9.7% in 1994 to 3.7% in 2002. Controlling for gestational age, the odds ratio (95% CI) for annual rate of decline in severe BPD was 0.890 (0.841-0.941). Controlling for gestational age, deaths before 36 weeks corrected GA also declined, with the odds ratio (CI) for the annual decline being 0.944 (0.896-0.996). CONCLUSIONS: In this study population, the odds of having of BPD remained constant after controlling for GA. However, the odds of having severe BPD declined on average 11% per year between 1994 and 2002.
Authors: Smith VC; Zupancic JA; McCormick MC; Croen LA; Greene J; Escobar GJ; Richardson DK
J Pediatr. 2005 Apr;146(4):469-73.
Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women’s Health Initiative Observational Study
BACKGROUND: Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women. METHODS: In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women’s Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality. RESULTS: At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein. CONCLUSIONS: The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.
Authors: Margolis KL; Manson JE; Greenland P; Rodabough RJ; Bray PF; Safford M; Grimm RH Jr; Howard BV; Assaf AR; Prentice R; Women's Health Initiative Research Group
Arch Intern Med. 2005 Mar 14;165(5):500-8.
Maternal and infant characteristics associated with perinatal arterial stroke in the infant
CONTEXT: Perinatal arterial ischemic stroke (PAS) is a common cause of hemiplegic cerebral palsy. Risk factors for this condition have not been clearly defined. OBJECTIVE: To determine maternal and infant characteristics associated with PAS. DESIGN, SETTING, AND PATIENTS: Case-control study nested within the cohort of all 199,176 infants born from 1997 through 2002 in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were confirmed by review of brain imaging and medical records (n = 40). Three controls per case were randomly selected from the study population. MAIN OUTCOME MEASURE: Association of maternal and infant complications with risk of PAS. RESULTS: The population prevalence of PAS was 20 per 100,000 live births. The majority (85%) of infants with PAS were delivered at term. The following prepartum and intrapartum factors were more common among case than control infants: primiparity (73% vs 44%, P = .002), fetal heart rate abnormality (46% vs 14%, P<.001), emergency cesarean delivery (35% vs 13%, P = .002), chorioamnionitis (27% vs 11%, P = .03), prolonged rupture of membranes (26% vs 7%, P = .002), prolonged second stage of labor (25% vs 4%, P<.001), vacuum extraction (24% vs 11%, P = .04), cord abnormality (22% vs 6%, P = .01), preeclampsia (19% vs 5%, P = .01), and oligohydramnios (14% vs 3%, P = .01). Risk factors independently associated with PAS on multivariate analysis were history of infertility (odds ratio [OR], 7.5; 95% confidence interval [CI], 1.3-45.0), preeclampsia (OR, 5.3; 95% CI, 1.3-22.0), prolonged rupture of membranes (OR, 3.8; 95% CI, 1.1-12.8), and chorioamnionitis (OR, 3.4; 95% CI, 1.1-10.5). The rate of PAS increased dramatically when multiple risk factors were present. CONCLUSIONS: Perinatal arterial ischemic stroke in infants is associated with several independent maternal risk factors. How these complications, along with their potential effects on the placenta and fetus, may play a role in causing perinatal stroke deserves further study.
Authors: Lee J; Croen LA; Backstrand KH; Yoshida CK; Henning LH; Lindan C; Ferriero DM; Fullerton HJ; Barkovich AJ; Wu YW
JAMA. 2005 Feb 9;293(6):723-9.
Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case-control study
OBJECTIVE: To investigate the association between physician-documented diagnoses of maternal autoimmune diseases, allergies, and asthma around the time of pregnancy and subsequent diagnoses of autism in children. DESIGN: A case-control study nested within a cohort of infants born between January 1995 and June 1999. SETTING: Northern California Kaiser Permanente Medical Care Program. PARTICIPANTS: Cases (n = 420) were children with at least 1 diagnosis of an autism spectrum disorder (ASD) recorded in Kaiser Permanente outpatient clinical databases. Controls (n = 2100) were children without an ASD diagnosis who were frequency matched to cases on sex, birth year, and hospital of birth. MAIN OUTCOME MEASURES: Frequencies of maternal immunologic disorders were compared between cases and controls with a chi2 statistic, and relative risks were estimated by crude and adjusted odds ratios and 95% confidence intervals using logistic regression. RESULTS: The final study population included 407 cases and 2095 controls. A similar proportion of case and control mothers had a diagnosis of any autoimmune disease in the 4-year period surrounding pregnancy (10.3% vs 8.2%, P = .15). After adjustment for maternal factors, only 1 autoimmune condition, psoriasis, was significantly associated with ASDs (adjusted odds ratio, 2.7; 95% confidence interval, 1.3-5.8). A greater than 2-fold elevated risk of ASD was observed for maternal asthma and allergy diagnoses recorded during the second trimester of pregnancy. CONCLUSIONS: These findings suggest that maternal autoimmune disorders present in women around the time of pregnancy are unlikely to contribute significantly to autism risk. Further etiologic investigations are needed to confirm these results and should include objective documentation of diagnoses and consider a larger set of maternal immune-related conditions, including asthma and allergies.
Authors: Croen LA; Grether JK; Yoshida CK; Odouli R; Van de Water J
Arch Pediatr Adolesc Med. 2005 Feb;159(2):151-7.
Neonatal hyperbilirubinemia and risk of autism spectrum disorders
OBJECTIVE: To investigate the association between neonatal hyperbilirubinemia and autism spectrum disorders (ASD). METHODS: We conducted a large case-control study nested within the cohort of singleton term infants born between 1995 and 1998 at a northern California Kaiser Permanente hospital. Case subjects (n = 338) were children with an ASD diagnosis recorded in Kaiser Permanente outpatient databases; control subjects (n = 1817) were children without an ASD diagnosis, who were randomly sampled and frequency-matched to case subjects according to gender, birth year, and birth hospital. RESULTS: Approximately 28% of case and control subjects received > or =1 bilirubin test in the first 30 days of life. No case-control differences were observed for maximal bilirubin levels of > or =15 mg/dL (10.1% vs 12.1%), > or =20 mg/dL (2.1% vs 2.5%), or > or =25 mg/dL (0.3% vs 0.2%). Compared with children whose maximal neonatal bilirubin levels were <15 mg/dL or not measured, children with any degree of bilirubin level elevation were not at increased risk of ASD, after adjustment for gender, birth facility, maternal age, maternal race/ethnicity, maternal education, and gestational age (for bilirubin levels of 15-19.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.5-1.2; for bilirubin levels of 20-24.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.3-1.6; for bilirubin levels of > or =25 mg/dL: odds ratio: 1.1; 95% confidence interval: 0.1-11.2). CONCLUSION: These data suggest that neonatal hyperbilirubinemia is not a risk factor for ASD.
Authors: Croen LA; Yoshida CK; Odouli R; Newman TB
Pediatrics. 2005 Feb;115(2):e135-8.
Preconception care in managed care: the translating research into action for diabetes study
OBJECTIVES: This study was undertaken to examine the rates of preconception counseling in managed care for women with diabetes and associated patient and physician characteristics. STUDY DESIGN: Participants included women aged 18 to 45 years enrolled in a study of diabetes care in managed care. Women were asked if they recalled discussions regarding glucose control before conception (n = 236) and use of family planning until glucose control was achieved (n = 227). Hierarchical logistic regression models accounted for patient and physician characteristics. RESULTS: Fifty-two percent of women recalled being counseled about glucose control and 37% recalled family planning advice. In adjusted models, patient age (years) (odds ratio [OR] 0.91, 95% CI 0.86-0.96) and body mass index (BMI) (kg/m2) (OR 0.96, 95% CI 0.93-0.99) remained significant predictors of glucose control counseling. Similarly, patient age (years) (OR 0.94, 95% CI 0.89-0.99) and BMI (kg/m2) (0.96, 95% CI 0.93-0.99) remained significant predictors of family planning counseling. CONCLUSIONS: Preconception counseling rates for diabetic women are low and associated with younger age and lower BMI.
Authors: Kim C; Ferrara A; McEwen LN; Marrero DG; Gerzoff RB; Herman WH; TRIAD Study Group
Am J Obstet Gynecol. 2005 Jan;192(1):227-32.
The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism
BACKGROUND: Thyroid imaging with isotopic iodide (123I) or technetium Tc 99m pertechnetate has been available for decades but is not routinely used in newborn infants diagnosed with congenital hypothyroidism (CH). Among clinicians who believe that presence, absence, or abnormal location of a thyroid does not alter management of CH, imaging is not advocated for anatomic diagnosis of CH. OBJECTIVE: To define the role of thyroid scintigraphy in diagnosing and managing newborn CH. METHODS: Retrospective review of 249 confirmed cases of CH seen at a large, group-model managed care organization during the 24-year period extending from September 1978 through December 2002. Neonatal thyroid scintigraphy was performed in 210 cases (86%): 123I was used in 143 cases (68%), and technetium Tc 99m pertechnetate was used in 67 cases (32%). To perform scintigraphy with 123I, 30 to 50 microCi ([1.11-1.85] x 10(6) Bq) of 123I was administered orally; an uptake image was taken in 3 to 6 hours; and, if necessary, another image was taken in 24 hours. For technetium, 0.5 to 1 mCi ([1.85-3.7] x 10(7) Bq) of technetium Tc 99m pertechnetate was administered intravenously with imaging 20 minutes later. Thyroid dysplasia was defined as an absent or ectopic gland requiring lifetime therapy and eutopic thyroid as a normal-appearing thyroid gland in the proper location but possibly malfunctioning and requiring therapy. RESULTS: Of the 210 infants with CH receiving scintigraphy, 90 (43%) had eutopic (normal-appearing) thyroid diagnosed, and 120 (57%) had ectopic or absent gland (25% ectopic, 32% absent) diagnosed. Of these 210 infants, ethnicity was known in 198; of these, 76 (38%) were Latino/Hispanic, and 122 (62%) of the infants were non-Latino/non-Hispanic. Prevalence of CH differed between ethnic groups in our population of >700,000 newborn infants; total prevalence of CH was 1 per 3139. Prevalence of CH in Latino/Hispanic infants was highest at 1 per 1750 infants (1:1357 females, 1:2463 males). Prevalence of CH in non-Latino/non-Hispanic infants was 1 per 4648 infants (1:3500 females, 1:6914 males). Given that the total Kaiser Permanente infant population was approximately 19% Latino/Hispanic, the percentage of Latino/Hispanic infants with CH was significantly higher than expected. Dysplastic thyroid was more common in Latino/Hispanic females (69%) than in non-Latino/non-Hispanic females (52%). The female-to-male ratio of patients with CH was 1.9:1. Among the 210 infants with CH, normal thyroid was diagnosed more by 123I scintigraphy (49% of cases) than by scintigraphy using technetium Tc 99m pertechnetate (31% of cases). Use of technetium Tc 99m pertechnetate could have diagnosed dysplastic thyroid in some cases that would be considered eutopic had 123I been used. Eight familial cases of CH were identified. COMMENTS: CH, a heterogeneous disorder with prevalence influenced by familial, ethnic, and gender factors, is more common in Latino/Hispanic females. When present, a eutopic thyroid is more likely to be detected by 123I scintigraphy; this method is therefore preferred over scintigraphy using technetium Tc 99m pertechnetate for optimal management of CH. Parents can then be counseled on either the certainty of lifetime therapy (for dysplastic thyroid) or the possibility of later discontinuing therapy (for eutopic thyroid, because CH may be transient in these children). If the dysplastic thyroid gland is absent or ectopic (usually a small sublingual gland), parents can be told that the infant will need lifetime thyroid therapy. If the thyroid gland is present in the normal position (eutopic) and the condition is transient (as shown by controlled withdrawal of thyroid in older children), lifelong treatment may not be needed. Parents rightly expect this maximal clinical and laboratory information in the immediate newborn period. Some clinicians hesitate to recommend neonatal scintigraphy for children with CH because of concern about delaying L-thyroxine therapy, concern about radiation exposure, or both. We believe that neither concern is warranted. 123I thyroid imaging has been used for many decades without evidence of risk for thyroid cancer. Treatment need not be delayed until scintigraphy is done. We did not use ultrasonography for thyroid imaging because this technique was not available in the early years of our study and may still not have sufficient sensitivity. Sources of discrepancy in our study could include scintigraphy interpreter bias due to lack of objective standards. We cannot estimate the true prevalence of transient CH because not all physicians give children with CH a trial off therapy at 2 to 3 years old, even if a eutopic thyroid is shown by 123I scintigraphy. Because therapy with L-thyroxine is simple and inexpensive and the outcome of untreated CH can be devastating, some parents and physicians are reluctant to discontinue treatment in children with CH, even when scans show a eutopic thyroid. Additionally, the clinical information contained in our database was not detailed enough to enable us to discover all cases of CH in which thyroxine therapy was discontinued. Because the study began in 1978 (>25 years ago), some patients were unavailable for long-term follow-up. In addition to allowing a more rational clinical approach to CH, 123I thyroid scintigraphy may help define underlying genetic factors and mechanisms of thyroid development and differentiation. This study’s findings, that prevalence of CH and of thyroid dysplasia differed between genders and among racial/ethnic groups, seem to support a genetic basis for CH. Our results confirm previously published reports from the State of California Department of Health Services, Genetic Disease Branch and other studies describing multiple genetic abnormalities associated with CH. CONCLUSIONS: Despite data limitations, we believe that neonatal diagnosis of CH represents perhaps the greatest success of newborn screening programs. Initial laboratory diagnosis is simple and sufficiently accurate; treatment is simple, inexpensive, and effective. Severe mental retardation and growth failure can be prevented. Considering today’s rapid advances in understanding the basic mechanisms of thyroid embryogenesis and gene abnormalities, thyroid scintigraphy may provide insight into clinical and genetic correlates in CH.
Authors: Schoen EJ; Clapp W; To TT; Fireman BH
Pediatrics. 2004 Dec;114(6):e683-8.
On the importance of using multiple methods of dietary assessment
BACKGROUND: Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial. METHODS: Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method. RESULTS: In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error. CONCLUSION: These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.
Authors: Natarajan L; Caan BJ; Pierce JP; et al.
Epidemiology. 2004 Nov;15(6):738-45.
Transmission of parentally shared human leukocyte antigen alleles and the risk of preterm delivery
OBJECTIVE: Our objective was to examine our hypothesis that the transmission of parentally shared human leukocyte antigen (HLA) alleles to offspring increases the risk of preterm delivery. METHODS: A population-based family study with participating children and their parents was conducted in Kaiser Permanente Medical Care Program, an integrated healthcare delivery system, in the Northern California Region. A total of 234 participants from 78 families with early preterm deliveries (35 weeks of gestation or greater) and 60 participants from 20 families with full-term births were included in the study. Buccal cells were collected from the first-born preterm cases and their parents to determine HLA-B (class I) and DRB1 (class II) types and the transmission of parental alleles to the offspring. The buccal samples were also collected from full-term deliveries to rule out possible segregation distortion at the studied HLA loci. RESULTS: Compared with the expected transmission probability based on Mendel’s laws (25%), transmission of parentally shared HLA-B or DRB1 alleles from both heterozygous parents to offspring (48% of 23 heterozygous parents) was associated with a more than 5-fold increased risk of preterm delivery (odds ratio 5.5; 95% confidence interval 1.2-51). Transmission of parentally shared HLA alleles from heterozygous mothers (83%) appears to be more important in the etiology of preterm delivery than transmission from fathers (57%). The transmission pattern of parentally shared HLA alleles in our full-term controls was almost identical to the expected pattern based on Mendel’s laws and demonstrated no segregation distortion at those HLA loci. CONCLUSION: Our findings provide evidence that the transmission of parentally shared HLA alleles may be an underlying mechanism for preterm delivery.
Authors: Li DK; Odouli R; Liu L; Vinson M; Trachtenberg E
Obstet Gynecol. 2004 Sep;104(3):594-600.
Perinatal stroke in children with motor impairment: a population-based study
OBJECTIVE: Risk factors for perinatal arterial stroke (PAS) are poorly understood. Most previous studies lack an appropriate control group and include only infants with symptoms in the newborn period. We set out to determine prenatal and perinatal risk factors for PAS. METHODS: In a population-based, case-control study nested within the cohort of 231 582 singleton infants who were born at >or=36 weeks’ gestation in Northern California Kaiser hospitals from 1991 to 1998, we searched electronically for children with motor impairment and reviewed their medical records to identify diagnoses of PAS. Control subjects were randomly selected from the study population. A medical record abstractor reviewed delivery records without knowledge of case status. RESULTS: The prevalence of PAS with motor impairment was 17/100,000 live births. Of 38 cases, 26 (68%) presented after 3 months of age with hemiparesis or seizures. All 12 newborns with acute stroke symptoms had seizures. A delayed presentation was more common in children with moderate to severe motor impairment than among infants with only mild motor abnormalities (24 of 31 vs 2 of 7). Prepartum risk factors significantly associated with PAS in multivariate analysis were preeclampsia (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1-11.4) and intrauterine growth restriction (OR: 5.3; 95% CI: 1.5-18.6). Newborns with PAS were also at higher risk of delivery complications, such as emergency cesarean section (OR: 6.8; 95% CI: 2.7-16.6), 5-minute Apgar <7 (OR: 23.6; 95% CI: 4.1-237), and resuscitation at birth (OR: 4.5; 95% CI: 1.6-12.3). CONCLUSIONS: Preeclampsia and intrauterine growth restriction (IUGR) may be independent risk factors for perinatal stroke resulting in motor impairment. Large multicenter studies that include all children with perinatal stroke are needed to determine further the risk factors and outcome of perinatal stroke.
Authors: Wu YW; March WM; Croen LA; Grether JK; Escobar GJ; Newman TB
Pediatrics. 2004 Sep;114(3):612-9.
Cultural competence policies and other predictors of asthma care quality for Medicaid-insured children
OBJECTIVE: More than half of Medicaid enrollees are now in managed care. Scant information exists about which policies of practice sites improve quality of care in managed Medicaid. Children with asthma are a sentinel group for Medicaid quality monitoring because they are at elevated risk for adverse outcomes. The objective of this study was to identify practice-site policies and features associated with quality of care for Medicaid-insured children with asthma. METHODS: A prospective cohort study with 1-year follow-up was conducted in 5 health plans in California, Washington, and Massachusetts. Data were collected via telephone interviews with parents at baseline and 1 year, surveys of practice sites and clinicians, and computerized databases. The practice site survey asked about policies to promote cultural competence, the use of several types of reports to clinicians, support for self-management of asthma, case management and care coordination, and access to and continuity of care. Quality of care was evaluated on the basis of 5 measures: 1) preventive medication underuse based on parent report; 2) the parent’s rating of asthma care; 3) the 1-year change in the child’s asthma physical status based on a standardized measure; 4) preventive medication underprescribing based on computerized data; and 5) the occurrence of a hospital-based episode. RESULTS: Of the 1663 children in the study population, 67% had persistent asthma at baseline based on parent report of symptoms and medications. At 1-year follow-up, 65% of the children with persistent asthma were underusing preventive medication based on parent report. In multivariate analyses, patients of practice sites with the highest cultural competence scores were less likely to be underusing preventive asthma medications based on parent report at follow-up (odds ratio [OR]: 0.15; 95% confidence interval [CI]: 0.06-0.41 for the highest vs lowest categories) and had better parent ratings of care. The use of asthma reports to clinicians was predictive of less preventive medication underprescribing based on computerized data (OR: 0.33; 95% CI: 0.16-0.69), better parent ratings of care, and better asthma physical status at follow-up. Patients of practice sites with policies to promote access and continuity had less underuse of preventive medications (OR: 0.56; 95% CI: 0.34-0.93). Among the 83 practice sites, the practice site’s size, organizational type, percentage of patients insured by Medicaid, mechanism of payment for specialty care, and other primary care features were not consistently associated with quality measures. CONCLUSIONS: Practice-site policies to promote cultural competence, the use of reports to clinicians, and access and continuity predicted higher quality of care for children with asthma in managed Medicaid.
Authors: Lieu TA; Finkelstein JA; Lozano P; Capra AM; Chi FW; Jensvold N; Quesenberry CP; Farber HJ
Pediatrics. 2004 Jul;114(1):e102-10.
Rehospitalization in the first year of life among infants with bronchopulmonary dysplasia
OBJECTIVE: To describe rates and identify risk factors for rehospitalization during the first year of life among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a retrospective cohort study of infants born at a gestational age (GA) <33 weeks, between 1995 and 1999. BPD was defined as requirement of supplemental oxygen and/or mechanical ventilation at 36 weeks' corrected GA. The outcome was rehospitalization for any reason before first birthday. RESULTS: In the first year of life, 118 of 238 (49%) infants with BPD were rehospitalized, more than twice the rate of rehospitalization of the non-BPD population, which was 309 of 1359 (23%) (P=<.0001). No measured factor discriminated between those infants with BPD who were and were not rehospitalized, even when only rehospitalizations for respiratory diagnoses were considered. CONCLUSIONS: Among premature infants, BPD substantially increases the risk of rehospitalization during the first year of life. Neither demographic nor physiologic factors predicted rehospitalization among the infants with BPD. Other factors, such as air quality of home environment, passive smoking exposure, respiratory syncytial virus prophylaxis, breast-feeding status, and/or parenting and primary care management styles, should be examined in future studies.
Authors: Smith VC; Zupancic JA; McCormick MC; Croen LA; Greene J; Escobar GJ; Richardson DK
J Pediatr. 2004 Jun;144(6):799-803.
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial
CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women’s Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
Authors: Anderson GL; Caan B; Women's Health Initiative Steering Committee; et al.
JAMA. 2004 Apr 14;291(14):1701-12.
Use of asthma medication dispensing patterns to predict risk of adverse health outcomes: a study of Medicaid-insured children in managed care programs
BACKGROUND: Regular use of inhaled anti-inflammatory (AI) medication improves outcomes for children with persistent asthma. OBJECTIVE: To relate 3 measures of asthma medication dispensing to physical health and hospital-based events among children with asthma who were enrolled in 1 of 5 managed care health plans. METHODS: Parents of Medicaid-insured children with asthma were interviewed at baseline and 1-year follow-up. Utilization data were collected from the health plans in which the children were enrolled. Subjects were stratified into 3 subgroups according to asthma severity: intermittent asthma; persistent asthma for which beta-agonist (BA) medication was dispensed infrequently (< or = 3 times per year); and persistent asthma for which BA medication was dispensed frequently (> or = 4 times per year). RESULTS: Baseline interviews were completed by 1,663 parents (63% response rate), 1,504 of whom were enrolled in their health plan for at least 11 months during the baseline year. Follow-up interviews were completed by 1,287 (86%) of the 1,504 parents. Among the subgroup of children with persistent asthma for whom BA was dispensed frequently, those who had 1 to 3 AI dispensings had a greater risk for hospital-based events than those with 6 or more AI dispensings. Baseline-year AI medication utilization patterns were not associated with follow-up-year outcomes. No clinically meaningful association was found in subgroups with less severe asthma; however, few AI medications were dispensed to these children. CONCLUSIONS: Policymakers and clinicians who wish to use medication-based measures to evaluate quality of asthma care should consider counting the number of times AI medication is dispensed among children with more severe asthma.
Authors: Farber HJ; Chi FW; Capra A; Jensvold NG; Finkelstein JA; Lozano P; Quesenberry CP Jr; Lieu TA
Ann Allergy Asthma Immunol. 2004 Mar;92(3):319-28.
An increase in the incidence of gestational diabetes mellitus: Northern California, 1991-2000
OBJECTIVE: Women with gestational diabetes mellitus (GDM) and their offspring are at increased risk of developing diabetes. Although increases in diabetes prevalence have been reported in the United States, it is unknown whether this trend is also occurring for GDM. We examined trends in the yearly cumulative incidence of GDM between the years 1991 and 2000. METHODS: A cohort study of 267,051 pregnancies screened for GDM that occurred among members of the Northern California Kaiser Permanente Medical Care Program, representing 86.8% of all eligible pregnancies, was undertaken. RESULTS: GDM was identified in 14,175 pregnancies according to the diagnostic plasma glucose thresholds of the American Diabetes Association (96.5%) or the World Health Organization (3.5%). An additional 2,743 pregnant women with GDM were identified by a hospital discharge diagnosis. The women screened in 2000 were slightly older (mean [standard deviation] age 28.8 [6.0] years) than were those screened in 1991 (28.2 [5.7] years) and more likely to be from minority ethnic groups (51.4% versus 37.3% identified as African American, Asian, Hispanic, and other). The age- and ethnicity-adjusted yearly cumulative incidence of GDM increased steadily from 5.1% in 1991 to 7.4% in 1997 and leveled off through 2000 (6.9%). DISCUSSION: The observed increase in yearly cumulative incidence of GDM was independent of changes in age and ethnicity of the study population. A true increase in GDM incidence might reflect or contribute to the increases in the prevalence of diabetes and obesity. Coordinated efforts are needed to alter this trend and to prevent chronic diabetes in GDM patients and their offspring. LEVEL OF EVIDENCE: II-2.
Authors: Ferrara A; Kahn HS; Quesenberry CP; Riley C; Hedderson MM
Obstet Gynecol. 2004 Mar;103(3):526-33.
Identifying environmental contributions to autism: provocative clues and false leads
The potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose-effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder.
Authors: Lawler CP; Croen LA; Grether JK; van de Water J
Ment Retard Dev Disabil Res Rev. 2004;10(4):292-302.
Chorioamnionitis and cerebral palsy in term and near-term infants
CONTEXT: Half of all cases of cerebral palsy (CP) occur in term infants, for whom risk factors have not been clearly defined. Recent studies suggest a possible role of chorioamnionitis. OBJECTIVE: To determine whether clinical chorioamnionitis increases the risk of CP in term and near-term infants. DESIGN, SETTING, AND PATIENTS: Case-control study nested within a cohort of 231 582 singleton infants born at 36 or more weeks’ gestation between January 1, 1991, and December 31, 1998, in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were identified from electronic records and confirmed by chart review by a child neurologist, and comprised all children with moderate to severe spastic or dyskinetic CP not due to postnatal brain injury or developmental abnormalities (n = 109). Controls (n = 218) were randomly selected from the study population. MAIN OUTCOME MEASURE: Association between clinical chorioamnionitis and increased risk of CP in term and near-term infants. RESULTS: Most CP cases had hemiparesis (40%) or quadriparesis (38%); 87% had been diagnosed by a neurologist and 83% had undergone neuroimaging. Chorioamnionitis, considered present if a treating physician made a diagnosis of chorioamnionitis or endometritis clinically, was noted in 14% of cases and 4% of controls (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.5-10.1; P =.001). Independent risk factors identified in multiple logistic regression included chorioamnionitis (OR, 4.1; 95% CI, 1.6-10.1), intrauterine growth restriction (OR, 4.0; 95% CI, 1.3-12.0), maternal black ethnicity (OR, 3.6; 95% CI, 1.4-9.3), maternal age older than 25 years (OR, 2.6; 95% CI, 1.3-5.2), and nulliparity (OR, 1.8; 95% CI, 1.0-3.0). The population-attributable fraction of chorioamnionitis for CP is 11%. CONCLUSION: Our data suggest that chorioamnionitis is an independent risk factor for CP among term and near-term infants.
Authors: Wu YW; Escobar GJ; Grether JK; Croen LA; Greene JD; Newman TB
JAMA. 2003 Nov 26;290(20):2677-84.
Hot tub use during pregnancy and the risk of miscarriage
To examine whether hot tub or whirlpool bath use during pregnancy increases the risk of miscarriage, the authors conducted a 1996-1998 population-based prospective cohort study at the Kaiser Permanente Medical Care Program in Oakland, California. Of 2729 eligible women, 1063 completed the interview. Miscarriage before 20 weeks of gestation was ascertained for all participants. Information on hot tub or whirlpool bath use was obtained during an in-person interview conducted early in the pregnancy. A Cox proportional hazards model was used to estimate the hazard ratio after adjustment for potential confounders. Compared with nonuse, use of a hot tub or whirlpool bath after conception was associated with a twofold increased risk of miscarriage (adjusted hazard ratio (aHR) = 2.0, 95% confidence interval: 1.3, 3.1). The risk seemed to increase with increasing frequency of use (aHR = 1.7 for less than once a week, aHR = 2.0 for once a week, and aHR = 2.7 for more than once a week) and with use during early gestation (aHR = 2.3 for initial use within the first 4 weeks of the last menstrual period and aHR = 1.5 for initial use after 4 weeks of the last menstrual period). Findings suggest an association between use of a hot tub or whirlpool bath during early pregnancy and the risk of miscarriage.
Authors: Li DK; Janevic T; Odouli R; Liu L
Am J Epidemiol. 2003 Nov 15;158(10):931-7.
Habitual tea consumption and risk of osteoporosis: a prospective study in the women’s health initiative observational cohort
The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women’s Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women’s Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.
Authors: Chen Z; Pettinger MB; Ritenbaugh C; LaCroix AZ; Robbins J; Caan BJ; Barad DH; Hakim IA
Am J Epidemiol. 2003 Oct 15;158(8):772-81.
The Women’s Health Initiative Dietary Modification trial: overview and baseline characteristics of participants
Authors: Ritenbaugh C; Patterson RE; Chlebowski RT; Caan B; Fels-Tinker L; Howard B; Ockene J
Ann Epidemiol. 2003 Oct;13(9 Suppl):S87-97.
Gestational diabetes mellitus and lesser degrees of pregnancy hyperglycemia: association with increased risk of spontaneous preterm birth
OBJECTIVE: To investigate whether different degrees of maternal glucose intolerance are associated with the risk of spontaneous preterm birth. METHODS: We performed a cohort study of 46,230 pregnancies screened by a 50-g, 1-hour oral glucose tolerance test between 24 and 28 gestation weeks at the Northern California Kaiser Permanente Medical Care Program. Spontaneous preterm birth was defined as an infant born at less than 37 gestation weeks with at least one of the following: spontaneous labor, preterm premature rupture of membranes, or incompetent cervix. Glucose tolerance status was categorized as normal screening (1-hour plasma glucose less than 140 mg/dL), abnormal screening (1-hour plasma glucose of at least 140 mg/dL with a normal diagnostic 100-g, 3-hour oral glucose tolerance test result), Carpenter-Coustan (plasma glucose measurements during the diagnostic oral glucose tolerance test met the thresholds but were lower than the National Diabetes Data Group thresholds), and gestational diabetes mellitus (GDM) by the National Diabetes Data Group criteria. RESULTS: One thousand nine hundred fifty-six spontaneous preterm births occurred. Age-adjusted incidences of spontaneous preterm birth were 4.0% in normal screening, 5.0% in abnormal screening, 6.7% in Carpenter-Coustan, and 6.7% in GDM. In a logistic regression model adjusted for age, race-ethnicity, preeclampsia-eclampsia-pregnancy-induced hypertension, chronic hypertension, polyhydramnios, and birth weight for gestational age, pregnancies with abnormal screening, Carpenter-Coustan, and GDM had a significantly higher risk of spontaneous preterm birth than pregnancies with normal screening (relative risk [95% confidence interval]: 1.23 [1.08, 1.41], 1.53 [1.16, 2.03], and 1.42 [1.15-1.77], respectively). CONCLUSION: The risk of spontaneous preterm birth increased with increasing levels of pregnancy glycemia. This association was independent of perinatal complications that could have triggered early delivery.
Authors: Hedderson MM; Ferrara A; Sacks DA
Obstet Gynecol. 2003 Oct;102(4):850-6.
Allergy and risk of breast cancer among young women (United States)
OBJECTIVE: To investigate the relationship between allergy and risk of breast cancer in women 45 years of age and younger. METHODS: Data were analyzed from a population-based case-control study of breast cancer in western Washington. Cases were women born after 1944 who were diagnosed with invasive breast cancer (n = 747) between January 1983 and April 1990. Controls (n = 958) were similarly aged women ascertained through random-digit dialing. Cases and controls were interviewed about their history of doctor diagnosed allergies, including detailed information on the specific types of allergies and the age of onset. Using logistic regression we examined the associations between allergy history and breast cancer. RESULTS: A history of allergies was associated with a reduced risk of breast cancer for women older than 35 (odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.60-0.99), but not for women 35 years or younger (OR = 1.30; 95% CI = 0.94-1.81). There was little difference in effect when age of first allergy onset was examined. No specific type of allergy was associated with breast cancer risk. CONCLUSION: Our results provide some evidence that a history of allergy may be associated with a reduced risk of breast cancer for women who develop breast cancer between 35 and 45 years of age. Future studies are needed to verify the relationship between immune responses and breast cancer risk.
Authors: Hedderson MM; Malone KE; Daling JR; White E
Cancer Causes Control. 2003 Sep;14(7):619-26.
Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study
OBJECTIVE: To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage. DESIGN: Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview. SETTING: Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States. PARTICIPANTS: 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days. MAIN OUTCOME MEASURES: Pregnancy outcomes up to 20 weeks of gestation. RESULTS: 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use. CONCLUSION: Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.
Authors: Li DK; Liu L; Odouli R
BMJ. 2003 Aug 16;327(7411):368.
DDT and DDE exposure in mothers and time to pregnancy in daughters
Reproductive-tract anomalies after administration of the potent oestrogen, diethylstilboestrol, in pregnant women raised concerns about the reproductive effects of exposure to weakly oestrogenic environmental contaminants such as bis[4-chlorophenyl]-1,1,1-trichloroethane (p,p’-DDT) or its metabolites, such as bis[4-chlorophenyl]-1,1-dichloroethene (p,p’-DDE). We measured p,p’-DDT and p,p’-DDE in preserved maternal serum samples drawn 1-3 days after delivery between 1960 and 1963. We recorded time to pregnancy in 289 eldest daughters 28-31 years later. Daughters’ probability of pregnancy fell by 32% per 10 microg/L p,p’-DDT in maternal serum (95% CI 11-48). By contrast, the probability of pregnancy increased 16% per 10 microg/L p,p’-DDE (6-27). The decreased fecundability associated with prenatal p,p’-DDT remains unexplained. We speculate that the antiandrogenic activity of p,p’-DDE may mitigate harmful androgen effects on the ovary during gestation or early life.
Authors: Cohn BA; Cirillo PM; Wolff MS; Schwingl PJ; Cohen RD; Sholtz RI; Ferrara A; Christianson RE; van den Berg BJ; Siiteri PK
Lancet. 2003 Jun 28;361(9376):2205-6.
Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial
OBJECTIVE: To assess whether, in children, oral magnesium oxide reduces migrainous headache frequency, severity, and associated features compared to placebo. BACKGROUND: There is no single, safe, widely well-tolerated, and effective prophylactic treatment for all children and adolescents with frequent migrainous headache. DESIGN: Randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: This study was conducted between June 1997 and January 2000 using 7 selected Northern California Kaiser Permanente sites. We recruited children of ages 3 to 17 years who reported a 4-week history of at least weekly, moderate-to-severe headache with a throbbing or pulsatile quality, associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with sleep, but no fever or evidence of infection. Subjects were randomly assigned to receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of headache days (days with at least one headache) during each of eight 2-week intervals was chosen to be the primary outcome variable. RESULTS: Of those enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44 placebo); 74 of 192 eligible subjects declined to participate. Baseline information on demographic factors, health status, and headache history was similar comparing the 2 groups. By intention-to-treat analysis, we found a statistically significant decrease over time in headache frequency in the magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although the slopes of these 2 lines were not statistically significantly different from each other (P =.88). The group treated with magnesium oxide had significantly lower headache severity (P =.0029) relative to the placebo group. CONCLUSIONS: This study does not unequivocally determine whether oral magnesium oxide is or is not superior to placebo in preventing frequent migrainous headache in children, but treatment with the active agent did lead to a significant reduction in headache days. Larger trials involving this safe, appealing complementary therapy are needed.
Authors: Wang F; Van Den Eeden SK; Ackerson LM; Salk SE; Reince RH; Elin RJ
Headache. 2003 Jun;43(6):601-10.
Changes in food sources of dietary fat in response to an intensive low-fat dietary intervention: early results from the Women’s Health Initiative
OBJECTIVE: To evaluate changes in food sources of dietary fat made by participants in the Women’s Health Initiative Low-Fat Dietary Modification Trial. DESIGN: This study compares sources of dietary fat intake, estimated by a food frequency questionnaire, between intervention and control participants at baseline, 1 year (year 1) and 2 years (year 2) after randomization. The outcome measure was intake of fat in grams per day. Results are given on consumption of fat from six food groups and the intervention effect, defined as mean change in the intervention group minus the change in controls, controlling for baseline fat intake. PARTICIPANTS: 5,004 intervention and 7,426 control postmenopausal women in 40 clinical centers across the United States. RESULTS: At baseline, the major sources of fat were added fats, such as butter, oils, and salad dressings (25%); meats (21%); and desserts (13%). From baseline to year 1, the intervention group reduced fat by 24.3 g/day compared with the control group. Reductions came primarily from added fats (9.1 g/day), meats (4.6 g/day), and desserts (3.9 g/day). White people reduced added fats more than other race/ethnicity groups did, white and Hispanic people were more likely to reduce fat intake from milk and cheese compared with other groups, and Hispanics reduced fat from mixed dishes more than did other race/ethnicity groups (P<.05 for all). APPLICATIONS/CONCLUSIONS: These data indicate that women in the Women's Health Initiative dietary change intervention made substantial changes in food choices. These results can facilitate future low-fat interventions, and also offer clinical applications, by identifying foods that may be refractory to change.
Authors: Patterson RE; Kristal A; Rodabough R; Caan B; Lillington L; Mossavar-Rahmani Y; Simon MS; Snetselaar L; Van Horn L
J Am Diet Assoc. 2003 Apr;103(4):454-60.
Infant sleeping position and the risk of sudden infant death syndrome in California, 1997-2000
To assess the association between infant sleeping position and risk of sudden infant death syndrome (SIDS) in an ethnically diverse US population, the authors conducted a population-based case-control study in 11 counties in California from May 1997 through April 2000. The authors conducted in-person interviews with the mothers of 185 SIDS cases and 312 randomly selected race/ethnicity- and age-matched controls to collect information on sleeping positions. Infants who had last been put down to sleep in the prone or side position were at greater risk of SIDS than were infants who had last been put down on their backs (adjusted odds ratio (AOR) = 2.6 (95% confidence interval (CI): 1.5, 4.5) and AOR = 2.0 (95% CI: 1.2, 3.4) for the prone and side positions, respectively). The risk of SIDS was especially high for an unstable side position in which an infant was placed on its side and found prone (AOR = 8.7, 95% CI: 3.3, 22.7). Infants who were usually placed on their backs to sleep but had last been put down in the prone or side position (an unaccustomed position) had a significantly high risk of SIDS (AOR = 8.2 (95% CI: 2.6, 26.0) and AOR = 6.9 (95% CI: 2.3, 20.6) for the prone and side positions, respectively). Infants placed in an unaccustomed prone or side sleeping position had a higher risk of SIDS than infants who were always placed prone or on the side.
Authors: Li DK; Petitti DB; Willinger M; McMahon R; Odouli R; Vu H; Hoffman HJ
Am J Epidemiol. 2003 Mar 1;157(5):446-55.
Changes in diet, physical activity, and supplement use among adults diagnosed with cancer
OBJECTIVE: To investigate the prevalence and predictors of changes in diet, physical activity, and dietary supplement use among cancer patients. Design/subjects Telephone interviews of a population-based sample of 126 breast, 114 prostate, and 116 colorectal cancer patients from the state of Washington. ANALYSIS: Logistic regression was used to estimate the odds ratio as a measure of the association of participant characteristics with lifestyle changes in the 12 months before the interview. RESULTS: Overall, 66.3% of patients reported making lifestyle changes: 40.4% made one or more dietary changes, 20.8% added new physical activity, and 48.0% started taking new dietary supplements. Compared with men, women were 2.2 times more likely to take new dietary supplements (P <.01). Compared with patients aged 35 to 59, those aged 60 to 69 and 70 or older were statistically significantly less likely to make dietary changes (odds ratio = 0.39 and 0.54, respectively) or to take new supplements (odds ratio = 0.42 and 0.69, respectively). Compared with patients who received only one medical treatment, those receiving three or more treatments were more likely to make dietary changes (odds ratio = 2.6) or to start new physical activity (odds ratio = 3.0). Patients diagnosed 12 to 24 months before the interview were as likely to report making lifestyle changes as those diagnosed within one year of the interview. Having a stronger desire for personal control or internal locus of control predicted use of new dietary supplements (P for trend <.05 for both). Applications/conclusions Cancer survivors are likely to be making lifestyle changes and represent a group that could benefit from counseling on diet and physical activity.
Authors: Patterson RE; Neuhouser ML; Hedderson MM; Schwartz SM; Standish LJ; Bowen DJ
J Am Diet Assoc. 2003 Mar;103(3):323-8.
Misunderstanding of asthma controller medications: association with nonadherence
OBJECTIVE: Nonadherence to regular inhaled anti-inflammatory medication use is a frequent contributor to poor control of persistent asthma and may result from misunderstanding of the preventive role of such medications. This study’s aims are to 1) test the hypothesis that misunderstanding is associated with decreased adherence to its daily use and 2) identify factors associated with increased risk of misunderstanding. STUDY DESIGN: A sample of parents of children with asthma insured by Medicaid and enrolled in managed care programs in Northern California, Washington, and Massachusetts were interviewed by telephone. This analysis focused on the subset that reported having an inhaled anti-inflammatory medication and whose medication use and symptom frequency in the 2 weeks before the interview suggested persistent asthma. Misunderstanding of the role of inhaled anti-inflammatory medication was defined as identifying it as being for treatment of symptoms after they begin and not for prevention of symptoms before they start. RESULTS: A total of 1663 parents of children with asthma (63% response rate) were interviewed. Of those, 571 subjects (34%) reported use of an inhaled anti-inflammatory medication and met our criteria for persistent asthma. Among those with persistent asthma, 23% (131 parents) misunderstood the role of their child’s inhaled anti-inflammatory. Misunderstanding of inhaled anti-inflammatory medication was associated with decreased adherence to its daily use (odds ratio [OR] 0.18, 95% confidence interval [CI], 0.11-0.29). The risk for misunderstanding was lower if the patient had seen a specialist (OR 0.42, 95% CI, 0.24-0.75) or had graduated high school (OR=0.54, 95% CI, 0.34-0.84). CONCLUSION: Misunderstanding of the role of inhaled anti-inflammatory medication is associated with reduced adherence to its daily use.
Authors: Farber HJ; Capra AM; Finkelstein JA; Lozano P; Quesenberry CP; Jensvold NG; Chi FW; Lieu TA
J Asthma. 2003 Feb;40(1):17-25.
Current use of unopposed estrogen and estrogen plus progestin and the risk of acute myocardial infarction among women with diabetes: the Northern California Kaiser Permanente Diabetes Registry, 1995-1998
BACKGROUND: Little is known about hormone replacement therapy (HRT) and risk for myocardial infarction (MI) in diabetic women. We examined associations of current HRT, estrogen dosage, and time since HRT initiation with risk of acute MI in diabetic women. METHODS AND RESULTS: Cox proportional hazards models, with current HRT modeled as a time-dependent covariate, were used to assess the 3-year risk of MI. Among 24 420 women without a recent MI (mean age 64.9 years), 1110 incident MIs were identified. After adjustment for cardiovascular risk factors, current HRT was associated with reduced MI risk (relative hazard [RH] 0.84, 95% CI 0.72 to 0.98). The RH for MI associated with current estrogen plus progestin use was 0.77 (95% CI 0.61 to 0.97), and the RH for MI associated with current unopposed estrogen use was 0.88 (95% CI 0.73 to 1.05). Women were at reduced MI risk if they were taking a low or medium dose of estrogen (equivalent to <0.625 or 0.625 mg of conjugated estrogen, respectively) but not a high dose (>0.625 mg of conjugated estrogen or its equivalent). Among those whose current use of HRT was <1 year, the RH for MI was 1.03 (95% CI 0.74 to 1.44), whereas among users for > or =1 year, the RH was 0.81 (95% CI 0.66 to 1.00). Among 580 women with a recent MI (mean age 69.2 years), 89 recurrent MIs were identified. An increased risk of recurrent MI was observed among current HRT users (RH 1.78, 95% CI 1.06 to 2.98), which was higher among those with current use for <1 year (RH 3.84, 95% CI 1.60 to 9.20). CONCLUSIONS: In women without a recent MI, use of estrogen plus progestin was associated with decreased risk of MI. However, HRT was associated with increased risk of MI in women with history of a recent MI. Data from clinical trials in diabetic women are needed.
Authors: Ferrara A; Quesenberry CP; Karter AJ; Njoroge CW; Jacobson AS; Selby JV; Northern California Kaiser Permanente Diabetes Registry
Circulation. 2003 Jan 7;107(1):43-8.
Thyroid hormone use and the risk of hip fracture in women > or = 65 years: a case-control study
BACKGROUND: There is controversy about whether thyroid hormone therapy may lead to osteoporosis, and less is known about the clinically more important end point of whether its use increases fracture risk. METHODS: We used a case-control study to examine the association between thyroid hormone use and hip fractures among older women in a large managed care organization in Northern California. The subjects were 501 women > or =65 years of age who were hospitalized for hip fractures and 533 age-matched controls without hip fractures. RESULTS: No difference in the ever use or duration of use of exogenous thyroid hormone was found between cases and controls (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.8,1.6). Hip fracture was associated with evidence of visual impairment, prior use of steroids, and number of falls. CONCLUSIONS: In women > or =65 years, an independent effect of thyroid hormone use on the risk of hip fracture was not found. This finding is reassuring, given the large number of women on thyroid hormone therapy today.
Authors: Van Den Eeden SK; Barzilay JI; Ettinger B; Minkoff J
J Womens Health (Larchmt). 2003 Jan-Feb;12(1):27-31.
On the twin risk in autism
Autism is considered by many to be the most strongly genetically influenced multifactorial childhood psychiatric disorder. In the absence of any known gene or genes, the main support for this is derived from family and twin studies. Two recent studies (Greenberg et al. 2001; Betancur et al. 2002) suggested that the twinning process itself is an important risk factor in the development of autism. If true, this would have major consequences for the interpretation of twin studies. Both studies compared the number of affected twin pairs among affected sib pairs to expected values in two separate samples of multiplex families and reported a substantial and significant excess of twin pairs. Using data from our epidemiological study in Western Australia, we investigated the possibility of an increased rate of autism in twins. All children born between 1980 and 1995 with autism, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) were ascertained. Of the 465 children with a diagnosis, 14 were twin births (rate 30.0/1,000) compared to 9,640 children of multiple births out of a total of 386,637 births in Western Australia between 1980 and 1995 (twin rate weighted to number of children with autism or PDD per year 26.3/1,000). These data clearly do not support twinning as a substantial risk factor in the etiology of autism. We demonstrate that the high proportion of twins found in affected-sib-pair studies can be adequately explained by the high ratio of concordance rates in monozygotic (MZ) twins versus siblings and the distribution of family size in the population studied. Our results are in agreement with those of two similar studies by Croen et al. (2002) in California and Hultman et al. (2002) in Sweden.
Authors: Hallmayer J; Glasson EJ; Bower C; Petterson B; Croen L; Grether J; Risch N
Am J Hum Genet. 2002 Oct;71(4):941-6. Epub 2002 Sep 12.
Prevalence of gestational diabetes mellitus detected by the national diabetes data group or the carpenter and coustan plasma glucose thresholds
OBJECTIVE: In 2000, the American Diabetes Association proposed the adoption of the Carpenter and Coustan criteria for diagnosis of gestational diabetes mellitus (GDM). The Carpenter and Coustan cutoffs are lower than the previously recommended National Diabetes Data Group (NDDG) values and would result in higher prevalence of GDM. Our aim is to estimate the magnitude of change in prevalence of GDM using the Carpenter and Coustan thresholds as compared with the NDDG thresholds by age and ethnicity. RESEARCH DESIGN AND METHODS: Cross-sectional study of 28,330 women aged 14-49 years who gave birth in 1996 and were members of the Northern California Kaiser Permanente Medical Care Program. Age, ethnicity, screening, and diagnostic test results were assessed from computerized hospitalization and laboratory systems. RESULTS: A total of 26,481 (94%) women were screened using a 50-g, 1-h oral glucose tolerance test, and 4,190 women underwent a diagnostic 100-g, 3-h oral glucose tolerance test after an abnormal screening. Overall, the GDM prevalence among screened women was 3.2% (95% CI 3.0-3.4) by NDDG and 4.8% (95% CI 4.5-5.1) by Carpenter and Coustan criteria, and based on either threshold, it increased with age (P < 0.001). The age-adjusted GDM prevalence by NDDG and Carpenter and Coustan criteria, respectively, was 5.0 and 7.4% in Asians, 3.9 and 5.6% in Hispanics, 3.0 and 4.0% in African-Americans, and 2.4 and 3.8% in whites. Proportional increments were larger in women aged <25 years (70%) and in whites (58%). CONCLUSIONS: -The prevalence of GDM increased, on average, by 50% with use of the Carpenter and Coustan thresholds. Relative increments were greater in low-risk age and ethnic groups. This information would be useful for clinical settings in predicting cost of GDM based on demographic characteristics of the population.
Authors: Ferrara A; Hedderson MM; Quesenberry CP; Selby JV
Diabetes Care. 2002 Sep;25(9):1625-30.
The changing prevalence of autism in California
We conducted a population-based study of eight successive California births cohorts to examine the degree to which improvements in detection and changes in diagnosis contribute to the observed increase in autism prevalence. Children born in 1987-1994 who had autism were identified from the statewide agency responsible for coordinating services for individuals with developmental disabilities. To evaluate the role of diagnostic substitution, trends in prevalence of mental retardation without autism were also investigated. A total of 5038 children with full syndrome autism were identified from 4,590,333 California births, a prevalence of 11.0 per 10,000. During the study period, prevalence increased from 5.8 to 14.9 per 10,000, for an absolute change of 9.1 per 10,000. The pattern of increase was not influenced by maternal age, race/ethnicity, education, child gender, or plurality. During the same period, the prevalence of mental retardation without autism decreased from 28.8 to 19.5 per 10,000, for an absolute change of 9.3 per 10,000. These data suggest that improvements in detection and changes in diagnosis account for the observed increase in autism; whether there has also been a true increase in incidence is not known.
Authors: Croen LA; Grether JK; Hoogstrate J; Selvin S
J Autism Dev Disord. 2002 Jun;32(3):207-15.
Descriptive epidemiology of autism in a California population: who is at risk?
We investigated the association between selected infant and maternal characteristics and autism risk. Children with autism born in California in 1989-1994 were identified through service agency records and compared with the total population of California live births for selected characteristics recorded on the birth certificate. Multivariate models were used to generate adjusted risk estimates. From a live birth population of more than 3.5 million, 4381 children with autism were identified. Increased risks were observed for males, multiple births, and children born to black mothers. Risk increased as maternal age and maternal education increased. Children born to immigrant mothers had similar or decreased risk compared with California-born mothers. Environmental factors associated with these demographic characteristics may interact with genetic vulnerability to increase the risk of autism.
Authors: Croen LA; Grether JK; Selvin S
J Autism Dev Disord. 2002 Jun;32(3):217-24.
Racial/ethnic variation in asthma status and management practices among children in managed medicaid
OBJECTIVE: Racial/ethnic disparities in hospitalization rates among children with asthma have been documented but are not well-understood. Medicaid programs, which serve many minority children, have markedly increased their use of managed care in recent years. It is unknown whether racial/ethnic disparities in health care use or other processes of care exist in managed Medicaid populations. This study of Medicaid-insured children with asthma in 5 managed care organizations aimed to 1) compare parent-reported health status and asthma care processes among black, Latino, and white children and 2) test the hypothesis that racial/ethnic variations in processes of asthma care exist after adjusting for socioeconomic status and asthma status. METHODS: This cross-sectional study collected data via telephone interviews with parents and computerized records for Medicaid-insured children with asthma in 5 managed care organizations in California, Washington, and Massachusetts. The American Academy of Pediatrics (AAP) Children’s Health Survey for Asthma was used to measure parent-reported asthma status. We used multivariate models to evaluate associations between race/ethnicity and asthma status while controlling for other sociodemographic variables. We evaluated racial/ethnic variations in selected processes of asthma care while controlling for other demographic variables and asthma status. RESULTS: The response rate was 63%. Of the 1658 children in the respondent group, 38% were black, 19% were Latino, and 31% were white. Black children had worse asthma status than white children on the basis of the AAP asthma physical and emotional health scores, symptom-days, and school days missed in the past 2 weeks. Latino children had equivalent AAP scores but missed more school days than white children. On the basis of the AAP asthma physical health score, the black-white disparity persisted after adjusting for other sociodemographic variables. After adjusting for sociodemographic variables and asthma status, black and Latino children were less likely to be using inhaled antiinflammatory medication than white children (relative risk for blacks: 0.69; relative risk for Latinos: 0.58). They were more likely to have home nebulizers. Other processes of asthma care, including ratings of providers and asthma care, use of written management plans, use of preventive visits and specialists, and having no pets or smokers at home, were equal or better for minority children compared with white children. CONCLUSIONS: Black and Latino children had worse asthma status and less use of preventive asthma medications than white children within the same managed Medicaid populations. Most other processes of asthma care seemed to be equal or better for minorities in the populations that we studied. Increasing the use of preventive medications is a natural focus for reducing racial disparities in asthma.
Authors: Lieu TA; Lozano P; Finkelstein JA; Chi FW; Jensvold NG; Capra AM; Quesenberry CP; Selby JV; Farber HJ
Pediatrics. 2002 May;109(5):857-65.
Pelvic organ prolapse surgery in the United States, 1997
OBJECTIVE: Our purpose was to describe the prevalence, regional rates and demographic characteristics, morbidity, and mortality of pelvic organ prolapse surgeries in the United States. STUDY DESIGN: We used data from the 1997 National Hospital Discharge Survey and the 1997 National Census to calculate rates of pelvic organ prolapse surgeries by age, race, and regional trends. RESULTS: In 1997, 225,964 women underwent surgery for prolapse (22.7 per 10,000 women). The mean age of these women was 54.6 years (+/-15.2). The South had the highest rate of surgery (29.3 per 10,000) and the Northeast had the lowest (16.1 per 10,000). The surgery rate for whites (19.6 per 10,000) was 3 times greater than that for African Americans (6.4 per 10,000). Although 16% of surgeries had complications, mortality was rare (0.03%). CONCLUSION: Pelvic organ prolapse surgery is common. Regional and racial differences in rates of surgery may reflect physician practice, patient preferences, and gynecologic care utilization.
Authors: Brown JS; Waetjen LE; Subak LL; Thom DH; Van Den Eeden S; Vittinghoff E
Am J Obstet Gynecol. 2002 Apr;186(4):712-6.
Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly
Authors: Croen LA; Shaw GM; Barber RC; Baker MM; Finnell RH; Lammer EJ
Am J Med Genet. 2002 Feb 15;108(1):75-7.
A population-based prospective cohort study of personal exposure to magnetic fields during pregnancy and the risk of miscarriage
To study the effect of magnetic fields on the risk of miscarriage, we conducted a population-based prospective cohort study among pregnant women within a large health maintenance organization. All women with a positive pregnancy test at less than 10 weeks of gestation and residing in the San Francisco area were contacted for participation in the study. We conducted in-person interviews to obtain information on risk factors for miscarriage and other potential confounders. All participants were also asked to wear a magnetic field-measuring meter for 24 hours and to keep a diary of their activities. Pregnancy outcomes were obtained for all participants by searching the health maintenance organization’s databases, reviewing medical charts, and telephone follow-up. We used the Cox proportional hazard model for examining the magnetic field-miscarriage association. A total of 969 subjects were included in the final analyses. Although we did not observe an association between miscarriage risk and the average magnetic field level, miscarriage risk increased with an increasing level of maximum magnetic field exposure with a threshold around 16 milligauss (mG). The rate ratio (RR) associated with magnetic field exposure > or = 16 mG (vs <16 mG) was 1.8 [95% confidence interval (CI) = 1.2-2.7]. The risk remained elevated for levels (in tertiles) of maximum magnetic field exposure > or = 16 mG. The association was stronger for early miscarriages (<10 weeks of gestation) (RR = 2.2, 95% CI = 1.2-4.0) and among 'susceptible' women with multiple prior fetal losses or subfertility (RR = 3.1, 95% CI = 1.3-7.7). After excluding women who indicated that their daily activity pattern during the measurements did not represent their typical daily activity during pregnancy, the association was strengthened; RR = 2.9 (95% CI = 1.6-5.3) for maximum magnetic field exposure > or = 16 mG, RR = 5.7 (95% CI = 2.1-15.7) for early miscarriage, and RR = 4.0 (95% CI = 1.4-11.5) among the susceptible women. Our findings provide strong prospective evidence that prenatal maximum magnetic field exposure above a certain level (possibly around 16 mG) may be associated with miscarriage risk. This observed association is unlikely to be due to uncontrolled biases or unmeasured confounders.
Authors: Li DK; Odouli R; Wi S; Janevic T; Golditch I; Bracken TD; Senior R; Rankin R; Iriye R
Epidemiology. 2002 Jan;13(1):9-20.
Developing a prediction rule from automated clinical databases to identify high-risk patients in a large population with diabetes
OBJECTIVE: To develop and validate a prediction rule for identifying diabetic patients at high short-term risk of complications using automated data in a large managed care organization. RESEARCH DESIGN AND METHODS: Retrospective cohort analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern California, aged > or =19 years. Data from 1994 to 1995 were used to model risk for macro- and microvascular complications (n = 3,977), infectious complications (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory records, pharmacy records, utilization records, and survey data. Using split-sample validation, the risk scores derived from logistic regression models in half of the population were evaluated in the second half. Sensitivity, positive predictive value, and receiver operating characteristics curves were used to compare scores obtained from full models to those derived using simpler approaches. RESULTS: History of prior complications or related outpatient diagnoses were the strongest predictors in each complications set. For patients without previous events, treatment with insulin alone, serum creatinine > or =1.3 mg/dl, use of two or more antihypertensive medications, HbA(1c) >10%, and albuminuria/microalbuminuria were independent predictors of two or all three complications. Several risk scores derived from multivariate models were more efficient than simply targeting patients with elevated HbA(1c) levels for identifying high-risk patients. CONCLUSIONS: Simple prediction rules based on automated clinical data are useful in planning care management for populations with diabetes.
Authors: Selby JV; Karter AJ; Ackerson LM; Ferrara A; Liu J
Diabetes Care. 2001 Sep;24(9):1547-55.
Hormone replacement therapy is associated with better glycemic control in women with type 2 diabetes: The Northern California Kaiser Permanente Diabetes Registry
OBJECTIVE: In women with diabetes, the changes that accompany menopause may further diminish glycemic control. Little is known about how hormone replacement therapy (HRT) affects glucose metabolism in diabetes. The aim of this study was to examine whether HbA(1c) levels varied by current HRT among women with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort of 15,435 women with type 2 diabetes who were members of a health maintenance organization, HbA(1c) and HRT were assessed by reviewing records in the health plan’s computerized laboratory and pharmacy systems. Sociodemographic and clinical information were collected by survey. RESULTS: The mean age was 64.7 years (SD +/- 8.7). The study cohort comprised 55% non-Hispanic whites, 14% non-Hispanic blacks, 12% Hispanics, 11% Asians, 4% ‘other’ ethnic groups, and 4% with missing ethnicity data. Current HRT was observed in 25% of women. HbA(1c) levels were significantly lower in women currently using HRT than in women not using HRT (age-adjusted mean +/- SE: 7.9 +/- 0.03 vs. 8.5 +/- 0.02, respectively, P = 0.0001). No differences in HbA(1c) level were observed between women using unopposed estrogens and women using opposed estrogens. In a Generalized Estimating Equation model, which took into account patient clustering within physician and adjusted for age, ethnicity, education, obesity, hypoglycemic therapy, diabetes duration, self-monitoring of blood glucose, and exercise, HRT remained significantly and independently associated with decreased HbA(1c) levels (P = 0.0001). CONCLUSIONS: HRT was independently associated with decreased HbA(1c) level. Clinical trials will be necessary to understand whether HRT may improve glycemic control in women with diabetes.
Authors: Ferrara A; Karter AJ; Ackerson LM; Liu JY; Selby JV; Northern California Kaiser Permanente Diabetes Registry
Diabetes Care. 2001 Jul;24(7):1144-50.
The epidemiology of mental retardation of unknown cause
OBJECTIVE: To describe selected infant and maternal characteristics for children with mild and severe mental retardation (MR) of unknown cause. STUDY DESIGN: Children with MR of unknown cause born in California between 1987 and 1994 were identified through service agency records and compared with the total population of California live births for selected characteristics recorded on the birth certificate. RESULTS: For both children with mild and severe MR, risk was increased among males, low birth weight children, and children born to women of black race, older age at delivery, and lower level of education. Increased risk for mild MR was found for multiple births, second or later-born children, and children whose mothers were born outside of California. Increased risk for severe MR was observed among children born to Hispanic mothers; children born to Asian mothers also had increased risk for severe MR but decreased risk for mild MR. CONCLUSIONS: These results provide clues for understanding the underlying causes of MR and suggest that both biological and social factors are important.
Authors: Croen LA; Grether JK; Selvin S
Pediatrics. 2001 Jun;107(6):E86.
Congenital abnormalities among children with cerebral palsy: More evidence for prenatal antecedents
OBJECTIVES: To investigate the association between cerebral palsy (CP) and congenital abnormalities among children with very low, low, and normal birth weight. Study design: A population-based, case-control study among the cohort of 155,636 live births delivered between 1983 and 1985 in 4 California counties. Children with moderate or severe congenital CP (n = 192) diagnosed by age 3 were identified from 2 California State service agencies, and 551 control children were randomly sampled from birth certificate files. Information on congenital abnormalities diagnosed by the age of 1 year was obtained from the California Birth Defects Monitoring Program registry. Odds ratios (OR) and 95% CIs were calculated to estimate risk for CP associated with congenital abnormalities. RESULTS: Among singletons, congenital abnormalities were present in 33 (19.2%) children with CP and 21 (4.3%) control children (OR = 5.2, 95% CI 2.8-9.7). For each birth weight group, the percent of children with congenital abnormalities among children with CP exceeded that among control children. Structural abnormalities of the central nervous system were more common among children with CP (OR = 16.2, 95% CI 5.8-49.3) than control children. In contrast, the percent of children with non-central nervous system abnormalities only was similar between case patients and control subjects. CONCLUSION: These findings provide further evidence that factors operating in the prenatal period contribute significantly to the etiology of CP.
Authors: Croen LA; Grether JK; Curry CJ; Nelson KB
J Pediatr. 2001 Jun;138(6):804-10.
Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation
There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
Authors: Nelson KB; Grether JK; Croen LA; Dambrosia JM; Dickens BF; Jelliffe LL; Hansen RL; Phillips TM
Ann Neurol. 2001 May;49(5):597-606.
Impact of the change in polio vaccination schedule on immunization coverage rates: a study in two large health maintenance organizations
OBJECTIVE: In January 1997, one of the most significant changes to United States vaccine policy occurred when polio immunization guidelines changed to recommend a schedule containing inactivated polio vaccine (IPV). There were concerns that parent or physician reluctance to accept IPV into the routine childhood immunization schedule would lead to lowered coverage. We determined whether adoption of an IPV schedule had a negative impact on immunization coverage. DESIGN: A cohort study of 2 large health maintenance organizations (HMOs), Group Health Cooperative and Kaiser Permanente Northern California, was conducted. For analysis at 12 months of age, children who were born between October 1, 1996, and December 31, 1997, and were commercially insured and covered by Medicaid were continuously enrolled; for analysis at 24 months of age, children who were born between October 1, 1996, and June 30, 1997, and were commercially insured and covered by Medicaid were continuously enrolled. The 3 measures of immunization status at 12 and 24 months of age were up-to-date status, cumulative time spent up-to-date, and the number of missed opportunity visits. RESULTS: At both HMOs, children who received IPV were as likely to be up to date at 12 months as were children who received oral poliovirus vaccine (OPV), whereas at Group Health, children who received IPV were slightly more likely to be up to date at 24 months (relative risk: 1.12; 95% confidence interval [CI]: 1.05, 1.19). These findings were consistent for children who were covered by Medicaid. At Kaiser Permanente, children who received IPV spent ~3 fewer days up to date in the first year of life, but this difference did not persist at 2 years of age. At Group Health, children who received IPV were no different from those who received OPV in terms of days spent up to date by 1 or 2 years of age. At Group Health, children who received IPV were less likely to have a missed opportunity by 12 months old (odds ratio [OR] 0.46; 95% CI: 0.31, 0.70), but this finding did not persist at 24 months of age. At Kaiser Permanente, children who received IPV were more likely to have a missed opportunity by 12 months (OR 2.06; 95% CI: 1.84, 2.30), and 24 months of age (OR 1.50; 95% CI: 1.36, 1.67). CONCLUSIONS: The changeover from an all-OPV schedule to one containing IPV had little if any negative impact on vaccine coverage. Use of IPV was associated with a small increase in the likelihood of being up to date at 2 years of age at one of the HMOs and conversely was associated with a small increase in the likelihood of having a missed-opportunity visit in the other HMO.polio, poliomyelitis, vaccination, immunization coverage.
Authors: Davis RL; Lieu TA; Mell LK; Capra AM; Zavitkovsky A; Quesenberry CP Jr; Black SB; Shinefield HR; Thompson RS; Rodewald LE
Pediatrics. 2001 Apr;107(4):671-6.
Variation in clinician recommendations for multiple injections during adoption of inactivated polio vaccine
OBJECTIVES: To describe variation in clinician recommendations for multiple injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large health maintenance organizations (HMOs), and to test the hypothesis that variation in recommendations would be associated with variation in immunization coverage rates. DESIGN: Cross-sectional study based on a survey of clinician practices 1 year after IPV was recommended and computerized immunization data from these clinicians’ patients. STUDY SETTINGS: Two large West Coast HMOs: Kaiser Permanente in Northern California and Group Health Cooperative of Puget Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds cared for by the clinicians during the study. RESULTS: More clinicians at Group Health (82%), where a central guideline was issued, had adopted the IPV/oral poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no central guideline was issued. Clinicians at both HMOs said that if multiple injections fell due at a visit and they elected to defer some vaccines, they would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At Kaiser, IPV users were more likely than OPV users to recommend the first HBV at birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV were as likely to be fully immunized at 8 months old as those whose clinicians used all OPV. At Kaiser, where there was variability in the maximum number of injections clinicians recommended at infant visits, providers who routinely recommended 3 or 4 injections at a visit had similar immunization coverage rates as those who recommended 1 or 2. At both HMOs, clinicians who strongly recommended all possible injections at a visit had higher immunization coverage rates at 8 months than those who offered parents the choice of deferring some vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS: Neither IPV adoption nor the use of multiple injections at infant visits were associated with reductions in immunization coverage. However, at the HMO without centralized immunization guidelines, IPV adoption was associated with changes in the timing of the first and third HBV. Clinical policymakers should continue to monitor practice variation as future vaccines are added to the infant immunization schedule.
Authors: Lieu TA; Davis RL; Capra AM; Mell LK; Quesenberry CP; Martin KE; Zavitkovsky A; Black SB; Shinefield HR; Thompson RS; Rodewald LE
Pediatrics. 2001 Apr;107(4):E49.
Maternal exposure to nitrate from drinking water and diet and risk for neural tube defects
In this population-based case-control study conducted in California between June 1989 and May 1991, the authors investigated the association between maternal periconceptional exposure to nitrate from drinking water and diet and risk for neural tube defects. The mothers of 538 cases and 539 nonmalformed controls were interviewed regarding residential history, consumption of tap water at home, and dietary intake during the periconceptional period. Dietary nitrate exposure was not associated with increased risk for neural tube defects. Exposure to nitrate in drinking water at concentrations above the 45 mg/liter maximum contaminant level was associated with increased risk for anencephaly (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.0, 15.4), but not for spina bifida. Increased risks for anencephaly were observed at nitrate levels below the maximum contaminant level among groundwater drinkers only (OR = 2.1, 95% CI: 1.1,4.1 for 5-15 mg/liter; OR = 2.3, 95% CI: 1.1, 4.5 for 16-35 mg/liter; and OR = 6.9, 95% CI: 1.9, 24.9 for 36-67 mg/liter compared with <5 mg/liter). Adjustment for identified risk factors for anencephaly did not substantially alter these associations, nor did control for maternal dietary nitrate, total vitamin C intake, and quantity of tap water consumed. The lack of an observed elevation in risk for anencephaly in association with exposure to mixed water containing nitrate at levels comparable with the concentration in groundwater may indicate that something other than nitrate accounts for these findings.
Authors: Croen LA; Todoroff K; Shaw GM
Am J Epidemiol. 2001 Feb 15;153(4):325-31.
Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma
Although inhaled corticosteroid (ICS) use is associated with a decreased risk of hospitalization for asthma, the impact of ICS on the risk of life-threatening asthma exacerbation is less clear. The effect of ICS and inhaled beta agonist (IBA) dispensing on the risk of intensive care unit admission for asthma, a surrogate for life-threatening exacerbation, is evaluated. Using computerized International classification of diseases (ICD)-9 discharge diagnoses, a cohort of all 2,344 adult Northern California members of a health maintenance organization hospitalized for asthma over a 2-yr period were identified. Computerized pharmacy data was used to ascertain asthma medications dispensed during the 3-,6-, and 12-month intervals preceding index hospitalization for asthma. During the 3-months preceding hospitalization, a minority of subjects had no IBA units dispensed (34%), with 14% receiving low level (1 unit), 20% medium level (2-3 units), and 32% high level (> or = 4 units) therapy. A substantial proportion received no ICS units (55%), whereas 13% had low, 16% medium, and 15% high level therapy. In multiple logistic regression analysis, high level IBA use was associated with a greater risk of intensive care unit (ICU) admission for asthma after controlling for asthma severity. There was no relationship, however, between low or medium level IBA use and ICU admission. Conversely, medium level and high level ICS use were associated with a reduced risk of ICU admission. Analysing 6- and 12-month medication dispensing data, similar risk patterns were observed. Inhaled corticosteroid dispensing was associated with reduced risk of intensive care unit admission among adults hospitalized for asthma, whereas the opposite applied for high dose beta agonist usage. This suggests that ICS prescription to adults with moderate-to-severe asthma could reduce the risk of life-threatening exacerbation.
Authors: Eisner MD; Lieu TA; Chi F; Capra AM; Mendoza GR; Selby JV; Blanc PD
Eur Respir J. 2001 Feb;17(2):233-40.
A comparison of health care experiences for medicaid and commercially enrolled children in a large, nonprofit health maintenance organization
BACKGROUND: Proponents of Medicaid managed care have argued that this type of care offers the potential to provide mainstream health care for poor children and the elimination of the 2-tier system of care that has long existed for poor and nonpoor children. However, few studies have attempted to assess whether differences in access, utilization, and satisfaction exist between Medicaid and commercially sponsored children who are enrolled in the same managed care plan. OBJECTIVE: To systematically answer the following research question: Within the same large, nonprofit, group-model health maintenance organization (HMO), how do children enrolled in Medicaid compare with children enrolled commercially across the domains of access, utilization, and satisfaction with care? METHODS: We compared access, satisfaction, and utilization of services between Medicaid and commercially sponsored children enrolled in Kaiser Permanente of Northern California during 1998 through use of a telephone survey and administrative data. Kaiser Permanente is a nonprofit, integrated, group HMO that serves 2.8 million members in more than 15 counties in northern California. The sample for this survey included 510 Medicaid-enrolled children and 512 commercially enrolled children. An overall response rate of 82% was achieved. Bivariate and multivariate analyses were used to compare Medicaid and commercially enrolled children. RESULTS: We found few differences between commercial and Medicaid enrollees across the domains of access, utilization, and satisfaction. Where access differences were present (problems in finding a personal care provider, problems getting care overall, and experiencing 1 or more barriers to care), the differences favored Medicaid-enrolled children. That is, Medicaid enrollees were reported to experience significantly fewer access problems and barriers than commercial enrollees, even after adjustment for confounding factors. Only one difference was found between Medicaid and commercial enrollees across the 6 utilization variables examined (volume of emergency department visits), and no differences were found among the 4 satisfaction and 2 global assessments of care received. Taken together, our results suggest that Medicaid-enrolled children experience as good as or better care than their commercially enrolled counterparts. However, there are other possible explanations for our findings. It may be that families of Medicaid-enrolled children hold their care providers to a lower standard than families of commercially enrolled children, given historic inequities in care between poor and nonpoor families. In addition, some degree of selection bias may be present in our sample, although that is true for both the Medicaid and commercial populations. CONCLUSIONS: Our findings suggest that large commercial HMOs are capable of eliminating the access barriers and stigma traditionally associated with the Medicaid program. However, this conclusion must be tempered with the knowledge that other explanations for our findings may also be at play.
Authors: Newacheck PW; Lieu T; Kalkbrenner AE; Chi FW; Ray GT; Cohen JW; Weinick RM
Ambul Pediatr. 2001 Jan-Feb;1(1):28-35.
Risk factors for cervical stenosis after loop electrocautery excision procedure.
OBJECTIVE: To assess frequency of and identify risk factors for the development of cervical stenosis after loop electrosurgical excision procedure. METHODS: We reviewed outpatient charts of women treated by loop excision for cervical dysplasia between August 1996 and January 1998 in the colposcopy clinic at Massachusetts General Hospital. One hundred sixty-four women were evaluated for cervical stenosis during follow-up. Stenosis was considered present if manual dilation was required to allow endocervical sampling with an endocervical currette 3 mm wide. Multivariable analysis with stepwise logistic regression was used to evaluate age, parity, tobacco use, hormonal status, use of oral contraceptives, pathology, previous loop excision, performance of additional endocervical excision, and dimensions of excision specimens as predictors of cervical stenosis. RESULTS: The average age was 32 years. Cervical stenosis occurred in ten of 164 women (6%, 95% CI 3%, 11%). Among factors analyzed, previous loop excision and volume of excision specimen were the only independent predictors of stenosis. CONCLUSION: Cervical stenosis correlated with history of loop excision and volume of tissue removed, suggesting that women who have second excisions or large excisions should be counseled that their risk of stenosis might be higher.
Authors: Suh-Burgmann EJ; Whall-Strojwas D; Chang Y; Hundley D; Goodman A
Obstet Gynecol. 2000 Nov;96(5 Pt 1):657-60.
The hidden costs of infant vaccination
Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant’s vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events (Ns=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.
Authors: Lieu TA; Black SB; Ray GT; Martin KE; Shinefield HR; Weniger BG
Vaccine. 2000 Aug 15;19(1):33-41.
Maternal pre-eclampsia/eclampsia and the risk of sudden infant death syndrome in offspring
To determine whether maternal exposure to pre-eclampsia/eclampsia during pregnancy increases the risk of sudden infant death syndrome (SIDS) in offspring, we conducted a population-based case-control study using the California linked birth and death certificate data. All infants who died of SIDS (ICD-9 code 798.0) during 1989-91 were identified as cases. More than 96% of the identified SIDS cases were diagnosed through autopsy. Ten controls who did not die from SIDS were randomly selected for each case from the birth certificate matched to the case on the year of birth. Among 2,029 cases and 21,037 controls included in the final analysis, mothers of 49 cases (2.4%) and 406 controls (1.9%) had a diagnosis of either pre-eclampsia or eclampsia noted on the birth certificate. After adjustment for maternal age, prenatal smoking, race/ethnicity, parity, maternal education, gestational age at the initial visit for prenatal care, infant year of birth and infant sex, maternal pre-eclampsia/ eclampsia during pregnancy was associated with a 50% increased risk of SIDS in the offspring (odds ratio = 1.5, 95% confidence interval 1.1, 2.0). Potential under-reporting of pre-eclampsia/eclampsia on the birth certificates was likely to be non-differential and is unlikely to explain the finding. Fetal hypoxia resulting from pre-eclampsia/ eclampsia or immunological aetiology affecting the risk of both pre-eclampsia/eclampsia and SIDS may explain the finding.
Authors: Li DK; Wi S
Paediatr Perinat Epidemiol. 2000 Apr;14(2):141-4.
Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children
CONTEXT: Pneumococcal conjugate vaccine for infants has recently been found effective against meningitis, bacteremia, pneumonia, and otitis media. OBJECTIVE: To evaluate the projected health and economic impact of pneumococcal conjugate vaccination of healthy US infants and young children. DESIGN: Cost-effectiveness analysis based on data from the Northern California Kaiser Permanente randomized trial and other published and unpublished sources. SETTING AND PATIENTS: A hypothetical US birth cohort of 3.8 million infants. INTERVENTIONS: Hypothetical comparisons of routine vaccination of healthy infants, requiring 4 doses of pneumococcal conjugate vaccine (at 2, 4, 6, and 12-15 months), and catch-up vaccination of children aged 2 to 4.9 years requiring 1 dose, with children receiving no intervention. MAIN OUTCOME MEASURES: Cost per life-year saved and cost per episode of meningitis, bacteremia, pneumonia, and otitis media prevented. RESULTS: Vaccination of healthy infants would prevent more than 12000 cases of meningitis and bacteremia, 53000 cases of pneumonia, 1 million episodes of otitis media, and 116 deaths due to pneumococcal infection. Before accounting for vaccine costs, the vaccination program would save $342 million in medical and $415 million in work-loss and other costs from averted pneumococcal disease. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose. At the manufacturer’s list price of $58 per dose, infant vaccination would cost society $80000 per life-year saved or $160 per otitis media episode prevented (other estimated costs would be $3200 per pneumonia case prevented, $15000 for bacteremia, and $280000 for meningitis). The cost-effectiveness of an additional program to administer 1 dose of vaccine to children aged 2 to 4.9 years would vary depending on the children’s ages, relative risks of pneumococcal disease, and vaccine cost. CONCLUSIONS: Pneumococcal conjugate vaccination of healthy US infants has the potential to be cost-effective. To achieve cost savings, its cost would need to be lower than the manufacturer’s list price. In addition to tangible costs, the vaccine should be appraised based on the less tangible value of preventing mortality and morbidity from pneumococcal disease.
Authors: Lieu TA; Ray GT; Black SB; Butler JC; Klein JO; Breiman RF; Miller MA; Shinefield HR
JAMA. 2000 Mar 15;283(11):1460-8.
Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy
To determine whether changing paternity affects the risk of preeclampsia or eclampsia in the subsequent pregnancy and whether the effect depends on a woman’s history of preeclampsia/eclampsia with her previous partner, a cohort study was conducted based on 140,147 women with two consecutive births during 1989-1991 identified through linking of annual California birth certificate data. Among women without preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% increase in the risk of preeclampsia/eclampsia in the subsequent pregnancy compared with those who did not change partners (95% confidence interval: 1.1, 1.6). On the other hand, among women with preeclampsia/eclampsia in the first birth, changing partners resulted in a 30% reduction in the risk of preeclampsia/eclampsia in the subsequent pregnancy (95% confidence interval: 0.4, 1.2). The difference of the effect of changing paternity on the risk of preeclampsia/eclampsia between women with and those without a history of this condition was significant (p < 0.05 for the interaction term). The above estimates were adjusted for potential confounders. These findings suggest that the effect of changing paternity depends on the history of preeclampsia/eclampsia with the previous partner and support the hypothesis that parental human leukocyte antigen sharing may play a role in the etiology of preeclampsia/eclampsia.
Authors: Li DK; Wi S
Am J Epidemiol. 2000 Jan 1;151(1):57-62.
Rehospitalization for respiratory syncytial virus among premature infants
OBJECTIVES: New interventions to prevent respiratory syncytial virus (RSV) have recently become available. Clinical decisions about the use of these interventions require a better understanding of the incidence of and risk factors for RSV. We sought to characterize the epidemiology of severe RSV disease among premature infants and to identify high-risk subgroups. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California, July 1992 to April 1996. PARTICIPANTS: One thousand seven hundred twenty-one premature infants born at 23 to 36 weeks who were discharged from a neonatal intensive care nursery (NICU) within 12 months before the December to March RSV season. A secondary analysis included 769 infants discharged during the RSV season. OUTCOME MEASURES: Hospitalization for RSV. RESULTS: Of 1721 infants already home from the NICU at the start of the season, 3.2% were rehospitalized for RSV. In a multivariate model, risk factors for RSV hospitalization included gestation /=28 days of perinatal oxygen (OR, 3.7), and NICU discharge during September to November (OR, 2.7). Predicted risk of hospitalization varied by subgroup, ranging from 1.2% to 24.6%. Among 769 infants discharged from the NICU during the RSV season, 3.5% were rehospitalized for RSV during the same season; gestation and perinatal oxygen were not associated with admission. CONCLUSIONS: Most premature infants in this population were at less risk of severe RSV disease than previous studies in other populations have suggested. Preterm infants with a lower gestational age, a prolonged perinatal oxygen requirement, and NICU discharge within 3 months of the RSV season were most likely to require hospitalization for RSV disease. Cost-effectiveness analyses are needed to help define the role of available prophylactic interventions.
Authors: Joffe S; Escobar GJ; Black SB; Armstrong MA; Lieu TA
Pediatrics. 1999 Oct;104(4 Pt 1):894-9.
Surveillance for endometrial cancer in women receiving tamoxifen.
Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.
Authors: Suh-Burgmann EJ; Goodman A
Ann Intern Med. 1999 Jul 20;131(2):127-35. doi: 10.7326/0003-4819-131-2-199907200-00009.
Expression of the HPV E7 oncoprotein mimics but does not evoke a p53-dependent cellular DNA damage response pathway.
Acute expression of the human papillomavirus E7 oncoprotein in preimmortal human fibroblasts induces changes in the abundances of multiple cellular regulatory proteins. These alterations include a destabilization of the retinoblastoma tumor suppressor protein pRB, stabilization of the tumor suppressor protein p53, and increases in the level of the cyclin-dependent kinase inhibitor p21(cip1). Since the HPV E7 oncoproteins can interfere with several cell cycle checkpoints and similar alterations in the levels of pRB, p53, and p21(cip1) are also observed in a p53-dependent response to DNA damage, we investigated whether E7 expression triggers this signal transduction pathway. The results demonstrate that E7-mediated destabilization of pRB does not require p53 activity and is independent of the ability of E7 to induce apoptosis. Moreover, E7-mediated increases in p21(cip1) levels are largely p53-independent and involve stabilization of the p21(cip1) protein. In contrast the decreases in pRB expression in response to DNA damage involve transcriptional downregulation of RB gene expression.
Authors: Jones DL; Thompson DA; Suh-Burgmann E; Grace M; Munger K
Virology. 1999 Jun 5;258(2):406-14. doi: 10.1006/viro.1999.9733.
The cost of medical care for patients with cystic fibrosis in a health maintenance organization
BACKGROUND: Cystic fibrosis (CF) is the most common life-shortening genetic disorder among white individuals worldwide. Previous estimates of the costs of medical care have been based on expert opinion rather than observed costs. Accurate cost estimates are needed to enable evaluation of the cost-effectiveness of new interventions and prenatal genetic screening recommendations. OBJECTIVE: To evaluate the cost of medical care for patients (N = 136) served by a health maintenance organization with a CF center. METHODS: Retrospective analysis of data from computerized cost databases and the Cystic Fibrosis Foundation annual survey. Severity of disease was classified based on the percent predicted forced expiratory volume at 1 second. RESULTS: The annual cost of medical care in 1996 averaged $13 300 and ranged from $6200 among patients with mild disease to $43 300 among patients with severe disease. Of total costs, 47% were from hospitalization, 18% were from DNase (Pulmozyme), 12% were from clinic visits, and 10% were from outpatient antibiotics. When the observed costs were used to estimate the costs of medical care for the entire population of CF patients in the United States, these costs were estimated to be $314 million per year in 1996 dollars. CONCLUSIONS: We conclude that the cost of medical care for CF varies greatly with severity but is substantial even among patients with mild disease. These findings underscore the need for strategies to ensure good health insurance coverage and high quality care for all individuals with this condition.
Authors: Lieu TA; Ray GT; Farmer G; Shay GF
Pediatrics. 1999 Jun;103(6):e72.
Excess maternal transmission of type 2 diabetes. The Northern California Kaiser Permanente Diabetes Registry
OBJECTIVE: To assess excess maternal transmission of type 2 diabetes in a multiethnic cohort. Previous studies have reported higher prevalence of diabetes among mothers of probands with type 2 diabetes than among fathers. This analysis is vulnerable to biases, and this pattern has not been observed in all populations or races. RESEARCH DESIGN AND METHODS: We assessed evidence for excess maternal transmission among 42,533 survey respondents with type 2 diabetes (probands) by calculating the prevalence of diabetes in their siblings and offspring. To assess data quality, we evaluated completeness of family history data provided. Accuracy of family information reported by probands was also evaluated by comparing survey responses in a subsample of 206 probands with family histories modified after further interviews with relatives. RESULTS: Siblings (n = 60,532) of probands with affected mothers had a greater prevalence of diabetes (20%) than those with affected fathers (17%) (P < 0.001 for adjusted odds ratios). Prevalence of diabetes was higher among the offspring (n = 72,087) of female (3.4%) versus male (2.2%) probands (P < 0.001 for adjusted odds ratios). These patterns were evident in all races and both sexes; however, the effect size was clinically insignificant in African-Americans and male offspring. In general, probands provided more complete data about diabetes status for the maternal arm of the pedigree than the paternal arm. Completeness of knowledge was not related to proband sex, but was related to education and race, and inversely to age. Accuracy of proband-reported family history was consistently good (kappa statistics generally > 0.70). CONCLUSIONS: Excess maternal transmission was observed in all races and both sexes, although the size of the excess was negligible in African-Americans and male offspring. Potential reporting and censoring biases are discussed.
Authors: Karter AJ; Rowell SE; Ackerson LM; Mitchell BD; Ferrara A; Selby JV; Newman B
Diabetes Care. 1999 Jun;22(6):938-43.
Computer-based models to identify high-risk adults with asthma: is the glass half empty of half full?
This study developed and evaluated the performance of prediction models for asthma-related adverse outcomes based on the computerized hospital, clinic, and pharmacy utilization databases of a large health maintenance organization. Prediction models identified patients at three- to four-fold increased risk of hospitalization and emergency department visits, and were valid for test samples from the same population. A model that identified 19% of patients as high risk had a sensitivity of 49%, a specificity of 84%, and a positive predictive value of 19%. We conclude that prediction models that are based on computerized utilization data can identify adults with asthma at elevated risk, but may have limited sensitivity and specificity in actual populations.
Authors: Lieu TA; Capra AM; Quesenberry CP; Mendoza GR; Mazar M
J Asthma. 1999 Jun;36(4):359-70.
Maternal placental abnormality and the risk of sudden infant death syndrome
To determine whether placental abnormality (placental abruption or placental previa) during pregnancy predisposes an infant to a high risk of sudden infant death syndrome (SIDS), the authors conducted a population-based case-control study using 1989-1991 California linked birth and death certificate data. They identified 2,107 SIDS cases, 96% of whom were diagnosed through autopsy. Ten controls were randomly selected for each case from the same linked birth-death certificate data, matched to the case on year of birth. About 1.4% of mothers of cases and 0.7% of mothers of controls had either placental abruption or placenta previa during the index pregnancy. After adjustment for potential confounders, placental abnormality during pregnancy was associated with a twofold increase in the risk of SIDS in offspring (odds ratio = 2.1, 95% confidence interval 1.3-3.1). The individual effects of placental abruption and placenta previa on the risk of SIDS did not differ significantly. An impaired fetal development due to placental abnormality may predispose an infant to a high risk of SIDS.
Authors: Li DK; Wi S
Am J Epidemiol. 1999 Apr 1;149(7):608-11.
Changing paternity and the risk of preterm delivery in the subsequent pregnancy
I studied whether changing a partner, and thus changing the likelihood of human leukocyte antigen (HLA) sharing between mating partners, affects the risk of preterm delivery in the subsequent pregnancy. I identified a total of 128,239 women who had two consecutive births during 1989-1991 through data linkage of the California birth certificates. Paternal date of birth and names on the records of the two consecutive births were compared to determine whether the same father was reported on both records. Three cohorts of women were formed on the basis of the gestational age of their first delivery: <34, 34-36, and >36 weeks. If parental HLA sharing is associated with preterm delivery, the likelihood of HLA sharing was expected to be in a decreasing order from most likely among a <34-week cohort to least likely among a >36-week cohort. Among women in the <34-week cohort, changing partners resulted in a 33% reduction in the risk of early preterm delivery in the subsequent pregnancy compared with those who did not change partners [95% confidence interval (CI), 0.52-0.88]. In contrast, among women in the >36-week cohort, changing partners led to a 16% increase in the risk of early preterm delivery in the subsequent pregnancy (95% CI = 1.04-1.30). Among women in the 34-36-week cohort, changing partners did not affect the risk of preterm delivery (95% CI = 0.78-1.25). These estimates were adjusted for maternal race/ethnicity, age, educational level, prenatal smoking, prenatal care, parity, and interval from birth to conception of the subsequent pregnancy. The findings from this study suggest that the effect of changing paternity depends on the pregnancy outcome with the previous partner and support the hypothesis that parental HLA sharing may be related to preterm delivery.
Authors: Li DK
Epidemiology. 1999 Mar;10(2):148-52.
Maternal history of subfertility and the risk of congenital urinary tract anomalies in offspring
I studied the relation between a maternal history of subfertility and the risk of congenital urinary tract anomalies (CUTAs) in a case-control study. I defined subfertility as having unprotected intercourse for more than 12 months without getting pregnant at any time before the conception of the index pregnancy. A maternal history of subfertility was associated with a slightly increased risk of CUTAs (adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) 0.8-2.4). Risk was higher for mothers whose subfertility occurred at 20 years of age or younger (OR = 2.2, 95% CI 1.0-4.9). The effect of a maternal history of subfertility on the risk of CUTAs was exacerbated by maternal smoking during the index pregnancy and by an early onset of smoking history.
Authors: Li DK
Epidemiology. 1999 Jan;10(1):80-2.
Issues in studying the effectiveness of health services for children
OBJECTIVES: To discuss issues in studying the effectiveness of health services for children, suggest areas in which more research is needed, and recommend strategies for future research. PRINCIPAL FINDINGS: Issues that should be considered include the choice of perspective, which will help determine the interventions studied and the measures of effectiveness and cost-effectiveness chosen. Unique challenges in this area include the fact that serious measurable morbidity is relatively uncommon in children, that causal relationships between services and outcomes may be difficult to establish, and that standard measures of cost-effectiveness may fail to accurately measure important benefits, such as reduced parental anxiety. More research is needed on high-risk and health-promoting behaviors, on critical parent behaviors, on classifying children by vulnerability status, on modes of delivery of preventive care, and on violence prevention. RECOMMENDATIONS: Group-randomized designs and observational research designs that take advantage of natural variations in practice may be increasingly useful in effectiveness studies. Parent- and patient-reported measures of health status and quality of life should be made briefer and more practical for routine use, and better measures of cost-effectiveness are needed. Future research efforts can best be supported by the concerted efforts of various constituencies, including health plans, providers, patients, researchers, and the government.
Authors: Lieu TA; Newman TB
Health Serv Res. 1998 Oct;33(4 Pt 2):1041-58.
Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients
BACKGROUND: Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. METHODS: On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. RESULTS: During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. CONCLUSIONS: These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.
Authors: Freedman JM; Li DK; Drasner K; Jaskela MC; Larsen B; Wi S
Anesthesiology. 1998 Sep;89(3):633-41.
Atypical squamous cells of undetermined significance: management patterns at an academic medical center.
OBJECTIVE: Our intent was to compare the management of patients with atypical squamous cells of undetermined significance on cytologic screening at an academic center to published guidelines. STUDY DESIGN: We reviewed the management of 223 atypical squamous cells of undetermined significance cervical smears. Patients with a history of dysplasia were excluded. The time interval to and nature of follow-up testing was determined, and the influence of atypical squamous cells of undetermined significance qualifiers and provider specialty analyzed. RESULTS: Initial follow-up consisted of repeat cytologic examination alone in 94% of cases. Of patients with follow-up, 29% were retested within 2 months and 68% within 4 months. No conclusive differences in management were found by qualifier type or by provider specialty. Subsequent high-grade dysplasia was found in 2.6% of patients. CONCLUSIONS: A discrepancy exists between published guidelines and actual management of patients with atypical squamous cells of undetermined significance smears at this medical center. Patients often undergo follow-up testing at shorter intervals than those suggested despite a low likelihood of finding high-grade disease.
Authors: Suh-Burgmann E; Darragh T; Smith-McCune K
Am J Obstet Gynecol. 1998 May;178(5):991-5. doi: 10.1016/s0002-9378(98)70537-x.
Unexpected vaginal bleeding and associated gynecologic care in postmenopausal women using hormone replacement therapy: comparison of cyclic versus continuous combined schedules
OBJECTIVE: To measure gynecologic resources required to care for women who have unexpected vaginal bleeding while using hormone replacement therapy (HRT). DESIGN: A retrospective cohort study based on review of medical records. SETTING: A large health maintenance organization. PATIENT(S): We studied 284 women using continuous combined HRT and 306 women receiving cyclic HRT. MAIN OUTCOME MEASURE(S): We noted episodes of unexpected vaginal bleeding and associated clinic visits and gynecologic procedures recorded during a mean follow-up period of 2 years. RESULT(S): Among women using cyclic HRT for the first time, 38.3% had > or = 1 visit for unexpected bleeding and 12.3% had > or = 1 endometrial biopsy. Among women starting continuous combined HRT, 41.6% had > or = 1 visit for unexpected bleeding and 20.1% had > or = 1 endometrial biopsy. After adjusting for potential confounding variables, we found that recipients of cyclic and continuous combined HRT had similar risks of unexpected bleeding and endometrial biopsy. However, among women continuing HRT for >2 years, those using the continuous combined regimen had somewhat lower rates of unexpected bleeding (22.3 events per 100 patient-years) and endometrial biopsy (10.3 events per 100 patient-years) than those using the cyclic regimen (37.8 episodes of unexpected bleeding per 100 patient-years and 13.9 endometrial biopsies per 100 patient-years). CONCLUSION(S): Unexpected vaginal bleeding and the gynecologic resources required to manage it decreased after 2 years in women using continuous combined HRT but did not decline among those using cyclic HRT.
Authors: Ettinger B; Li DK; Klein R
Fertil Steril. 1998 May;69(5):865-9.
Effectiveness and cost-effectiveness of letters, automated telephone messages, or both for underimmunized children in a health maintenance organization
BACKGROUND: Immunization rates have improved in the United States, but are still far from the national 90% goal for the year 2000. There is scant evidence about the effectiveness and costs of automated telephone messages to improve immunization rates among privately insured children. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of sending letters, automated telephone messages, or both to families of underimmunized 20-month-olds in a health maintenance organization (HMO). METHODS: In this randomized trial, underimmunized 20-month-olds identified by the HMO’s computerized immunization tracking system were assigned to one of four interventions: 1) an automated telephone message alone; 2) a letter alone; 3) an automated telephone message followed by a letter 1 week later; and 4) a letter followed by an automated telephone message 1 week later. The primary outcome was receipt of any needed immunization by 24 months of age. Decision analysis was used to evaluate the projected cost-effectiveness of the alternative strategies. RESULTS: A total of 648 children were randomized. A letter followed by a telephone message (58% immunized) was significantly better than either a letter alone (44% immunized) or a telephone message alone (44% immunized). A telephone message followed by a letter (53% immunized) also was more effective than either alone, although the differences were not statistically significant. Among a similar comparison group that received no systematic intervention, 36% were immunized. The estimated cost per child immunized was $7.00 using letters followed by automated telephone messages, $9.80 using automated telephone messages alone, and $10.50 using letters alone. Under alternative cost assumptions for automated telephone messages and mailed messages, the cost per child immunized ranged from $2.20 to $6.50. CONCLUSIONS: For underimmunized 20-month-olds in this HMO setting, letters followed by automated telephone messages were more effective and cost-effective than either message alone. The cost-effectiveness of automated telephone messages and letters may vary widely depending on the setting, and choices among strategies should be tailored to the populations being served.
Authors: Lieu TA; Capra AM; Makol J; Black SB; Shinefield HR
Pediatrics. 1998 Apr;101(4):E3.
Computer-based models to identify high-risk children with asthma
Effective management of populations with asthma requires methods for identifying patients at high risk for adverse outcomes. The aim of this study was to develop and validate prediction models that used computerized utilization data from a large health-maintenance organization (HMO) to predict asthma-related hospitalization and emergency department (ED) visits. In this retrospective cohort design with split-sample validation, variables from the baseline year were used to predict asthma-related adverse outcomes during the follow-up year for 16,520 children with asthma-related utilization. In proportional-hazard models, having filled an oral steroid prescription (relative risk [RR]: 1.9; 95% confidence interval [CI]: 1.3 to 2.8) or having been hospitalized (RR: 1.7; 95% CI: 1.1 to 2.7) during the prior 6 mo, and not having a personal physician listed on the computer (RR: 1.6; 95% CI: 1.1 to 2.3) were associated with increased risk of future hospitalization. Classification trees identified previous hospitalization and ED visits, six or more beta-agonist inhalers (units) during the prior 6 mo, and three or more physicians prescribing asthma medications during the prior 6 mo as predictors. The classification trees performed similarly to proportional-hazards models, and identified patients who had a threefold greater risk of hospitalization and a twofold greater risk of ED visits than the average patient. We conclude that computer-based prediction models can identify children at high risk for adverse asthma outcomes, and may be useful in population-based efforts to improve asthma management.
Authors: Lieu TA; Quesenberry CP; Sorel ME; Mendoza GR; Leong AB
Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1173-80.
Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group
The Women’s Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components–dietary modification (DM) or hormone replacement therapy (HRT)–of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.
Authors: Valanis B; Stevens V; Whitlock E; Karanja N; Clark A; Hiatt R; Caan B; Ettinger B; Sidney S; Bailey G
Control Clin Trials. 1998 Feb;19(1):61-109.
Varicella serology among school age children with a negative or uncertain history of chickenpox
BACKGROUND: Clinicians who offer varicella vaccination to school age children face the dilemma of whether to serotest or vaccinate presumptively. Varicella seroprevalence among 7- to 12-year-old children with negative or uncertain histories has not previously been studied. Our main objective was to describe varicella seroprevalence among children ages 7 to 12 years with a negative or uncertain history of chickenpox. METHODS: This was a cross-sectional study of children whose clinicians had ordered varicella serotesting. Guidelines from the medical group’s regional pediatric infectious disease specialists recommended obtaining varicella serology on all children 7 to 12 years old with a negative or uncertain history. Parents were interviewed by telephone about the child’s history of chickenpox before test results were completed. RESULTS: Varicella seroprevalence ranged from 9% among 7-year-olds whose parents said they had definitely not had chickenpox to 68% among 11-year-olds whose parents were not sure whether they had had chickenpox. Among children whose parents were uncertain about their chickenpox history, almost one-half (48%) were seropositive. Twenty-five percent of children whose parents said they definitely had not and 32% of children whose parents said they had probably not had chickenpox were seropositive. Of parents whose children had experienced serotesting, 73% said they would prefer to have the blood test first rather than presumptive vaccination. For a large health maintenance organization, it was projected to be most cost-effective (in terms of cost per chickenpox case prevented) to recommend testing for children 9 to 12 years old with uncertain histories of chickenpox. CONCLUSIONS: We conclude that among children 7 to 12 years old with negative or uncertain histories of chickenpox, varicella seroprevalence ranges from 9 to 68% depending on age and clinical history. Parents are generally receptive to serotesting, although individual preferences vary. In the population we studied it would be most cost-effective to recommend testing before deciding about vaccination for children 9 to 12 years old with uncertain histories of chickenpox.
Authors: Lieu TA; Black SB; Takahashi H; Ray P; Capra AM; Shinefield HR; Adler NE
Pediatr Infect Dis J. 1998 Feb;17(2):120-5.
Differences in fertility associated with caffeinated beverage consumption
OBJECTIVES: The effect of caffeine consumption on fertility was examined prospectively in 210 women. METHODS: Women reported on caffeinated beverage consumption and pregnancy status monthly. Odds ratios for becoming pregnant were calculated for both high and moderate vs low consumption. RESULTS: No significant association was found for any of the caffeinated beverages except tea. Drinking one-half cup or more of tea daily approximately doubled the odds of conception per cycle. CONCLUSIONS: These data suggest that caffeine may not be the responsible agent for variation in fertility associated with consumption of the beverages examined.
Authors: Caan B; Quesenberry CP Jr; Coates AO
Am J Public Health. 1998 Feb;88(2):270-4.
Quality of life, health care utilization, and costs among women undergoing hysterectomy in a managed-care setting
OBJECTIVE: We compared quality of life, utilization, and costs for women undergoing elective abdominal, laparoscopically assisted vaginal, or vaginal hysterectomy within a managed-care organization. STUDY DESIGN: A prospective study of 287 women who underwent an elective hysterectomy was performed. RESULTS: Patients undergoing a vaginal hysterectomy reported returning to normal activity levels sooner and had more favorable quality-of-life scores than did those undergoing laparoscopically assisted vaginal hysterectomy or abdominal hysterectomy. Laparoscopically assisted vaginal hysterectomy was often nearly as favorable as vaginal hysterectomy, particularly at 28 days after the operation, whereas the abdominal hysterectomy group consistently reported the poorest postoperative quality-of-life scores. No significant differences were noted in utilization or costs in the 60-day preoperative period, whereas hospitalization and postoperative costs were highest among the abdominal hysterectomy group and lowest for those undergoing a vaginal hysterectomy. CONCLUSIONS: Vaginal hysterectomy resulted in better quality-of-life outcomes and lower utilization and costs compared with laparoscopically assisted vaginal or abdominal hysterectomy.
Authors: Van Den Eeden SK; Glasser M; Mathias SD; Colwell HH; Pasta DJ; Kunz K
Am J Obstet Gynecol. 1998 Jan;178(1 Pt 1):91-100.
