Hydroxychloroquine and Preeclampsia in a Diverse Cohort of Women with SLE

Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as preeclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce preeclampsia risk in lupus pregnancy. Using a cohort of pregnancies in prevalent SLE patients at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ use in early pregnancy reduced the risk of preeclampsia/eclampsia. Among SLE pregnancies from 2011-2020, we assessed HCQ use from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of use. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RR) and 95% confidence intervals of the association between HCQ and preeclampsia/eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody status was investigated through stratified analysis. There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and preeclampsia/eclampsia. The RRs were consistently lower among the nullipara pregnancies, and RRs were consistently protective but not statistically significant among the high-risk subgroup of those with history of nephritis, aPL positivity, or pregestational hypertension (both nullipara and multipara). Although this study found no reduced risk of HCQ on preeclampsia/eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data.

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