OBJECTIVES: Among hospitalized NICU infants, preimmunization apnea is a well-recognized predictor of postimmunization apnea. However, predictors for postimmunization apnea among NICU infants without preimmunization apnea have not been investigated. METHODS: Using a large NICU database in the Northern California Kaiser Permanente Medical Care Program, we abstracted NICU charts of infants who were hospitalized for > or = 53 days and who were also immunized, capturing preimmunization (24 hours before immunization) and postimmunization (48 hours after immunization) events. We assessed factors associated with postimmunization apnea by using multivariate logistic regression. RESULTS: Of 16,146 infants admitted to the NICU, 557 received > or = 1 vaccine and 497 met the criteria for study entry. All infants with preimmunization apnea (n = 27) and all except 3 infants with postimmunization apnea (n = 65) had gestational ages of < 31 weeks. Multivariate analyses revealed preimmunization apnea as the most important predictor of postimmunization apnea, although higher 12-hour Score for Neonatal Acute Physiology II and age of < 67 days (mean cohort age) were also associated. Multivariate analysis exclusively among infants without preimmunization apnea similarly found elevated Score for Neonatal Acute Physiology II, age of < 67 days, and weight of < 2000 g to be associated with postimmunization apnea. Forty-nine infants without preimmunization apnea and with > or = 1 apnea predictor were discharged within 48 hours after immunization; 2 were subsequently readmitted because of apnea. CONCLUSIONS: For infants in the NICU without apnea during the 24 hours immediately before immunization, younger age, smaller size, and more severe illness at birth are important predictors of postimmunization apnea.