Risk of Major Malformations Following First-Trimester Exposure to Olanzapine

Purpose/Background Since its US Food and Drug Administration approval in 1996, olanzapine has been one of the most commonly prescribed atypical antipsychotics, making a better understanding of its reproductive safety profile critical. The goal of the current analysis was to determine the risk of major malformations among infants exposed to olanzapine during pregnancy compared with a group of nonexposed infants. Methods/Procedures The National Pregnancy Registry for Psychiatric Medications is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Labor and delivery and pediatric medical records were screened for evidence of major malformations followed by adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to olanzapine were compared with controls without second-generation antipsychotic exposure. Findings/Results As of April 18, 2022, 2619 women have enrolled in the study. At the time of data extraction, 49 olanzapine-exposed infants and 1156 infants in the comparison group were eligible for these analyses. There were no major malformations associated with olanzapine exposure in the first trimester. The absolute risk for major malformations in the exposure group was 0.00% (95% confidence interval, 0.00–7.25) for olanzapine compared with 1.64% (95% confidence interval, 0.99–2.55) in the control group. Implications/Conclusions In this prospective cohort, no major malformations were associated with olanzapine exposure during the first trimester. Although these data are preliminary and cannot rule out more modest effects, they are nonetheless important, adding to the growing reproductive safety data for olanzapine.