Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study

Abstract

Objective: To evaluate maternal medical and perinatal outcomes associated with antipsychotic drug use in pregnancy.

Design: High dimensional propensity score (HDPS) matched cohort study.

Setting: Multiple linked population health administrative databases in the entire province of Ontario, Canada.

Participants: Among women who delivered a singleton infant between 2003 and 2012, and who were eligible for provincially funded drug coverage, those with ≥ 2 consecutive prescriptions for an antipsychotic medication during pregnancy, at least one of which was filled in the first or second trimester, were selected. Of these antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a HDPS algorithm.

Main outcome measures: The main maternal medical outcomes were gestational diabetes, hypertensive disorders of pregnancy, and venous thromboembolism. The main perinatal outcomes were preterm birth (<37 weeks), and a birth weight <3rd or >97th centile. Conditional Poisson regression analysis was used to generate rate ratios and 95% confidence intervals, adjusting for additionally prescribed non-antipsychotic psychotropic medications.

Results: Compared with non-users, women prescribed an antipsychotic medication in pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio 1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to 1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate, though high among antipsychotic users (14.5%) and matched non-users (14.3%), was not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight <3rd centile or >97th centile was associated with antipsychotic drug use in pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively).

Conclusions: Antipsychotic drug use in pregnancy had minimal evident impact on important maternal medical and short term perinatal outcomes. However, the rate of adverse outcomes is high enough to warrant careful assessment of maternal and fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.

Fig 1 Main maternal medical outcomes in a cohort of 1021 women who were prescribed an antipsychotic drug during pregnancy and who were matched 1:1 with 1021 non-users by means of a high dimensional propensity score (HDPS) algorithm. Relative risks compare antipsychotic drug users—restricted to use of any atypical antipsychotic drug, and specifically, quetiapine, olanzapine, or risperidone—with matched non-users

Fig 2 Main perinatal outcomes in a cohort of 1021 women who were prescribed an antipsychotic drug during pregnancy and who were matched 1:1 with 1021 non-users by means of a high dimensional propensity score (HDPS) algorithm. Relative risks compare antipsychotic drug users—restricted to use of any atypical antipsychotic drug, and specifically, quetiapine, olanzapine, or risperidone—with matched non-users