Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: a cohort study

Objectives Second-generation antipsychotics (SGAs), in conjunction with other psychotropic medications, are increasingly used to treat psychiatric disorders in pregnancy. The few available studies investigating the reproductive safety of SGAs did not reach conclusive results, and none have compared monotherapy with polytherapy involving other psychotropic medications. Design Descriptive cohort study using a prospectively collected database. Setting Motherisk Program, The Hospital for Sick Children, Toronto, Canada. Participants 133 women exposed to SGAs and other psychotropic drugs and 133 matched healthy controls were assessed and analysed. Outcomes of mother-child pairs exposed to SGAs in monotherapy (N=37) were compared with those exposed to SGAs with other psychotropic medications (in polytherapy; N=96). Main outcome measures Maternal, pregnancy, delivery and neonatal outcomes. Results 72% of exposed women received SGAs in polytherapy, and 101 women took their medications throughout pregnancy. These women had significantly higher pre-pregnancy weight, experienced more associated comorbidities and instrumental deliveries, and delivered a greater proportion of large for gestational age neonates. There were no differences in maternal weight gain in pregnancy between the exposed and comparison groups and between the monotherapy-exposed and polytherapy-exposed subgroups. The exposed neonates were more likely to be born premature, were admitted more often to the neonatal intensive care unit, presented with poor neonatal adaptation signs and had higher rates of congenital malformations. All the aforementioned neonatal outcomes were found mainly in the polytherapy subgroup. Conclusions The use of SGAs in polytherapy was prevalent in the assessed cohort and was associated with adverse pregnancy outcomes for both the mother and the child. In utero exposure to SGA monotherapy appears to be associated with less risk to the fetus. Future research should focus on polytherapy in pregnancy in order to define its reproductive safety and to separate the effects of medication exposure, underlying psychopathology and associated comorbidities.