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

Abstract

ObjectivesSecond-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.DesignDescriptive cohort study using a prospectively collected database.SettingMotherisk Program, The Hospital for Sick Children, Toronto, Canada.Participants133 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 measuresMaternal, pregnancy, delivery and neonatal outcomes.Results72% 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.ConclusionsThe 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.

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…Extrapyramidal and withdrawal symptoms have been described in neonates following late pregnancy exposure to antipsychotic medication (Gentile, 2010;Habermann et al, 2013;Sadowski et al, 2013 effects-or-withdrawal-symptoms-in-newborns) have issued relevant safety labelling, and recommended relevant monitoring for neonates. However, studies that adequately controlled for confounding did not find a specific association between antipsychotic exposure and poor neonatal adaptation (Petersen et al, 2016;Vigod et al, 2015).…”

“…In general, studies that compare women exposed to antipsychotics in pregnancy to healthy unexposed women report moderately increased risks for several adverse maternal and infant outcomes (including congenital malformations, pre-term birth, fetal growth abnormalities and poor neonatal adaptation) (Boden et al, 2012b;Habermann et al, 2013;Reis and Kallen, 2008;Sadowski et al, 2013). By contrast, the few studies that used a comparison group of women with psychiatric illness but unexposed to antipsychotics (Boden et al, 2012a;Lin et al, 2010; National Institute for Health and Care Excellence, 2015a; Petersen et al, 2016), or studies that adequately controlled for confounding (Vigod et al, 2015), report few associations between antipsychotics and adverse maternal or infant outcomes.…”

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

“…Other research on antipsychotic treatment in pregnancy includes pharmacovigilance studies from drug companies' safety databases 76,77 as well as cohort studies based on various data sources. 38,50,[78][79][80][81][82][83][84][85] A systematic review 19 of many of these studies suggested that women requiring antipsychotic treatment during pregnancy have a higher risk of adverse birth outcomes. However, there was substantial heterogeneity between the studies and Coughlin et al 19 emphasise that most studies had limited adjustment for potential confounding and therefore the observed associations may not be causal.…”

Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach

“…Studies have suggested that antipsychotics are not or only slightly associated with increased risk of congenital malformations. [71][72][73][74][75][76] At the present time, it is difficult to define a clear connection between the development of malformations and the use of antipsychotics due to the lack of meta-analyses, systematic reviews, and adequate numbers of well-designed studies. Nevertheless, there are growing concerns on this issue.…”

“…When compared with healthy women, the risk was 1.5-2.5 times higher. [72][73][74]77 Overall, first generation antipsychotics (FGAs) and second generation antipsychotics (SGAs) have similar prevalence rates with regard to congenital malformations. 72,73 A prospective cohort study with a large sample size suggested that the increased risk of specific organ malformations was related solely to the cardiovascular system.…”