1. Prenatal exposure to commonly prescribed antipsychotic medications did not appear to meaningfully increase risk of neurodevelopmental disorders in offspring.
2. The potential risk of neurodevelopmental disorder associated with aripiprazole requires further validation before causality can be assumed.
Evidence Rating Level: 2 (Good)
Study Rundown: Preclinical studies in animal models have demonstrated the neurocognitive sequelae of prenatal exposure to antipsychotic medications, however, its effect in humans during pregnancy has not been well described. This large-scale epidemiologic study nested in nationwide public and private health care utilization databases evaluated the association between in utero exposure to antipsychotic drugs and neurodevelopmental disorders (NDDs) in children. The main outcomes included autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disability, speech or language disorder, developmental coordination disorder, intellectual disability, behavioral disorder, and the composite outcome of any NDD. Among 3.4 million children with up to 14 years of follow-up, commonly prescribed antipsychotic medications did not appear to meaningfully increase NDD risk in offspring, with the possible exception of exposure to aripiprazole. Although the benefits of antipsychotic treatment for pregnant women with severe mental illness are clear, close monitoring of neurodevelopment in offspring is recommended to ensure early intervention and support. A limitation of this study was that antipsychotic drug exposure was based solely on prescription status in the databases and not on clinical evidence of exposure leading to potential misclassification and confounding in the exposure group.
In-Depth [prospective cohort]: This birth cohort study included data from publicly (MAX, 2000-2014) and privately insured (MarketScan, 2003-2015) mother-child dyads, assessed for risks of NDD after prenatal exposure to any antipsychotic drug during the second half of pregnancy. The MAX cohort consisted of 2 034 883 unexposed and 9551 exposed pregnancies to antipsychotic medications (mean [SD] age, 26.8 [6.1] years). The MarketScan cohort consisted of 1 306 408 unexposed and 1221 exposed pregnancies (mean [SD] age, 33.1 [5.0] years). Hazard ratios (HRs) were estimated using Cox proportional hazards regression and combined through meta-analysis. After adjusting for confounding factors, risks were not meaningfully increased for exposure-outcome contrasts (eg, pooled unadjusted vs adjusted HRs [95%CI] for any NDD after any antipsychotic exposure: 1.91 [1.79-2.03] vs 1.08 [1.01-1.17]), with the possible exception of aripiprazole (1.36 [1.14-1.63]).
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