Antipsychotic use during pregnancy and risk of specific neurodevelopmental disorders and learning difficulties in children: a multinational cohort study

Background: Antipsychotics are commonly prescribed to treat a range of psychiatric conditions in women of reproductive age and during pregnancy, including schizophrenia, bipolar disorder, anxiety, depression, autism spectrum disorder, and insomnia. This study aimed to evaluate whether children exposed to antipsychotic medication prenatally are at increased risk of specific neurodevelopmental disorders and learning difficulties. Methods: Our population-based cohort study used nationwide register data (1 January 2000-31 December 2020) on pregnant women diagnosed with a psychiatric disorder and their live-born singletons from Denmark, Finland, Iceland, Norway, and Sweden. Cox proportional hazard regression yielded propensity score-weighted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of intellectual-, speech or language-, learning-developmental disorders, and a composite outcome of the listed disorders. We defined poor performance as scoring within the lowest quartile on national school tests in mathematics and language arts. We estimated propensity score-weighted risk ratios (aRRs) using Poisson regression. We analysed data from Denmark separately and pooled results using random effects meta-analysis. Findings: Among 213,302 children (median follow-up: 6.7 years), 11 626 (5.5%) were exposed to antipsychotics prenatally. Adjusted risk estimates did not suggest an increased risk of neurodevelopmental disorders: aHR of 1.06 (95% CI 0.94-1.20) for the composite outcome, or for poor academic performance: aRR of 1.04 (95% CI 0.91-1.18) in mathematics, and of 1.00 (95% CI 0.87-1.15) in language arts. Results were generally consistent across individual medications, trimesters of exposure, sibling- and sensitivity analyses. Interpretation: The findings of this large multinational cohort study suggest there is little to no increased risk of child neurodevelopmental disorders or learning difficulties after prenatal exposure to antipsychotics. Our findings can assist clinicians and women managing mental illness during pregnancy. Funding: This study was funded by the NordForsk Nordic Program on Health and Welfare (Nordic Pregnancy Drug Safety Studies, project No. 83539), by the Research Council of Norway (International Pregnancy Drug Safety Studies, project No. 273366) and by the Research Council of Norway through its Centres of Excellence funding scheme (project No. 262700), and UNSW Scientia Programme Awards (PS46019, PS46019-A).