Associations between prenatal exposure to antipsychotics and attention-deficit/hyperactivity disorder, autism spectrum disorder, preterm birth and small for gestational age: a population-based cohort study

Abstract

Importance: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear. / Objective: To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems. / Design, Setting, Participants: This population-based cohort study included children born between 2001–2015 with follow-up to 2019, identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestational-exposed and gestational non-exposed with propensity score fine-stratification. Additional analyses included gestational-exposed versus past-exposed and sibling-matched analysis to evaluate the effect of confounding by indication. / Exposures: Prenatal antipsychotic exposure. Main outcomes and measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children. / Results: The cohorts included 333,749 mother-child pairs for ADHD and 411,251 pairs for ASD/preterm birth/small for gestational age analyses. There were 13,196 children (3.95%) diagnosed with ADHD, 8,715 (2.12%) with ASD, 33,891 (8.24%) preterm, and 7,009 (1.70%) small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% confidence interval [CI]=0.83-1.61) for ADHD and 1.06 (95%CI=0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95%CI=1.13-1.75) for preterm birth and 1.36 (95%CI=0.86-2.14) for small for gestational age, when comparing gestational-exposed to gestational non-exposed. Additional analyses showed no association when comparing gestational-exposed to past-exposed (ADHD: wHR=0.99, 95%CI=0.60-1.61); ASD: wHR=1.10, 95%CI=0.58-2.08; preterm birth: wOR=0.93, 95%CI=0.70-1.24; small for gestational age: wOR=1.21, 95%CI=0.66-2.20), and in sibling-matched analysis (ADHD: wHR=0.41, 95%CI=0.04-4.93; ASD: wHR=0.90, 95%CI=0.40-2.01; preterm birth: wOR=1.25, 95%CI=0.85-1.82; small for gestational age: wOR=0.86, 95%CI=0.32-2.31). / Conclusions and Relevance: We found no evidence that prenatal antipsychotics exposure increased the risk of ADHD, ASD or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestational-exposed to past-exposed and comparing gestational exposed to gestational non-exposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to stop their regular antipsychotic treatment during pregnancy