Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age | Attention Deficit/Hyperactivity Disorders | JAMA Internal Medicine | JAMA Network
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    Original Investigation
    August 16, 2021

    Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age

    Author Affiliations
    • 1Research Department of Practice and Policy, UCL School of Pharmacy, London, England
    • 2Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
    • 3Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region, China
    • 4Groningen Research Institute of Pharmacy, Unit of PharmacoTherapy, Epidemiology and Economics, University of Groningen, Groningen, the Netherlands
    • 5Department of Paediatrics and Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
    • 6Murdoch Children’s Research Institute, Melbourne, Australia
    • 7Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
    • 8Department of Child and Adolescent Psychiatry, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, England
    JAMA Intern Med. 2021;181(10):1332-1340. doi:10.1001/jamainternmed.2021.4571
    Key Points

    Question  Does prenatal exposure to antipsychotics increase the risk of preterm birth, small for gestational age, attention-deficit/hyperactivity disorder (ADHD), or autism spectrum disorder (ASD)?

    Findings  In this cohort study of 411 251 mother-child pairs, there was not an increased risk of ADHD, ASD, preterm birth, and small for gestational age with prenatal use of antipsychotics. Maternal psychiatric disorders were associated with a significantly increased risk of ADHD and ASD, but not with preterm birth or small for gestational age in neonates.

    Meaning  The findings of this study suggest that there is no association between prenatal exposure to antipsychotics and ADHD, ASD, preterm birth, and small for gestational age; however, underlying maternal psychiatric disorders may be associated with the risk of ADHD and ASD in children.


    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, and Participants  This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a 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 (mean [SD] maternal age at delivery, 31.46 [5.03] years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean [SD] maternal age at delivery, 31.56 [5.01] years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% 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 gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (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 a 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  In this cohort study, the findings did not suggest 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 gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed 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 discontinue receipt of their regular antipsychotic treatment during pregnancy.