Systematic Review: Antipsychotic Medication in Pregnancy and Neurodevelopmental Outcomes in Children - 23/07/25

Doi : 10.1016/j.jaac.2025.04.008

Carly A. Kaplan, BS ^a, Eline M.P. Poels, MD, PhD ^b, Marion I. van den Heuvel, PhD ^c, Hilmar H. Bijma, MD, PhD ^b, Veerle Bergink, MD, PhD ^a, Anna-Sophie Rommel, PhD ^a, Thalia Robakis, MD, PhD ^b,^⁎
^a Icahn School of Medicine at Mount Sinai, New York City, New York
^b Erasmus University Medical Center, Rotterdam, the Netherlands
^c Tranzo Scientific Center for Care and Wellbeing, Tilburg University, The Netherlands

^∗Correspondence to Thalia Robakis MD, PhD, 1425 Madison Avenue L4-45, New York, NY 100291425 Madison Avenue L4-45New YorkNY10029

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 23 July 2025

Abstract

Objective

Antipsychotic medications are widely prescribed, including during pregnancy, and pregnant individuals worry about the potential sequelae for the child. Although antipsychotics do not seem to be teratogenic, the long-term neurodevelopmental impact of prenatal exposure remains unclear. A systematic review was conducted to determine if intrauterine antipsychotic exposure increases the risk of adverse neurodevelopmental outcomes.

Method

A systematic search was performed in MEDLINE, Cochrane, Embase, and PsycINFO for studies published before September 7, 2024. We included original studies assessing cognitive, motor, behavioral, social, and psychiatric outcomes in children prenatally exposed to antipsychotics, excluding case reports, reviews, preclinical studies, and studies without a control group. Quality and risk of bias were assessed using the Newcastle-Ottawa Scale.

Results

Of 1,349 studies identified, full text of 56 was screened, and 16 were included in the review. The number of exposed participants ranged from 11 to >15,000. In the 8 studies assessing motor development, early motor delays were observed but did not persist into later childhood. Neurodevelopmental disorders were assessed in 7 studies. Crude estimates showed greater risk in exposed children, but after adjusting for confounders, most studies found no significant risk. The mean NOS score was 7.1.

Conclusion

Transient motor delays may be associated with antipsychotic use during pregnancy, although future studies adjusting for confounding factors should clarify this risk. After adjustment for confounders, the risk of neurodevelopmental disorders in school-age children does not seem to be increased. Studies with longer follow-up time are required to further investigate the risk of neurodevelopmental disorders.

Study registration information

Neurodevelopmental Consequences of Antenatal Exposure to Antipsychotic Medication: A Systematic Review and Meta-Analysis; CRD42024499352.

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Key words : antipsychotic, neurodevelopment, neurodevelopmental disorders, offspring, pregnancy

Plan

Assessment of Risk of Bias and Study Quality

Results

Motor Development

Neurodevelopmental and Psychiatric Disorders

School Performance

Other Neurodevelopmental Measures

Risk of Bias and Quality of Included Studies

Discussion

Caveats and Confounding Factors

Clinical Recommendations

Future Directions

CRediT authorship contribution statement

	This study was funded by the National Institutes of HealthEunice Kennedy Shriver National Institute of Child Health & Human Development (# R01HD111117, PI: Robakis) and by the National Institutes of Mental Health (#R01MH122869, PI: Bergink).
	Data Sharing: Data collected for the study will not be made available to others.
	The authors would like to thank Gloria Willson, MLIS, MPH, Director of Library Education & Research Services at Levy Library of Icahn School of Medicine at Mount Sinai, for the work she contributed by assisting the research team in building and executing the search for this review.
	Disclosure: Thalia Robakis provides consulting services to the Motherhood Center of New York and serves on a Data Safety and Monitoring Board for Reunion Neuroscience. Carly A. Kaplan, Eline M.P. Poels, Marion I. van den Heuvel, Hilmar H. Bijma, Veerle Bergink, and Anna-Sophie Rommel have reported no biomedical financial interests or potential conflicts of interest.