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Systematic Review: Antipsychotic Medication in Pregnancy and Neurodevelopmental Outcomes in Children
Carly A Kaplan1, Eline M P Poels2, Marion I van den Heuvel3
1Icahn School of Medicine at Mount Sinai, New York City, New York.
Insights
Prenatal exposure to antipsychotic medications may cause temporary motor delays in children. However, adjusted analyses indicate no increased risk of neurodevelopmental disorders in school-aged children following such exposure.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Psychopharmacology
Background:
- Antipsychotic medications are frequently prescribed, including during pregnancy.
- Pregnant individuals express concerns regarding potential adverse effects on child development.
- While not teratogenic, the long-term neurodevelopmental impact of in utero antipsychotic exposure requires thorough investigation.
Purpose of the Study:
- To systematically review existing literature to ascertain if intrauterine antipsychotic exposure elevates the risk of adverse neurodevelopmental outcomes in children.
- To synthesize evidence on cognitive, motor, behavioral, social, and psychiatric outcomes following prenatal antipsychotic exposure.
Main Methods:
- A comprehensive systematic search was conducted across major databases (MEDLINE, Cochrane, Embase, PsycINFO) for relevant studies published up to September 7th, 2024.
- Included were original studies with control groups assessing child neurodevelopmental outcomes; case reports, reviews, and pre-clinical studies were excluded.
- Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale (NOS).
Main Results:
- Out of 1349 identified studies, 16 met the inclusion criteria for the review.
- Eight studies on motor development indicated transient early motor delays, which did not persist into later childhood.
- Seven studies assessing neurodevelopmental disorders found no significant increased risk after adjusting for confounding factors, despite initial crude estimates suggesting otherwise.
Conclusions:
- Transient motor delays may be associated with antenatal antipsychotic exposure, warranting further investigation with adjusted analyses.
- Current evidence suggests no increased risk of neurodevelopmental disorders in school-aged children following adjustment for confounders.
- Longer follow-up studies are necessary to definitively assess the long-term neurodevelopmental risks associated with in utero antipsychotic exposure.
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.
Plain Language Summary:
This systematic review of research examines the mental, behavioral, and cognitive health outcomes of children whose mothers took antipsychotics during pregnancy. Sixteen articles were included in the review; the number of exposed participants in each study ranged from 11 to >15,000. The authors found that the majority of studies, especially those with longer-term follow-up and larger samples, did not identify increased neurodevelopmental problems in children who were exposed to antipsychotics during pregnancy. Some studies noted transient motor delays in exposed infants, but the authors found that they did not sufficiently account for the potential influence of severe maternal mental illness on this association.
Clinical Guidance:
• Antipsychotic use during pregnancy may be indicated for effective treatment of severe mental illness in pregnant women. • A discussion that involves the risks of untreated maternal mental illness alongside existing data on antipsychotic exposure in pregnancy and its potential neurodevelopmental impact on children is an important step in supporting informed decision making.
Study Registration Information:
Neurodevelopmental Consequences of Antenatal Exposure to Antipsychotic Medication: A Systematic Review and Meta-Analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024499352.
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