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Risk of neurotoxic effects of prenatal antipsychotic exposure appears low, but questions linger

JAMA Internal Medicine
Reuters Health - 28/03/2022 - Babies exposed to antipsychotic medication in the womb do not appear to have a "meaningfully increased" risk of neurodevelopmental disorders, according to a large study. 

"Although antipsychotic drugs cross the placenta and animal data suggest potential neurotoxic effects, information regarding human neurodevelopmental teratogenicity is limited," researchers note in JAMA Internal Medicine. 

The findings suggest that antipsychotic medications "may not have important neurotoxic effects," although a "potential signal" identified for aripiprazole requires further study, say Dr. Loreen Straub of Brigham and Women's Hospital in Boston and colleagues. 

The birth-cohort study included data on roughly 3.4 million children followed for up to 14 years, including 3.34 million children with no prenatal antipsychotic exposure and 10,765 with prenatal exposure during the second half of pregnancy. 

In unadjusted analysis, the results were consistent with a roughly two-fold increased risk for most neurodevelopmental disorders (unadjusted hazard ratio, 1.91; 95% CI, 1.79 to 2.03). 

However, these risks were no longer "meaningfully increased" after adjustment for confounding by maternal characteristics and other factors that may negatively affect the fetal environment (adjusted HR, 1.08; 95% CI, 1.01 to 1.17), the researchers say. 

The possible exception was prenatal exposure to aripiprazole (adjusted HR, 1.36; 95% CI: 1.14 to 1.63). "Post hoc analyses to explore the positive association observed for aripiprazole did not allow us to rule out causality," the authors caution. 

"These findings provide much needed clarity regarding NDD risk and may help to inform treatment decision-making in pregnancy, which is a sophisticated trade-off between benefits and risks," they write. 

"The benefits of antipsychotic treatment for pregnant women with severe mental illness are undisputed," they point out. 

"Although the observed two-fold increase in risk of NDD is not causally related with in utero exposure to antipsychotic drugs, it does highlight the importance of closely monitoring the neurodevelopment of the offspring of women with mental illness to ensure that early intervention and support can be instituted when needed," they add. 

Support for the study was provided by the National Institutes of Health. Dr. Straub has no relevant disclosures. 

SOURCE: https://bit.ly/3iMbvd3  JAMA Internal Medicine, online March 28, 2022. 

By Reuters Staff

© 2023 The Author(s). Published by Medicom Medical Publishers.
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