Antipsychotics exposure during pregnancy increases risk of neurodevelopmental disorders: JAMA

USA: The higher incidence of neurodevelopmental disorders (NDD) among children born to mothers who used antipsychotic medicines late in pregnancy appears to be explained by maternal factors rather than prenatal antipsychotic exposure, says an article published in the Journal of American Medical Association - Internal Medicine.

Although antipsychotic medications enter the placenta and animal studies indicate possible neurotoxic effects, data on human neurodevelopmental teratogenicity is sparse. Loreen Straub and colleagues undertook this investigation to determine whether children exposed to antipsychotic medication during pregnancy are at an elevated risk of neurodevelopmental disorders.

This birth cohort research analyzed data from the Medicaid Analytic eXtract (MAX, 2000-2014) and the IBM Health MarketScan Research Database (MarketScan, 2003-2015) for a nationwide sample of publicly (MAX) and privately (MarketScan) insured mother-child dyads during a 14-year period. The MAX cohort included 2 034 883 children who were not prenatally exposed to antipsychotic drugs and 9551 children who were prenatally exposed; the MarketScan cohort had 1 306 408 and 1221 children, respectively. Participants who received at least one medication dispensation during the second half of pregnancy were evaluated for any antipsychotic medicine, at the class level (typical and atypical), and for the most commonly used medications.

The key findings are as follow:

1. This MAX cohort included 2 034 883 unexposed pregnancies and 9551 pregnancies with one or more antipsychotic drug dispensing among women with a mean (SD) age of 26.8 (6.1) years, 204 (2.1%) of whom identified as 2720 (28.5%) as Black, 500 (5.2%) as Hispanic/Latino, Asian/Pacific Islander and 5356 (56.1%) as White.

2. The MarketScan cohort included 1 306 408 unexposed and 1221 exposed pregnancies among women aged 33.1 (5.0) years; race and ethnicity data were not available.

3. With the probable exception of aripiprazole, the uncorrected results were consistent with an approximately 2-fold elevated risk for most exposure-outcome comparisons.

4. However, risks were no longer appreciably increased following adjustment.

5. The findings were similar across all sensitivity studies.

In conclusion, the findings give much-needed clarification about NDD risk and may assist to influence treatment decisions during pregnancy, which is a complex trade-off between benefits and hazards. The advantages of antipsychotic medication for pregnant women suffering from severe mental disorders are undeniable. Although the observed 2-fold increase in the risk of NDD is not causally related to in utero antipsychotic drug exposure, it emphasizes the significance of monitoring the neurodevelopment of the children of women with mental illness to make sure that early interventions and supports are available.

Reference:

Straub, L., Hernández-Díaz, S., Bateman, B. T., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B., McDougle, C. J., Suarez, E. A., Zhu, Y., Zakoul, H., Mogun, H., & Huybrechts, K. F. (2022). Association of Antipsychotic Drug Exposure in Pregnancy With Risk of Neurodevelopmental Disorders. In JAMA Internal Medicine. American Medical Association (AMA). https://doi.org/10.1001/jamainternmed.2022.0375

Keywords: pregnancy, developmental disorder, neurology, antipsychotic, maternal, psychiatry, mental disorder, IQ, JAMA, Loreen Straub, neurodevelopmental disorders