Children prenatally exposed to antipsychotics do not have increased risk for neurodevelopmental disorders

Children of women who took antipsychotic medications late in their pregnancy did not demonstrate increased risk of neurodevelopmental disorders, according to findings published in JAMA Internal Medicine.

Women who take these drugs are at risk for having children with neurodevelopmental problems, but it is due to other lifestyle and medical factors, not the drugs; so we really need to be doing more to support these mothers with psychiatric illness."

Katherine Wisner, MD, the Norman and Helen Asher Professor of Psychiatry and Behavioral Sciences in the Division of General Psychiatry and of Obstetrics and Gynecology and co-author of the study

In the U.S., antipsychotic medications are commonly prescribed to women of childbearing age to treat severe mental disorders, including bipolar, major depressive and anxiety disorders. Furthermore, the expansion of approved and off-label antipsychotic drug prescriptions has led to increased antipsychotic drug use among pregnant women over the last two decades.

While previous studies using animal test subjects have demonstrated that antipsychotic medications may cause some degree of neurotoxicity, there was little known about the impact on children prenatally exposed to antipsychotic medications.

In the current study, the investigators utilized two publicly available prospective datasets — the Medicaid Analytic eXtract (MAX) and the IBM Health MarketScan Research Database (MarketScan) — both of which contain data regarding publicly and privately insured mothers in the U.S. and their children who received up to 14 years of follow-up analysis.

The MAX cohort consisted of more than two million pregnancies without antipsychotic drugs and more than 9,500 pregnancies in which women took one or more antipsychotic medication during the second half of their pregnancy. These women were an average age of 27 years old; 2.1 percent were Asian or Pacific Islander, 28.5 percent were Black, 5.2 percent were Hispanic or Latino, and 56.1 percent were white.

The MarketScan cohort consisted of approximately 1.3 million pregnancies without antipsychotic drugs and 1,200 pregnancies in which antipsychotics were used. Pregnant women who took antipsychotic drugs were an average age of 33 years, however race and ethnicity data were not available.

"The reason we focused on the second half of pregnancy is because in the literature, the vast majority of exposures associated with neurodevelopmental problems occurred in the second trimester," said Wisner, who is also director of the Asher Center for the Study and Treatment of Depressive Disorders.

After controlling for maternal characteristics and other factors that may negatively affect the fetal environment, the investigators found that the increased risk of neurodevelopmental disorders in children born to women who took antipsychotic medications was related to maternal characteristics and not to the exposure to antipsychotic medication.

The authors did note a low-level association with exposure to the antipsychotic medication aripiprazole, which is commonly used to treat adults and children with schizophrenia, however further investigation is warranted.

Overall, the findings highlight the importance of closely monitoring the neurodevelopment of children born to women with mental illnesses and implementing interventions for these women earlier, according to the authors.

"We need to treat these women, but also know that they’re at risk of having a child with neurodevelopmental problems and that we need to provide child developmental support," Wisner said.

Source:
Journal reference:

Straub, L., et al. (2022) Association of Antipsychotic Drug Exposure in Pregnancy With Risk of Neurodevelopmental Disorders. A National Birth Cohort Study. JAMA Internal Medicine. doi.org/10.1001/jamainternmed.2022.0375.

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