Childhood autism may be linked to prenatal exposure to antiseizure medication

Key takeaways:

• Autism spectrum disorder risk was similar with prenatal topiramate or lamotrigine vs. no antiseizure medication exposure.
• Prenatal valproate was tied to a dose-dependent increased autism spectrum disorder risk.

Autism spectrum disorder incidence was higher for children with prenatal exposure to antiseizure medications vs. the general population, but some associations weakened after adjusting for treatment indication, researchers reported.

“Data to inform neurodevelopmental outcomes in children exposed to topiramate in utero have been limited and mixed. A recent Nordic study showed an increased risk for autism spectrum disorder after prenatal exposure to topiramate on the basis of a small number of cases in exposed children,” Sonia Hernández-Díaz, MD, DrPH, professor of epidemiology at the Harvard T.H. Chan School of Public Health, and colleagues wrote. “Future evaluation of the risk of autism spectrum disorder among children with prenatal exposure to topiramate is needed to inform its safety for women with epilepsy or other potential indications, including bipolar disorder, migraine and weight loss.”

Hernández-Díaz and colleagues conducted a population-based cohort study, published in The New England Journal of Medicine, with data from 4,292,539 pregnancies within two health care utilization databases in the U.S. from 2000 to 2020. Researchers defined exposure to specific antiseizure medications based on prescription fills of topiramate, lamotrigine or valproate from 19 weeks’ gestation through delivery. Valproate was used as a positive control and lamotrigine was used as a negative control.

Researchers compared autism spectrum disorder incidence among children who were prenatally exposed to topiramate during the second half of pregnancy with children not exposed to any antiseizure medications during pregnancy.

Overall, 8,815 children born to mothers with epilepsy had no exposure to antiseizure medications, 4,205 had prenatal lamotrigine exposure, 1,030 had prenatal topiramate exposure and 800 had prenatal valproate exposure.

At age 8 years, estimated cumulative autism spectrum disorder incidence was 1.89% for children not exposed to any antiseizure medications during pregnancy. Among children born to mothers with epilepsy, autism spectrum disorder incidence was 4.21% for no exposure to antiseizure medications, 6.15% for prenatal topiramate exposure, 10.51% for prenatal valproate exposure and 4.08% for prenatal lamotrigine exposure.

Among children born to mothers with epilepsy, the weighted average HRs were 0.96 (95% CI, 0.56-1.65) for prenatal topiramate exposure, 2.67 (95% CI, 1.69-4.2) for prenatal valproate exposure and 1 (95% CI, 0.69-1.46) for prenatal lamotrigine exposure compared with no exposure to antiseizure medication.

In addition, HRs tied to prenatal valproate exposure were larger with the use of higher vs. lower doses and were lower for exposure early vs. later in pregnancy compared with no exposure to antiseizure medication.

“Overall, results suggest no substantially increased risk of autism spectrum disorder after prenatal exposure to either topiramate or lamotrigine and a dose-dependent increased risk of autism spectrum disorder associated with prenatal valproate exposure,” the researchers wrote.