A large cohort study examining the risk of autism spectrum disorder following prenatal exposure to antiseizure medications found differing impacts for three commonly prescribed drugs: topiramate, valproate, and lamotrigine.

In the study, published in the The New England Journal of Medicine, investigators analyzed 2000 to 2020 data from U.S. health care databases and revealed that while prenatal exposure to these medications increased the risk of autism spectrum disorder (ASD) in pediatric patients compared with the general population, the risk varied significantly across the drugs.

Among pediatric patients born to mothers with epilepsy, the incidence of ASD at 8 years of age was 10.5% for those exposed to valproate, 6.2% for those exposed to topiramate, and 4.1% for those exposed to lamotrigine. In comparison, patients who were not exposed to any antiseizure medication during pregnancy had an incidence of ASD of 4.2%.

The study's propensity score-adjusted hazard ratios (HR) revealed a significant increase in the risk of ASD associated with valproate exposure (HR = 2.67, 95% confidence interval [CI] = 1.69–4.20), whereas no significant association was found with topiramate (HR = 0.96, 95% CI = 0.56–1.65) or lamotrigine (HR = 1.00, 95% CI = 0.69–1.46).

The cumulative incidence of ASD at 8 years among those in the general population, which did not include exposure to any antiseizure medication, was 1.9%. This figure highlighted the increased risk observed in pediatric patients exposed to valproate, a finding that was consistent with prior research indicating valproate's association with neurodevelopmental disorders.

The study, which adjusted for confounding factors such as the indication for use (epilepsy), showed that following adjustment, the association between prenatal exposure to topiramate and ASD was substantially attenuated. Similarly, lamotrigine exposure did not show a significant risk increase for ASD. In contrast, the increased risk for valproate remained significant, reinforcing previous findings regarding its potential teratogenic effects.

"The incidence of autism spectrum disorder was higher among [pediatric patients] prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate," indicated lead study author Sonia Hernández-Díaz, MD, DrPH, of the Department of Epidemiology at the Harvard T.H. Chan School of Public Health, and her colleagues.

While the risk of ASD was elevated in pediatric patients exposed to topiramate, valproate, and lamotrigine during pregnancy, the data suggested a strong association between valproate use and increased ASD risk, consistent with earlier findings. The results of the study emphasized the importance of careful medication management during pregnancy, particularly among women with epilepsy, where balancing seizure control with potential neurodevelopmental risks is crucial.