Cohort Study: Elevated autism spectrum disorder risk in children exposed to valproate during pregnancy

Study Design and Population: This cohort study utilized two health care utilization databases in the United States, covering the period from 2000 to 2020, to investigate the association between prenatal exposure to antiseizure medications and the risk of autism spectrum disorder (ASD) in children. The study compared children exposed to topiramate, valproate, or lamotrigine during the second half of pregnancy to those unexposed to any antiseizure medication, specifically focusing on a population-based cohort of pregnant women and their offspring.

Main Findings: The cumulative incidence of ASD at 8 years of age was found to be higher in children exposed to these medications compared to the general population. Notably, the incidence was 6.2% for children exposed to topiramate, 10.5% for valproate, and 4.1% for lamotrigine among children born to mothers with epilepsy. However, after adjusting for potential confounders, the increased risk of ASD remained significant only for valproate exposure, with a hazard ratio of 2.67, indicating a substantial risk compared to unexposed children. Topiramate and lamotrigine showed no significant increase in risk after adjustment.

Implications for Practice: The findings underscore the importance of carefully considering the risks and benefits of using antiseizure medications during pregnancy. Specifically, valproate should be used with caution, if at all, given its significant association with an increased risk of ASD in offspring. This study supports the need for targeted counseling and monitoring of pregnant women with epilepsy and highlights the necessity for further research to fully understand the neurodevelopmental impact of prenatal exposure to antiseizure medications.

Reference: Sonia Hernández-Díaz et al. (2024). Cohort Study: Assessing Autism Spectrum Disorder Risk in Children Exposed to Antiseizure Medications During Pregnancy. N Engl J Med, 390(13), 1069-1079. DOI: 10.1056/NEJMoa2309359. Access the study here: [Link]