Prenatal Topiramate Exposure and the Risk of Autism

Maternal use of Valproate during pregnancy may increase the risk of neurodevelopmental disorders in children. There is a lack of data on the risk of autism spectrum disorder associated with maternal topiramate use.

A recent study compared the children exposed to topiramate during the second half of pregnancy with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. The study used Valproate as a positive control and lamotrigine as a negative control and found-

• The estimated cumulative incidence of autism spectrum disorder at eight years of age for children who had not been exposed to antiseizure medication was 1.9%
• In children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication, 6.2% with exposure to topiramate, 10.5% with exposure to Valproate, and 4.1% with exposure to lamotrigine. 
• Propensity score-adjusted hazard ratios compared to no exposure to antiseizure medication were 0.96 for exposure to topiramate, 2.67 for exposure to Valproate, and 1.00 for exposure to lamotrigine.

This study proves that the incidence of autism spectrum disorder is higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, this association can be substantially attenuated after adjustment for indication and other confounders for topiramate and lamotrigine, yet the risk persists for Valproate; thus, it should be cautiously used.

Hernández-Díaz S, Loreen Straub PH, Bateman BT, et al. Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure. N Engl J Med 2024;390:1069-1079. DOI: 10.1056/NEJMoa2309359