Risk of neurodevelopmental disorders after fetal topiramate exposure: a systematic review

Recent studies suggest an association between fetal topiramate exposure and an increased risk of neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD), intellectual disability (ID) and attention deficit hyperkinetic disorder (ADHD). This systematic review aimed to evaluate the evidence for such an association.

A systematic literature search was conducted in Medline, Cochrane, and Embase on 16 December 2024, with automatic updates running until submission. Articles were examined if they included any number of offsprings of persons with epilepsy of childbearing potential (PWECP) exposed to topiramate during pregnancy. The main comparison was offspring of pregnant people without epilepsy and no antiseizure medication use, or alternatively antiseizure medication apart from topiramate. The search was limited to English language articles 2014-2024. The study followed PRISMA guidelines for reporting.

14 studies were included. The number of topiramate-exposed children ranged from 2 to 1,000. Most studies had a small group exposed to topiramate, and a large control group. Seven studies found a relationship between NDD outcomes and topiramate, three studies found no increased risk, and four studies were inconclusive. However, the risk seems mainly to be increased relative to no ASM use, and in many studies the risk was similar for lamotrigine and seemed lower than for valproate. Methodological approaches varied. Eleven studies were considered to be of good or fair quality, whereas three studies were considered to be of poor quality.

This systematic review shows that topiramate prescribing requires caution in PWECP and that topiramate use during pregnancy warrants special attention to the neurodevelopment of the child. The risk seems to be increased relative to no ASM use, is not necessarily higher than the risk for lamotrigine, and lower than the risk of valproate.