Topiramate use during pregnancy has minimal effect on autism risk in children

Most women with epilepsy are treated with antiseizure medication throughout pregnancy. Valproate is a known teratogen and, when taken during pregnancy, has been associated with an increased risk of neurodevelopmental disorders in children, including decreased neurocognitive function, and increased risks of autism spectrum disorder and attention-deficit hyperactivity disorder. Most studies of other antiseizure medications have not shown increased risks of these neurodevelopmental disorders. Studies have generally not linked maternal lamotrigine use with adverse neurodevelopmental outcomes, but there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use. A new study, funded by the US National Institute of Mental Health, examined a population-based cohort of pregnant women and their children using two US healthcare utilization databases, with data collected from 2000 through 2020. Antiseizure medication exposure was based on prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, while lamotrigine was used as a negative control. Propensity score overlap weighting was used to adjust for measured baseline confounders when each antiseizure medication was compared with the unexposed reference group.Results showed the following:The study included 4,292,539 eligible pregnancies; 2,469 had at least one prescription dispensed for topiramate during the second half of pregnancy, 1,392 for valproate, and 8,464 for lamotrigine, while 4,199,796 were not dispensed any antiseizure medications.Among 28,952 women with a recorded epilepsy diagnosis, 1,030 had at least one prescription for topiramate dispensed during the second half of pregnancy, 800 for valproate and 4,205 for lamotrigine; 8,815 did not have prescriptions for any antiseizure medications dispensed in the 90 days before and during pregnancy.The estimated cumulative incidence of autism spectrum disorder at eight years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). When restricted to children born to mothers with epilepsy, the incidence of autism spectrum disorder was 4.2% with no exposure to antiseizure medication (8,815 children), 6.2% with exposure to topiramate (1,030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4,205 children). Propensity score–adjusted hazard ratios (in comparison with no exposure to antiseizure medication) were 0.96 for exposure to topiramate (95% confidence interval [CI], 0.56–1.65), 2.67 for exposure to valproate (95% CI, 1.69–4.20) and 1.00 for exposure to lamotrigine (95% CI, 0.69–1.46).The authors concluded that the incidence of autism spectrum disorder was higher among children prenatally exposed to topiramate, valproate or lamotrigine than in the general population. However, after adjustment for confounders, the association with autism spectrum disorder was substantially reduced for topiramate and lamotrigine, whereas an increased risk remained for valproate. Reference:1. Hernández-Díaz S, Straub L, Bateman BT, et al. Risk of autism after prenatal topiramate, valproate, or lamotrigine exposure. N Engl J Med 2024;390:1069-79. (accessed April 4, 2024).

Topiramate use during pregnancy has minimal effect on autism risk in children

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