A study by American researchers suggests that the incidence of autism spectrum disorder is higher among children exposed to topiramate in the second half of pregnancy compared with the general population of children without exposure to anti-seizure medications in utero.
Sonia Hernández‑Díaz, MD DrPH from the Harvard TH Chan School of Public Health in Boston, and colleagues identified a population-based cohort of pregnant women and their children within two healthcare utilisation databases.
MedicalXpress reports that exposure to specific anti-seizure medications was defined based on prescription fills from gestational week 19 until delivery.
The researchers found that at eight-years-old, the estimated cumulative incidence of autism spectrum disorder was 1.9% for the 4 199 796 children who had not been exposed to anti-seizure medications.
On restriction to children born to mothers with epilepsy, the incidence was 4.2, 6.2, 10.5, and 4.1% with no exposure to anti-seizure medications, exposure to topiramate, exposure to valproate, and exposure to lamotrigine, respectively.
Compared with no exposure to anti-seizure medications, propensity score-adjusted hazard ratios were 0.96 (95% confidence interval, 0.56 to 1.65), 2.67 (95% confidence interval, 1.69 to 4.20), and 1.00 (95% confidence interval, 0.69 to 1.46) for exposure to topiramate, valproate, and lamotrigine, respectively.
“After adjustment for indication, the association was substantially attenuated for topiramate and lamotrigine, whereas a dose-dependent increased risk remained for valproate,” the authors write in the New England Journal of Medicine.
Study details
Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure
Sonia Hernández-Díaz, Loreen Straub, Brian Bateman, Yanmin Zhu, Helen Mogun, Katherine Wisner, Kathryn Gray, Barry Lester, Christopher McDougle, Elyse DiCesare, Page Pennell, Krista Huybrechts.
Published in New England Journal of Medicine on 21 March 2024.
Abstract
Background
Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other anti-seizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.
Methods
We identified a population-based cohort of pregnant women and their children within two health care utilisation databases in the United States, with data from 2000 through 2020. Exposure to specific anti-seizure medications was defined on the basis of 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 anti-seizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.
Results
The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to anti-seizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to anti-seizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score–adjusted hazard ratios in a comparison with no exposure to anti-seizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.
Conclusions
The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied anti-seizure 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.
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