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The associations between prenatal exposure to certain antiseizure medications (ASMs) and epilepsy risk among children are attenuated in sensitivity analyses, according to a study published online Feb. 26 in JAMA Network Open.

Julie Werenberg Dreier, Ph.D., from Aarhus University in Denmark, and colleagues examined whether use of valproate and other ASMs in pregnancy among mothers with epilepsy is associated with the risk for epilepsy in their children. The study included 38,663 children of mothers with epilepsy; children were followed from birth for a mean of 7.2 years.

The researchers found that the risks for epilepsy were increased for children of mothers who used valproate in pregnancy compared with 22,207 children of mothers not using an ASM in pregnancy (adjusted hazard ratios [aHRs], 2.18 and 2.10 for monotherapy and polytherapy, respectively). No dose-dependent association was seen, and the risk for epilepsy was similar in siblings who were exposed and unexposed to valproate. An increased risk for epilepsy was seen in association with prenatal exposure to topiramate monotherapy (aHR, 2.32); the risk was greater for higher doses and was attenuated in comparisons with children of mothers who discontinued topiramate before pregnancy. An increased risk for epilepsy was also seen in association with prenatal exposure to clonazepam monotherapy (aHR, 1.90), but further analyses were precluded by limited follow-up and low numbers.

“These findings suggest that prenatal ASM exposure may not increase epilepsy risk in children of mothers with epilepsy and indicate that differences were more likely associated with other underlying factors (e.g., possibly the heritability of the maternal epilepsy),” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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