ADVERTISEMENT
Prenatal Exposure to Antiseizure Medications May Not Increase Risk of Epilepsy in Children
No association was found between exposure to antiseizure medications (ASMs), including valproate, during pregnancy and children developing epilepsy, in a recent prospective, population-based register cohort study results published in JAMA Network Open.
“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 (eg, possibly the heritability of the maternal epilepsy),” researchers noted.
>>NEWS: Odds of Epilepsy With Moderate Traumatic Brain Injury Higher in Nondeployed Veterans
The study was conducted in Denmark, Finland, Iceland, Norway, and Sweden, covering singletons born to mothers with epilepsy from January 1, 1996, to December 31, 2017. The main outcome, epilepsy in children, was determined through diagnoses from hospital care based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Secondary analyses included dose-response evaluations, comparisons with children of mothers who ceased ASM use before pregnancy, and sibling analyses to enhance the robustness of the findings. Data analysis spanned from October 2022 to December 2023.
In total, 38,663 children born to mothers with epilepsy were followed, with a mean follow-up of 7.2 years. Researchers found increased risks of epilepsy in children exposed to valproate during pregnancy (monotherapy: AHR, 2.18; 95% CI, 1.70-2.79; polytherapy: AHR, 2.10; 95% CI, 1.49-2.96), regardless of whether it was used alone or in combination with other medications. However, there was no dose-dependent association with valproate, and siblings exposed and unexposed to valproate showed similar epilepsy risks (AHR, 0.95; 95% CI, 0.50-1.82).
Additionally, prenatal exposure to topiramate and clonazepam monotherapy was associated with increased epilepsy risk (AHR, 1.90; 95% CI, 1.16-3.12), with higher doses exacerbating the risk for topiramate. No significant associations were observed for lamotrigine, levetiracetam, carbamazepine, or oxcarbazepine.
Researchers noted several limitations that could have affected study results. For one, their use of register-based identification of epilepsy could have led to some misclassification of participants’ epilepsy status and made it more difficult to certify the subtype of maternal epilepsy, they said.
With these study results, researchers hypothesize that epilepsy risk in children may depend more on other factors like heritability rather than medication use. “These analyses suggest that the increased risk of epilepsy found in children with prenatal valproate exposure was likely confounded by underlying factors associated with both maternal valproate use and the child’s risk of epilepsy (eg, the type of maternal epilepsy).”
