Neurodevelopmental outcomes in children exposed to newer antiseizure medications: A systematic review

As prenatal exposure to certain older antiseizure medications (ASMs) has been linked with poorer neurodevelopmental outcomes in children, the use of newer ASMs throughout pregnancy has increased. The current review aimed to delineate the impact of in utero exposure to these newer ASMs on child neurodevelopment. A systematic search of MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature Plus, and PsycINFO was conducted, limiting results to articles available in English and published after the year 2000. Studies investigating neurodevelopmental outcomes following in utero exposure to the following ASMs were eligible for inclusion in the review: eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, topiramate, and zonisamide. Thirty-five publications were identified, and a narrative synthesis was undertaken. Methodological quality was variable, with distinct patterns of strengths/weaknesses attributable to design. Most studies examined lamotrigine exposure and reported nonsignificant effects on child neurodevelopment. Comparatively fewer high-quality studies were available for levetiracetam, limiting conclusions regarding findings to date. Data for topiramate, gabapentin, and oxcarbazepine were so limited that firm conclusions could not be drawn. Concerningly, no studies investigated eslicarbazepine, lacosamide, perampanel, or zonisamide. Exposure to certain newer ASMs, such as lamotrigine and levetiracetam, does not thus far appear to impact certain aspects of neurodevelopment, but further delineation across the different neurodevelopmental domains and dosage levels is required. A lack of data cannot be inferred to represent safety of newer ASMs, which are yet to be investigated.