While much data focuses on the risk of prenatal exposure to antiepileptic drugs (AEDs) and the risk of congenital malformations, there is a growing body of literature to indicate that  that exposure to certain antiepileptic drugs, most notably valproic acid (VPA, Depakote)  during critical periods of development may be associated with long-lasting neurodevelopmental deficits across multiple domains. While some of the newer AEDs (e.g., lamotrigine, leviceteram) appear to pose little risk, multiple reports have linked in utero exposure to valproate with adverse neurodevelopmental sequelae, including lower IQ and developmental delays in offspring. Several studies have shown that exposure to valproic acid (Depakote) may be associated with increased risk of autism spectrum disorders or autistic traits and/or attentional problems.

In a recent review, Kellogg and Meador review the current data on prenatal exposure to AEDs and neurodevelopmental outcomes (free text HERE).  Exposure to valproic acid has been implicated in a variety of adverse outcomes described in this review.  In contrast, prenatal exposure to lamotrigine and leviceteram have not been shown to adversely affect neurodevelopmental outcomes. The authors note, however, that many AEDs have not been adequately assessed.

In the second article listed below, Meador and colleagues highlight the importance of folic acid in women taking AEDs (FULL TEXT HERE). Recent studies support the positive neuropsychological effects of periconceptional folic acid in both healthy children and children exposed to AEDs.  Looking at data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, it appears that periconceptional folate improves neurodevelopmental outcomes in children with prenatal exposure to AEDs.

 

Ruta Nonacs, MD PhD

 

Kellogg M, Meador KJ.  Neurodevelopmental Effects of Antiepileptic Drugs. Neurochem Res. 2017 Jul;42(7):2065-2070. Free article. 

Meador KJ, Pennell PB, May RC, Brown CA, Baker G, Bromley R, Loring DW, Cohen MJ; NEAD Investigator Group.  Effects of periconceptional folate on cognition in children of women with epilepsy: NEAD study.  Neurology. 2020 Feb 18;94(7):e729-e740. PMID: Free article.

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