Educational outcomes associated with prenatal exposure to antiseizure medications: A systematic literature review and meta-Analysis

Abstract

Objective

To systematically review and meta-analyse evidence of the associations between prenatal exposure to antiseizure medications (ASMs) and educational outcomes in childhood, including educational difficulties, learning difficulties and academic performance.

Methods

We conducted a systematic review following the PICOS framework and PRISMA guidelines. MEDLINE (Ovid), CINAHL, PubMED, ERIC, and PsycINFO databases, along with Google Scholar, were searched from inception to 28 June 2024. Study quality was assessed using the Newcastle-Ottawa Scale and ROBINS-E. Relevant outcomes included record of special education needs, school-related behavioural problems, learning difficulties, and examination scores in core academic subjects. Pooled estimates were derived where appropriate and bias and heterogeneity assessed using funnel plots, Egger’s tests, and I² tests.

Results

Seventeen studies (12 cohort, 5 case-control) were included, encompassing 854,142 participants. Pooled estimates indicated that prenatal exposure to ASMs was associated with increased educational difficulties (RR 1.3, 95 % CI 1.01–1.69, p = 0.04), with sodium valproate showing the strongest association (RR 2.38, 95 % CI 1.25–4.53, p = 0.01). Carbamazepine and other first-generation ASMs showed no significant associations. Narrative findings suggested associations between newer-generation ASMs and educational difficulties, but limited data precluded quantitative synthesis. Studies assessing academic outcomes suggested lower academic performance among children exposed to sodium valproate or ASM polytherapy but could not undergo meta-analysis due to methodological heterogeneity.

Conclusions

Prenatal exposure to first-generation ASMs, especially sodium valproate, was associated with increased educational support needs. Newer-generation ASMs appear to have a more favourable risk profile, though evidence remains limited, underscoring the need for further high-quality research to inform clinical practice.