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Record W4414003212 · doi:10.1016/j.seizure.2025.08.016

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

2025· article· en· W4414003212 on OpenAlexaboutno aff
Alexia Karain, Lama A Shakhshir, Jill P. Pell, Daniel Mackay, Scott M. Nelson, Sarjit Singh, Michael Fleming

Bibliographic record

VenueSeizure · 2025
Typearticle
Languageen
FieldMedicine
TopicPharmacological Effects and Toxicity Studies
Canadian institutionsnot available
FundersHealth Data Research UKEconomic and Social Research CouncilChief Scientist Office, Scottish Government Health and Social Care DirectorateMedical Research CouncilPublic Health AgencyScottish GovernmentBritish Heart FoundationUK Research and InnovationEngineering and Physical Sciences Research CouncilHealth and Social Care Research and Development DivisionNational Institute for Health and Care ResearchCancer Research UKHealth and Care Research Wales
KeywordsMeta-analysisMedicinePsychologyInternal medicine

Abstract

fetched live from OpenAlex

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 I 2 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.919
Threshold uncertainty score0.464

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.357
Teacher spread0.332 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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