Association of maternal epilepsy with perinatal outcomes, and an exploration of prenatal antiseizure medication: A population-based retrospective cohort study

Paolo Pieirino Mazzone; Jacqueline Stephen; Christopher J Weir; Sohinee Bhattacharya; Mairead Black; Richard F M Chin

doi:10.1111/epi.18484

Association of maternal epilepsy with perinatal outcomes, and an exploration of prenatal antiseizure medication: A population-based retrospective cohort study

Epilepsia. 2025 Jun 16. doi: 10.1111/epi.18484. Online ahead of print.

Authors

Paolo Pieirino Mazzone^{1

2}, Jacqueline Stephen³, Christopher J Weir^{1

3}, Sohinee Bhattacharya^#⁴, Mairead Black⁴, Richard F M Chin^{1

2

5}

Affiliations

¹ Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.
² Child Life and Health, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
³ Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK.
⁴ Aberdeen Centre for Women's Health Research, The Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
⁵ Royal Hospital for Children and Young People, Edinburgh, UK.

^# Contributed equally.

PMID: 40522274
DOI: 10.1111/epi.18484

Abstract

Objective(s): Pregnancy in women with epilepsy is associated with adverse perinatal outcomes, but debate remains as to role of epilepsy or of prenatal antiseizure medication (ASM), or both. We aimed to investigate the association between maternal epilepsy and perinatal outcomes, and to explore the role of prenatal ASM exposure.

Methods: Retrospective population-based cohort study using linked routinely-collected health data (Scotland, 2009-2021). We included women with at least one singleton pregnancy. Our exposures included (1) maternal epilepsy, identified using International Classification of Diseases, Tenth Revision codes; (2) prenatal ASM, defined as dispensed within the prenatal period. We conducted multi-level multiple regressions accounting for covariates and multiple pregnancies comparing: (1) women with (WWE) and without epilepsy (WWoE), (2) all pregnancies exposed and unexposed to prenatal ASMs, and (3) individual prenatal ASM monotherapy vs without ASM.

Results: A total of 629 200 pregnancies occurred from 2009-2021 (WWE = 2022, WWoE = 627 178; with ASM = 4406, without ASM = 624 794). WWE had increased odds of preterm birth, induced labor, cesarean section, preeclampsia, neonatal intensive care unit admission, low birth weight, and 5-min Apgar score <7. In fully adjusted models, only induced labor adjusted odds ratio aOR [95 CI]b 1.17 (95% confidence interval [CI]: 1.02-1.34) remained associated. Compared to women without ASM, those with ASM had increased odds of preterm birth (aOR 1.47, 95% CI: 1.25-1.74), induced labor (1.38, 1.25-1.52), cesarean section (1.14, 1.01-1.27), neonatal congenital conditions (1.34, 1.04-1.73), neonatal intensive care unit admission (1.54, 1.33-1.78), and low birthweight (1.47, 1.23-1.75). Increased odds were also observed for specific ASM monotherapies.

Significance: Maternal epilepsy is associated with many adverse perinatal outcomes, but most are driven by prenatal ASM exposure. We postulate that joint comprehensive care between obstetricians and epileptologists or other specialists who prescribe ASMs could improve perinatal outcomes. Research into models of care and prescribers and the effect on outcomes is needed.

Keywords: epilepsy; maternal; neonatal; perinatal; pregnancy.