Large-Scale Meta-Analysis Demonstrates Worsened Perinatal Outcomes in Women With Epilepsy


Increased odds of miscarriage, stillbirth, preterm birth, and maternal birth were documented in women with epilepsy. These odds were increased with greater use of antiseizure medication.

Paolo Mazzone, PhD student, University of Edinburgh

Paolo Mazzone

Recently published findings from an updated systematic review and meta-analysis showed that women with epilepsy have worse perinatal outcomes compared with women without epilepsy, including a 5-fold increase in the odds of maternal death.1

Using Ovid MEDLINE, Embase, CINAHL, and PsychINFO, investigators included 76 articles in the meta-analyses, comprising of retrospective (n = 45), prospective (n = 21), case-control (n = 9), and cross-sectional (n = 1) studies. Relative to women without epilepsy, those with epilepsy had increased odds of gestational hypertension (OR, 1.32; 95% CI, 1.11-1.58), preeclampsia (OR, 1.36; 95% CI, 1.05-1.77), IUGR (OR, 1.89; 95% CI, 1.42-2.52), miscarriage (OR, 1.62; 95% CI, 1.15-2.29), preterm birth (OR, 1.41; 95% CI, 1.32-1.51), induced labor (OR, 1.33; 95% CI, 1.22-1.46), stillbirth (OR, 1.37; 95% CI, 1.29-1.47), cesarean delivery (OR, 1.54; 95% CI, 1.43-1.65), and maternal death (OR, 5.00; 95% CI, 1.38-18.04).

"When counseling pregnant women with epilepsy and those of childbearing age, clinicians should consider these findings," lead investigator Paolo Mazzone, PhD student, University of Edinburgh, and colleagues concluded.1 "In addition, clinicians and women with epilepsy should bear in mind the increased odds of negative adverse maternal and neonatal outcomes."

Neonates born to women with epilepsy showed increased odds of 1-minute and 5-minute Apgar scores less than 8, NICU admission (OR, 1.99; 95% CI, 1.58-2.51), SGA (OR, 1.38; 95% CI, 1.22-1.55), birth weigh less than 2500 g (OR, 1.35; 95% CI, 1.20-1.53), neonatal and infant death (OR, 1.87; 95% CI, 1.56-2.24), and congenital conditions (OR, 1.88; 95% CI, 1.66-2.12). Additionally the presence of epilepsy was associated with reduced birth weight, mean body length, mean head circumference, and mean gestational age for neonates.

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Women with epilepsy who were taking antiseizure medications also showed higher odds of induced labor, as well as increased odds of NICU admission, SGA, birth weight loss less than 2500 g, neonatal and infant death, and congenital conditions in their neonate. In terms of type of treatment approach, polytherapy had increased odds of cesarean delivery relative to monotherapy. Neonates of women with epilepsy taking ASM polytherapy had increased odds of NICU admission, SGA, and congenital conditions.

Adjusted and unadjusted models for maternal, fetal, and neonatal outcomes showed slight differences. Specifically, the pooled adjusted meta-analysis indicated increased odds of preeclampsia, preterm birth, APH, SGA, cesarean delivery, induced labor, maternal death, PPH, and congenital conditions in offspring for women with epilepsy vs those without epilepsy.

"Our results support the UK national guideline that women with epilepsy should receive prepregnancy counseling at time of epilepsy diagnosis and regularly during management, including preconception counseling on the risk of ASM use during pregnancy to offspring," Mazzone et al concluded.1 "In addition, advice about ASM use during pregnancy should come from an epilepsy specialist, and a complex care pathway is most suitable for women with epilepsy during pregnancy and childbirth."

1. Mazzone PP, Hogg KM, Weir CJ, et al. Comparison of perinatal outcomes for women with and without epilepsy: a systematic review and meta-analysis. JAMA Neurol. Published online March 13, 2023. doi:10.1001/jamaneurol.2023.0148
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