Pregnant Women With Epilepsy Have Higher Odds of Worse Perinatal Outcomes

Perinatal outcomes are worse among women with epilepsy relative to women without epilepsy, according to the results of a systematic review and meta-analysis published in JAMA Neurology.

Most studies on epilepsy in the setting of pregnancy focus on the risks of exposure to antiseizure medications (ASMs) on offspring. However, maternal factors are also important for optimizing fetal outcomes.

For the study, researchers from the University of Edinburgh in the United Kingdom searched publication databases through December 2022 for studies focusing on maternal, fetal, and neonatal outcomes. A total of 76 studies were included in this analysis. The studies were of retrospective (n=45) or prospective (n=21) cohort, case-control (n=9), and cross-sectional (n=1) designs.

Out of the 21 maternal and fetal outcomes and 14 neonatal outcomes, all but 6 of the maternal/fetal (all P £.04) and all but 3 of the neonatal outcomes (all P £.04) differed significantly between women with and without epilepsy. In the adjusted analysis, epilepsy was associated with higher rates of:

• maternal death (adjusted odds ratio [aOR], 9.41; 95% CI, 5.36-16.53);
• congenital conditions (aOR, 1.69, 95% CI, 1.62-1.78);
• preeclampsia (aOR, 1.42; 95% CI, 1.08-1.86);
• antepartum hemorrhage (aOR, 1.38; 95% CI, 1.31-1.45);
• postpartum hemorrhage (aOR, 1.37; 95% CI, 1.28-1.48);
• cesarean delivery (aOR, 1.36; 95% CI, 1.23-1.51);
• preterm birth (aOR, 1.34; 95% CI, 1.11-1.61);
• small for gestational age (aOR, 1.17; 95% CI, 1.01-1.36); and
• induced labor (aOR, 1.14; 95% CI, 1.12-1.16).

When stratified by medication use, many of the outcomes remained associated with epilepsy among women who were not taking ASM compared with women without epilepsy, such as:

• risk for preterm birth (odds ratio [OR], 1.65; 95% CI, 1.58-1.73; P <.001);
• placental abruption (OR, 1.64; 95% CI, 1.43-1.87; P <.001);
• cesarean delivery (OR, 1.37; 95% CI, 1.21-1.55; P <.001);
• neonatal intensive care unit (NICU) admission (OR, 1.27; 95% CI, 1.14-1.41; P <.001); and
• postpartum hemorrhage (OR, 1.17; 95% CI, 1.08-1.28; P <.001).

Among women with epilepsy, few maternal and fetal outcomes differed signifcaintly between women using and not using ASMs, with the exception of induced labor (OR, 1.37; P =.02). However, the following were associated with use of ASM compared with no use:

• adverse neonatal outcomes of neonatal or infant death (OR, 2.96; 95% CI, 1.23-7.12; P =.02);
• NICU admissions (OR, 1.53; 95% CI, 1.32-1.78; P <.001);
• birth weight <2500 g (OR, 1.49; 95% CI, 1.17-1.90; P =.001);
• congenital conditions (OR, 1.32; 95% CI, 1.10-1.58; P =.002); and
• small for gestational age (OR, 1.29; 95% CI, 1.09-1.53; P =.003).

Similar trends were observed for polytherapy compared with monotherapy, in which polytherapy was associated with higher rates of:

• small for gestational age (OR, 1.87; 95% CI, 1.31-2.67; P <.001);
• cesarian delivery (OR, 1.64; 95% CI, 1.33-2.02; P <.001);
• NICU admissions (OR, 1.64; 95% CI, 1.28-2.08; P <.001); and
• congenital conditions (OR, 1.53; 95% CI, 1.17-1.99; P =.002).

The limitations of this analysis included the fact that some studies recruited women with symptomatic epilepsy and there were missing data.

Overall, the researchers’ findings highlight that compared with women without epilepsy, those with epilepsy have worse perinatal outcomes. The researchers concluded, “Women with epilepsy should receive pregnancy counseling from an epilepsy specialist who can also optimize their antiseizure medication regimen before and during pregnancy.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.