Pregnant Women With Epilepsy Experience Worse Perinatal Outcomes

Women with epilepsy may be more likely to experience maternal and fetal complications, according to study findings published recently in JAMA Neurology.

Adequate pregnancy planning and management are essential to improve outcomes for women with epilepsy and their offspring, noted researchers, as understanding their pregnancy risks helps shape treatment plans and contributes to reducing poor outcomes, such as congenital conditions.

One notable risk concerning maternal epilepsy is exposure to antiseizure medications (ASMs), which is the primary treatment for the neurocognitive condition. Prior research has shown that exposure to ASMs has been associated with perinatal risks, including maternal death and preterm birth, in women with epilepsy.

Seeking to further assess perinatal outcomes (from the beginning of pregnancy up to 1 year post delivery) for women with epilepsy compared with those without epilepsy, researchers conducted a systematic review and meta-analysis of studies registered in the Ovid MEDLINE, Embase, CINAHL, and PsycINFO databases from inception through December 6, 2022.

Searches also included OpenGrey and Google Scholar and manual searching in journals and reference lists of included studies. The associations of ASM exposure and epilepsy were also investigated, including comparisons between women with epilepsy who were taking ASM vs women without epilepsy, women with epilepsy taking ASM and those not taking ASM, and women with epilepsy taking polytherapy ASM compared with monotherapy ASM.

Several maternal, fetal, and neonatal outcomes were assessed:

• Maternal and fetal outcomes: cesarean delivery, preterm birth, induced labor, gestational diabetes, intrauterine growth restriction, antepartum hemorrhage, preeclampsia, miscarriage, stillbirth, gestational hypertension, any pregnancy loss, postpartum hemorrhage, placental abruption, fetal distress, maternal death, bleeding in pregnancy, premature rupture of membranes, eclampsia, placenta previa, induced abortion, and assisted delivery (forceps or vacuum extraction)
• Neonatal outcomes: neonatal intensive care unit (NICU) admission, small for gestational age, birth weight less than 2500 g, neonatal and infant death, 5-minute Apgar score less than 8, large for gestational age, 1-minute Apgar score less than 8, mean birth weight, mean body length, mean 1-minute Apgar score, mean 5-minute Apgar score, mean head circumference, and mean gestational age
• Assessed congenital conditions comprised those with or without a known genetic condition resulting in major or minor structural anomalies, including those of the nervous system, eye, face, and heart
  

Of 8313 articles identified, a total of 76 were included in the meta-analyses, including 45 retrospective and 21 prospective cohort studies, 9 case-control studies, and 1 cross-sectional study.

Findings showed that women with epilepsy were associated with increased odds of miscarriage (odds ratio [OR], 1.62; 95% CI, 1.15-2.29; 12 articles, 25,478 pregnancies), stillbirth (OR, 1.37; 95% CI, 1.29-1.47; 20 articles, 28,134,229 pregnancies), preterm birth (OR, 1.41; 95% CI, 1.32-1.51; 37 articles, 29,268,866 pregnancies) and maternal death (OR, 5.00; 95% CI, 1.38-18.04; 4 articles, 23 288 083 pregnancies), compared with those without epilepsy.

Moreover, newborn children of women with epilepsy exhibited increased odds of congenital conditions (OR, 1.88; 95% CI, 1.66-2.12; 29 articles, 24,238,334 pregnancies), NICU admission (OR, 1.99; 95% CI, 1.58-2.51; 8 articles, 1,204,428 pregnancies), and neonatal or infant death (OR, 1.87; 95% CI, 1.56-2.24; 13 articles, 1,426,692 pregnancies).

The increased odds of poor perinatal outcomes were shown to increase with greater use of ASM for women with epilepsy vs those without, as well as for women with epilepsy taking ASM vs those not taking ASM and women with epilepsy receiving ASM polytherapy vs ASM monotherapy.

As analyses were unadjusted due to differences in individual study characteristics and adjustments made in statistical analyses, researchers noted that future research should attempt to account for potentially confounding variables that they were unable to adjust for, such as epilepsy severity or type, maternal age, deprivation, parity, and smoker status.

“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,” concluded the researchers.

“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.”

Reference

Mazzone PP, Hogg KM, Weir CJ, Stephen J, Bhattacharya S, Chin RFM. Comparison of perinatal outcomes for women with and without epilepsy: a systematic review and meta-analysis. JAMA Neurol. 2023;e230148. doi: 10.1001/jamaneurol.2023.0148