Women With Epilepsy Face Higher Risks of Severe Maternal and Perinatal Outcomes, Study Finds

Neda Razaz, PhD

A recently published multinational study of more than 4.5 million pregnancies showed that maternal epilepsy was associated with an increased risk of maternal and perinatal mortality and severe morbidity. Despite the fact that most women with epilepsy will have normal, uncomplicated pregnancies, investigators concluded that there is an urgent need for enhanced prepregnancy counseling, close monitoring and perinatal support, and access to specialized care for safe deliveries in all women with epilepsy.¹

The study included 4,511,267 deliveries of which 4,475,984 were to women without epilepsy and 35,283 to mothers with epilepsy. Among deliveries to women with epilepsy, 16,240 offspring were exposed to an antiseizure medication (ASM) during pregnancy (46%). Results showed that women with epilepsy had higher severe maternal morbidity, with 36.9 deaths per 1000 deliveries vs 25.3 for those without epilepsy. In addition, this group also had a significantly higher risk of death during delivery, with 2.3 deaths per 10,000 pregnancies, relative to those without epilepsy (0.4 deaths per 10,000 pregnancies).

Published in JAMA Neurology, the mean age at delivery for women in the epilepsy cohort was 29.9 (SD, 5.3) years. Between the 2 groups included, women with epilepsy also showed considerably higher rates of severe preeclampsia, hemorrhage, emobolism, sepsis, cerebrovascular events, surgical complications, and severe maternal health. This group continued to show higher rates of maternal death (adjusted OR, 3.86; 95% CI, 1.84-8.10) and higher rates of severe maternal morbidity (adjusted OR, 1.23; 95% CI, 1.16-1.31) even after adjusting for maternal characteristics and prepregnancy factors.

According to the study authors, led by Neda Razaz, PhD, an assistant professor at the Karolinska Institute, this was the largest study on the association between maternal epilepsy with mortality and other clinically significant maternal and perinatal complications. The cohort study included information on all singleton births at 22 or more completed gestational weeks in the 5 Nordic countries, namely, Denmark (1997 to 2017), Finland (1996 to 2016), Iceland (2004 to 2017), Norway (2005 to 2017), and Sweden (2006 to 2017).

READ MORE: Efficacy of Oral Anticoagulants in Epilepsy and Atrial Fibrillation Not Impacted by Antiseizure Medications

Results from the study also revealed higher odds of perinatal death/severe neonatal morbidity among offspring of women with epilepsy (0.47 vs 0.3 per 1000 births). After adjusting for potential confounders, women with epilepsy had 1.18-fold higher odds of stillbirth (95% CI, 1.00-1.40), 1.23-fold higher odds of neonatal death (95% CI, 0.98-1.55), and a 1.48-fold higher odds of composite severe neonatal morbidity (95% CI, 1.40-1.56), compared with women without epilepsy. Furthermore, neonates of women with epilepsy showed increased risk of hypoxic ischemic encephalopathy, neonatal convulsions, respiratory distress syndrome, and retinopathy of prematurity, even after adjustments.

In the study, women exposed to ASM showed increased odds of composite severe maternal morbidity (adjusted OR, 1.24; 95% CI, 1.10-1.40). In addition, those exposed to an ASM during pregnancy had increased risk of preeclampsia, severe hemorrhage, and cerebrovascular events relative to other women with epilepsy not exposed. In terms of specific ASMs, valproate (adjusted OR, 1.67; 95% CI, 1.26-2.23) had the highest odds of severe maternal morbidity, followed by carbazepine (adjusted OR, 1.53; 95% CI, 1.08-2.17) and carbamazepine (adjusted OR, 1.46; 95% CI, 1.14-1.87).

The data also revealed that fetuses and infants of women with epilepsy exposed to ASMs had higher rates of perinatal death/severe neonatal morbidity (composite outcome 56.2 vs 39.9 per 1000 total births) compared with fetuses and infants of women with epilepsy not exposed to ASM. After adjustment, models showed that neonates of women with epilepsy exposed to ASM during pregnancy had elevated odds of neonatal death (adjusted OR, 2.40; 95% CI, 1.44-3.99) and composite severe neonatal morbidity (adjusted OR, 1.37; 95% CI, 1.23-1.52).

Increased odds of perinatal death/severe neonatal morbidity was seen across several ASMs, including clonazepam, pregabalin, gabapentin, valproate, and carbamazepine. Compared with neonates not exposed to ASM, those exposed to polytherapy with valproate had a 2.21-fold higher odds of perinatal mortality and severe morbidity (95% CI, 1.70-2.87).

REFERENCE
1. Razaz N, Igland J, Bjork MH, et al. Risk of perinatal and maternal morbidity and mortality among pregnant women with epilepsy. JAMA Neurol. Published online August 5, 2024. doi:10.1001/jamaneurol.2024.2375