Epilepsy, Antiseizure Medications, and Perinatal Outcomes: What’s the Link?

Most adverse perinatal outcomes associated with maternal epilepsy are driven by exposure to antiseizure medications (ASMs), according to study results published in Epilepsia.

Previous studies on the effects of ASMs on perinatal outcomes have typically focused on specific ASMs, failed to adjust for potential confounders, and did not include women without epilepsy (WWoE).

To clarify the relationship between ASM exposure and perinatal outcomes in women with epilepsy (WWE) and WWOE, researchers from the University of Edinburgh in the United Kingdom conducted a retrospective population-based cohort study with data sourced from the National Health Service Scotland (NHSS), a tax-funded free-at-the-point-of-use health care. Girls and women aged 16 years and older who had 1 or more singleton pregnancy (N=629,200) between 2009 and 2021 were evaluated for perinatal outcomes on the basis of epilepsy status and use of ASMs.

The WWE (n=2022) and WWoE (n=627,178) were aged less than 35 years (81.9% and 78.6%), had a previous pregnancy (58.1% and 56.2%), and had normal body mass index (BMI; 41.3% and 43.9%), respectively. WWE had increased odds of pre-existing hypertension, obesity, smoking, being aged 35 years and older, and illicit drug use/drug misuse.

Among WWE and WWoE, 76% and 0.5% had prenatal ASM exposure, respectively. Pregnancy with ASM exposure occurred in 4406 pregnancies (WWoE, 2867; WWE, 1539) with exposure to topiramate (n=391, carbamazepine (n=600), levetiracetam (n=832), lamotrigine (n=1469), and sodium valproate monotherapy (n=315).

In the adjusted analyses compared with WWoE, WWE were at higher risk for:

• induced labor (adjusted odds ratio [aOR], 1.48; 95% CI, 1.32-1.66),
• preterm birth (aOR, 1.46; 95% CI, 1.21-1.77),
• preeclampsia (aOR, 1.46; 95% CI, 1.21-1.77),
• cesarean section (aOR, 1.16; 95% CI, 1.02-1.32),
• low birth weight (aOR, 1.49; 95% CI, 1.22-1.82),
• neonatal intensive care unit (NICU) admission (aOR, 1.36; 95% CI, 1.14-1.62), and
• their offspring having an Apgar score less than 7 at 5 minutes (aOR, 1.52; 95% CI, 1.17-1.97).

Compared with women not exposed to ASMs, those exposed to ASMs were at higher risk for:

• preterm birth (aOR, 1.47; 95% CI, 1.25-1.74),
• induced labor (aOR, 1.38; 95% CI, 1.25-1.52),
• cesarean section (aOR, 1.14; 95% CI, 1.01-1.27),
• NICU admission (aOR, 1.54; 95% CI, 1.33-1.78),
• low birth weight (aOR, 1.47; 95% CI, 1.23-1.75), and
• congenital conditions (aOR, 1.34; 95% CI, 1.04-1.73).

In fully adjusted models, pregnancies with prenatal exposure to any of the 5 ASMs were associated with increased odds of negative prenatal outcomes, including congenital conditions (valproate [3.91, 2.36– 6.49]; carbamazepine [1.90, 1.16–3.10]) and induced labor (topiramate [1.48, 1.12–1.96]; carbamazepine [1.48, 1.18–1.86]; and valproate exposure [1.65, 1.20–2.27]).

Study limitations included the inability to account for epilepsy characteristics, reliance on pregnancy records to identify WWE, inability to account for length of ASM treatment or trimester of dispensation, and lack of investigation of other reasons for ASMS use aside from epilepsy.

“Maternal epilepsy is associated with many adverse perinatal outcomes, but many of these may be linked primarily with prenatal ASM exposure,” the researchers concluded.

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