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Epilepsy Linked to Severe Pregnancy Complications

<ѻý class="mpt-content-deck">— Though overall risks were low, mothers and offspring faced more severe morbidity, death
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 An EEG recording of an epileptic seizure.

Women with epilepsy had a higher risk of severe pregnancy complications, including a substantial mortality risk, according to a Nordic population-based study.

Epilepsy in pregnant women was associated with a higher rate of severe maternal morbidity and mortality (36.9 vs 25.4 per 1,000 deliveries), reported Neda Razaz, PhD, of Karolinska University Hospital, in Sweden, and colleagues in .

After adjustment for other factors, the risk with epilepsy was significantly elevated by 23% for morbidity and 3.86-fold for mortality, albeit with a low absolute incidence of the latter (0.23 vs 0.05 deaths per 1,000 deliveries).

Fetuses and infants of women with epilepsy also had higher odds of death (adjusted OR 1.20, 95% CI 1.05-1.38) and severe neonatal morbidity (adjusted OR 1.48, 95% CI 1.40-1.56).

It's notable that elevated risks were apparent "even in high-income Nordic countries with universal healthcare," Razaz and colleagues wrote, which "underscore the urgent need for increased vigilance and comprehensive care throughout pregnancy and the postpartum period."

Reasons for these higher risks are likely multifactorial, said Daniel Friedman, MD, of the NYU Grossman School of Medicine in New York City, who was not involved with the study.

In this analysis, antiseizure medication (ASM) use was associated with higher odds of severe maternal morbidity among women with epilepsy.

"Pregnancy can be a time of worsening seizure control for some women with epilepsy, and that's because pregnancy affects seizure medication levels," Friedman told ѻý. In addition to losing sleep, "women may have nausea, vomiting; they can't keep medicines down."

However, Razaz emphasized the overall low risk for these patients: "96% of all women with epilepsy in our study had a completely uncomplicated pregnancy with a normal outcome," she said. "I don't want our results to scare women away from having children."

The study was part of SCAN-AED, a larger Scandinavian . Longitudinal data came from the health registries of Denmark, Finland, Iceland, Norway, and Sweden, spanning from 1997-2017. Singleton births at 22 or more gestational weeks were included. The epilepsy cohort included only women with active epilepsy or with onset before their child's birth.

Women who filled an ASM prescription between their last missed period and the day of birth were included in the exposure group. The unexposed group included those who had not filled an ASM prescription within 90 days of their last missed period through to delivery.

The maternal death measure included those that occurred from 22 weeks' gestation to 42 days postpartum. The composite outcome of severe maternal morbidity included surgical complications, sepsis, and obstetric shock, with at least one inpatient stay during pregnancy or within 42 days postpartum.

In offspring, perinatal mortality encompassed stillbirth and neonatal death. Composite severe neonatal morbidity included intracranial hemorrhage, periventricular leukomalacia, pneumothorax, and severe birth trauma, among other adverse outcomes.

Of the 4.5 million deliveries identified in the registries, 35,283 were to mothers with epilepsy, with 16,240 offspring exposed to ASMs. The mean age for the epilepsy cohort was 29.9 years.

Women with epilepsy had a higher risk of severe preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome or eclampsia, embolism, cerebrovascular events, and severe mental health conditions than women without epilepsy. Infants were at elevated risk of hypoxic ischemic encephalopathy, neonatal convulsions, respiratory distress syndrome, and retinopathy of prematurity.

Elevated risks of hospitalization for psychiatric disorders were also seen in women with epilepsy during pregnancy and postpartum, leading the researchers to call for better screening and treatment of perinatal mental health conditions.

Friedman said pregnant patients, especially those with drug-resistant epilepsy, should receive good multidisciplinary perinatal care at high-risk obstetric clinics, if possible, with appropriate monitoring, including of serum medication levels and fetal development.

The study relied on prescription refills to determine ASM use, but actual compliance with treatment was unknown, the authors acknowledged. There were also country-specific variations in data, and no information on seizure frequency and epilepsy control during pregnancy. Multiple births were excluded, as were pregnancies delivered earlier than 22 weeks gestation. Confounding from unmeasured comorbidities was also possible.

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    Sophie Putka is an enterprise and investigative writer for ѻý. Her work has appeared in the Wall Street Journal, Discover, Business Insider, Inverse, Cannabis Wire, and more. She joined ѻý in August of 2021.

Disclosures

Funding for the study came from NordForsk, the Research Council of Norway, the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation, the Lundbeck Foundation, the Norwegian Epilepsy Association, and the Independent Research Fund Denmark.

Razaz reported no conflicts of interest. Co-authors reported numerous financial relationships, including with industry.

Friedman reported no conflicts of interest.

Primary Source

JAMA Neurology

Razaz N, et al "Risk of perinatal and maternal morbidity and mortality among pregnant women with epilepsy" JAMA Neurol 2024; DOI: 10.1001/jamaneurol.2024.2375.