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. 2024 Sep 1;81(9):985-995.
doi: 10.1001/jamaneurol.2024.2375.

Risk of Perinatal and Maternal Morbidity and Mortality Among Pregnant Women With Epilepsy

Neda Razaz  1 , Jannicke Igland  2   3 , Marte-Helene Bjørk  4   5 , K S Joseph  6   7 , Julie Werenberg Dreier  4   8   9 , Nils Erik Gilhus  4   5 , Mika Gissler  10   11 , Maarit K Leinonen  10 , Helga Zoega  12   13 , Silje Alvestad  4   14 , Jakob Christensen  8   15   16 , Torbjörn Tomson  17
Affiliations

Risk of Perinatal and Maternal Morbidity and Mortality Among Pregnant Women With Epilepsy

Neda Razaz et al. JAMA Neurol. .

Abstract

Importance: Maternal epilepsy is associated with adverse pregnancy and neonatal outcomes. A better understanding of this condition and the associated risk of mortality and morbidity at the time of delivery could help reduce adverse outcomes.

Objective: To determine the risk of severe maternal and perinatal morbidity and mortality among women with epilepsy.

Design, setting, participants: This prospective population-based register study in Denmark, Finland, Iceland, Norway, and Sweden took place between January 1, 1996, and December 31, 2017. Data analysis was performed from August 2022 to November 2023. Participants included all singleton births at 22 weeks' gestation or longer. Births with missing or invalid information on birth weight or gestational length were excluded. The study team identified 4 511 267 deliveries, of which 4 475 984 were to women without epilepsy and 35 283 to mothers with epilepsy.

Exposure: Maternal epilepsy diagnosis recorded before childbirth. Prenatal exposure to antiseizure medication (ASM), defined as any maternal prescription fills from conception to childbirth, was also examined.

Main outcomes and measures: Composite severe maternal morbidity and mortality occurring in pregnancy or within 42 days postpartum and composite severe neonatal morbidity (eg, neonatal convulsions) and perinatal mortality (ie, stillbirths and deaths) during the first 28 days of life. Multivariable generalized estimating equations with logit-link were used to obtain adjusted odds ratios (aORs) and 95% CIs.

Results: The mean (SD) age at delivery for women in the epilepsy cohort was 29.9 (5.3) years. The rate of composite severe maternal morbidity and mortality was also higher in women with epilepsy compared with those without epilepsy (36.9 vs 25.4 per 1000 deliveries). Women with epilepsy also had a significantly higher risk of death (0.23 deaths per 1000 deliveries) compared with women without epilepsy (0.05 deaths per 1000 deliveries) with an aOR of 3.86 (95% CI, 1.48-8.10). In particular, maternal epilepsy was associated with increased odds of severe preeclampsia, embolism, disseminated intravascular coagulation or shock, cerebrovascular events, and severe mental health conditions. Fetuses and infants of women with epilepsy were at elevated odds of mortality (aOR, 1.20; 95% CI, 1.05-1.38) and severe neonatal morbidity (aOR, 1.48; 95% CI, 1.40-1.56). In analyses restricted to women with epilepsy, women exposed to ASM compared with those unexposed had higher odds of severe maternal morbidity (aOR ,1.24; 95% CI, 1.10-1.48) and their neonates had an increased odd of mortality and severe morbidity (aOR, 1.37; 95% CI, 1.23-1.52).

Conclusion and relevance: This multinational study shows that women with epilepsy were at considerably higher risk of severe maternal and perinatal outcomes and increased risk of death during pregnancy and postpartum. Maternal epilepsy and maternal use of ASM were associated with increased maternal morbidity and perinatal mortality and morbidity.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Igland reported to be the head of the Core Facility for Biostatistics and Data analysis at the University of Bergen, which has received funding from Sanofi and Novartis to do postmarketing drug safety research not related to the submitted work. Dr Bjork reported grants from The Research Council of the Nordic Countries (NordForsk) and grants from The Research Council of Norway during the conduct of the study; speaking honoraria and consulting fees from Novartis, Eisai, Pfizer, Lundbeck, Angelini Pharma, Teva, Lilly, Jazz Pharmaceutical, AbbVie, and grants from The Norwegian Epilepsy Foundation outside the submitted work. Dr Dreier reported grants from Independent Research Fund Denmark (1133-00026B) and from the Independent Research Fund Denmark (3166-00134B) outside the submitted work. Dr Gilhus reported personal fees from UCB, Argenx, Janssen, Merck, Roche, Dianthus Dinka, Amgen, Grifols, Taneka, Huma, Immunovant, Argenx, Grifols, Roche, Merck, Dianthus, Dinka, Takeda, Janssen, Huma, Immunovant, and Amgen outside the submitted work. Dr Leinonen reported grants from Janssen and Merckin paid to their institution outside the submitted work. Dr Alvestad reported grants from NordForsk (Nordic Counsil of Ministers) during the conduct of the study and personal fees from Eisai outside the submitted work. Dr Christensen reported personal fees from Eisai and travel fees from UCB during the conduct of the study. Dr Tomsom reported grants to support the International Registry of Antiepileptic Drugs and Pregnancy from NordForsk to their institution during the conduct of the study and grants from Accord, Angelini, Bial, GlaxoSmithKline, Eisai, Glenmark, Ecupharma, UCB, Sanofi, Teva, Zentiva, Jazz, and SF Group, and personal fees from Angelini, Eisai, and UCB outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Adjusted Odds Ratios (ORs) of Severe Maternal and Perinatal Morbidity and Mortality Among Mothers With or Without Epilepsy and Among Women With Epilepsy by Antiseizure Medications (ASM) Use During Pregnancy in 5 Nordic Countries, 1997 to 2017
HELLP indicates hemolysis, elevated liver enzymes and low platelets; NA, not applicable. aAdjusted for maternal age, parity, birth year, child’s sex mother’s education, marital status, country, maternal psychiatric morbidity, number of chronic conditions, and number of prepregnancy hospitalizations. bData from Iceland excluded from analyses where mortality is included in the outcome because of lack of data on maternal mortality.
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