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Original Investigation
August 2017

Association Between Pregnancy and Perinatal Outcomes Among Women With Epilepsy

Author Affiliations
  • 1Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 3Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
JAMA Neurol. 2017;74(8):983-991. doi:10.1001/jamaneurol.2017.1310
Key Points

Question  What are the associations between maternal epilepsy, antiepileptic drug use during pregnancy, and risks of pregnancy and perinatal outcomes?

Findings  In this population-based cohort study including more than 1.4 million singleton births, we found that antiepileptic drug use during pregnancy is generally not associated with adverse maternal and fetal or neonatal outcomes. However, a diagnosis of epilepsy still implies moderately increased risks of adverse pregnancy, delivery, and perinatal outcomes.

Meaning  Women with epilepsy should not be advised to discontinue their treatment, if this is clinically indicated. Preventive strategies aimed at mitigating the effect of maternal epilepsy on pregnancy and perinatal outcomes are warranted.


Importance  To date, few attempts have been made to examine associations between exposure to maternal epilepsy with or without antiepileptic drug (AED) therapy and pregnancy and perinatal outcomes.

Objectives  To investigate associations between epilepsy in pregnancy and risks of pregnancy and perinatal outcomes as well as whether use of AEDs influenced risks.

Design, Setting, and Participants  A population-based cohort study was conducted on all singleton births at 22 or more completed gestational weeks in Sweden from 1997 through 2011; of these, 1 424 279 were included in the sample. Information on AED exposure was available in the subset of offspring from July 1, 2005, to December 31, 2011. Data analysis was performed from October 1, 2016, to February 15, 2017.

Main Outcomes and Measures  Pregnancy, delivery, and perinatal outcomes. Multivariable Poisson log-linear regression was used to estimate adjusted risk ratios (aRRs) and 95% CIs, after adjusting for maternal age, country of origin, educational level, cohabitation with a partner, height, early pregnancy body mass index, smoking, year of delivery, maternal pregestational diabetes, hypertension, and psychiatric disorders.

Results  Of the 1 429 652 births included in the sample, 5373 births were in 3586 women with epilepsy; mean (SD) age at first delivery of the epilepsy cohort was 30.54 (5.18) years. Compared with pregnancies of women without epilepsy, women with epilepsy were at increased risks of adverse pregnancy and delivery outcomes, including preeclampsia (aRR 1.24; 95% CI, 1.07-1.43), infection (aRR, 1.85; 95% CI, 1.43-2.29), placental abruption (aRR, 1.68; 95% CI, 1.18-2.38), induction (aRR, 1.31; 95% CI, 1.21-1.40), elective cesarean section (aRR, 1.58; 95% CI, 1.45-1.71), and emergency cesarean section (aRR, 1.09; 95% CI, 1.00-1.20). Infants of mothers with epilepsy were at increased risks of stillbirth (aRR, 1.55; 95% CI, 1.05-2.30), having both medically indicated (aRR, 1.24; 95% CI, 1.08-1.43) and spontaneous (aRR, 1.34; 95% CI, 1.20-1.53) preterm birth, being small for gestational age at birth (aRR, 1.25; 95% CI, 1.13-1.30), and having neonatal infections (aRR, 1.42; 95% CI, 1.17-1.73), any congenital malformation (aRR, 1.48; 95% CI, 1.35-1.62), major malformations (aRR, 1.61; 95% CI, 1.43-1.81), asphyxia-related complications (aRR, 1.75; 95% CI, 1.26-2.42), Apgar score of 4 to 6 at 5 minutes (aRR, 1.34; 95% CI, 1.03-1.76), Apgar score of 0 to 3 at 5 minutes (aRR, 2.42; 95% CI, 1.62-3.61), neonatal hypoglycemia (aRR, 1.53; 95% CI, 1.34-1.75), and respiratory distress syndrome (aRR, 1.48; 95% CI, 1.30-1.68) compared with infants of unaffected women. In women with epilepsy, using AEDs during pregnancy did not increase the risks of pregnancy and perinatal complications, except for a higher rate of induction of labor (aRR, 1.30; 95% CI, 1.10-1.55).

Conclusions and Relevance  Epilepsy during pregnancy is associated with increased risks of adverse pregnancy and perinatal outcomes. However, AED use during pregnancy is generally not associated with adverse outcomes.