Literature Review

Epilepsy and Increased Risk of Adverse Pregnancy Outcomes: What Is the Real Risk?

A population-based cohort study suggests that epilepsy itself, and not antiepileptic drug use, during pregnancy may be associated with adverse outcomes.


Epilepsy during pregnancy is associated with a moderately increased risk of adverse pregnancy, delivery, and perinatal outcomes, according to research published in the August issue of JAMA Neurology. The use of antiepileptic drugs (AEDs), however, is not associated with adverse outcomes, according to the researchers.

Neda Razaz, PhD

“Our findings reveal that the increased risks of complications during pregnancy, labor, and the neonatal period might be due to pathologic factors related to epilepsy as a chronic disease more than being the effect of AEDs per se,” said Neda Razaz, PhD, a postdoctoral fellow at the Reproductive Epidemiology Research Unit of Karolinska Institutet in Stockholm.

Information From National Registries

Data suggesting associations between AEDs and the risk of congenital malformations have received much attention in recent years. But population-based evidence about the association between maternal epilepsy itself and risks of adverse outcomes has been scarce.

Dr. Razaz and colleagues conducted a retrospective study of all singleton births in Sweden from 1997 through 2011. The investigators obtained information from the country’s Medical Birth Register, the National Patient Register, and the Prescribed Drug Registry. They included information about 1,429,652 pregnancies (869,947 mothers without epilepsy and 3,586 mothers with epilepsy). Mean age at first delivery for women with epilepsy was 31. Data on AED exposure were available for offspring born between July 1, 2005, and December 31, 2011. Lamotrigine and carbamazepine were the most commonly used AEDs.

Relative Risks

Pregnancies in women with epilepsy were associated with increased risks of pre-eclampsia (adjusted risk ratio [aRR], 1.24), infection (aRR, 1.85), placental abruption (aRR, 1.68), induction (aRR, 1.31), elective cesarean section (aRR, 1.58), and emergency cesarean section (aRR, 1.09), compared with pregnancies in women without epilepsy. After adjustment for potential confounders, neonates of women with epilepsy had significantly higher risks of stillbirth, being born small for gestational age, medically indicated and spontaneous preterm births, any and major congenital malformations, neonatal infections, asphyxia-related complications, low five-minute Apgar scores, and neonatal hypoglycemia and respiratory distress, compared with neonates of women without epilepsy.

Among women with epilepsy, the rate of pre-eclampsia was higher in those who received AEDs, compared with women who did not receive AEDs (aRR, 1.39). In the propensity score-adjusted analyses, however, increased risk of induced labor (aRR, 1.30) was the only pregnancy and delivery outcome significantly associated with use of AEDs.

Offspring of women exposed to AEDs had a higher frequency of major malformation (6.7% vs 4.7%), respiratory distress (6.0% vs 4.5%), and being small for gestational age (9.5% vs 6.9%) at birth, compared with nonexposed offspring. Propensity score-adjusted analyses, however, showed no significantly increased risk of adverse neonatal outcomes.

Women with epilepsy who receive AEDs during pregnancy “may receive extra surveillance ... from their clinicians that may have contributed to the comparable outcomes observed in our study,” said the researchers. The study results may improve counseling for pregnant women with epilepsy who contemplate discontinuing treatment.

—Erik Greb

Suggested Reading

Razaz N, Tomson T, Wikström AK, Cnattingius S. Association between pregnancy and perinatal outcomes among women with epilepsy. JAMA Neurol. 2017;74(8):983-991.

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