Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis

Background: Antenatal care of women with epilepsy is varied. The association of epilepsy and antiepileptic drug exposure with pregnancy outcomes needs to be quantified to guide management. We did a systematic review and meta-analysis to investigate the association between epilepsy and reproductive outcomes, with or without exposure to antiepileptic drugs.

Methods: We searched MEDLINE, Embase, Cochrane, AMED, and CINAHL between Jan 1, 1990, and Jan 21, 2015, with no language or regional restrictions, for observational studies of pregnant women with epilepsy, which assessed the risk of obstetric complications in the antenatal, intrapartum, or postnatal period, and any neonatal complications. We used the Newcastle-Ottawa Scale to assess the methodological quality of the included studies, risk of bias in the selection and comparability of cohorts, and outcome. We assessed the odds of maternal and fetal complications (excluding congenital malformations) by comparing pregnant women with and without epilepsy and undertook subgroup analysis based on antiepileptic drug exposure in women with epilepsy. We summarised the association as odds ratio (OR; 95% CI) using random effects meta-analysis. The PROSPERO ID of this Systematic Review's protocol is CRD42014007547.

Findings: Of 7050 citations identified, 38 studies from low-income and high-income countries met our inclusion criteria (39 articles including 2,837,325 pregnancies). Women with epilepsy versus those without (2,809,984 pregnancies) had increased odds of spontaneous miscarriage (OR 1·54, 95% CI 1·02-2·32; I(2)=67%), antepartum haemorrhage (1·49, 1·01-2·20; I(2)=37%), post-partum haemorrhage (1·29, 1·13-1·49; I(2)=41%), hypertensive disorders (1·37, 1·21-1·55; I(2)=23%), induction of labour (1·67, 1·31-2·11; I(2)=64%), caesarean section (1·40, 1·23-1·58; I(2)=66%), any preterm birth (<37 weeks of gestation; 1·16, 1·01-1·34; I(2)=64%), and fetal growth restriction (1·26, 1·20-1·33; I(2)=1%). The odds of early preterm birth, gestational diabetes, fetal death or stillbirth, perinatal death, or admission to neonatal intensive care unit did not differ between women with epilepsy and those without the disorder.

Interpretation: A small but significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy. This increased risk should be taken into account when counselling women with epilepsy.

Funding: EBM CONNECT Collaboration.