ObjectivesTo estimate the risk of hypertensive pregnancy complications in women with epilepsy, with and without antiepileptic drugs, and assess the risk associated with the four most common antiepileptic drugs.DesignA population-based cohort study using linked data from the Medical Birth Registry of Norway and the Norwegian Prescription Database. Women with epilepsy with and without antiepileptic drugs were compared with women without epilepsy.SettingNorway, 2004–2012.ParticipantsAll first pregnancies of women with epilepsy and women without epilepsy were included.Primary and secondary outcome measuresMain outcome measures were hypertensive pregnancy complications: a compound variable of any hypertensive disorder, gestational hypertension, mild pre-eclampsia, severe pre-eclampsia, early onset pre-eclampsia, eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelets).ResultsIn total, 1778 pregnancies in women with epilepsy and 221 662 in women without epilepsy were analysed. 682 of the women with epilepsy used antiepileptic drugs, the most common in monotherapy being: lamotrigine (n=280), carbamazepine (n=94), levetiracetam (n=71) and valproate (n=51). There was an increased risk of any hypertensive disorder in women with epilepsy (adjusted OR (aOR) 1.2, 95% CI 1.0 to 1.5) and in the subcategory using valproat (aOR 2.9, 95% CI 1.3 to 6.4). The most frequent hypertensive complication was mild pre-eclampsia and the risk was increased in women with epilepsy (aOR 1.4, 95% CI 1.1 to 1.8) and women with epilepsy with valproat (aOR 3.3, 95% CI 1.2 to 9.4).ConclusionsWomen with epilepsy have an increased risk of mild pre-eclampsia, but not for the severe types of hypertensive pregnancy complications. Lamotrigine and levetiracetam do not predispose for mild pre-eclampsia, whereas valproate was associated with an increased risk of mild pre-eclampsia.

Second births in women with epilepsy do not represent an increased risk of non-iatrogenic complications, independent of antiepileptic drug use. There is a significant reduction in complications from first to second births in women with epilepsy.

ObjectiveObstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy.MethodsThis was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999–2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses.Results426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005).ConclusionsDuring 1999–2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.