Hypertensive pregnancy complications in women with epilepsy and antiepileptic drugs: a population-based cohort study of first pregnancies in Norway

OBJECTIVES: To 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. DESIGN: A 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. SETTING: Norway, 2004–2012. PARTICIPANTS: All first pregnancies of women with epilepsy and women without epilepsy were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Main 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). RESULTS: In 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). CONCLUSIONS: Women 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.