Antiepileptic drug use of women with epilepsy and congenital malformations in offspring

TLDR

The study compared the risk of congenital malformations in children of women with epilepsy who continued antiepileptic drugs during pregnancy to those who stopped medication before conception. Using a Finnish population‑based cohort of 20,101 epilepsy patients first eligible for AED reimbursement between 1985 and 1994, the authors linked birth records from 1991–2000 with medical records to determine AED exposure and pregnancy outcomes. Offspring of women on AEDs had a higher malformation rate (4.6% vs 2.8%, p = 0.02), with valproate monotherapy or polytherapy driving the risk (OR 4.18 and 3.54, respectively), while polytherapy without valproate and use of carbamazepine, oxcarbazepine, or phenytoin did not increase risk.

Abstract

<b>Objective: </b> To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. <b>Methods: </b> All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. <b>Results: </b> Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (<i>p</i> = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. <b>Conclusion: </b> Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).