Antiepileptic treatment with levetiracetam during the first trimester and pregnancy outcome: An observational study

Abstract

ObjectiveLevetiracetam is increasingly used in pregnant women with epilepsy. Although teratogenic effects have not been observed so far, data on the risks of spontaneous abortion and major birth defects are still limited, especially for the frequently used dual therapy of levetiracetam and lamotrigine. Our primary aim was to analyse rates of major birth defects and spontaneous abortion after maternal levetiracetam treatment.MethodsCohort study based on pregnancies recorded by the Embryotox Center from 2000‐2017. Outcomes of prospectively ascertained pregnancies with first trimester levetiracetam monotherapy (n=221) were compared to pregnancies with lamotrigine monotherapy for epilepsy (n=469). In addition, all pregnancies with levetiracetam (n=364) exposure during the first trimester were analysed in comparison to a non‐exposed cohort (n=729). Pregnancies with the most frequently used combination therapy comprising levetiracetam and lamotrigine (n=80) were evaluated separately.ResultsThere was no significantly increased risk for major birth defects or for spontaneous abortions after first trimester exposure to levetiracetam. Birth weight of male neonates was significantly lower after levetiracetam monotherapy compared to lamotrigine monotherapy. Dual therapy with levetiracetam and lamotrigine resulted in a significantly increased risk for spontaneous abortion (HRadj 3.01, 95% CI 1.43 ‐ 6.33) and a non‐significant effect estimate for major birth defects (7.7%, n=5/65; ORadj 1.47, 95% CI 0.48 ‐ 4.47) compared to a non‐exposed cohort.SignificanceOur study confirms the use of levetiracetam as suitable antiepileptic drug in pregnancy. The lower birth weight of male neonates after maternal levetiracetam monotherapy and the unexpectedly high risk for spontaneous abortion and birth defects after dual therapy with levetiracetam and lamotrigine require further investigation.