Evaluation of pregnancy outcomes after maternal first trimester exposure to levetiracetam
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 364
研究概览
简要总结
OBJECTIVE: Levetiracetam 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 analyze rates of major birth defects and spontaneous abortion after maternal levetiracetam treatment. METHODS: This was a cohort study based on pregnancies recorded by the Embryotox Center from 2000 to 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 analyzed in comparison to a nonexposed cohort (n = 729). Pregnancies with the most frequently used combination therapy comprising levetiracetam and lamotrigine (n = 80) were evaluated separately. RESULTS: There was no significantly increased risk of major birth defects or of 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 of spontaneous abortion (adjusted hazard ratio = 3.01, 95% confidence interval [CI] = 1.43-6.33) and a nonsignificant effect estimate for major birth defects (7.7%, n = 5/65, adjusted odds ratio = 1.47, 95% CI = .48-4.47) compared to a nonexposed cohort. SIGNIFICANCE: Our study confirms the use of levetiracetam as a suitable antiepileptic drug in pregnancy. The lower birth weight of male neonates after maternal levetiracetam monotherapy and the unexpectedly high risk of spontaneous abortion and birth defects after dual therapy with levetiracetam and lamotrigine require further investigation.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- one 至 one（—）
- 性别
- Female
入选标准
- •For both cohorts: Enrollment of pregnancies, of which neither the outcome nor pathological results of prenatal diagnostics are known at the first contact. An analysis of these prospectively ascertained pregnancies can therefore be used for risk quantification of the defined endpoints.
排除标准
- •Exclusion Criteria comparison cohort: cases with levetiracetam exposure during pregnancy.
- •Exclusion criteria (applies for the exposed and comparison groups): therapy of maternal malignancies during pregnancy and cases with maternal exposure considered as potent teratogens or fetotoxicants: i.e. valproate, topiramate and carbamazepine as well as acenocoumarol, ACE-inhibitors and AT1-antagonists (exposure in 2nd and 3rd trimester), lenalidomide, methotrexate, mycophenolate, phenobarbital, phenprocoumon, phenytoin, retinoids (acitretin, adapalen, isotretinoin, tazaroten, tretinoin), thalidomide and warfarin.