Teratogenic effects of antiepileptic drugs: Use of an international database on malformations and drug exposure (MADRE)
Teratogenic effects of antiepileptic drugs: Use of an international database on malformations and drug exposure (MADRE)
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DOI：
10.1111/j.1528-1157.2000.tb00119.x
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发表时间：
2000-11-01
期刊：
影响因子：
5.6
通讯作者：
Mastroiacovo, P
中科院分区：
文献类型：
--
作者：
Arpino, C;Brescianini, S;Mastroiacovo, P
目的：本研究的目的是评估致畸作用的抗癫痫药物（AEDs）通过使用的监测系统（MADRE）的婴儿畸形。方法：所有畸形婴儿（1990-1996年）与母亲的第一个三个月的药物暴露的信息收集的国际出生缺陷和监测系统（ICBDMS）。病例被定义为表现出特定畸形的婴儿，对照被定义为表现出任何其他出生缺陷的婴儿。暴露定义为妊娠前三个月使用AED。AEDs与畸形的关联，然后估计通过计算的比值比与95%的置信区间和测试其同质性registrations.Results：在8005例畸形，299名婴儿在子宫内暴露于AEDs。在接受单药治疗的患者中，65例暴露于苯巴比妥，10例暴露于甲基苯巴比妥，80例暴露于丙戊酸，46例暴露于卡马西平，24例暴露于苯妥英，16例暴露于其他AED。暴露于苯巴比妥和甲基苯巴比妥的婴儿显示出口腔裂的风险增加。发现心脏畸形与苯巴比妥、甲基苯巴比妥、丙戊酸和卡马西平有关。尿道下裂与丙戊酸有关。脑穿通症和其他特定的异常的大脑，异常的脸，主动脉缩窄，肢体复位缺陷被发现与丙戊酸。结论：使用MADRE系统，我们证实了已知的致畸作用的抗癫痫药物。我们还发现从未报道过的与AED相关的畸形风险增加，或者病例报告提示了这种相关性。
Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations.Methods: Information on all malformed infants (1990-1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries.Results: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs, Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid.Conclusions: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports.