Teratogenic Effects of Antiepileptic Drugs: Use of an International Database on Malformations and Drug Exposure (MADRE)

Epilepsia - Tập 41 Số 11 - Trang 1436-1443 - 2000
Carla Arpino1, Sonia Brescianini1, Elisabeth Robert2, Eduardo E. Castilla3, Guido Cocchi4, Martina C. Cornel5, Catherine De Vigan6, Paul A.L. Lancaster7, Paul Merlob8, Y. Sumiyoshi9, Giuseppe Zampino10, Cristina Renzi1, Aldo Rosano1, Pierpaolo Mastroiacovo10,1
1International Centre for Birth Defects, Rome, Italy
2Institut Européen des Génomutations, Lyon, France
3ECLAMC at Dep. Genetica, Instituto Oswaldo Cruz, Rio de Janeiro, Brasil, and Cemic, Buenos Aires, Argentina
4Istituto Clinico di Pediatria Preventiva e Neonatologia, Bologna, Italy
5Department of Medical Genetics, Groningen, the Netherlands
6Birth Registry of Congenital Anomalies, INSERM, Epidemiological Research Unit on Woman and Child, Paris, France
7AIHW National Perinatal Statistics Unit, The University of New South Wales, Sydney, Australia
8Department of Neonatology, Rabin Medical Center, Petah Tiqva, Israel
9Yokohama City University, Yokohama, Japan
10Birth Defects Unit, Catholic University, Rome, Italy

Tóm tắt

Summary: 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.

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Epilepsia

Tập 41 Số 11

1436-1443

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