Progress in clinical management, together with policies for increased access to prenatal diagnosis, has resulted in both a substantial increase in the prenatal diagnosis and considerable reductions in early neonatal mortality of CHD in the Parisian population.

Objectives To assess at a population-based level the frequency with which severe structural congenital malformations are detected prenatally in Europe and the gestational age at detection, and to describe regional variation in these indicators. MethodsIn the period 1995-1999, data

Objectives To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects.

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)(1991)(1992)(1993)(1994)(1995)(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. Key Words: Antiepileptic drugs-Teratogenesis- Malformation registries-Risk factorsThe assessment of the teratogenic effects of antiepileptic drugs (AEDs) through epidemiological studies has often provided conflicting results (1-5). Cohort studies are limited by the low incidence of congenital malformations and thus reach adequate power only if a large multicenter approach is adopted. On the other hand, case-control studies on birth defects usually select Accepted June 1, 2000. Address correspondence and reprint requests to Prof. Pierpaolo Mastroiacovo at International Centre for Birth Defects, via Pilo Albertelli 9, 00195 Roma, Italy. E-mail: icbd@icbd.org healthy infants as controls, and there is a major risk of recall bias (i.e., the quality of the information given by the mothers regarding exposures during pregnancy differs between cases and controls). A registry-based system represents a relatively simple and inexpensive way of gathering information on intrauterine drug exposure in a large number of malformed infants (6). The use of controls presenting with malformations other than the malformation under study may reduce the recall bias and thus the overestimation of the effect.The main objective of our study was to test the effe...

Cases with CHD were more likely to have been conceived following ART when compared with malformed controls. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.