Most studies confirmed the expected relationship between indicators of PHC accessibility and hospitalization for ambulatory care sensitive conditions (ACSCs), showing lower hospitalization rates for ACSC in areas with greater access to PHC. The findings support the use of ACSC hospitalization as an indicator of primary care quality, with the precaution of applying appropriate adjustment factors.

Study objective-To provide an international perspective on the impact of congenital anomalies on infant mortality from 1950 to 1994. Design-Population-based study based on data obtained from vital statistics reported to the World Health Organisation. Settings-36 countries from Europe, the Middle East, the Americas, Asia, and the South Pacific. Results-On average, infant mortality declined 68.8 per cent from 1950 to 1994. In the countries studied, infant mortality attributable to congenital anomalies decreased by 33.4 per cent, although it recently increased in some countries in Central and Latin America and in Eastern Europe. Anomalies of the heart and of the central nervous system accounted for 48.9 per cent of infant deaths attributable to congenital anomalies. During 1990-1994, infant mortality attributable to congenital anomalies was inversely correlated to the per capita gross domestic product in the countries studied. At the same time, the proportion of infant deaths attributable to congenital malformations was directly correlated with the per capita gross domestic product. Conclusions-Congenital malformations account for an increasing proportion of infant deaths in both developed and developing countries. Infant mortality attributable to congenital anomalies is higher in poorer countries although as a proportion of infant deaths it is greater in wealthier countries. Conditions such as spina bifida, whose occurrence can be reduced through preventive strategies, still cause many infant deaths. The apparent increase of infant mortality because of congenital anomalies in some countries should be investigated to confirm the finding, find the causes, and provide prevention opportunities.

Data provided by nine registries based in European and Latin America countries were analyzed to assess whether there is an excess of malformations in twins compared to singletons. Specific congenital malformations were coded according to the ninth revision of the International Classification of Diseases (ICD). Malformation rates and rate ratios (RR) for twins compared to singletons were calculated for each registry, and the homogeneity of the RRs was tested using the test of Breslow and Day. If departure from homogeneity in the different registries was not significant, registry-adjusted RRs with 95% confidence intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were reported. A total of 101 different types of malformations or groups of defects was identified, and a homogeneous estimate of the RRs among registries was found for 91.1% of the malformations. Thirty-nine of the 92 malformations with homogeneous estimates of RRs were more common in twins than in singletons. For the remaining nine malformations, heterogeneous estimates of RRs were obtained. This study confirms the majority of already known associations and further identifies previously unreported malformations associated with twins. In conclusion, there is an excess of malformations in twins compared with singletons, and all anatomical sites are involved. The number of specific malformations associated with twins is higher than that previously reported in smaller studies.

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...

If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.