Civilians living in southern Vietnam are likely to be among the most highly exposed population to dioxin, secondary to the widespread spraying of Agent Orange and other herbicides during the Vietnam War. While the magnitude of health effects of dioxin is still a matter of debate, there is preliminary evidence from studies by Vietnamese scientists indicating an elevation in the incidence of birth defects among exposed individuals, although exposure assessment in these investigations has not been adequate to provide convincing proof of association. The investigators propose a case-control study of three specific types of birth defects in southern Vietnam, with both cases and controls obtained from three large maternity hospitals in Ho Chi Minh City. These hospitals serve maternity patients from all of southern Vietnam. The investigators will study cases of a) cleft lip/cleft palate, b) neural tube defects, including spina bifida, anecephaly and microcephaly, and c) limb abnormalities/limb reduction. One control will be recruited for each case, giving three controls against each case of a particular birth defect type. Cases and controls will be recruited within two days of birth. After obtaining informed consent, a slight modification of the National Birth Defects Prevention Study questionnaire will be administered to the mother. Blood will be obtained from the mother for serum dioxin and furans (total plus 17 individual isomers plus WHO TEQs including PCBs, performed by AXYS Analytical Services Ltd., British Columbia), total plus 111 PCB congeners and up to 78 pesticides (performed in Albany) and single nucleotide polymorphisms of the aryl hydrocarbon (Ah) receptor (performed in Cincinnati). On the basis of the assumption that 50% of the mothers in southern Vietnam will have significant exposure from Agent Orange, the investigators calculate that a total of at least 163 cases of each of the three types of birth defect, and at least 489 controls will provide power to detect an elevated risk of each of these types of birth defects from dioxin exposure with an odds ratio of 1.7.
