1999 WHRG Grant Program

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Functional ADH2 Polymorphism and Incidence of Birth Defects in Infants Exposed to Alcohol in Utero
Darryl Arfsten, M.S.
School of Medicine, University of Maryland, Baltimore

Despite education and health advisories, many pregnant women continue to consume alcohol in the United States. It is well known that heavy and frequent alcohol consumption is potentially teratogenic in the developing fetus. However, little information is available on the effects of moderate or occasional drinking during pregnancy on birth outcome. Also, there is new evidence that ADH2 genotype of both the mother and the infant can have an impact on the risk of alcohol-related birth defects (McCarver et al., 1997). ADH2 is the most important enzyme for the clearance (i.e., detoxification) of alcohol and exists as three subtypes, ADH2*1, ADH2*2, ADH2*3, each encoded for by genes of the same designation. The ADH2*2 and ADH2*3 alleles are associated with rapid clearance of alcohol from the blood stream and ADH2*3 may therefore be protective against the risks for alcohol-related deficits in infant growth and mental development (McCarver et al., 1997). We are proposing an epidemiological study that will attempt to characterize the effects of infant ADH2 genotype and maternal alcohol exposure on the risks for infant growth retardation and congenital heart defects. Our study will involve 341 congenital heart defect cases and 1,380 infants free of congenital heart defects born in Maryland between 1981-89 for which DNA samples (i.e., dried blood spots) were obtained from the Maryland Newborn Screening Program Family history of cardiac malformations, reproductive and medical histories, sociodemographic factors, and exposure information for medications, cigarettes, alcohol, recreational drugs, and household and occupational chemicals was gathered from the infants' mothers via interview by trained professionals during home visits within one year of the infant's birth. This data set contains extensive information on maternal alcohol exposure including frequency of exposure, maximum number of drinks consumed per occasion, the trimester(s) of exposure, and type of alcohol consumed (i.e., beer, wine, or spirits). Congenital heart defects were confirmed by the first year of life by echocardiography, cardiac catheterization, surgery, or autopsy. All infants will be genotyped for the ADH2*3 allele using a PCR-based method developed by Groppi et al., 1990. Infant genotype will be linked with clinical and maternal exposure data. Phase I of our study will seek to determine if increasing levels of maternal alcohol consumption are associated with increased risk of intrauterine growth retardation and whether ADH2*3 genotype protects against these alcohol-related effects among the 1,380 infants free from congenital heart defects. Phase II will determine if increasing levels of maternal alcohol consumption are associated with increased risks for specific types of congenital heart defects and whether ADH2*3 is protective of these effects among 341 congenital heart defect cases versus the 1,380 control infants free from congenital heart defects. These studies will provide an more accurate picture for women and others, public health advisors, on potential risks for adverse pregnancy outcomes and measures of low to moderate maternal alcohol consumption. It is anticipated that the preliminary results will lead to extramural funding to look at a greater range of alcohol-related genes (i.e., CYP2E1, ALDH) in a wide range of birth defects and other adverse pregnancy outcomes associated with fetal alcohol exposure.