Remarkably little is known about the health consequences of chronic inorganic arsenic (InAs) exposure in pregnant women and children, typically perceived to be the most vulnerable to environmental exposures. InAs is a known to teratogen in animals, particularly in species that are inefficient in methylating it to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). We have identified a region of Bangladesh (Sonargaon) where drinking water contains a uniquely wide range concentrations of InAs. We propose to conduct these studies which will test hypotheses concerning the health effects and metabolism of InAs in the pregnant women and children. In year -01, through a retrospective study of past pregnancy outcomes in approximately 2000 women, we will examine the relations between InAs exposure, assess through measurements of drinking water and urinary As, and later spontaneous abortion and stillbirth. In years -02 and -03, we will recruit approximately 100 women at 12-20 weeks of gestation to test the hypothesis that As methylation can be facilitated through the administration of multi-vitamins, or multi-vitamins + addition folate. This randomized trial will examine urinary excretion of InAs, MMA and DMA before and after the provision of such supplements. Third, among the same pregnant women, we will describe at delivery the relationships between maternal and umbilical cord InAs, MMA and DMA; we will also examine the relation between plasma homocyst(e)ine (a marker of folate and B12 status) and InAs, MMA and DMA. Finally, in years -04 and -05, we will conduct cross-sectional studies of children aged-6 and 10-years, respectively, to examine association between InAs exposure and selected biomarkers of health outcomes.
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