Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss.
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