Both animal and in vitro studies support an association of low level arsenic exposure with impaired immune function as reflected in suppression of innate immunity and increased pathogen load. The few epidemiologic studies of this association are primarily from heavily exposed populations -and often involve small sample sizes or rely on ecologic exposure measures, and may not be generalizable to other regions of the world. Arsenic exposure in these heavily exposed populations has been variously associated with an increased risk of respiratory infection, bronchiectasis, and parasitic infection as well as with changed markers of immune function including, e.g., cytokine levels (IL-7, IL-2) and T-cell (CD4/CD8) ratios. The overall goal of this study is to assess the relationship of environmentally relevant levels of arsenic with maternal and infant immune function among 1,000 women and infants enrolled in an ongoing pregnancy cohort study of reproductive toxicities of arsenic. This ongoing longitudinal study is being conducted among mother-infant pairs who are residents of New Hampshire and obtain household water from wells which are a potential source of arsenic exposure. Specifically, we will expand this ongoing study to test the following new hypotheses: (1) prenatal and early life arsenic exposure (via water, food) is associated with an increased risk of infection during the 1st year of life; (2) arsenic exposure is associated with an increased risk of infection during pregnancy. Secondarily, we will assess the relation of pre- and post-natal arsenic exposure with vaccine response at age one year (antibody titers to tetanus and diphtheria) and whether individual variation in arsenic metabolism (maternal urinary metabolite profiles and polymorphisms in arsenic metabolism genes) and other factors (e.g., smoking, folate intake) modify the effects of arsenic on infant or maternal infection. Altered immune function, particularly in pregnancy and early childhood, can have a profound impact on both perinatal and subsequent health. To the best of our knowledge, studying immune effects of arsenic in a U.S. population of mothers and infants with both individual biomarkers of exposure and measures related to likely susceptibility, has not been done previously.

Public Health Relevance

Low level and moderate exposure to As is ubiquitous;characterizing important health risks from such common exposures in a vulnerable time of life (pregnancy and infancy) is critical to strategizing future, public health interventions for both exposure prevention and infectious disease risk reduction.

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