Parent Title:
Children's Environmental Health & Disease Prevention Research Center at Dartmouth
Grant Number:
Principal Investigator:
Karagas, Margaret Rita (Contact); Nadeau, Kari C (subcontract, Stanford University)
Institution:
Dartmouth College
Most Recent Award Year:
2010
Lifestage of Participants:
Exposure:
Prenatal; Infant (0-1 year); Adulthood (mother)
Assessment:
Infant (0-1 year); Adulthood (mother)
Exposures:
Metals:
Arsenic; Cadmium; Lead; Manganese; Mercury/methylmercury; Zinc
Mixtures:
Nutrition/Diet/Supplements:
Folate; Selenium
Health Outcomes:
Immune Outcomes:
Immune function; Infection
Biological Sample:
Blood; Urine (mother)
Other Participant Data:
Vaccine response (antibody titers to tetanus and diphtheria)
Genes or Other DNA Products Studied:
Genes involved in arsenic metabolism
Abstract:
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.
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Related NIEHS-Funded Study Populations
The New Hampshire Birth Cohort Study
Principal Investigator:
Karagas, Margaret
| Study Population Page Study Population c108
Institution:
Dartmouth College
Location:
New Hampshire; Vermont
Number of Participants::
2,000+ Mother-infant pairs
Brief Description::
This is a prospective pregnancy cohort study of mothers who use private wells for household water in New Hampshire designed to evaluate maternal/child health impacts of arsenic and other contaminants. The study has recruited over 2,500 mother-infant pairs (over 4,000 individuals) since 2009.