Grant Number:
Principal Investigator:
Christiani, David C
Institution:
Harvard University
Most Recent Award Year:
2007
Lifestage of Participants:
Exposure:
Prenatal; Adulthood (mother)
Assessment:
Infant (0-1 year)
Exposures:
Metals:
Arsenic
Health Outcomes:
Birth Outcomes:
Biological Sample:
Blood (mother); Cord blood; Fingernails/toenails; Hair; Placenta; Urine; Umbilical cord
Environmental Sample:
Drinking water sample
Genes or Other DNA Products Studied:
GWAS on cord blood
Epigenetic Mechanisms Studied:
MicroRNA expression profiles in placenta; DNA methylation in maternal blood, cord blood, and umbilical endothelial cells
Abstract:
Inorganic Arsenic is a toxic compound with significant public health impact. The Environmental Protection Agency (EPA) has identified 1,300 sites on its National Priorities List (NPL), and arsenic has been found in at least 781 of these sites. Arsenic is also a by-product of coal combustion, as well as a naturally occurring water contaminant in many regions of the world, including the USA, Exposure may occur by a variety of pathways including inhalation of dusts in air, ingestion of contaminated soil or water, or through the food chain. Arsenic has been associated with a number of adverse health effects. However, the precise relation of arsenic to pregnancy outcomes has not been established. Thus, we wish to extend the previous work we conducted in Taiwan and Bangladesh to an assessment of birth outcomes in a prospective, repeated measures study of expectant mothers and their newborns in Bangladesh. Currently, an estimated 133 million people in Bangladesh are at risk of disease from drinking arsenic-contaminated drinking water. The proposed studies will evaluate standard birth outcomes at exposure levels that are relevant not only to the U.S. population, but also globally. The proposed studies will assess this risk in a population with a wide range of exposure, from low to high. Together, these data will add substantially to the existing risk assessment information by elucidating birth outcomes after arsenic exposure; the role of methylated forms of arsenic in the urine as biomarkers of exposure and risk; and an evaluation of a new potential marker of adverse outcome (proteomic profiles), as well as the influence of candidate genetic susceptibility traits as risk modifiers. This project is relevant to the overall strategic plan of the NIEHS in several ways. Firstly, we will examine a range of health effects of a significant environmental toxicant, arsenic. Secondly, we will define human biomarkers of exposure, early effects, and genetic susceptibility to arsenic exposure. Thirdly, we will examine exposure-response relationships for arsenic-induced birth outcomes. Fourthly, we will incorporate new, sensitive toxicogenomic technology (proteomics) to assess potentially novel biomarkers of exposure and effect in a molecular epidemiologic setting. Lastly, the study is international, sited in the developing world. The proposed human studies will fill important research gaps in our knowledge of arsenic toxicity and inform clinical and public health interventions.
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Related NIEHS-Funded Study Populations
Children with In Utero Arsenic Exposure: Bangladesh
Principal Investigator:
Christiani, David
| Study Population Page Study Population c34
Institution:
Harvard University
Location:
Bangladesh
Number of Participants::
1,613 Pregnant women and 1,189 Mother-infant pairs
Brief Description::
This is a prospective birth cohort study in Bangladesh examining the impact of chronic arsenic exposure on birth, neurodevelopmental, and respiratory outcomes. A total of 1,613 pregnant mothers were recruited from Sirajdikhan and Pabna Sadar Upazilas Districts of Bangladesh from 2008-2011. Women were eligible to participate if they were 18 years or older with an ultrasound confirmed singleton pregnancy of ≤16 weeks gestation, used a tube well as their primary source of drinking water and had been using the same drinking water source for at least six months, and intended to live in her current residence throughout pregnancy. At the end of follow-up, 1,189 livebirths, 259 preterm births, 72 stillbirths, and 132 miscarriages were recorded. The neurodevelopment study involves continued follow-up of 812 children.