Grantee Research Project Results

2010 Progress Report: Arsenic and Maternal and Infant Immune Function

EPA Grant Number: R834599C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834599
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Children's Environmental Health and Disease Prevention Center - Dartmouth College
Center Director: Karagas, Margaret Rita
Title: Arsenic and Maternal and Infant Immune Function
Investigators: Karagas, Margaret Rita , Korrick, Susan A. , Enelow, Richard I.
Current Investigators: Karagas, Margaret Rita , Korrick, Susan A. , Enelow, Richard I. , Madan, Juliette
Institution: University of Miami , Dartmouth Medical School , Dartmouth College
Current Institution: Dartmouth Medical School
EPA Project Officer: Callan, Richard
Project Period: February 15, 2010 through February 14, 2013 (Extended to February 14, 2014)
Project Period Covered by this Report: February 15, 2010 through February 14,2011
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

The primary objectives of the research are to: 1) test the hypothesis that prenatal and early life exposure to arsenic (i.e., via drinking water and food) is associated with an increased risk of infant infections during the first year of life; and 2) test the hypothesis that arsenic (As) exposure is related to an increased risk of maternal infection during pregnancy. A secondary/exploratory objective is to assess whether individual variation in arsenic (As) metabolism (based on maternal urinary As metabolites or As metabolism genes, e.g., GSTO1, GSTO2, AS3T, PNP) and other factors (e.g., cigarette smoking, folate intake or polymorphisms in one carbon metabolism genes) modify the effects of arsenic on infant or maternal infection. The primary and secondary objectives remain unchanged.

Progress Summary:

This project extends the work of The New Hampshire Birth Cohort Study, an ongoing longitudinal study of women and infants who are residents of New Hampshire/Vermont and who obtain household water from wells that are a potential source of As exposure. As part of Project 1, we are prospectively following infants enrolled in our cohort through: (1) interval interviews with the mothers at 4, 8 and 12 months of age, (2) screening infant pediatric records covering the first year of life, 3) reviewing prenatal records for information on maternal infections and collecting data regarding infections on the post-partum questionnaire self-administered to women through the parent study. Project 1 further collaborates with Pilot Project 2, Food borne exposure to arsenic during the first year of life to obtain pilot feeding practices (e.g., breast or bottle feeding) and other dietary information and Pilot Project 4, entitled Determining How Arsenic Modulates Hedgehog Signaling During Development by providing placenta biopsies from our cohort.

While obtaining the necessary permissions to proceed with the research, we continued to refine the study protocols including the questionnaires for this aspect of the study (e.g., the 1 year interval interviews) and made necessay procedural modifications. The designed study forms and protocols integrate Project 1 and Pilot Project 2 objectives. To cost-effectively administer the interval interviews (by phone) and the mailed diet surveys for Pilot Project 2 at 12 months, we engaged the services of the University of New Hampshire (UNH) Survey Center. From September to December we finalized contract details with the UNH Survey Center and completed the programming of the questionnaire for use with a Computer Assisted Telephone Inteviewing (CATI) instrument. This instrument tracks the data and progress of all phases of the 1 year follow-up activities for Project 1. The first subjects who have consented to the interval interviews turned 4 months old in October and we began the interview process.

Also in this reporting period, we enlisted the participation of one other prenatal clinic to bolster accrual, and refined our recruitment methods per recommendations of our Scientific Advisory Committee. We are actively engaging new investigators in our research and providing opportunities for professional development of these investigators. Postdoctoral candidate Diane Gilbert-Diamond is a recent graduate of the Nutritional Epidemiology Program at Harvard School of Public Health. Project 1 investigators have presented work related to the study at scientific conferences. Additionally, to date we have published two manuscripts. One manuscript provides the rationale for our study of maternal/infant infections in relation to arsenic exposure, and the other, done in collaboration with Pilot Project 4, justifies the pursuit of hedgehog signaling biomarkers. Two collborative publications with Pilot Project 2 currently are under review, and another is in preparation. We further submitted two collabortive grant applications to enhance the Center’s research (one in collaboration with Pilot Project 2).

Other preliminary work completed this first study year includes the development of data entry screens and data management tools and systems, and preliminary analysis of urinary arsenic metabolities in pregnant women in relation to diet and other factors. We continue to develop laboratory protocols for DNA extraction from placental tissue and meconium for our parent study.

Future Activities:

In the next year of support, we will continue to conduct the interval interviews (e.g., at 4, 8 and 12 months) continue medical record reviews, begin data and laboratory analyses and continue collaborations with Pilot Projects 2 and 4. We will continue to evaluate our new recruitment methods at the new study sites. We also will continue to conduct preliminary analyses, make scientific presentations and prepare manuscripts for publication. Additionally, we will continue to seek opportunity for building upon our project’s work and extend collaborations/interactions within our center, and with centers at other institutions, agencies, organizations and the community.

Journal Articles:

No journal articles submitted with this report: View all 39 publications for this subproject

Supplemental Keywords:

water, drinking water, ground water, exposure, risk, health effects, human health, vulnerability, sensitive populations, population, infants, children, susceptibility, metals, heavy metals, public policy, decision making, community-based, public good, environmental chemistry, biology, geography, epidemiology, immunology, analytical, surveys, measurement methods, Northeast, EPA Region 1, food processing, water safety, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, Water, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Environmental Policy, Biology, Environmental Chemistry, Exposure, Children's Health, Biochemistry, Drinking Water, Risk Assessment, dietary exposure, biological markers, growth & development, perinatal exposure, prenatal exposure, arsenic, children's vulnerablity, arsenic exposure, birth defects, developmental disorders

Relevant Websites:

http://www.dartmouth.edu/~childrenshealth/index.html Exit

Progress and Final Reports:

Original Abstract

2011

2012 Progress Report

Final Report

Main Center Abstract and Reports:

R834599 Children's Environmental Health and Disease Prevention Center - Dartmouth College

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834599C001 Arsenic and Maternal and Infant Immune Function
R834599C002 Food Borne Exposure to Arsenic During the First Year of Life
R834599C003 An Integrated Geospatial and Epidemiological Study of Associations Between Birth Defects and Arsenic Exposure in New England
R834599C004 Determining How Arsenic (As) Modulates Sonic Hedgehog (Shh) Signaling During Development

Top of Page

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.