Grantee Research Project Results
2010 Progress Report: An Integrated Geospatial and Epidemiological Study of Associations Between Birth Defects and Arsenic Exposure in New England
EPA Grant Number: R834599C003Subproject: this is subproject number 003 , 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: An Integrated Geospatial and Epidemiological Study of Associations Between Birth Defects and Arsenic Exposure in New England
Investigators: Karagas, Margaret Rita , Moeschler, John B. , Onega, Tracy L. , Gui, Jiang , Rees, Judy , Shi, Xun
Current Investigators: Shi, Xun , Purvis, Lisa A. , Moeschler, John B. , Onega, Tracy L. , Gui, Jiang , Rees, Judy , Miller, Stephanie
Institution: University of Miami , Dartmouth Medical School , Dartmouth College
Current Institution: Dartmouth College , 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:
In this pilot project, our multidisciplinary team will:
1) establish a methodology integrating geospatial and epidemiological analyses to quantitatively and geographically monitor, characterize, and evaluate the associations between birth defects and arsenic exposure (i.e., inorganic arsenic) in New England; and
2) conduct a feasibility study for testing associations on an individual level. Epidemiologic studies indicate that birth defects relate to various environmental exposures and specifically suggest arsenic as a possible concern.
Geospatial analyses in some regions have revealed considerable non-random spatial variation in the occurrence of birth defects, leading to the hypothesis that this may be due to spatial variation of environmental factors. The combination of geospatial and epidemiological analyses has the potential to create an economic, efficient, and effective procedure covering data preparation, spatial variation detection, case-control sampling, disease-environment relationship modeling, and finally risk mapping.
In this project we intend to establish such a procedure and apply it to modeling the birth defect-arsenic exposure relationship in New Hampshire through two integrated specific aims:
Aim 1: Establishing and testing a methodology for characterizing the spatial variation in the associations between birth defects and arsenic exposures in NH. Specifically, we will a) characterize the spatial distribution of birth defect occurrence and detect the presence of special patterns, particularly “hot spots”; and b) based on a), we will evaluate spatial associations between birth defect occurrence and arsenic exposures.
Aim 2: Assisted by the findings from Aim 1, examining the birth defect-arsenic exposure relationship in NH through a pilot case-control study.
Progress Summary:
For Aim 1, In the first several months we successfully acquired all the datasets as planned in the application. We went through the required Institutional Review Board (IRB) processes and proactively pursued the acquisition of data from various sources. The data we have acquired include:
• Birth defect data in the format of tabular records from the New Hampshire Birth Conditions Program (NHBCP);
• Data on all births in the format of tabular records from the New Hampshire Department of Human and Health Services (NH DHHS);
• LandScan data of population distribution from the Oakridge National Lab;
• Census data of demographics from the US Census; and
• Arsenic exposure data from the USGS, containing the probabilities of water in bedrock wells exceeding 5 micrograms per liter.
• Arsenic concentration values of 8,765 sampled wells in NH (both public and private wells) from the Dartmouth groundwater research program (Karagas).
We compiled these data into an integrated GIS database for quantitative spatial analysis. All the data layers have been cut to the spatial extent of New Hampshire and projected to the New Hampshire State Plane System for them to spatially match each other.
We then conducted an initial exploration of the data. We created GIS data layers of the birth defect records and all birth records at the town level. Using these two layers, we calculated a simple birth defect rate (number of birth defect babies over all births) for each town and created a map of it. Several data and scientific issues were identified through this exploration. For example, the data reveal that birth defects have strong association with the mother’s age, which confirms that age is a strong confounding factor in environmental health analysis of birth defects. We also find that there are quite some cases in which one infant has multiple defects, or twins and triplets are involved, which should be given special considerations.
We then processed the data and sent them into the formal spatial statistical analysis to generate a risk map of birth defects based on existing cases. We first used identified unique infants, avoiding counting multiple defects on the same infant multiple times. We also exclude twins and triplets, which only account for a small proportion in the data, from analysis since there is no consensus on how to deal with them. To address the mother’s age factor, we divided the birth defect cases (infants) and all births into 6 age categories and run analysis for each separately. We disaggregated the town level data (the birth defect cases and all birth data are only available to us at the town level) using a restricted and controlled randomization based on town boundaries and detailed demographic data generated through integrating the LandScan data and Census data. The disaggregated data were used to calculate the density of birth defect cases over the all-birth background. A Monte Carlo process was used to estimate the probability of the density at a location. The final risk map was created by integrating the probability maps created for individual age categories.
For Aim 2, we have been detailing the design of the epidemiologic part of this project by reviewing the details of the study design with various epidemiological experts regarding the best use of limited birth defects data to produce statistically significant and generalizable results; specifically, we have been:
• Designing and preparing the collection kits for maternal and child buccal cell, fingernails, and drinking water samples.
• Developing the participant questionnaires.
• Developing and implementing a survey for subjects who decline participation (including reasons declined, demographics).
• Developing a study protocol and preparing an IRB application for the study.
Our participant survey is based on the Computer Aided Telephone Interview (CATI) Version 5 questionnaire that is used in the National Birth Defects Prevention Study (NBDPS), a Center for Disease Control and Prevention (CDC) funded birth defects study. We have used this particular questionnaire because it has already been used for several years in the CDC study and has been thoroughly reliability and validity tested. We are planning to add specific questions to the existing survey related to drinking water and arsenic exposures well as to revise the daily food frequency section to be more specific to potential sources of arsenic in food. To date, we have obtained electronic versions of the CATI, informed consent, and biological sample collection kit fact sheets. In addition, the Project 3 team has discussed the use of saliva collection kits as opposed to the brush kit method for buccal cell collection. It has been decided that we will use the saliva collection method due to a much higher yield of DNA as compared to the check brush method . The Project 3 team has also reviewed the NBDPS survey in its entirety (85 pages) and revised it to be more specific to our needs for the proposed study.
Given the budget constraints that occurred in the first year of this project as well as the increase in cost for the saliva collection kits, we are likely going to be able to enlist less maternal/child pairs then we originally planned for in New Hampshire. However, we will attempt to maximize enrollment in our study.
Expansion to Maine: We have continued communication with the state of Maine regarding this study and still plan to include this additional data source in our study by first obtaining Maine data to include in Aim 1 of our proposal. Further expansion to Maine, particularly for the epidemiological study, will be considered for the next 5-year Children's Center grant.
Future Activities:
For Aim 1, we will perform sophisticated spatial analyses to detect the associations of birth outcomes, including birth defects and low birth weight births, to arsenic exposure through ground water. The outputs of those analyses are high-resolution raster maps with values at each pixel, i.e., they are not limited by subjectively defined polygons (e.g., towns or zip code). The analytic procedure was established in an earlier lung cancer study, but needs to be expanded and adjusted to adapt to the current study that features a narrower cohort and aggregated data.
For Aim 2, we will finish the preparation of the IRB protocol and all related study materials (fact sheets, biological sample collection kit instructions, etc.) for the study cohort in New Hampshire and submit it to the Dartmouth College Committee for the Protection of Human Subjects. Submission of a separate IRB application to the Maine Department of Health will occur following approval from the NH IRB. When the results from Aim 1 are available and the New Hampshire IRB protocol is approved, we will implement recruitment for the epidemiological study in New Hampshire.
Journal Articles:
No journal articles submitted with this report: View all 9 publications for this subprojectSupplemental 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,
Relevant Websites:
Progress and Final Reports:
Original AbstractMain 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
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.
Project Research Results
1 journal articles for this subproject
Main Center: R834599
76 publications for this center
29 journal articles for this center