2011 Progress Report: Arsenic and Maternal and Infant Immune Function

EPA Grant Number: R834599
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 , Enelow, Richard I. , Korrick, Susan A. , Madan, Juliette
Current Investigators: Karagas, Margaret Rita , Cottingham, Kathryn L. , Enelow, Richard I. , Folt, Carol L. , Gui, Jiang , Korrick, Susan A. , Madan, Juliette , Miller, Stephanie , Moeschler, John B. , Onega, Tracy L. , Punshon, Tracy , Purvis, Lisa A. , Rees, Judy , Robbins, David J , Shi, Xun
Institution: Dartmouth College , Dartmouth Medical School
Current Institution: Dartmouth Medical School , Dartmouth College , Dartmouth Hitchcock Medical Center , Harvard Medical School , University of Miami
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, 2011 through February 14,2012
Project Amount: $1,079,663
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

The objective of the research remains unchanged 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 also remains unchanged:  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. Another exploratory objective, to conduct exploratory analysis of the relation between pre- and post-natal arsenic exposure and infant vaccine response (e.g., to tetanus toxoid and diphtheria) measured at 1 year of age, will be pursued as funding permits as this was recognized as promising by the Scientific Advisory Committee.

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, which are a potential source of As exposure. As part of Project 1, we are prospectively following infants enrolled in our cohort through: (1) interval phone interviews with the mothers at 4, 8 and 12 months of age; (2) screening infant pediatric records covering in the first year of life; and (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.

We continue to make progress on data collection and follow-up aspects of the study with interval interviews being conducted with participants along with a mailed food frequency questionnaire at 12 months (in collaboration with project 2). We have established laboratory protocols for DNA extraction from placental tissue and have begun preliminary analyses in collaboration with Pilot Project 4. We added Dr. Juliette Madan, a pediatrician and researcher at Dartmouth-Hitchcock Medical Center as a co-investigator for our project. Dr. Madan has begun pilot analyses on infant microbiome as a marker of infant immunity and infection status. We are also working closely with Pilot Project 2 to establish protocols for infant biomarker collection. We continue to develop our EPA Quality Assurance Project Plan (QAPP) for this project, data entry screens, data management tools and protocols for additional analyses and continue our collaborative work with Projects 2 and 4.

We are actively engaging new investigators in our research and providing opportunities for these investigators. Dr. Devin Koestler who received his Ph.D. in Biostatistics from Brown University was recently hired as postdoctoral fellow and has begun working on methods for microbiome analyses. Dr. Shohreh Farzan, a postdoctoral fellow with a Ph.D. in Pharmacology and Toxicology was recently hired to cross-train in epidemiology.

Our work resulted in several manuscripts submitted this year (see publications list) and multiple presentations and participation at national and international meetings. Dr. Margaret Karagas presented at the annual Children’s Center meeting in Washington, D.C., in March 2012 and participated in a workshop and scientific sessions at the Mercury 2011 meeting in Halifax, Nova Scotia, this past summer. This fall, we presented several papers at the International Society for Environmental Epidemiology Annual Meeting in Barcelona, Spain. To promote translation and community engagement for the project, Project Research Director, Vicki Sayarath, M.P.H. attended the Environmental Health Communication: Methods, Research and Training Meeting sponsored by the Partnerships for Environmental Public Health (PEPH) in Bethesda, Maryland, in July, and Dr. Karagas presented a PEPH webinar on arsenic in food in April 2012. Drs. Karagas and Korrick are serving on committees and workshops for NAS, EPA and NIEHS. In addition, we continue to actively seek additional support to expand our research. Additional grants submitted over the past year include: an R21 with Dr. Kari Nadeau of Stanford University (resubmitted November 2012), a Centers of Biomedical Excellence (COBRE) grant (submitted February 2012) and Superfund Research Program grant (submitted April 2012).

Overall our findings underscore the importance of evaluating the effects of in utero and early life exposure to arsenic on children’s health, and the potential impacts of this exposure later in life.

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, data and laboratory analyses and collaborative work with Pilot Projects 2 and 4. We will continue to seek funding opportunities to conduct additional markers of immune response, including vaccine response, and will continue microbiome analyses with Dr. Juliette Madan. We will conduct additional preliminary analyses, make scientific presentations, prepare manuscripts for publication and participate in outreach and translational activities. We will pursue opportunities for building upon our project’s work and extend collaborations/interactions within our center, with centers at other institutions, agencies, organizations and the community.


Journal Articles: 29 Displayed | Download in RIS Format

Other center views: All 76 publications 29 publications in selected types All 29 journal articles
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Journal Article Carey AM, Norton GJ, Deacon C, Scheckel KG, Lombi E, Punshon T, Guerinot ML, Lanzirotti A, Newville M, Choi Y, Price AH, Meharg AA. Phloem transport of arsenic species from flag leaf to grain during grain filling. New Phytologist 2011;192(1):87-98. R834599 (2012)
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  • Journal Article Carey A-M, Lombi E, Donner E, de Jonge MD, Punshon T, Jackson BP, Guerinot ML, Price AH, Meharg AA. A review of recent developments in the speciation and location of arsenic and selenium in rice grain. Analytical and Bioanalytical Chemistry 2012;402(10):3275-3286. R834599 (2012)
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  • Journal Article Cottingham KL, Karimi R, Gruber JF, Zens MS, Sayarath V, Folt CL, Punshon T, Morris JS, Karagas MR. Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water. Nutrition Journal 2013;12:149. R834599 (2011)
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  • Journal Article Davis MA, Mackenzie TA, Cottingham KL, Gilbert-Diamond D, Punshon T, Karagas MR. Rice consumption and urinary arsenic concentrations in U.S. children. Environmental Health Perspectives 2012;120(10):1418-1424. R834599 (2012)
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  • Journal Article Farzan SF, Karagas MR, Chen Y. In utero and early life arsenic exposure in relation to long-term health and disease. Toxicology and Applied Pharmacology 2013;272(2):384-390. R834599 (Final)
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  • Journal Article Farzan SF, Korrick S, Li Z, Enelow R, Gandolfi AJ, Madan J, Nadeau K, Karagas MR. In utero arsenic exposure and infant infection in a United States cohort: a prospective study. Environmental Research 2013;126:24-30. R834599 (Final)
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  • Journal Article Fei DL, Sanchez-Mejias A, Wang Z, Flaveny C, Long J, Singh S, Rodriguez-Blanco J, Tokhunts R, Giambelli C, Briegel KJ, Schulz WA, Gandolfi AJ, Karagas M, Zimmers TA, Jorda M, Bejarano P, Capobianco AJ, Robbins DJ. Hedgehog signaling regulates bladder cancer growth and tumorigenicity. Cancer Research 2012;72(17):4449-4458. R834599 (2012)
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  • Journal Article Fei DL, Koestler DC, Li Z, Giambelli C, Sanchez-Mejias A, Gosse JA, Marsit CJ, Karagas MR, Robbins DJ. Association between In Utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study. Environmental Health 2013;12:58 (8 pp.). R834599 (Final)
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  • Journal Article Gilbert-Diamond D, Cottingham KL, Gruber JF, Punshon T, Sayarath V, Gandolfi AJ, Baker ER, Jackson BP, Folt CL, Karagas MR. Rice consumption contributes to arsenic exposure in US women. Proceedings of the National Academy of Sciences of the United States of America 2011;108(51):20656-20660. R834599 (2011)
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  • Journal Article Gruber JF, Karagas MR, Gilbert-Diamond D, Bagley PJ, Zens MS, Sayarath V, Punshon T, Morris JS, Cottingham KL. Associations between toenail arsenic concentration and dietary factors in a New Hampshire population. Nutrition Journal 2012;11:45 (10 pp.). R834599 (2011)
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  • Journal Article Jackson BP, Taylor VF, Punshon T, Cottingham KL. Arsenic concentration and speciation in infant formulas and first foods. Pure and Applied Chemistry 2012;84(2):215-223. R834599 (2012)
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  • Journal Article Jackson BP, Taylor VF, Karagas MR, Punshon T, Cottingham KL. Arsenic, organic foods, and brown rice syrup. Environmental Health Perspectives 2012;120(5):623-626. R834599 (2011)
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  • Journal Article Karagas MR. Arsenic-related mortality in Bangladesh. The Lancet 2010;376(9737):213-214. R834599 (Final)
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  • Journal Article Karagas MR, Wasson JH. A World Wide Web-based survey of non-medical tattooing in the United States. Journal of the American Academy of Dermatology 2012;66(1):e13-e14. R834599 (2011)
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  • Journal Article Karagas MR, Choi AL, Oken E, Horvat M, Schoney R, Kamai E, Cowell W, Grandjean P, Korrick S. Evidence on the human health effects of low-level methylmercury exposure. Environmental Health Perspectives 2012;120(6):799-806. R834599 (2011)
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  • Journal Article Karagas MR, Andrew AS, Nelson HH, Li Z, Punshon T, Schned A, Marsit CJ, Morris JS, Moore JH, Tyler AL, Gilbert-Diamond D, Guerinot ML, Kelsey KT. SLC39A2 and FSIP1 polymorphisms as potential modifiers of arsenic-related bladder cancer. Human Genetics 2012;131(3):453-461. R834599 (2011)
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  • Journal Article Koestler DC, Christensen B, Karagas MR, Marsit CJ, Langevin SM, Kelsey KT, Wiencke JK, Houseman EA. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: a validation analysis. Epigenetics 2013;8(8):816-826. R834599 (Final)
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  • Journal Article Koestler DC, Avissar-Whiting M, Houseman EA, Karagas MR, Marsit CJ. Differential DNA methylation in umbilical cord blood of infants exposed to low levels of arsenic in utero. Environmental Health Perspectives 2013;121(8):971-977. R834599 (2011)
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  • Journal Article Lesseur C, Gilbert-Diamond D, Andrew AS, Ekstrom RM, Li Z, Kelsey KT, Marsit CJ, Karagas MR. A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire. Toxicology Letters 2012;210(1):100-106. R834599 (2011)
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  • Journal Article Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Current Opinion in Pediatrics 2012;24(6):753-759. R834599 (2012)
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  • Journal Article Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA, Housman ML, Moore JH, Guill MF, Morrison HG, Sogin ML, Hampton TH, Karagas MR, Palumbo PE, Foster JA, Hibberd PL, O'Toole GA. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. mBio 2012;3(4):e00251-12 (10 pp.). R834599 (2012)
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  • Journal Article Nadeau KC, Li Z, Farzan S, Koestler D, Robbins D, Fei DL, Malipatlolla M, Maecker H, Enelow R, Korrick S, Karagas MR. In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort. Clinical Immunology 2014;155(2):188-197. R834599 (2011)
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  • Journal Article Oken E, Choi AL, Karagas MR, Marien K, Rheinberger CM, Schoeny R, Sunderland E, Korrick S. Which fish should I eat? Perspectives influencing fish consumption choices. Environmental Health Perspectives 2012;120(6):790-798. R834599 (2011)
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  • Journal Article Punshon T, Tappero R, Ricachenevsky FK, Hirschi K, Nakata PA. Contrasting calcium localization and speciation in leaves of the Medicago truncatula mutant cod5 analyzed via synchrotron X-ray techniques. The Plant Journal 2013;76(4):627-633. R834599 (Final)
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  • Journal Article Punshon T, Ricachenevsky FK, Hindt MN, Socha AL, Zuber H. Methodological approaches for using synchrotron X-ray fluorescence (SXRF) imaging as a tool in ionomics: examples from Arabidopsis thaliana. Metallomics 2013;5(9):1133-1145. R834599 (Final)
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  • Journal Article Shi X, Miller S, Mwenda K, Onda A, Rees J, Onega T, Gui J, Karagas M, Demidenko E, Moeschler J. Mapping disease at an approximated individual level using aggregate data: a case study of mapping New Hampshire birth defects. International Journal of Environmental Research and Public Health 2013;10(9):4161-4174. R834599 (Final)
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  • Journal Article Sunderland EM, Amirbahman A, Burgess NM, Dalziel J, Harding G, Jones SH, Kamai E, Karagas MR, Shi X, Chen CY. Mercury sources and fate in the Gulf of Maine. Environmental Research 2012;119:27-41. R834599 (2011)
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  • Journal Article Wilhelm-Benartzi CS, Koestler DC, Karagas MR, Flanagan JM, Christensen BC, Kelsey KT, Marsit CJ, Houseman EA, Brown R. Review of processing and analysis methods for DNA methylation array data. British Journal of Cancer 2013;109(6):1394-1402. R834599 (Final)
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  • Journal Article Yang J, Punshon T, Guerinot ML, Hirschi KD. Plant calcium content: ready to remodel. Nutrients 2012;4(8):1120-1136. R834599 (2012)
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  • Supplemental Keywords:

    water, drinking water, groundwater, 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, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Exposure, Environmental Chemistry, Biochemistry, Environmental Monitoring, Children's Health, Environmental Policy, Biology, Risk Assessment, birth defects, prenatal exposure, drinking water, perinatal exposure, children's vulnerablity, biological markers, arsenic exposure, dietary exposure, growth & development, developmental disorders

    Relevant Websites:

    Children's Environmental Health and Disease Prevention Research Center at Dartmouth Exit

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2012 Progress Report
  • Final Report
  • 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