Final 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 , Enelow, Richard I. , Korrick, Susan A. , Madan, Juliette
Institution: Dartmouth Medical School , Harvard Medical School
EPA Project Officer: Callan, Richard
Project Period: February 15, 2010 through February 14, 2013 (Extended to February 14, 2014)
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 aims of Project 1 were 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. This project extended the work of the New Hampshire Birth Cohort Study (NHBCS), an ongoing longitudinal study of women and infants who are residents of New Hampshire/Vermont and who obtain household water from wells, which are potential sources of arsenic exposure. Mother/infant dyads have been recruited into the study and were prospectively followed by interval telephone interviews, and by reviewing prenatal medical records for information on post-partum information on infections, allergies, breast feeding/formula/solid food and other information.

Summary/Accomplishments (Outputs/Outcomes):

Studies in highly exposed populations have been important for identifying adverse health effects of metals such as arsenic, but often they are unable to provide risk information at lower levels of exposure commonly found in the United States. Also, the generalizability of results from other countries has been brought into question. Moreover, individual differences in the ability to counteract the effects of metals, exposure to other contaminants and dietary factors may have greater effects in populations with relatively low exposures. Further assessment of exposure to arsenic during pregnancy and early in life has not been extensively explored. Yet, the developing fetus and infant are especially vulnerable to environmental contaminants.

Infant infections remain prevalent in the first year of life even in developed countries, e.g., ear infection (otitis media, OM). In the United States, infections are among the most common indications for doctor visits and antibiotic prescription in early childhood. OM-related hearing loss can be associated with delays in language and cognitive development. The impact of arsenic on immune function has been explored only to a limited extent epidemiologically. However, such findings would have widespread public health implications, including on emerging infections and children’s ability to elicit a vaccine response. As metals such as arsenic are ubiquitous exposures in the US and worldwide, establishing the health risks from common levels of exposure is paramount to strategizing future public health interventions.

We have obtained data on infant infections through interval phone interviews (e.g., at 4, 8 and 12 months) with response rates of about 80%. Dr. Juliette Madan conducted pilot analyses on infant microbiome as a marker of infant immunity and infection status, which yielded several novel manuscripts (see publications), and new investigator funding opportunities.

Our work proved to be truly collaborative during this formative phase of our Center, as we worked closely with all of the pilot projects i.e., infant diet and biomarker collection (urine, stool and breast milk) with Project 2, mapping areas with prevalent arsenic contamination with Project 3, and providing placenta tissue for gene expression analyses with project 4). We also pilot tested protocols for neurobehavioral assessments on newborns using the validated NICU Network Neurobehavioral Scale (NNNS). We carry this momentum and collaborative spirit into the full Children’s Center (P01 ES022832, RD835442), and are furthering our collaborative endeavors with other Children’s Centers, such as UC Berkeley/Stanford and hopefully others.

Throughout the course of our formative Center, we have supported the training and development of new and talented early career investigators, such as Dr. Gilbert-Diamond (now co-leader of P01 Project 2), and Drs. Shohreh Farzan, Devin Koestler and Alison Appleton—all whom have published exciting findings from the Center’s research. We have expanded our translational work, which segued into the P01 Community Outreach and Translation Core.

In our final year of support through the no cost extension, we continued to conduct the interval interviews and medical record reviews, data and laboratory analyses, and collaborative work with Pilot Projects 2 and 4 (as referenced above). We continued to conduct additional preliminary analyses, make scientific presentations, prepare manuscripts for publication, and participate in outreach and translational activities.

Conclusions:

We are very excited to have been funded for P01 Center to continue this work, and look forward to continuing our research to 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.


Journal Articles on this Report : 20 Displayed | Download in RIS Format

Other subproject views: All 39 publications 21 publications in selected types All 21 journal articles
Other center views: All 76 publications 29 publications in selected types All 29 journal articles
Type Citation Sub Project Document Sources
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, 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, 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 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 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 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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  • 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, ENVIRONMENTAL MANAGEMENT, Water, HUMAN HEALTH, Exposure, Environmental Chemistry, Biochemistry, Children's Health, Environmental Policy, Drinking Water, Biology, Risk Assessment, birth defects, prenatal exposure, perinatal exposure, children's vulnerablity, arsenic exposure, biological markers, dietary exposure, growth & development, arsenic, 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
  • 2011
  • 2012 Progress 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