2005 Progress Report: Metals, Nutrition, and Stress in Child Development

EPA Grant Number: R831725C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R831725
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Harvard Center for Children’s Environmental Health and Disease Prevention Research
Center Director: Hu, Howard
Title: Metals, Nutrition, and Stress in Child Development
Investigators: Wright, Robert , Bellinger, David , Hatley, Earl
Current Investigators: Wright, Robert
Institution: Harvard University
EPA Project Officer: Callan, Richard
Project Period: June 1, 2004 through May 31, 2009 (Extended to May 31, 2011)
Project Period Covered by this Report: June 1, 2005 through May 31, 2006
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Children's Health , Human Health


The objectives of this research project are to:  (1) devise a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions; and (2) explore potential effect of stress from living near toxic waste.

Progress Summary:

To date, we have enrolled 425 mother-infant pairs and have collected blood samples, archived hair, and collected survey data.  We have seen 219 mother-infant pairs at 1-year followups and have just had our first 65 children return for a 2-year follow-up.  Mean blood Mn levels are summarized in Table 1.

Table 1.   Blood Mn Levels
Table 1. Blood Mn Levels

In the winter of 2004, we conducted a study of 32 sixth-grade children living within the Tar Creek Superfund Site to test our hypothesis that mixtures of As and Mn were neurotoxic, as part of our renewal application for the Superfund Program.  In linear regression models, both hair As and hair Mn were significantly inversely associated with both full-scale and verbal IQ.  Hair Pb and hair Cd did not significantly predict any IQ test score.  These results currently are in press at the journal Neurotoxicology.  We are planning to measure hair As as well as blood Pb and Mn levels in our birth cohort and have applied for funding to cover the additional costs of these As measures.  Our results for the effects of Mn and As on IQ in sixth-grade students in Tar Creek are intriguing and parallel recent work conducted in Bangladesh by Wasserman, et al., 2004.  We have applied for this additional funding through the Harvard School of Public Health (HSPH) Superfund Basic Research Program Project Grant.  Our project application received a favorable review (project score 1.4, overall application score 192).  If funded, we will measure hair As and add research on proteomics and genetic susceptibility to metals to the overall project.  The exposure assessment data in Project 2 (R831725C002) largely has been collected and will be analyzed for metal content in Year 3 of this project to allow us to develop the intervention protocol for Year 4.

We also conducted or participated in several local community seminars this past year.  Ami Zota, a graduate student working on Projects 1 and 2, met with community representatives in July and November 2005.  Dr. Wright and Ann Backus (Community Outreach and Training Core) participated in the Local Environmental Action Demanded Agency (known as L.E.A.D. Agency) annual Tar Creek Forum in Miami, Oklahoma, in May 2005.  Adrienne Ettinger (Center Scientist) from HSPH also made presentations to the community in April and October 2005.  Our study on metals and IQ in sixth-grade students used community-based recruitment methods, and Drs. Bellinger and Wright have made community presentations to explain the study both before and after the study was conducted.


We have laid a solid foundation for this community-based participatory birth cohort.  Our current recruitment of 425 mother-infant pairs represents a significant sample size to study neurodevelopmental effects from exposure to metal mixtures.  To our knowledge, these are the only data on blood Mn collected on 1- and 2-year-old children available, as we have found no comparable data in the medical literature.  Metal levels in the Tar Creek area are two to three  times higher than nonpregnant adult populations.

Future Activities:

We have completed geographic information systems (GIS) mapping of the chat piles this past year and will use these data to determine spatial relationships between blood Mn and Pb levels and chat piles in 1-year-old children as these data come in.  We now have a sufficient sample size to determine associations between maternal and newborn metal biomarkers and birth outcomes (birthweight, hearing, and head circumference).  We continue to collect neurodevelopmental outcomes (Bayley Scales) to address our aims and in Year 3 will plan and develop the intervention to lower exposure to metals in children.


Wright R. Environmental Health Perspectives 2004;112(13):1329-1333.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other subproject views: All 20 publications 20 publications in selected types All 20 journal articles
Other center views: All 35 publications 26 publications in selected types All 25 journal articles
Type Citation Sub Project Document Sources
Journal Article Lanphear BP, Wright RO, Dietrich KN. Environmental neurotoxins. Pediatrics in Review 2005;26(6):191-198.
abstract available  
R831725 (2009)
R831725C001 (2005)
R829389 (2003)
R829389 (2004)
R829389 (2005)
R829389 (Final)
  • Abstract from PubMed
  • Abstract: AAP-Abstract
  • Journal Article Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu H, Rich-Edwards JW, Gillman MW. Maternal fish consumption, hair mercury, and infant cognition in a U.S. cohort. Environmental Health Perspectives 2005;113(10):1376-1380.
    abstract available   full text available
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2005)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. NeuroToxicology 2006;27(2):210-216.
    abstract available   full text available
    R831725 (2005)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2005)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
  • Other: ScienceDirect-Full Text PDF
  • Supplemental Keywords:

    children, Native American, tribal, mixtures, lead, PBPK, community, Superfund, intervention, environmental management,, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, Waste, Environmental Chemistry, Health Risk Assessment, Biochemistry, Hazardous Waste, Children's Health, Hazardous, Risk Assessment, community-based intervention, fate and transport , epidemiology, developmental toxicity, biological response, Human Health Risk Assessment, neurodevelopmental toxicity, children's environmental health, mining waste, metal wastes, metals, human health risk, metal contamination, mining wastes

    Relevant Websites:

    http://www.hsph.harvard.edu/niehs/children Exit

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2006
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009
  • Final

  • Main Center Abstract and Reports:

    R831725    Harvard Center for Children’s Environmental Health and Disease Prevention Research

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R831725C001 Metals, Nutrition, and Stress in Child Development
    R831725C002 Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport, and Exposure Patterns
    R831725C003 Manganese, Iron, Cadmium, and Lead Transport from the Environment to Critical Organs During Gestation and Early Development in a Rat Model
    R831725C004 Metals Neurotoxicity Research Project