2007 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
Institution: Harvard T.H. Chan School of Public Health
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, 2007 through May 31,2008
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Objective:

The Center for Children’s Environmental Health and Disease Prevention at the Harvard School of Public Health is now in its fourth year. Our fifth year of funding begins on April 1, 2008. More and more, this Center is emerging as a model of effective translational research. Our Center uses animal models to address fundamental mechanisms of metal pharmacokinetics and mechanisms of injury. It utilizes exposure measurements in humans, and is also measuring health outcomes in humans. Most importantly, we involve the community. Especially we have established communications with individuals in that community, as well as with government stake-holders. This year continued to see functioning partnerships with our community-based colleagues and with other collaborating institutions.

Year 04 was marked by substantial progress in all Projects and Cores.

Progress Summary:

The community-based participatory birth cohort, which is the focus of Project 1, is now well-established; more than 500 mother-infant pairs have been enrolled. Data have now been collected on over 240 children at 1 year of age and 135 at 2 years of age. We have information both in regard to Bayley scales as well as biomarker data for both Mn and Pb. Our preliminary results continue to demonstrate an inverse association between maternal blood Mn at delivery and 24 month Bayley scale scores. We also see an inverse relationship between blood Pb at 24 months and MDI scores. We believe this is especially interesting since our mean blood Pb level at this age is 2.6 μg/dL, which is lower than any other study reported in the literature. Importantly, these results to date support the concept that there may be no lower threshold for lead poisoning.

Other activities we conducted this past grant year included preparing an application for additional funding to maintain the cohort. Dr. Bellinger and Dr. Wright submitted an R01 to continue follow-up of the cohort, which has now been funded. This grant will fund efforts at measuring Zn, Cd, and As in our archived samples of hair and blood and will include gene by environment interaction work. This study will also continue follow-up at 4 years of age and continue it to age 6 years. Through this new project we can maintain contact with subjects not seen due to weather-related phenomena and hire additional staff to assist with tracking. We decided to reinstitute new enrollment due to our long field team closure in year 4 and in anticipation of the future follow-up of children at 2 and 4 years of age, which should allow us to meet our sample size goals. We note that the new RO1 will facilitate visits at 2 and 4 years of age for subjects enrolled in the current grant year.

We also collaborated with Dr. Manish Arora, D.D.S., on a pilot study of salivary cadmium levels as a predictor of dental caries in young children. We worked with a local dentist in Tar Creek, and the study was conducted in our cohort among children at age 3 years. This study demonstrates our strong ties to the community and provided a mechanism to maintain contact with participants beyond 2 years of age. Preliminary results show an inverse relationship between salivary Cd and dental caries and we plan to submit this as an abstract to the 2008 ISEE meeting in California. This work also directly led to an analysis of blood/urine Cd and dental caries in NHANES, which was recently accepted for publication in EHP.

We have laid a solid foundation for this community-based participatory birth cohort. Our current recruitment of 542 mother-infant pairs represents a significant sample size to study neurodevelopmental effects from exposure to metal mixtures. Also, to our knowledge, these are the only data on blood Mn collected on 1- and 2-year-old children, as we have found no comparable data in the medical literature. Blood Mn levels in Tar Creek are 2 to 3 times higher than non-pregnant adult populations. We note that following advice from our external advisory board, we have begun collecting data on HOME scores (short form survey) in our population; we have successfully done so in over 90% of subjects seen at 1 and 2 years of age and continue to collect this data. We are also continuing to collect data on the important covariates of maternal IQ (K-BIT) and maternal education.


Journal Articles on this Report : 12 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 Arora M, Weuve J, Schwartz J, Wright RO. Association of environmental cadmium exposure with pediatric dental caries. Environmental Health Perspectives 2008;116(6):821-825. R831725 (2007)
R831725 (2009)
R831725C001 (2007)
R831725C001 (2008)
R831725C003 (2007)
R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 2006;34(3):330-337. R831725 (2005)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ATS-Full Text HTML
    Exit
  • Other: ATS-Full Text PDF
    Exit
  • Journal Article Heilig EA, Thompson KJ, Molina RM, Ivanov AR, Brain JD, Wessling-Resnick M. Manganese and iron transport across pulmonary epithelium. American Journal of Physiology–Lung Cellular and Molecular Physiology 2006;290(6):L1247-L1259. R831725 (2005)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: American Journal of Physiology-Full Text HTML
    Exit
  • Other: American Journal of Physiology-Full Text PDF
    Exit
  • Journal Article Heilig E, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats. American Journal of Physiology–Lung Cellular and Molecular Physiology 2005;288(5):L887-L893. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: American Journal of Physiology-Full Text HTML
    Exit
  • Other: American Journal of Physiology-Full Text PDF
    Exit
  • Journal Article Hu H, Shine J, Wright RO. The challenge posed to children’s health by mixtures of toxic waste: the Tar Creek Superfund Site as a case-study. Pediatric Clinics of North America 2007;54(1):155-175. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: ScienceDirect-Abstract
    Exit
  • Journal Article Schaider LA, Senn DB, Brabander DJ, McCarthy KD, Shine JP. Characterization of zinc, lead, and cadmium in mine waste: implications for transport, exposure, and bioavailability. Environmental Science and Technology 2007;41(11):4164-4171. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C004 (2007)
  • Abstract from PubMed
  • Abstract: ACS-Abstract
    Exit
  • Journal Article Surkan PJ, Schnaas L, Wright RJ, Tellez-Rojo MM, Lamadrid-Figueroa H, Hu H, Hernandez-Avila EM, Bellinger DC, Schwartz J, Perroni E, Wright RO. Maternal self-esteem, exposure to lead, and child neurodevelopment. NeuroToxicology 2008;29(2):278-285. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C001 (2008)
    R831725C003 (2007)
    R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. Journal of Nutrition 2006;136(12):3010-3014. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Journal of Nutrition-Full Text HTML
    Exit
  • Other: Journal of Nutrition-PDF
    Exit
  • Journal Article Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicology and Applied Pharmacology 2006;210(1-2):17-23. R831725 (2005)
    R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2005)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article Thompson K, Molina RM, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB Journal 2007;21(1):223-230. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: FASEB-Abstract
    Exit
  • Journal Article Thompson K, Molina RM, Donaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. American Journal of Physiology-Gastrointestinal and Liver Physiology 2007;293(3):G640-G644. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C003 (2008)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: AJPGI-Full Text HTML
    Exit
  • Other: AJPGI-Full Text PDF
    Exit
  • Journal Article Wright RO, Baccarelli A. Metals and neurotoxicology. The Journal of Nutrition 2007;137(12):2809-2813. R831725 (2007)
    R831725 (2009)
    R831725C001 (2007)
    R831725C003 (2007)
    R831725C004 (2007)
  • Abstract from PubMed
  • Full-text: OUP-Full Text HTML
    Exit
  • Other: OUP-Full Text PDF
    Exit
  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, ENVIRONMENTAL MANAGEMENT, Waste, Environmental Chemistry, Health Risk Assessment, Hazardous Waste, Biochemistry, 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

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006
  • 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