2008 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, 2008 through May 31,2009
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:

As noted in last year’s report, we have dropped Aim 1 - “We will test the hypothesis that participation in a multi- component intervention program for mothers of 1 year old children in Tar Creek will be associated with lower child blood lead levels.”
 
Primary Aims 2 & 3 (observational aims of blood Mn as predictor of Bayley scales of Infant development and maternal stress as predictor of Bayley) are unchanged.
 
Secondary Aims are unchanged.
 

Progress Summary:

As noted last year, project 1’s (R831725C001) field work has been hampered due to weather related events impacting the study activities. In addition to the flood and ice storms of 2007, which closed our field office for nearly the entire year of 2007, in February 2008, an ice storm took out electrical power in Ottawa County, including our study field team offices. There was no electricity for 6 weeks and our office was again forced to close. We had re-opened following the June Neosho River flood in November 2007, and the timing of this second storm somewhat slowed our efforts to rebuild the lost enrollment and follow-up of the previous year. In addition, this summer a tornado hit Picher, Oklahoma, and directly impacted a chat pile. The daughter-in-law of a part-time field staff worker died in the tornado and many study families were again affected by a natural disaster. Our team and community remain committed to this project and despite these obstacles, we have successfully relocated to a new field office and our activities have renewed. We began by assessing the impact of our prolonged shut-down on participant recruitment, retention, field team morale, and the adequacy of local resources. It was clear that our staff was overwhelmed by these events, which not only impacted their work but also impacted their personal lives as well as the personal lives of our study participants. We lost the ability to both enroll and conduct the follow-up visits that would have occurred during times we were shut down. Even after re-opening, we could not bring in some families whose lives had not yet recovered from the flood or ice storm. We estimate that we likely were unable to enroll 150 participants and more than 100 follow-up visits were lost.
 
As this was an unexpected series of events, we found that our field team needed additional on site assistance and direction in order to re-organize and track subjects who were missed in 2007 and early 2008 while maintaining the day to day work of the office. Therefore, we decided that we needed to restructure. Fortunately, with combined funding obtained via a new RO1 (ES016283-01Metal Exposure and Children’s Preschool Neurodevelopment), which is a tag on study to the MATCH cohort, we had some additional resources to add to the program. We recruited help from within Harvard for a unique position. We are very pleased that Dr. Marianne Hopkins, MD, MPH, a child psychiatrist, has taken a position with our group as a research associate. Dr. Hopkins’ position is unique in that she will live on site in Tar Creek, Oklahoma, and direct the field team. She moved there on August 1st and has taken the lead on organizing our recruitment and retention efforts. She has directed the field staff on strategies towards increasing retention and tracking participants lost due to the weather events and simultaneously has begun the start-up of the new RO1. Her considerable expertise has had a major positive impact. We were able to reorganize by July and in the current grant year have recruited more than 80 new mothers, most of whom were recruited after September. Although funding is due to end in March 2009, with the new RO1, the study will continue to 2013, and we plan to recruit for 1 additional year to increase our overall sample size and reach a follow-up sample of 600 children. We believe we can do this while simultaneously conducting the work of the new RO1 as the study populations are identical, Dr. Wright and Dr. Bellinger are co-PIs of each project and the field staff and resources are shared. The new RO1 will follow subjects till age 6. In addition, because not all subjects will be 6 years old by the time recruitment begins, we will see all subjects recruited in the coming year at birth at age 4 years and can conduct all the intelligence tests of the RO1 and thereby will increase its sample size as well.
 
Our current recruitment is 627 mother-infant pairs (263 seen at 1 year and 179 seen at 2 years). We have maintained contact with families who missed follow-up visits due to our field office being flooded and closed. Overall, 164 mothers are either lost to follow-up (66) or have stated they are not interested in further participation (98). Overall our retention rate is 70%. Although retention has been hurt due to an unusual series of weather events, we have a plan to retain those subjects missed in the RO1 study and will continue recruitment for at least 1 more year. We believe this will represent 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, as we have found no comparable data in the medical literature. Blood Mn levels in Tar Creek are 2-3 times higher than non-pregnant adult populations. We plan to present preliminary results to the community in the fall of 2009, as we believe at this point of the study our effect estimates should be relatively stable. As part of the new RO1, we will begin genotyping the cohort for iron and cholesterol metabolism genes and anticipate that we will publish several papers based on these analyses.
 

Future Activities:

We will continue recruitment and follow-up of the birth cohort even after Year 5. Dr. Wright traveled to Tar Creek and met with the Community Advisory Board. He presented the rationale for not conducting the intervention described in the proposal as Specific Aim 1. We now have a sufficient sample size to determine associations between maternal and newborn metal biomarkers and birth outcomes (birth weight, for example) and have recently published a paper on this data (Zota, et al). We continue to collect neurodevelopmental outcomes (Bayley Scales) to address our aims and should have sufficient data on main effects of Mn, and we believe we also will be able to test the interaction between blood Mn and Pb as well.
 
Other activities we conducted this past grant year include the start up of the aforementioned RO1 to maintain the cohort. This grant will fund efforts at measuring Zn and As in our archived samples of hair and blood and will include gene by environment interaction work and these sample analyses already have begun. We also continue to collaborate with Dr. Manish Arora, D.D.S., on a pilot study of salivary cadmium levels as a predictor of dental caries in young children. Some of this work was recently published and there are data still being analyzed. We have sufficient sample size to conduct studies of metals and stress on birth outcomes and the first of these studies was recently accepted for publication (Zota, et al., in press). We also are planning to submit a new RO1 on metal mixtures, which will combine data from Tar Creek with birth cohorts in Mexico and Bangladesh in a pooled analysis that will allow for greater power to detect 2 and 3 way interactions among Pb, Mn, and As. This project also will be part of a resubmission of our Superfund Basic Research Program application. In 2008, the overall program received a score of 230, while this project (pooled analysis of Tar Creek, Bangaldesh and Mexico) received a score of 141.
 


Journal Articles on this Report : 7 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 Hopkins MR, Ettinger AS, Hernandez-Avila M, Schwartz J, Tellez-Rojo MM, Lamadrid-Figueroa H, Bellinger D, Hu H, Wright RO. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives 2008;116(9):1261-1266. R831725 (2009)
    R831725C001 (2008)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • 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)
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  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Other: ScienceDirect-Full Text PDF
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  • Journal Article Wright RO, Fields N. Therapeutics and toxicology. Current Opinion in Pediatrics 2008;20(2):171. R831725 (2009)
    R831725C001 (2008)
  • Abstract from PubMed
  • Abstract: Ovid-Excerpt
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  • Other: Current Opinion in Pediatrics-Citation
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  • Journal Article Wright RO. Neurotoxicology: what can context teach us? Journal of Pediatrics 2008;152(2):155-157. R831725 (2009)
    R831725C001 (2008)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: The Journal of Pediatrics-Full Text HTML
    Exit
  • Other: Journal of Pediatrics-Full Text PDF
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  • Journal Article Wright RO. New morbidities: new challenges. Current Opinion in Pediatrics 2009;21(2):220-221. R831725 (2009)
    R831725C001 (2008)
  • Abstract from PubMed
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  • Journal Article Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO. Maternal blood manganese levels and infant birth weight. Epidemiology 2009;20(3):367-373. R831725 (2009)
    R831725C001 (2008)
  • Full-text from PubMed
  • Abstract from PubMed
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  • Abstract: Epidemiology-Abstract
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  • Supplemental Keywords:

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

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006
  • 2007 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