2017 Progress Report: Biomarker Epidemiology of In Utero Environmental Exposures and Child Development

EPA Grant Number: R836155C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R836155
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Biomarker Epidemiology of In Utero Environmental Exposures and Child Development
Investigators: Meeker, John D. , Swan, Shanna Helen , Watkins, Deborah Jean , Calafat, Antonia , Mukherjee, Bhramar
Institution: University of Michigan , Centers for Disease Control and Prevention , Mount Sinai Medical Center
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2020)
Project Period Covered by this Report: September 1, 2016 through August 31,2017
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

It has been documented that there are particularly high rates for a number of developmental conditions, as well as elevated exposure to environmental contaminants, in Puerto Rico. Most human studies to date on environmental exposures and child health have focused on metals or persistent organic pollutants, but there is a great need for more data on emerging chemicals of concern, such as those currently used in a wide array of industrial and consumer applications. Chemicals such as phenols and parabens disrupt endocrine function, induce oxidative stress, and cause other alterations that may result in reduced fetal or child growth, preterm birth, neurodevelopmental delays, reproductive tract anomalies, obesity, allergies/asthma, and others. While near-ubiquitous exposures to these chemicals have been documented among pregnant women, well-designed human studies are greatly needed to determine whether developmental impacts are related to early life in utero exposure. In addition, few studies have addressed the real life situation of considering multiple exposures and susceptibility factors. To fill these gaps, researchers will use state-of-the-art epidemiologic approaches among an underserved and potentially highly exposed population. Researchers will leverage an ongoing NIH-funded pregnancy cohort study in Puerto Rico (P42ES017198) that is building a rich dataset on environmental, clinical, social, demographic, behavioral, dietary, and other factors among 1,800 pregnant women on the island’s Northern coast. The study will follow 600 children born into the cohort through the age of 4 years. This project will link with Project 1 to test the impacts of exposure to multi-pollutant mixtures, and Project 2 to exchange information about mechanisms and test mixtures for our biomarker epidemiology study and their toxicity screening study.

Progress Summary:

This year, researchers have continued to build the infrastructure required for child follow-up with the research support core and the other projects, including setting up a new clinic space for participants, implementing the non-nutritive suck (NNS) sampler, setting up air monitoring locations, training study personnel, and obtaining IRB approval from all necessary institutions. Recruitment has begun and study staff already have recruited 113 infants into the study.

Thus far, phenols and parabens from more than 500 mothers across all three trimesters of pregnancy have been analyzed by the CDC National Laboratory in Atlanta. Another batch of 549 samples was sent to the lab in November and those results are expected shortly. In addition, a new batch of 472 serum and cord samples have been analyzed by UM CLASS lab for thyroid and reproductive hormones (testosterone, progesterone, estriol, SHBG, T4, free T4, T3, TSH, CRH). These data have been entered, formatted, and added to the database. Additional batches of serum and urine also are in the process of being selected for analysis of measures of oxidative stress and inflammation.

This past year the analysis of our earlier and smaller dataset of phenols/parabens and hormone levels was published in Environmental Research (Aker, et al., Environ Res, 2016;151:31-37).  In that analysis researchers found a number of associations, both in cross-sectional analysis by pregnancy visit and in mixed effects models that take advantage of the repeated measures study design. Researchers plan to update this analysis with the new data (472 additional samples) and hormones (e.g., testosterone, CRH, estriol) that were recently measured.

For this progress report researchers have conducted an exploratory analysis of urinary phenols/parabens and birth weight (Table 1). Researchers observed inverse associations with birth weight for dichlorphenols at Visit 1, but increased birth weight in relation to parabens at Visit 3. Researchers plan to re-do these analyses in the next couple of months after adding in the new exposure data as well as data for important covariates. 


Table 1: Associations between urinary phenols/parabens and birth weight

 

 

Future Activities:

Researchers will continue to work with the core and other projects on ensuring effective participant recruitment and efficient collection of quality data and samples. Researchers will continue working with the various laboratories to obtain state-of-the-art data on environmental exposure, hormone levels, oxidative stress, and inflammation. We plan to take our first look at the data being collected on maternal stress, and how they relate to exposure and intermediate outcome measures. Finally, researchers also will begin examining preliminary relationships between in utero phenol and paraben exposure and outcome measures collected at birth, including preterm birth, birth size, NNS, and anogenital distance (AGD).


Journal Articles on this Report : 9 Displayed | Download in RIS Format

Other subproject views: All 12 publications 9 publications in selected types All 9 journal articles
Other center views: All 30 publications 15 publications in selected types All 15 journal articles
Type Citation Sub Project Document Sources
Journal Article Aker AM, Watkins DJ, Johns LE, Ferguson KK, Soldin OP, Anzalota Del Toro LV, Alshawabkeh AN, Cordero JF, Meeker JD. Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women. Environmental Research 2016;151:30-37. R836155 (2017)
R836155C003 (2017)
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  • Journal Article Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environmental Health Perspectives 2015;123(9):895-901. R836155C003 (2017)
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  • Journal Article Ferguson KK, Cantonwine DE, McElrath TF, Mukherjee B, Meeker JD. Repeated measures analysis of associations between urinary bisphenol-A concentrations and biomarkers of inflammation and oxidative stress in pregnancy. Reproductive Toxicology 2016;66:93-98. R836155 (2017)
    R836155C003 (2017)
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  • Journal Article Ferguson KK, Meeker JD, Cantonwine DE, Chen Y-H, Mukherjee B, McElrath TF. Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environment International 2016;94:531-537. R836155 (2017)
    R836155C003 (2017)
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    R835436 (2016)
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  • Journal Article Johns LE, Ferguson KK, Meeker JD. Relationships between urinary phthalate metabolite and bisphenol A concentrations and vitamin D levels in U.S. adults: National Health and Nutrition Examination Survey (NHANES), 2005-2010. Journal of Clinical Endocrinology and Metabolism 2016;101(11):4062-4069. R836155 (2017)
    R836155C003 (2017)
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  • Journal Article Lewis RC, Johns LE, Meeker JD. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011-2012. International Journal of Environmental Research and Public Health 2015;12(6):6098-6114. R836155C003 (2017)
    R835436 (2014)
    R835436 (2015)
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  • Journal Article Watkins DJ, Fortenberry GZ, Sanchez BN, Barr DB, Panuwet P, Schnaas L, Osorio-Valencia E, Solano-Gonzalez M, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM, Meeker JD. Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: distribution and relationships with child neurodevelopment. Environmental Research 2016;147:307-313. R836155 (2017)
    R836155C003 (2017)
    R835436 (2015)
    R835436 (2016)
    R835436 (2017)
    R835436 (Final)
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  • Journal Article Yuan Y, Meeker JD, Ferguson KK. Serum polybrominated diphenyl ether (PBDE) concentrations in relation to biomarkers of oxidative stress and inflammation: the National Health and Nutrition Examination Survey 2003-2004. Science of the Total Environment 2017;575:400-405. R836155 (2017)
    R836155 (2018)
    R836155C003 (2017)
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  • Journal Article Watkins DJ, Ferguson KK, Anzalota Del Toro LV, Alshawabkeh AN, Cordero JF, Meeker JD. Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico. International Journal of Hygiene and Environmental Health 2015;218(2):212-219. R836155C003 (2017)
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  • Supplemental Keywords:

    biomarkers, environmental exposure, phenols, parabens, endocrine disrupters, child development

    Progress and Final Reports:

    Original Abstract
  • 2016 Progress Report
  • 2018
  • 2019

  • Main Center Abstract and Reports:

    R836155    Center for Research on Early Childhood Exposure and Development in Puerto Rico

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R836155C001 Air Pollution Impacts on Neonatal and Early Childhood Development
    R836155C002 Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
    R836155C003 Biomarker Epidemiology of In Utero Environmental Exposures and Child Development