2017 Progress Report: Center for Research on Early Childhood Exposure and Development in Puerto Rico

EPA Grant Number: R836155
Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Investigators: Alshawabkeh, Akram
Institution: Northeastern University
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: July 1, 2016 through June 30,2017
Project Amount: $2,099,537
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

The Center for Research on Early Childhood Exposure and Development in Puerto Rico (CRECE) investigates the impact of a mixture of environmental exposures and modifying factors on fetal and early childhood health and development in this under-served, highly-exposed population. Since 2010, our interdisciplinary research team has been conducting a highly productive NIEHS-funded pregnancy study of a cohort of 1800 pregnant women in Puerto Rico to investigate links between exposure to groundwater contamination and the unusually high preterm birth rate on the island. The CRECE Center leverages this rich dataset and the infrastructure established to study a cohort of 600 mothers and follow up on 510 children whose prenatal exposures were documented in the PROTECT study, tracking them through age four.

CRECE research projects couple air-pollution epidemiology (Project 1), high throughput toxicity screening of multi-media pollutant mixtures (Project 2), and biomarker epidemiology (Project 3) to analyze the impacts of early life exposure (both specific stressors and mixture effects) on fetal/child health and development, taking into account environmental, clinical, social, demographic, behavioral, dietary, and other factors. Through CRECE’s centralized Human Subjects Core (facility/service core), observed, self-reported, and biological measures are collected, providing new information characterizing the early life exposures to air and water pollution, including contaminants of emerging concern (CECs).

Progress Summary:

Aim 1: Investigate the impact of prenatal and early childhood exposure to air pollution and prenatal exposure to chemicals, including CECs, on fetal/child health and development.

During Year 2, the CRECE team continued its efforts to characterize concentrations of fine particles with aerodynamic diameters under 2.5 microns (PM2.5) and its components in the Northern Shore of Puerto Rico (Project 1). Air monitoring stations were set up at three locations on the island and are fully operational; samples are collected on a weekly basis and shipped to Northeastern University for analysis each month. Analysis of these filters is ongoing, with analysis of PM2.5 and black carbon (BC), a tracer of motor vehicle pollution, conducted each month. In addition, to characterize historical PM2.5 and component concentrations, the CRECE team has obtained PM2.5 and PM10 filters collected by the Puerto Rico Department of Environmental Protection in 2010 and 2011. These filters are being catalogued and will be analyzed further for BC and the elements. The team also is working on updating the protocol for analysis of the metals by X-ray fluorescence (XRF) to optimize XRF performance for the expected mass of PM2.5 collected on sampled filters.

Recruitment and follow-up of CRECE participants is ongoing. In 2016, our ability to recruit and follow CRECE participants was substantially improved through the openings of additional clinic spaces. Our main clinic was officially opened (Figure 2) at Calle Hernandez Carrion E-13 in Manatí, Puerto Rico. This space is close to the Manatí Medical Center, which allows our researchers to meet with our mothers and infants in a centralized, familiar location where the patients will feel comfortable being interviewed for our study. Additionally, we opened two new clinics, in Lares and Camuy, to increase recruitment.

Through March 1, 2017, our recruitment of CRECE participants meets our proposed goals, with a total of 113 participants agreeing to participate in the study. These participants are being regularly evaluated at the main Manatí clinic and at the Morovis Community Health Center. Evaluations are comprehensive, including a complete physical examination, anthropometric (growth and development) measurement, anogenital distance (AGD), Ages and Stages Questionnaire (ASQ), and Battelle Developmental Inventory, Version 2 (BDI-2) assessment. These measures currently are being evaluated, with additional metrics being considered. To facilitate this evaluation and consideration, team members from the Human Subjects Core, Project 1, Project 3, and the CRECE Scientific Advisory Board traveled to the University of Illinois in April 2017, to observe and review the developmental testing. The team in Puerto Rico will begin taking the Non-Nutritive Suck measure at the clinic in May 2017.

CRECE Project 3 team analyzed phenols and parabens from more than 500 mothers across all three trimesters of pregnancy with the CDC National Laboratory in Atlanta. The team conducted an exploratory analysis of urinary phenols/parabens and birth weight. We observed inverse associations with birth weight for dichlorophenols at Visit 1, but increased birth weight in relation to parabens at Visit 3. We 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.

Aim 2: Provide evidence for biological mechanisms (Projects 2 and 3) that may mediate the impact of early life exposure to air pollution (Project 1) and chemicals, including CECs (Project 3), and fetal/child health and development.

As described previously, the air monitoring stations are in place and are regularly producing air quality samples for analysis. Sampling also has begun for well water and tap water. As of March 2017, our recruitment reached 113 CRECE participants agreeing to participate in the study. This allowed us to start the tap water and urine sample collections from these participants. Quantitative measures of pathway-specific and chemical-specific biomarkers of exposure to water contaminants, including CECs and metals, and associated toxicity fingerprints have been performed for the initial batch of water sample using HTS assays for oxidative stress, DNA damage, and inflammation. Biological samples from the mothers continue to be collected and analyzed. In addition to the analysis of samples collected during pregnancy for phenols and parabens, Project 3 is measuring thyroid and reproductive hormone levels. Additional samples have been sent for analysis of oxidative stress and inflammation, and are expected to be returned in the next few months. In the next year, further analysis under this goal will be conducted.

Aim 3: Evaluate effect modification for individual risk factors including socioeconomic status and maternal stress on the relationship between environmental exposure and fetal/child health and development (Projects 1 and 3).

The CRECE center continues to conduct questionnaires and assessments related to individual risk factors such as socioeconomic status and maternal stress for all participants. Protocols are being developed for compiling location-based data for each participant while maintaining participant anonymity, and information on neighborhood characteristics (including socioeconomic status, proximity to roads, and racial composition) is being compiled. Analysis on these measures will begin in the next year.

Aim 4: Explore effects (Projects 1 and 3) and relevant mechanistic pathways (Project 2) of early life exposure to mixtures of multiple pollutants in relation to fetal/child health and development.

Sampling of tap water and well water began in Year 2, and pathway-specific toxicity analysis has been conducted on 15 samples so far. Project 2 also conducted non-targeted organic chemical analysis, metals analysis, and targeted analysis of volatile DBPs (disinfection by-products), and DEHP. The protocols have been refined for the special study of urine samples and analysis, and the first samples have been taken and shipped to Northeastern University. In addition, Project 2 has established preliminary protocols for air sample (PM2.5) extraction. The toxicity impacts of PM2.5 components will be assessed using HTS assays for oxidative stress and DNA damage for the air samples collected in Project 1.

As mentioned previously, the CRECE team is working with experts in the field of child development to refine the neurodevelopmental measures being taken. Currently, the evaluation process for participants includes a physical examination, the ASQ, and the BDI-2. Analysis of the effects of pollutant mixtures on early development is expected to begin in the next year.

Aim 5: Engage stakeholders (COTC) to support environmental health practice, innovation and policy, professional development, and awareness around our theme.

CRECE has conducted a number of outreach events to the community and other researchers. The COTC team has begun meeting with mothers who participate in CRECE to discuss the method and structure of report back of results to participants and the wider community. The team also held an educational event at the CRECE clinic that presented information on child development and educational resources to parents of CRECE participants. Both the COTC and the HSC have continued to work closely with the community health centers, particularly Manatí Medical Center and Morovis Community Health Center. In 2016, the Morovis center administration provided a second clinic space to the CRECE team for evaluating participants who may have difficulty traveling to Manatí.

Future Activities:

During the next reporting period, we will continue to focus on recruitment of participants, including in the special urine study for Project 2. We will ensure that routine collection of air filters continues, and work to acquire additional historical air filters when available. Collection of the NNS data will begin in May 2017, and will be a regular part of the first visit going forward. The team will finalize the adjustments to the neurodevelopmental measurements during the next couple of months, and will implement the changes accordingly.

Now that the data collection systems and recruitment procedures are completely or nearly in place, we can begin to focus more on the analysis of the data in the coming year. The projects and cores will work together to implement a data sharing plan and to begin conducting cross-project analyses.

We will continue to present our findings to other research institutions as well as the general public, and will continue to provide training opportunities to students, postdoctoral associates, and faculty whenever possible. 


Journal Articles: 15 Displayed | Download in RIS Format

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)
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  • Journal Article Aker AM, Johns L, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD. Associations between maternal phenol and paraben urinary biomarkers and maternal hormones during pregnancy: a repeated measures study. Environment International 2018;113:341-349. R836155 (2018)
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  • Journal Article Aung MT, Johns LE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: a repeated measures study. Environment International 2017;104:33-40. R836155 (2018)
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  • Journal Article Bedrosian LD, Ferguson KK, Cantonwine DE, McElrath TF, Meeker JD. Urinary phthalate metabolite concentrations in relation to levels of circulating matrix metalloproteinases in pregnant women. Science of the Total Environment 2018;613-614:1349-1352. R836155 (2018)
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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 Cathey A, Ferguson KK, McElrath TF, Cantonwine DE, Pace G, Alshawabkeh A, Cordero JF, Meeker JD. Distribution and predictors of urinary polycyclic aromatic hydrocarbon metabolites in two pregnancy cohort studies. Environmental Pollution 2018;232:556-562. R836155 (2018)
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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)
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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)
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  • Journal Article Ferguson KK, McElrath TF, Pace GG, Weller D, Zeng L, Pennathur S, Cantonwine DE, Meeker JD. Urinary polycyclic aromatic hydrocarbon metabolite associations with biomarkers of inflammation, angiogenesis, and oxidative stress in pregnant women. Environmental Science & Technology 2017;51(8):4652-4660. R836155 (2018)
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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)
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  • Journal Article Lan J, Gou N, Rahman SM, Gao C, He M, Gu AZ. A quantitative toxicogenomics assay for high-throughput and mechanistic genotoxicity assessment and screening of environmental pollutants. Environmental Science & Technology 2016;50(6):3202-3214. R836155C002 (2016)
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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)
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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)
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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)
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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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  • Progress and Final Reports:

    Original Abstract
  • 2016 Progress Report
  • 2018 Progress Report
  • 2019
  • 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