Grantee Research Project Results
2016 Progress Report: Biomarker Epidemiology of In Utero Environmental Exposures and Child Development
EPA Grant Number: R836155C003Subproject: 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.
Current Investigators: Meeker, John D. , Swan, Shanna Helen , Watkins, Deborah Jean , Calafat, Antonia , Mukherjee, Bhramar
Institution: University of Michigan
Current Institution: University of Michigan , Centers for Disease Control and Prevention , Mount Sinai School of Medicine
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2021)
Project Period Covered by this Report: September 1, 2015 through August 31,2016
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health
Objective:
There is growing evidence and concern that exposure to environmental chemicals may contribute to the recent rise in child developmental disorders. Additionally, disparities exist in both incidence rates of adverse health conditions and level of pollutant exposure. It has been documented, for example, 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, we will use state-of-the-art epidemiologic approaches among an underserved and potentially highly exposed population. We 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 1800 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; Project 2 to exchange information about mechanisms and test mixtures for our biomarker epidemiology study and their toxicity screening study; Human Subjects Core to collaborate on the clinical and developmental data and samples; and Community Engagement Core to provide data on individual exposure levels and aggregated data on predictors (e.g., product use) of elevated exposures.
Progress Summary:
In Year 1, the majority of efforts have been in building the infrastructure required for implementing the CRECE project, including setting up a new clinic space for participants, optimizing the non-nutritive suck (NNS) sampler, identifying air monitoring locations, training study personnel, and obtaining IRB approval from all necessary institutions. We also have conducted a small pilot with a small number of infants to ensure that study visits and examinations run smoothly. As a result of these efforts, recruitment of infants for follow-up began in May 2016. In addition 928 urine samples, collected from mothers across all three trimesters of pregnancy, were shipped from Puerto Rico to the CDC National Laboratory for analysis of phenols and parabens. We expect to receive these data from the CDC by the end of July 2016. In addition, we shipped 472 maternal serum samples (collected during the first and third prenatal visits) and 16 cord serum samples from Puerto Rico to the University of Michigan. We have received the results of these analyses in recent weeks. In preliminary studies, we found significant relationships of urinary concentrations of certain phenols and parabens with thyroid and reproductive hormones in pregnancy (Tables 1 and 2). For example, an interquartile range (IQR) increase in butyl paraben was associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI -18.31, -0.38) in the ratio of estradiol to progesterone. In addition, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. We also found that associations varied by timing of exposure in pregnancy.
Table 1: Percent change in reproductive hormone level in relation to the interquartile range increase in urinary exposure biomarker (ng/mL), adjusted for maternal age, education and BMI.
Estradiol (N=175) | Progesterone (N=179) | SHBG (N=147) | Estradiol/Progesterone (N=175) | ||
---|---|---|---|---|---|
IQR | % Δ (95%) | % Δ (95%) | % Δ (95%) | % Δ (95%) | |
BPA | 2.80 | 1.47 (-5.97, 8.91) | -4.24 (-9.79, 1.65) | 0.12 (-5.32, 5.56) | 4.19 (-3.64, 12.01) |
BP-3 | 104 | -2.79 (-10.44, 4.86) | -3.38 (-9.18, 2.80) | 0.67 (-4.75, 6.10) | 1.74 (-6.36, 9.85) |
2,4-DCP | 1.85 | 0.26 (-7.81, 8.33) | -4.64 (-10.62, 1.74) | -1.70 (-6.88, 3.47) | 2.85 (-5.67, 11.38) |
2,5-DCP | 38.9 | -1.15 (-8.94, 6.65) | -4.31 (-10.12, 1.89) | -1.92 (-7.01, 3.17) | 2.33 (-5.91, 10.57) |
TCS | 110 | -3.48 (4.93, -0.03) | -5.66 (-12.81, 2.08) | -1.44 (-8.16, 5.27) | -1.69 (-12.09, 8.71) |
MPB | 293 | 4.13 (-5.14, 13.40) | -4.35 (-11.23, 3.09) | 7.70* (1.50, 13.90) | 5.83 (-3.97, 15.63) |
BPB | 3.30 | -8.46* (-16.92, 0.00) | 1.72 (-5.09, 9.01) | 1.26 (-4.99, 7.50) | -9.34* (-18.31, -0.38) |
PPB | 86.4 | 2.48 (-7.70, 12.66) | 0.09 (-7.81, 8.65) | 3.68 (-3.35, 10.70) | 2.65 (-8.12, 13.43) |
*p<0.05 |
Table 2: Percent change in thyroid hormone level in relation to the interquartile range increase in urinary exposure biomarker (ng/mL), adjusted for maternal age, education and BMI.
TSH (n=181) | FT3 (n=181) | FT4 (n=181) | ||
---|---|---|---|---|
IQR | % Δ (95%) | % Δ (95%) | % Δ (95%) | |
BPA | 2.80 | 5.63 (-1.97, 13.83) | 0.81 (-2.01, 3.63) | 4.11* (0.12, 8.10) |
BP-3 | 104 | -3.05 (-10.70, 5.23) | -3.00* (-5.89, -0.12) | -0.34 (-4.34, -3.66) |
2,4-DCP | 1.85 | -0.05 (-8.15, 8.76) | -1.21 (-4.28, 1.83) | 0.60 (-3.67, 4.87) |
2,5-DCP | 38.9 | 0.78 (-7.19, 9.43) | -1.19 (-4.16, 1.77) | 1.65 (-2.46, 5.77) |
TCS | 110 | 4.90 (-5.28, 16.17) | -1.07 (-4.78, 2.64) | -3.44 (-8.60, 1.71) |
MPB | 293 | 8.46 (-1.74, 19.71) | 0.14 (-3.40, 3.69) | 0.39 (-4.50, 5.28) |
BPB | 3.30 | -1.59 (-10.24, 7.89) | -0.11 (-3.35, 3.14) | 5.64* (1.26, 10.02) |
PPB | 86.4 | 0.09 (-19.26, 11.54) | -0.59 (-4.47, 3.29) | 0.32 (-1.60, 2.25) |
*p<0.05 |
Future Activities:
Recruitment of mother-infant pairs into the CRECE project is well underway, and will continue in future years. In the coming months, we will receive data from biological samples sent to the CDC and UM laboratories for analysis of environmental exposures and hormones, respectively, and we will continue to send samples for analyses in future years. During this time, we will also begin examining preliminary relationships between in utero phenol and paraben exposure and outcome measures collected at birth, including preterm birth, birth size, non-nutritive suck (NNS), and anogenital distance (AGD).
Journal Articles:
No journal articles submitted with this report: View all 12 publications for this subprojectSupplemental Keywords:
biomarkers, environmental exposure, phenols, parabens, endocrine disruptersProgress and Final Reports:
Original AbstractMain 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
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
9 journal articles for this subproject
Main Center: R836155
68 publications for this center
47 journal articles for this center