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Final Progress Reports: Northeastern University: Biomarker Epidemiology of Exposure to Mixtures, Oxidative Stress, and Adverse Pregnancy Outcomes in Puerto Rico

Superfund Research Program

Biomarker Epidemiology of Exposure to Mixtures, Oxidative Stress, and Adverse Pregnancy Outcomes in Puerto Rico

Project Leader: John D. Meeker (University of Michigan)
Co-Investigators: Bhramar Mukherjee (University of Michigan), Deborah J. Watkins (University of Michigan)
Grant Number: P42ES017198
Funding Period: 2010-2025
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Final Progress Reports

Year:   2019  2013 

Studies and Results

Since the inception of the Center, the Phthalate Exposure and Molecular Epidemiologic Markers of Preterm Birth among Women in Puerto Rico project has been working with the Human Subjects and Sampling Core on the recruitment of pregnant women in Puerto Rico, which is going well. As of December 2013, Dr. Meeker and his research team have recruited 653 participants with a recruitment rate of 82% and retention rate of 80%. While many participants are still pregnant and much of the clinical data is still to be abstracted, the research team now has over 332 live births in the study with a preterm birth rate of ~15%.

The Phthalate Exposure and Molecular Epidemiologic Markers of Preterm Birth among Women in Puerto Rico project has continued to analyze urine and blood samples for the project aims during this past year as sample batches become available. Thus far, five batches of urine samples (over 700 samples total) have been analyzed for phthalate metabolites by the CDC's Personal Care Products Laboratory. As part of the research team's collaboration the CDC has also screened for a number of other exposures in the PROTECT population, including pesticides and environmental phenols in a subset of urine samples, with plans to measure brominated flame retardants and PCBs in a subset of serum samples over the next few months. Analysis for serum hormone levels and markers of oxidative stress and inflammation in blood and urine samples is also underway at the University of Michigan, with some very compelling initial results. Two batches of blood samples from participants have also been screened for a number of different metals in collaboration with the UM NIEHS P30 Core Center.

This past year Dr. Meeker and his team began publishing their first papers from the original data being collected in the PROTECT cohort study in top environmental health journals. They have published their initial findings on distributions, variability, and predictors of phthalate exposures among pregnant women in Puerto Rico (Cantonwine et al. 2013), where they reported that levels of most phthalates in their population appear to be somewhat greater than those among U.S. women in the same age group from NHANES 2009-10. One particularly notable result was for MEHP, the bioactive metabolite of DEHP, for which levels among women in PROTECT were twice as high as those in women of reproductive age from U.S. NHANES. In another published paper, the research team demonstrated that urinary levels of several phenols, including triclosan, benzophenone-3 and 2,5-dichlorophenol, are significantly (up to 2-3 times) higher in this Puerto Rican cohort compared to women in U.S. NHANES (Meeker et al. 2013). This paper also represents the first empirical data on predictors of exposure to many of the phenols measured, which should be of wide interest and highly useful in efforts to reduce exposures among pregnant women. The team is currently working on 2-3 additional manuscripts describing exposure distributions and exposure determinants of other agents. The research team's initial analysis of markers of inflammation, oxidative stress, and endocrine disruption has resulted in some very interesting findings. In a paper that they have submitted for publication, they found significant positive associations between urinary metabolites of DEHP and other phthalates in relation to levels of IL-6, isoprostane, and 8-OHdG in blood or urine. A second paper they are preparing shows an inverse relationship between DEHP metabolites and free T4 levels. This is consistent with their previous work among adults in U.S. NHANES (Meeker and Ferguson 2011) and could have broad implications for pregnancy outcomes and child development.

While recruitment in PROTECT was being set up and carried out, the Phthalate Exposure and Molecular Epidemiologic Markers of Preterm Birth among Women in Puerto Rico project has tested hypotheses consistent with their aims in other datasets. This work has involved PROTECT trainees and collaboration with other projects, and has included work on phthalates or other relevant exposures in relation to adverse birth outcomes or relevant mechanistic pathways. Most recently, Dr. Meeker and his research team conducted a case-control study at Brigham and Women's Hospital where they reported that concentrations of several phthalate metabolites in pregnant women were associated with significantly increased odds of preterm birth (Ferguson et al. 2014). These associations became much stronger when limiting cases to spontaneous preterm births, which may be consistent with their hypothesized mechanisms of action. It is also important to point out that the phthalates most strongly associated with preterm birth were the same phthalates that were measured in higher concentrations in PROTECT compared to U.S. NHANES. This paper was recently published in JAMA Pediatrics and received widespread media coverage.

Significance

Most, if not all, people in the United States are exposed to phthalates and other Superfund-related endocrine disrupting chemicals on a daily basis. The team's work suggests that adverse effects and biologic pathways relevant to preterm birth may be associated with exposure to phthalates and other emerging chemicals of concern. Due to widespread exposure, the public health significance could be huge.

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