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Significance: Most, if not all, people in the US are exposed to phthalates and other Superfund-related endocrine disrupting chemicals on a daily basis. Our 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.
This project applies state-of-the-art molecular epidemiological methods to a prospective cohort study designed to explore environmental, clinical, demographic, behavioral and other factors that contribute to preterm birth risk in Puerto Rico. The project also aims to provide much needed information on the potential mechanistic pathways involved in preterm birth as it relates to environmental factors, and data on important predictors of phthalate exposure among pregnant women. Phthalates were chosen as the primary pollutants of interest because they are common contaminants of Superfund sites in Puerto Rico and elsewhere (several phthalates are on the ATSDR Substance Priority List), and recent studies show widespread exposure to phthalates in the U.S. population. Using data and samples generated by recruitment efforts of the Human Subjects and Sampling Core (Core C) and the Data Management integration provided by Core D, we are collecting detailed questionnaire data, clinical information, and measure phthalate metabolites in urine samples collected from pregnant women at multiple time points in pregnancy. We are evaluating phthalate metabolite levels for associations with residence, water sources, water phthalate contamination, diet, activities, and product use to identify determinants of high exposure and opportunities for exposure reduction strategies. Using innovative statistical methods, we will assess the association between exposure to phthalates and risk of preterm birth, both as individual chemicals and as phthalate mixtures. We are exploring relationships between phthalate exposure and biomarkers of oxidative stress, inflammation, and endocrine disruption measured at multiple times during pregnancy to provide data on biologic pathways that may link environmental exposures with early parturition. The proposed study will provide much needed information on preterm birth risk factors in Puerto Rico and a rich resource for future investigations and follow-up. Identifying modifiable environmental risk factors for preterm birth could have huge public health impact since interventions aimed at preventing preterm birth to date remain largely ineffective.
Through the PROTECT cohort study, we have analyzed urine samples from women for a suite of 11 phthalate metabolites and compared results with those reported among women aged 18-40 years in US NHANES 2009-2010. The results suggest that phthalate exposure of women in northern Puerto Rico is higher than the U.S. general population, highlighting the need for detailed human health studies of the effects of phthalate exposure among this at-risk population. Most striking was the observation that the geometric mean concentration for MEHP, the bioactive metabolite of DEHP, was more than twice as high among women in PROTECT (p<0.05)(Cantonwine et al. In Press). Our next step will be to assess relationships between these phthalate levels and preterm birth or other adverse birth outcomes, as well as between phthalates and intermediate markers of effect that may be along the mechanistic pathway. We have also explored publicly available US NHANES data and found a number of relationships (significant or suggestive associations in hypothesized directions) between urinary phthalate metabolites and intermediate biomarkers of mechanisms that may be relevant to preterm birth. These mechanisms include oxidative stress, inflammation, and endocrine disruption (Ferguson et al. 2011; 2012; Meeker and Ferguson 2011). These results are an important linkage to our mechanistic toxicology work and provide further evidence for potentially diverse yet overlapping impacts of phthalates on multiple pathways relevant to preterm birth in our study population. They also serve as further justification to assess the impact of exposure to multiple phthalates as mixtures as well as individually.
John Meeker, Project Leader
Associate Professor, Environmental Health Sciences
Environmental Health Sciences, School of Public Health, University of Michigan
Bhramar Mukherjee, Investigator
Associate Professor, Department of Biostatistics
Biostatistics, School of Public Health, University of Michigan
Antonia Calafat, Collaborator
Former Association of Public Health Laboratories Fellow and current CDC employee
Public Health Service, Centers for Disease Control and Prevention
See Project 1 Leader John Meeker’s TED-style talk on Endocrine Disruptors, given as part of the UMich Environmental Sciences Department’s 125th anniversary celebration.