Preterm birth, the leading cause of neonatal mortality in the United States, is also associated with a number of chronic health conditions and developmental disabilities that cause lifelong consequences. In Puerto Rico, the preterm birth rate is 17.7% of live births. At 50% above the U.S. average, it is the highest rate of any United States jurisdiction, below only Malawi (18.1%) globally. The researchers investigations suggest that the higher preterm birth rates in Puerto Rico cannot be explained by changes in obstetric practices, and that there is compelling preliminary evidence that exposure to hazardous chemicals contributes to preterm birth. Puerto Rico has 16 active Superfund sites and 200+ hazardous waste sites. Risk of exposure to contamination is high as many of these sites are unlined landfills that overlie Karst aquifers which present highly susceptible pathways for exposure to contamination. PROTECT (Puerto Rico Testsite for Exploring Contamination Threats) brings together multidisciplinary researchers study the transport, exposure, health impact and remediation of contaminants, with particular attention to chlorinated solvents and phthalates commonly found at Superfund sites, as both suspect and model agents in the high to preterm birth rates in Puerto Rico. To do so, PROTECT uses an innovative, holistic, source-to-outcome structure, integrating epidemiological, toxicological, and analytical, fate-transport, and remediation studies along with a unified sampling infrastructure, a centralized, indexed data repository and a data management system. Administrative, research translation, training and community engagement cores engage and inform stakeholders, provide knowledge-transfer activities to the greater SRP and environmental health community, and provide extensive cross-disciplinary training. PROTECT is responsive to NIEHS, EPA and CDC strategic goals, and addresses priority areas identified by the Institute of Medicine Committee on preterm birth. Since the Center's inception in 2010, PROTECT researchers have obtained significant and novel results indicating 1) extensive groundwater contamination in the northern Karst region of Puerto Rico;2) potential mechanisms by which chemicals can stimulate preterm birth;and, 3) suspect chemicals that are elevated in the women in this study. The investigators have also developed a new environmentally-friendly technique for efficient decontamination of groundwater and an improved large-volume urinalysis technique. Research results have been documented in over 50 journal papers and 2 full patent applications. In addition, over 480 pregnant study subjects have been enrolled (200 of whom have completed their pregnancies), and over 70 trainees have participated in the Center. PROTECT will build on these successes with continued research and training to provide the much needed understanding of the role of hazardous chemicals and other environmental factors in preterm birth, and to develop new methods for contaminant remediation in Puerto Rico and beyond. This work will advance environmental health science in general, and potentially lead to a reduction in preterm birth rates.

Public Health Relevance

PROTECT is exploring the link between exposure to hazardous chemicals and the high rate of preterm birth in Puerto Rico, which has both 16 active Superfund sites and a preterm birth rate of 17.7% of live births, the highest rate of any U.S. jurisdiction ad below only Malawi (18.1%) globally. Improved understanding of the link between preterm birth and contamination, together with developing sustainable technologies to remove contamination, will have direct impact in Puerto Rico (a disadvantaged population) and beyond. INDIVIDUAL RESEARCH PROJECTS PROJECT 1: Molecular Epidemiology Study of Phthalate Exposure and Preterm Birth in Puerto Rico (Meeker) DESCRIPTION (provided by applicant) Preterm birth is a significant global health challenge as a leading cause of infant mortality and costly long-term morbidity. Rates of preterm birth in the U.S. have increased in recent decades for reasons that remain uncertain. The recent escalation in preterm births in Puerto Rico is especially alarming, where rates have increased from just above the U.S. average (12%) in 1997 to nearly 18% in 2009. While known risk factors for preterm birth have failed to account for this increase, there is growing evidence that environmental factors may play a key role. However, these factors remain understudied and underappreciated. The proposed Project will apply state-of-the-art molecular epidemiological methods to a prospective cohort study of over 1,200 live births 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. In the investigators'preliminary work and in recent studies by others, multiple phthalates have been associated with preterm birth, reduced gestational age, and other adverse impacts potentially linked with preterm birth such as oxidative stress, inflammation, and endocrine disruption. The preliminary data also suggests elevated exposure to certain phthalates in Puerto Rico compared to the U.S. 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, the investigators will collect detailed questionnaire data, clinical information, and measure phthalate metabolites in urine samples collected from pregnant women at multiple time points in pregnancy. They will evaluate 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, the investigators will assess the association between exposure to phthalates and risk of preterm birth, both as individual chemicals and as phthalate mixtures. The investigators will also explore 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. Public Health Relevance: The rising rate of preterm births in the U.S. represents a significant public health challenge. The problem is even more urgent in Puerto Rico, where preterm births have increased sharply since 1990 and now account for more than one in every six babies born on the island. This prospective cohort study will use state-of-the-art molecular epidemiological methods to provide much needed information on environmental and other factors that contribute to preterm birth risk in Puerto Rico to facilitate effective prevention strategies.

Agency
National Institute of Health (NIH)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
3P42ES017198-05S1
Application #
8884307
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Henry, Heather F
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northeastern University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
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