Research Projects- Industrial Hygiene 

PROJECT SUMMARY The effect of early environmental exposures on child health and development is an important area of public health that no single cohort, or even a few, can answer alone – particularly when coupled with social determinants of health (SDOH) that may influence these exposures and modify their effects. Determining this effect becomes more challenging when considering that these exposures influence multiple interrelated health outcomes such as obesity, neurodevelopment and reproductive development. The ECHO-PROTECT Cohort Site in Puerto Rico (PR) will focus on these health outcomes, taking advantage of the rich and large sample size, diversity, and longitudinal nature of the national ECHO Cohort and multi-disciplinary expertise across the ECHO consortium. ECHO-PROTECT will contribute innovative research to (Aim 1) examine the influence of SDOH on maternal diet and obesity during pregnancy, child diet and obesity during early to middle childhood, and the relationship between maternal-child diet and onset of puberty and (Aim 2) determine the relationship between in utero and early childhood exposure to environmental chemicals, individually and as mixtures, and neurodevelopment and reproductive development, across early childhood, middle childhood, and adolescence. Most importantly, ECHO-PROTECT will build upon the ongoing ECHO-PROTECT cohort in PR (Aim 3) to follow up and collect data and biospecimens from the 1,100 children that are participating in the current ECHO- PROTECT cohort, as well as recruit an additional 1,200 pregnant participants, yielding 1,000 more children, for a total of 2,100 children contributing data and biospecimens to the ECHO Cohort from Puerto Rico – an underserved, highly-exposed population. The proposed 1,200 new pregnancies will include at least 125 completed pregnancies with preconception data (Aim 4), tracked from a cohort of 500 potential preconception participants and, if available, their conceiving partner. ECHO-PROTECT research will contribute meaningfully to ECHO’s mission, offering (a) an important cohort that will enrich consortium wide data, (b) significant, innovative science on the influence of SDOH and exposure to multiple chemicals on multiple interrelated health outcomes such as obesity, neurodevelopment, and reproductive development, and (c) expertise to lead and participate in additional new scientific directions involving biomarkers of exposure or biologic response, child brain or reproductive development, and statistical methods in collaboration with the ECHO consortium, to answer impactful and cutting-edge research questions. Results from our study will inform future clinical intervention, risk assessment and policy-setting efforts, with direct relevance to both the underserved population of Puerto Rico and the U.S. general population.

NIEHS: R01

 

Preterm birth is a significant public health challenge due to increasing rates over time, as well as serious consequences for infant mortality, childhood morbidity, and economic costs to society. Conditions that contribute to preterm birth remain unclear, though an influence by environmental chemical exposures is suspected but poorly understood. Establishing links with common environmental chemicals could have huge public health impact since many exposures could be modifiable through remediation, policies or other interventions. Low birth weight and fetal growth restriction also represent a great public health challenge, as they too have increased in recent decades and may be influenced by modifiable exposures to environmental chemicals. This project proposes to leverage the established Boston Lifecodes cohort study (N~4,000) of risk factors for preterm birth and other adverse pregnancy outcomes, with a focus on exposure to mixtures of commonly-encountered chemicals. We propose to select 1,000 singleton births from Lifecodes with detailed information and samples collected at multiple times during pregnancy. We will then utilize state-of-the-art methods to estimate biomarkers of exposure to chemical mixtures (per- and polyfluorinated substances [PFAS], phthalates and phthalate replacement chemicals, polycyclic aromatic hydrocarbons [PAH], and metals/metalloids), in addition to intermediate biomarkers of effect and repeated ultrasound measures of fetal growth, in order to provide much needed human data on environmental and other predictors of pregnancy outcomes and insights on the biological pathways involved. Results from our preliminary work show that oxidative stress may be an important link between exposure and outcome that needs to be explored in more depth using the proposed pathway-specific biomarkers. To accomplish our aims we will develop innovative statistical and machine learning approaches for analyzing mixtures and mediation with high-dimensional mediator sets, with the goal of improving our ability to discover and define these relationships. Finally, a study sub-aim is to identify conditions/activities contributing to high exposures that can inform exposure reduction strategies. The expected outcomes of this study are new and much needed information on the magnitude, sources, and impacts of exposure to commonly encountered chemicals, both individually and in combination, among pregnant women, and innovative methods for identifying relevant biological pathways and assessing health impacts from exposure to mixtures. Our findings will have a significant impact on public health given widespread exposure to the target chemicals, the growing need to identify environmental agents that adversely impact pregnancy, and the need to discover contributors to the high rates of preterm birth in the U.S. and beyond that could be prevented. Our study will also provide new information on the role of oxidative stress in adverse pregnancy outcomes which may inform future therapeutic or preventative interventions, and contribute new statistical and machine learning methods for investigating mixtures, mediation, and birth outcomes.

NIEHS: R01

 

 

A rapidly growing body of research shows that exposure to common environmental chemicals can disrupt endocrine and metabolic function, and negatively impact pregnancy outcomes and child development. Studies also demonstrate that certain pregnancy conditions (e.g., preeclampsia) and outcomes (e.g., preterm birth) are associated with adverse health later in the life of the mother. However, research is lacking on the relationships between exposures in pregnancy and later health of the mother, and how pregnancy outcomes impact those associations. Puerto Rico suffers from elevated rates of numerous morbidities compared to the mainland U.S., including preterm birth and Type II diabetes. Puerto Rico also has a history of extensive contamination with increased human exposure to a range of pollutants. We established the PROTECT cohort in the northern coast of Puerto Rico to study the impacts of exposure to an array of environmental chemicals during gestation and adverse pregnancy outcomes. We have developed an incredibly rich dataset on exposures, biomarkers of intermediate effects, questionnaires, and health record information. PROTECT is also a participating cohort within the newly established US-wide ECHO study, following the development of children born into PROTECT. We propose building upon this vast dataset and continued recruitment in PROTECT, along with the repeated participant contact during the ECHO follow-up visits, to investigate status and longitudinal trajectories of maternal metabolic health and endocrine function for up to five years following pregnancy among 1000 women in Puerto Rico. We have exposure biomarker data from repeated samples collected in pregnancy on urinary phthalate metabolites, phenols/parabens, and PAH metabolites, as well as 17 metals measured in both urine and blood. In this study, with new data and sample collection on PROTECT mothers at 6 months, 1 year, 2 years, and 5 years following delivery, we aim to: 1) Determine whether maternal exposures during pregnancy are associated with measures and trajectories of metabolic health (i.e., body size, body composition, physical strength, clinical diagnoses, blood pressure, and blood glucose, insulin, lipids, HbA1c) in short- and long-term follow-up assessments after delivery; 2) Investigate the relationships between maternal exposures during pregnancy and longitudinal measures of endocrine function (e.g., estradiol, testosterone, SHBG, FSH and AMH) in the follow-up assessments after delivery; and 3) Explore effect modification of the associations between pregnancy exposures and later women’s health from the first two aims by pregnancy complications (gestational diabetes, preeclampsia, preterm birth), and/or by social determinants (socioeconomic status, social support, depression, stress, life experiences, and others) and other physical determinants of health (body size, physical activity, breast feeding, polycystic ovarian syndrome, menstrual patterns, and others). The expected outcomes of this study are to provide new and much needed information on the impacts of pregnancy exposures, pregnancy outcomes, and social factors on women’s health.

NIEHS: P30

ABSTRACT (Pilot Project Program) The Pilot Project Program (PPP) contributes to the mission of the Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD) by supporting pilot projects that encourage innovation, creativity, and multidisciplinary collaborations, especially among basic scientists, clinical researchers, and community and regulatory stakeholders. The Pilot Project Program is an important mechanism for attracting new individuals to our Center and for providing support to generate preliminary data to compete for external funding. The aims of the Pilot Project Program are to: 1) attract established investigators new to our Center who can provide new insights and approaches to questions regarding the relationships between lifestage environmental exposures and disease; 2) encourage innovation, creativity, and multidisciplinary collaborations, especially between basic scientists, clinical researchers, and community and regulatory stakeholders; 3) facilitate our Center members’ ability to respond quickly and effectively to new and quick-turnaround research opportunities, especially those from NIEHS; and 4) provide important support for early-stage investigators to generate preliminary data for developing independent research projects and compete for independent funding. This approach was successful in the previous funding periods as evidenced by the number of junior faculty supported, the new collaborations that were formed, the participation of scientists new to environmental health research that participated in Center activities as a result of the Pilot Project Program, the number of external grant applications submitted, the number of resulting publications, and career advancement, all as summarized in the Research Strategy. Important advances in the administration of the Pilot Project Program during the last cycle include: 1) the further advancement and refinement of a reviewer consortium with other P30 centers to help improve objectivity of the reviews as well as avoid conflicts of interest that can result from reviews by others in the same institution; 2) a modified scoring system and additional pilot funds to enhance community engagement; and 3) a rapid response mechanism for funding exploratory work in high priority areas with a very short turnaround time. In the next cycle of the Pilot Project Program, we will build on the momentum generated in the current funding period by continuing the wide distribution of the Request for Applications throughout the School of Public Health and the Medical School, continuing the reviewer consortium and continuing to promote the use of our Core facilities. We will also continue our practice of including a CEC member on the review committee responsible for ranking of the proposals to assure their input. Together, these practices will continue the groundbreaking research developed in the initial cycles of the Pilot Project Program to advance a comprehensive and integrated environmental health paradigm.

NIEHS: P42

 

PROJECT SUMMARY Preterm birth – delivery at less than 37 weeks gestation – is a significant global public health challenge, and preterm rates in the United States are considerably higher than they were several decades ago. Explanations for these increases remain elusive, and environmental risk factors are an understudied but potentially important area for discovery of modifiable risk factors and high-impact interventions. Compared to the United States overall, significantly higher rates of preterm birth exist in Puerto Rico, where nearly 12% of all births are preterm. Rates of other adverse pregnancy outcomes are also much higher in Puerto Rico than in the US, and Puerto Rico has a large number of Superfund and other hazardous waste sites, and additional factors that may result in elevated exposures to environmental pollution, such as hurricanes, flooding, and other events. This project proposes to continue our prospective cohort study of novel risk factors for preterm birth and other adverse pregnancy outcomes, with a focus on exposure to mixtures of Superfund-relevant chemicals. We propose to expand our cohort to include 2,000 live births in northern Puerto Rico with detailed information and samples collected at multiple times during pregnancy. We will then utilize state-of-the-art methods to estimate biomarkers of exposure to chemical mixtures, in addition to intermediate biomarkers of effect in order to provide much needed human data on environmental and other predictors of pregnancy outcomes in Puerto Rico, and insights on the biological pathways involved. Results from our study thus far suggest that oxidative stress may be an important link between exposure and outcome that needs to be explored in more depth. The study aims to develop and incorporate innovative statistical techniques for mixtures and mediation, and identify conditions and activities contributing to high exposures that can inform effective exposure reduction strategies. Our specific aims are to: 1) Investigate exposure to a range of Superfund-relevant chemicals (phthalates, polycyclic aromatic hydrocarbons [PAHs], and metals, both as individual chemicals and as mixtures) and adverse pregnancy outcomes, including preterm birth, impaired fetal growth (using data from repeat ultrasound scans), birth weight, preeclampsia, and gestational diabetes; 2) Determine demographic, geographic, behavioral, weather, and other factors associated with higher exposure biomarker concentrations, both for individual chemicals and multiple chemicals concurrently to inform exposure and risk reduction efforts; and 3) Utilize state-of-the-art biomarkers and innovative statistical methods to discover oxidative stress pathways involved in the relationships between chemical exposures and adverse pregnancy outcomes. The expected outcomes of this study are new and much needed information on the magnitude, sources, and impacts of exposure to Superfund-related chemicals, both individually and in combination, among pregnant women in this high-risk population, and innovative methods for identifying relevant biological pathways and assessing health impacts from exposure to mixtures. Our findings are likely to have a significant positive impact on public health.