R01ES031591

Applying and Advancing Modern Approaches for Studying the Joint Impacts of Environmental Chemicals on Pregnancy Outcomes

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 a 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.

Regents Of The University Of Michigan

TO FOSTER UNDERSTANDING OF HUMAN HEALTH EFFECTS OF EXPOSURE TO ENVIRONMENTAL AGENTS IN THE HOPE THAT THESE STUDIES WILL LEAD TO: THE IDENTIFICATION OF AGENTS THAT POSE A HAZARD AND THREAT OF DISEASE, DISORDERS AND DEFECTS IN HUMANS, THE DEVELOPMENT OF EFFECTIVE PUBLIC HEALTH OR DISEASE PREVENTION STRATEGIES, THE OVERALL IMPROVEMENT OF HUMAN HEALTH EFFECTS DUE TO ENVIRONMENTAL AGENTS, THE DEVELOPMENT OF PRODUCTS AND TECHNOLOGIES DESIGNED TO BETTER STUDY OR AMELIORATE THE EFFECTS OF ENVIRONMENTAL AGENTS, AND THE SUCCESSFUL TRAINING OF RESEARCH SCIENTISTS IN ALL AREAS OF ENVIRONMENTAL HEALTH RESEARCH. SUPPORTED GRANT PROGRAMS FOCUS ON THE FOLLOWING AREAS: (1) UNDERSTANDING BIOLOGICAL RESPONSES TO ENVIRONMENTAL AGENTS BY DETERMINING HOW CHEMICAL AND PHYSICAL AGENTS CAUSE PATHOLOGICAL CHANGES IN MOLECULES, CELLS, TISSUES, AND ORGANS, AND BECOME MANIFESTED AS RESPIRATORY DISEASE, NEUROLOGICAL, BEHAVIORAL AND DEVELOPMENTAL ABNORMALITIES, CANCER, AND OTHER DISORDERS, (2) DETERMINING THE MECHANISMS OF TOXICITY OF UBIQUITOUS AGENTS LIKE METALS, NATURAL AND SYNTHETIC CHEMICALS, PESTICIDES, AND MATERIALS SUCH AS NANOPARTICLES, AND NATURAL TOXIC SUBSTANCES, AND THEIR EFFECTS OF ON VARIOUS HUMAN ORGAN SYSTEMS, ON METABOLISM, ON THE ENDOCRINE AND IMMUNE SYSTEMS, AND ON OTHER BIOLOGICAL FUNCTIONS, (3) DEVELOPING AND INTEGRATING SCIENTIFIC KNOWLEDGE ABOUT POTENTIALLY TOXIC AND HAZARDOUS CHEMICALS BY CONCENTRATING ON TOXICOLOGICAL RESEARCH, TESTING, TEST DEVELOPMENT, VALIDATION AND RISK ESTIMATION, (4) IDENTIFYING INTERACTIONS BETWEEN ENVIRONMENTAL STRESSORS AND GENETIC SUSCEPTIBILITY AND UNDERSTANDING BIOLOGIC MECHANISMS UNDERLYING THESE INTERACTIONS, INCLUDING THE STUDY OF ENVIRONMENTAL INFLUENCES ON EPIGENOMICS AND TRANSCRIPTIONAL REGULATION, (5) CONDUCTING ENVIRONMENTAL PUBLIC HEALTH RESEARCH, INCLUDING IN AREAS OF ENVIRONMENTAL JUSTICE AND HEALTH DISPARITIES, THAT REQUIRES COMMUNITIES AS ACTIVE PARTICIPANTS IN ALL STAGES OF RESEARCH, DISSEMINATION, AND EVALUATION TO ADVANCE BOTH THE SCIENCE AND THE DEVELOPMENT OF PRACTICAL MATERIALS FOR USE IN COMMUNITIES, WITH A FOCUS ON TRANSLATING RESEARCH FINDINGS INTO TOOLS, MATERIALS, AND RESOURCES THAT CAN BE USED TO PREVENT, REDUCE, OR ELIMINATE ADVERSE HEALTH OUTCOMES CAUSED BY ENVIRONMENTAL EXPOSURES, (6) EXPANDING AND IMPROVING THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) EXPANDING AND IMPROVING THE STTR PROGRAM TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO IN

93.113 - Environmental Health

National Institute of Environmental Health Sciences (NIEHS) [HHS - NIH]

Ann Arbor, Michigan 481091276 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 384% from $632,023 to $3,056,116.