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Gestational PFAS Mixture Exposures, Longitudinal Metabolomic Profiles, and Adolescent Cardiometabolic Health

妊娠期 PFAS 混合物暴露、纵向代谢组学特征和青少年心脏代谢健康

基本信息

批准号：
10673054
负责人：
Joseph M Braun
金额：
$ 56.63万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-25 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10673054
关键词：
12 year old Acceleration Address Adolescent Adolescent obesity Adult Affect Age Amino Acids Analytical Chemistry Animals Area Biological Biological Markers Biometry Biostatistical Methods Blood Canada Cardiometabolic Disease Cardiovascular Diseases Carnitine Chemical Exposure Chemicals Child Childhood Cohort Studies Collaborations Collection Commerce Coupled Data Databases Diet Dimensions Dissociation Dyslipidemias Elderly Environment Epidemiologist Epidemiology Evaluation Exposure to Fatty Acids Fire - disasters Food Food Contamination Food Packaging Growth Health Home Human Hypertension Individual Industry Insulin Resistance Ions Knowledge Life Link Measures Mediating Metabolic Metabolism Modeling Obesity Ohio Oils Outcome Pathway interactions Pediatrics Persons Plasma Poly-fluoroalkyl substances Populations at Risk Predisposition Pregnancy Pregnant Women Productivity Prospective cohort Publishing Recording of previous events Regulation Research Personnel Resolution Risk Risk Factors Sampling Serum Syndrome Techniques Testing Textiles Time Toxic effect Training United States Water adolescent health blood pressure elevation cardiometabolic risk cardiometabolism cardiovascular disorder risk contaminated drinking water critical period disorder risk drinking water early adolescence early life exposure environmental chemical environmental chemistry health assessment improved innovation landfill liquid chromatography mass spectrometry manufacture manufacturing facility maternal serum metabolome metabolomics microbiome neonate novel obesity risk prenatal prenatal exposure response small molecule

项目摘要

Project Abstract Exposure to environmental chemical mixtures may increase the risk of cardiometabolic disease. Of particular concern are prenatal exposure to perfluoroalkyl substances (PFAS), a class of chemicals used as processing aids for oil/water repellant textiles, fluoropolymer manufacturing, food packaging, cleaning products, and firefighting foams. PFAS exposure is ubiquitous, deriving from contaminated food and drinking water. Over 6 million people in the US have PFAS contaminated drinking water, and many more have low-level exposure. Animal and human studies show that prenatal PFAS exposure may increase the risk of obesity, insulin resistance, dyslipidemia, and hypertension – components of the cardiometabolic syndrome that markedly increase the risk of adulthood cardiovascular diseases. However, few studies have investigated the health effects of PFAS mixtures, and the biological pathways underlying these effects are poorly understood. Guided by our preliminary studies and the hypothesis that biological pathways represented in the serum metabolome are sensitive to early life PFAS mixture exposure and predictive of later life cardiometabolic health, we will use non-targeted high-resolution metabolomics to quantify the associations between prenatal PFAS mixtures, the metabolome, and cardiometabolic disease. Building upon two established and ongoing prospective cohorts of pregnant women and their children from Canada (MIREC Study, n=500) and Cincinnati, Ohio (HOME Study, n=250), we will measure >25,000 features of the serum metabolome at delivery and ages 3-5, and 7-12 years. We will link these data to previously collected or to be measured prenatal PFAS biomarkers and cardiometabolic outcomes at age 7-12 years. We will use sophisticated biostatistical techniques to reduce the dimensionality of these data and discover metabolomic signatures associated with both prenatal PFAS mixtures and cardiometabolic outcomes in MIREC, replicating our findings using HOME. Specifically, we will: 1) characterize trajectories of the serum metabolome in the first 12 years of life; 2) identify features of serum metabolome trajectories in the first 12 years of life that predict adolescent cardiometabolic disease; 3) determine if metabolome features mediate the association of prenatal exposure to PFAS mixtures with adolescent cardiometabolic disease; and 4) determine the chemical identity of metabolome features discovered in Aim 3. This interdisciplinary proposal that includes epidemiologists, clinicians, biostatisticians, and chemists will efficiently leverage two ongoing cohort studies to address these timely aims. Ultimately, the proposed studies will have substantial impact by improving our knowledge of the health effects of PFAS, identifying novel metabolic alterations associated with PFAS mixtures and adolescent health, and improving our understanding of biological pathways affecting cardiometabolic disease. These results are critical to ongoing evaluations of PFAS toxicity and may help identify exposed populations at risk of cardiometabolic disease and potentially ameliorate the effects of PFAS exposure.

项目摘要