Critical effects associated with developmental PFAS exposure profiles

与发育 PFAS 接触情况相关的关键影响

基本信息

批准号：
10352511
负责人：
PHILIPPE ADAM GRANDJEAN
金额：
$ 36.67万
依托单位：
UNIVERSITY OF RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10352511
关键词：
14 year old 5 year old 9 year old Achievement Adaptive Immune System Adult Adverse effects Affect Age Age-Months Antibodies Antibody Formation Antibody Response Apolipoproteins C Biological Markers Birth Blood Blood specimen Bone Mineral Contents Breast Feeding COVID-19 severity Child Childhood Cholesterol Clinical Clinical Data Cohort Studies Communicable Diseases Complement Data Dependence Development Dual-Energy X-Ray Absorptiometry Endocrine Endocrine disruption Environmental Pollutants Environmental Pollution Equation Etiology Exposure to Faeroe Islands Frequencies General Population Goals Health Human Human Development Human Milk Human Papilloma Virus Vaccine Immune Immune System Diseases Immune system Immunologic Markers Incidence Infection Inflammation Insulin-Like Growth Factor I Joints Lactation Lead Life Link Lipids Lymphocyte Count Measures Metabolic Metabolic Diseases Modeling Non-Insulin-Dependent Diabetes Mellitus Obesity Osteoporosis Outcome Pathogenesis Pathway interactions Pattern Play Poly-fluoroalkyl substances Prediabetes syndrome Predisposition Pregnancy Prevention Prospective Studies Puberty Public Health Regression Analysis Reporting Research Risk Risk Assessment Role Sampling Scanning Serum Serum Markers Signal Recognition Particle Skinfold Thickness Source Statistical Methods Time Toxoids Umbilical Cord Blood Vaccination Vaccines adipokines clinical examination clinical phenotype clinically relevant cohort early life exposure environmental chemical epidemiology study immune function immune system function immunotoxicity improved infancy inflammatory marker insight next generation postnatal prenatal prospective sexual dimorphism vaccine failure vaccine-induced antibodies

项目摘要

PROJECT SUMMARY/ABSTRACT – PROJECT 2 CRITICAL EFFECTS Metabolic diseases, including obesity and type 2 diabetes, are major public health problems of multifactorial etiology, in which early-life exposures to environmental pollutants, such as per- and polyfluoroalkyl substances (PFAS), appear to play a role. In parallel, a critical effect of PFAS exposure is immunotoxicity that paves the way for immune dysfunction and infectious disease. STEEP Project 2 (P2–Critical Effects) will examine the role of developmental exposure profiles for these high-priority environmental pollutants and determine outcomes up to ages 5 and 14 years to allow identification of windows of susceptibility. We will rely on two birth cohorts from the Faroe Islands (total N >1000) to prospectively explore the associations between exposure profiles of PFAS and outcomes, including immune deficiencies (suboptimal antibody production after vaccinations, and increased frequency of infectious disease) and metabolic abnormalities (excess adiposity, hyperlipidaemia, low bone mineral content, and prediabetes). P2–Critical Effects will further evaluate the possible usefulness of clinically relevant biomarkers in serum (such as cholesterol subfractions, adipocytokines, insulin-like growth factor-1). Exposure data are already available from analyses of maternal pregnancy, cord blood and postnatal serum at ages 18 months, 5 and 9 years from the oldest Cohort 5, and clinical data, including DXA scans, are available for comparisons with age 14 years. The youngest Cohort 6 is currently being formed, with blood samples and human milk being taken during infancy for PFAS analyses that will allow determination of PFAS transfer from lactation. Multiple regression analyses with adjustment for other environmental chemicals will be complemented by structural equation models and other advanced statistical methods. Thus, the proposed study will aim at providing prevention potentials and new insights into the pathogenesis of major public health problems that are associated with early-life exposures to high-priority environmental pollutants.

项目摘要/摘要 – 项目 2 的关键影响包括肥胖和2型糖尿病在内的代谢性疾病是多因素共同作用的主要公共卫生问题病因学，其中生命早期暴露于环境污染物，例如全氟烷基物质和多氟烷基物质同时，PFAS 暴露的一个关键影响是免疫毒性，从而铺平了道路。 STEEP 项目 2（P2-关键效应）将检查免疫功能障碍和传染病的方法。这些高度优先的环境污染物的发育暴露概况的作用并确定直到 5 岁和 14 岁的结果，以便确定易感性窗口我们将依靠两次出生。来自法罗群岛的队列（总数 >1000）前瞻性地探索暴露之间的关联 PFAS 概况和结果，包括免疫缺陷（治疗后抗体产生不理想）疫苗接种和传染病发生频率增加）和代谢异常（过度肥胖、高脂血症、低骨矿物质含量和糖尿病前期）将进一步评估血清中临床相关生物标志物的可能用途（例如胆固醇亚组分、脂肪细胞因子、胰岛素样生长因子-1）的暴露数据已可从母体分析中获得。年龄最大的第 5 队列中 18 个月、5 岁和 9 岁时的妊娠、脐带血和产后血清，以及临床数据（包括 DXA 扫描）可用于与 14 岁年龄进行比较。目前正在组建，在婴儿期采集血液样本和母乳进行 PFAS 分析，将允许确定哺乳期的 PFAS 转移，并调整其他因素。环境化学品将得到结构方程模型和其他先进统计的补充因此，拟议的研究旨在提供预防潜力和新的见解。与生命早期接触高优先级物质有关的主要公共卫生问题的发病机制环境污染物。