Critical effects associated with developmental PFAS exposure profiles

与发育 PFAS 接触情况相关的关键影响

• 批准号: 10704011
• 负责人: PHILIPPE ADAM GRANDJEAN
• 金额: $ 48.25万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 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/10704011
• 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; Equation; Etiology; Exposure to; Faeroe Islands; Frequencies; General Population; Genetic; 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; Life; Link; Lipids; Lymphocyte Count; Measures; Metabolic; Metabolic Diseases; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Osteoporosis; Outcome; Pathogenesis; Pathway interactions; Pattern; Poly-fluoroalkyl substances; Prediabetes syndrome; Predisposition; Pregnancy; Prevention; Prospective Studies; Puberty; Public Health; Regression Analysis; Reporting; Research; Risk; Risk Assessment; Rodent; 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

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关键效果 代谢疾病，包括肥胖和2型糖尿病，是多因素的主要公共卫生问题 病因，其中早期暴露于环境污染物，例如per和多氟烷基物质 （PFA），似乎起着作用。同时，PFAS暴露的关键作用是免疫毒性，可以铺平 免疫功能障碍和传染病的方法。陡峭的项目2（P2-关键效应）将检查 这些高优先性环境污染物的发育暴露概况的作用并确定 最高5岁和14岁的结果可以识别易感性的窗户。我们将依靠两个出生 从法罗群岛（总计n> 1000）的人群前瞻性地探索暴露之间的关联 PFA和结果的特征，包括免疫缺陷（次优抗体产生 疫苗接种，传染病的频率增加）和代谢异常（肥胖过多， 高脂血症，低骨矿物质含量和糖尿病前）。 P2 - 关键效应将进一步评估 临床上相关生物标志物在血清中的可能有用性（例如胆固醇亚构件， 脂肪细胞因子，胰岛素样生长因子1）。暴露数据已经可以从母体分析中获得 怀孕，脐带血和产后血清，年龄在18个月，最古老的队列5和9年 包括DXA扫描在内的临床数据可与14岁的临床数据进行比较。最年轻的队列6是 目前正在形成，在婴儿期为PFA分析中采用血液样本和人乳 将允许确定PFA从泌乳中转移。多次回归分析，并调整其他 环境化学品将通过结构等效模型和其他高级统计来完成 方法。拟议的研究将旨在为预防潜力和新见解 与早期生活相关的主要公共卫生问题的发病机理 环境污染物。