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: 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
• 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

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的关键效果