Critical effects associated with developmental PFAS exposure profiles

项目总结/摘要-项目2关键效应 代谢性疾病，包括肥胖和2型糖尿病，是多因素影响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，如全氟烷基和多氟烷基物质 （PFAS），似乎发挥了作用。与此同时，PFAS暴露的一个关键影响是免疫毒性， 免疫功能障碍和传染病的途径。STEEP项目2（P2-关键影响）将检查 这些高度优先的环境污染物的发展接触概况的作用，并确定 5岁和14岁的结果，以便识别易感性窗口。我们将依靠两个出生 法罗群岛的队列（总N >1000），以前瞻性地探索暴露与 PFAS的特征和结果，包括免疫缺陷（免疫缺陷后的次优抗体产生） 接种疫苗，以及感染性疾病的频率增加）和代谢异常（过度肥胖， 糖尿病、低骨矿物质含量和前驱糖尿病）。P2-Critical Effects将进一步评估 血清中临床相关生物标志物（例如胆固醇亚组分， 脂肪细胞因子、胰岛素样生长因子-1）。通过对孕妇的分析，已经获得了接触数据。 年龄最大队列5的18个月、5岁和9岁时的妊娠、脐带血和出生后血清，以及 临床数据，包括DXA扫描，可用于与14岁的年龄进行比较。最年轻的第6组是 目前正在形成，在婴儿期采集血样和人乳进行PFAS分析， 将允许测定从泌乳转移的PFAS。调整其他因素的多元回归分析 环境化学品将由结构方程模型和其他先进的统计方法补充。 方法.因此，拟议的研究将旨在提供预防潜力和对 与生命早期暴露于高优先级环境相关的重大公共卫生问题的发病机制 环境污染物

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.