Critical effects associated with developmental PFAS exposure profiles

项目摘要/摘要--项目2关键影响 代谢性疾病，包括肥胖和2型糖尿病，是多因素导致的主要公共卫生问题 病因学，早期接触环境污染物，如全氟烷基和多氟烷基物质 (全氟化碳)，似乎发挥了作用。同时，暴露于PFAS的一个关键影响是免疫毒性，它为 治疗免疫功能障碍和传染病的方法。陡峭项目2(P2-关键影响)将检查 这些高优先级环境污染物的发育暴露曲线的作用，并确定 5岁和14岁以下的结果，以便能够确定易感窗口。我们将依靠两个孩子 来自法罗群岛(总计N&GT；1000)的队列，前瞻性地探索接触之间的联系 PFAS的概况和结果，包括免疫缺陷(术后抗体产生不佳 接种疫苗和增加传染病的频率)和代谢异常(过度肥胖， 高脂血症、低骨矿含量和糖尿病前期)。P2-Critical Effect将进一步评估 血清中与临床相关的生物标记物(如胆固醇亚组分， 脂肪细胞因子、胰岛素样生长因子-1)。接触数据已经可以从对产妇的分析中获得 妊娠、脐带血和出生后血清，年龄分别为18个月、5岁和9岁，来自年龄最大的5个队列，以及 包括DXA扫描在内的临床数据可用于与14岁的儿童进行比较。最年轻的6号队列是 目前正在形成，血液样本和母乳在婴儿时期被采集用于PFAS分析 将允许确定从哺乳期转移的全氟辛烷磺酸。对其他因素进行调整的多元回归分析 环境化学品将得到结构方程模型和其他高级统计的补充 方法：研究方法。因此，拟议的研究将旨在提供预防潜力和对 与早期高优先级暴露相关的主要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.