Prenatal & Childhood POP Exposures, Obesity & Cardiovascular Risks in Children -Resubmission-1

项目摘要 越来越多的文献表明，环境污染物，如持久性有机污染物， 可能会影响肥胖、心血管疾病和其他慢性疾病的风险，包括肾脏疾病和 代谢综合征。实验室研究表明，持久性有机污染物(POP) 全氟烷酸(PFAA)、有机氯农药(OCP)、多氯联苯(PCbs)和 多溴联苯醚(PBDE)可扰乱发育的内分泌过程，并引发氧化剂 压力，心血管和肾脏风险的主要病理生理机制。虽然有些人 流行病学研究调查了接触持久性有机污染物或相关污染物与肥胖和 心血管效应，较早的研究可能没有反映当前暴露的影响，因为它们先于 淘汰某些持久性有机污染物和出现替代品。初步分析表明， 性二型的PFAA体重增加，肾小球滤过率(GFR)降低。过去时 研究也未能检查多次低水平POP暴露的相互作用和潜在的联合影响。 很少有研究研究这些风险在不同的拉丁裔人群中受到肥胖的不成比例影响， 心脏代谢和肾脏风险，不仅包括墨西哥裔美国人，还包括其他亚群。检视 作为心脏代谢和肾脏风险的产前和儿童流行音乐暴露，我们将利用 很早就开始了一项由美国资助的针对533对拉丁裔母婴的随机对照试验 农业部(2011-68001-30207)，以审查产前和早期生活流行音乐的关联 随着临床前和中间终点的发展而暴露，表明早期代谢和 心脏肾风险。我们将包括至少400对母婴，从早期开始并测量产前 暴露于持久性有机污染物，使用储存的新生儿血点，同时增加预期的尿液和血液采集和 每年在4-7岁时就诊。这项研究为利用现有资源提供了一个独特的机会 以及一个积极参与的研究群体，以评估幼儿关注的新污染物。我们 假设胎儿期和儿童期接触持久性有机污染物与体重、血液升高有关 血压、动脉僵硬增加、肾功能降低和氧化应激生物标记物增加 童年。这种生物标志物检测到的变化可以通过以下方法停止或逆转 修改风险因素，强调识别早期风险因素和生物标志物的重要性 年轻人群的心脏肾风险。通过反复测量儿童时期接触持久性有机污染物，我们的 开始的早期研究的延长为评估心血管和肾脏的影响提供了一个独特的机会 早期的生命暴露。

Project Summary A growing body of literature indicates that environmental contaminants, such as persistent organic pollutants, may affect risk of obesity, cardiovascular disease, and other chronic diseases, including renal disease and metabolic syndrome. Laboratory studies suggest that persistent organic pollutants (POPs) such as perfluoroalkylacids (PFAAs), organochlorine pesticides (OCP), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDE) can disrupt developmental endocrine processes and provoke oxidant stress, a major pathophysiologic mechanism underlying cardiovascular and renal risks. While some epidemiological studies have investigated exposure to POPs or related contaminants in relation to obesity and cardiovascular effects, older studies may not reflect the effects of current exposures because they preceded phase-outs of certain POPs and emergence of substitutes. Preliminary analyses suggest associations of PFAAs with sexually dimorphic increases in body mass and reduced glomerular filtration rate (GFR). Past studies have also failed to examine interactions and potential joint effects of multiple low-level POP exposures. Few studies have examined these risks in diverse Latino populations disproportionately affected by obesity, cardiometabolic and renal risks, including not only Mexican Americans but also other subgroups. To examine prenatal and childhood POP exposures as cardiometabolic and renal risks, we will leverage the resources of Starting Early, an established randomized controlled trial of 533 Latino mother-infant pairs funded by the US Department of Agriculture (2011-68001-30207), to examine the association of prenatal and early life POP exposures with the development of preclinical and intermediate endpoints indicative of early metabolic and cardiorenal risks. We will include at least 400 mother-infant pairs from Starting Early and measure prenatal exposure to POP using banked newborn blood spots, while adding prospective urine and blood collection and clinical visits annually at ages 4-7. This study provides a unique opportunity to capitalize on existing resources and an engaged study population to evaluate emerging contaminants of concern to young children. We hypothesize that prenatal and childhood exposure to POPs are associated with body mass, elevated blood pressure, increased arterial stiffness, reduced renal function, and increased oxidant stress biomarkers in childhood. It is possible that alterations detected by such biomarkers can be halted or reversed with modification of risk factors, highlighting the importance of identifying early risk factors and biomarkers of cardiorenal risk in younger populations. With repeated measures of POPs exposure during childhood, our extension of the Starting Early study presents a unique opportunity to evaluate cardiovascular and renal effects of early life exposures.