Pre- and Peri-natal Predictors of Childhood Obesity

描述（由申请人提供）：随着儿童进入青春期早期，肥胖对心血管和代谢的影响变得更加明显。对年龄较大的儿童的研究表明，肥胖和中心脂肪分布与这些结果有关。但孩子们最初是如何到达那里的呢？这是慢性病预防的一个关键问题。现在大量的动物实验文献和越来越多的人体实验文献表明，在人类发育的早期阶段——甚至在出生前——起作用的因素可能对肥胖和心脏代谢结果产生终生的影响。然而，关于产前和围产期因素如何通过体重增加和肥胖来影响这些结果的主要问题仍然存在。在上一期“儿童肥胖的产前和围产期预测因素”的分析中，研究结果表明，出生时的内分泌环境与以后的生活不同，而且它可能是生命最初几个月体重增加的关键驱动因素，它本身是后来肥胖和并发症的有力预测因素。虽然这些观察结果与动物实验中出现的内分泌知识一致，但它们提出了几个问题：7产前因素，如母体营养（如脂肪酸、维生素D）、吸烟、妊娠期体重增加和妊娠期糖尿病，在多大程度上与围产期激素水平相关？还有哪些激素参与了这些途径？特别是，与瘦素水平相关的胰岛素和胰岛素样生长因子（igf）的作用是什么？如果这些激素影响儿童体重增加，它们是否也影响青春期早期肥胖、脂肪分布、代谢综合征成分和血管功能障碍的增加？这些影响在多大程度上是由肥胖相关炎症介导的？R01 HD 034568-10基因更新的总体目标是研究潜在可改变的产前因素、脐带血激素水平、儿童期体重增加和肥胖、肥胖相关炎症和青春期早期心脏代谢结果之间的关系。包括代谢综合征的组成部分，颈动脉内膜-中膜厚度和内皮功能障碍。将富有成效的产前队列研究项目Viva延长至11岁，为应对这一挑战提供了机会。这项研究的结果将带来关于儿童生长和肥胖驱动因素的新科学知识，并很可能为预防肥胖、糖尿病和心血管疾病提供新的途径。

DESCRIPTION (provided by applicant): As children enter early adolescence, cardiovascular and metabolic consequences of obesity become more apparent. Studies in older children show that obesity and central fat distribution are associated with these outcomes. But how did the children get there in the first place? This is a key question for chronic disease prevention. A now-vast animal experimental literature and a growing human counterpart demonstrate that factors operating at the earliest stages of human development-even before birth-can have lifelong consequences for obesity and cardiometabolic outcomes. Yet major questions still exist regarding how pre- and peri-natal factors operate, through gain in weight and adiposity, to influence these outcomes. In analyses from the previous cycle of "Pre- and peri-natal predictors of childhood obesity, the findings imply both that the endocrine milieu at the time of birth is different from later in life, and that it is likely to be a key driver of weight gain in the first months of life, itself a strong predictor of later obesity and cormorbidities. While these observations are consistent with endocrine knowledge emerging from animal experiments, they raise several questions: 7 To what extent are prenatal factors such as maternal nutrition (e.g., fatty acids, vitamin D), smoking, gestational weight gain, and gestational diabetes associated with perinatal hormone levels? 7 What other hormones are involved in these pathways? In particular, what are the roles of insulin and insulin-like growth factors (IGFs), which are correlated with leptin levels? 7 If these hormones influence childhood weight gain, do they also influence gain in adiposity, fat distribution, components of the metabolic syndrome and vascular dysfunction in early adolescence? 7 To what extent are these influences mediated by adiposity-related inflammation? The overall goal of this renewal of R01 HD 034568-10 is to examine associations of potentially modifiable prenatal factors, hormone levels in umbilical cord blood, gains in weight and adiposity in childhood, adiposity- related inflammation, and cardiometabolic outcomes in early adolescence. including components of the metabolic syndrome, carotid intima-media thickness, and endothelial dysfunction. Extending the productive pre-birth cohort study Project Viva through the age of 11 years provides the opportunity to meet this challenge. The results of this research will lead to new scientific knowledge about the drivers of growth and adiposity in childhood and may very well lead to new avenues for prevention of obesity, diabetes, and cardiovascular disease.