EXPOSOME BIOCHEMICAL ANALYSIS FOR BIRTH WEIGHT/OBESITY

校内人口健康研究部，NICHD，是唯一的定位是在麻烦的研究的前沿，因为它的校内指定是符合高风险研究的行为，许多前瞻性怀孕队列，产生了丰富的数据库，纵向收集（在不同程度上）可获得人类发育敏感窗口期的生物标本，统计司拥有生物统计学家，他们具备制定适当分析方法所需的专门知识水平。这些资源使该司的调查人员有机会在棘手的范式内设计研究举措。 也许最早和最关键的敏感窗口之一发生在人类生殖和发育期间。目前，该司正在进行一项概念验证研究，利用现有的妊娠队列研究（结局正常）来描述和量化妊娠困扰。本研究的目标是建立在我们以前的工作，重点是正常妊娠麻烦的表征，通过将相同的方法扩展到婴儿出生在极端出生体重的“正常”孕妇，对于出生体重<第10百分位数定义为小于胎龄儿（SGA）和出生体重>从既往分析中排除第90百分位数（Brenner，1976）。[20]低出生体重和高出生体重都与短期发病率和死亡率增加有关，并且还反复与晚年慢性疾病风险增加有关，如心血管疾病和2型糖尿病。[21]对与出生体重相关的暴露量的全面调查可能会提高我们对慢性病早期决定因素的了解，并有助于制定终生慢性病的早期预防策略。有证据表明，母亲肥胖的长期影响也会增加肥胖和心脏代谢风险。[22]另外值得注意的是，我们努力确保两组的采样框架具有可比性，因为所有符合条件的妇女在妊娠<13周和每个三个月期间都采集了初始生物标本。仅限于采集妊娠早期生物标本的女性对于评估妊娠期间的纵向变化至关重要，因为妊娠会导致受孕和着床后的许多生理变化。因此，随机选择两组仅在婴儿出生体重方面不同的“正常”孕妇将使我们能够表征和量化这两个孕妇样本中每一个的怀孕期间的麻烦。这一战略是我们在2013财年提交给该部门的初步工作的一部分，但后来由于担心用于研究目的的生物标本的完整性，仅限于前一组。我们现在证明，样品的完整性是存在的，变化可以量化。我们的第二个目标是抽样第三组“正常”的孕妇谁是肥胖和谁是最相关的，因为肥胖症在当代产科人口的患病率不断增加。

The Division of Intramural Population Health Research, NICHD, is uniquely positioned to be on the forefront of exposome research, in that its intramural designation is consistent with the conduct of high risk research, many prospective pregnancy cohorts that have generated rich databases with longitudinally collected (in varying degrees) biospecimens during sensitive windows of human development are available, and the Division has biostatisticians with the level of expertise needed to develop appropriate analytical methods. These resources afford Division investigators an opportunity to design research initiatives within the exposome paradigm. Perhaps one of the earliest and most critical sensitive windows occurs during human reproduction and development. Currently the Division has a proof-of-concept study underway to characterize and quantify the pregnancy exposome using an existing pregnancy cohort study with normal outcomes. The goal of the present study is to build upon our previous work that focuses on the characterization of the normal pregnancy exposome by extending the same methodology to 'normal' pregnant women whose infants were born at the extremes of birth weight, as women with offspring small for gestational age (SGA) defined as birth weight < 10th percentile and large for gestational age (LGA) defined as birth weight > 90th percentile (Brenner, 1976) were excluded from the prior analysis. [20] Both low and high birth weight are associated with increased short term morbidity and mortality,and also have been repeatedly related to Increased risk of chronic diseases in later life, such as cardiovascular disease and type 2 diabetes. [21] Comprehensive Investigation of the exposome related to birth weight would potentially improve our understanding or early life determinants of the chronic diseases and help develop early preventive strategies of life long chronic diseases. Evidence has also linked the long-term impact of exposure to maternal obesity to increase risk of obesity and cardiometabolic risk. [22] Of added note is our effort to ensure comparable sampling frameworks for both groups in that all eligible women have their Initial biospecimens collected <13 weeks gestation and during each trimester. Restricting to women with a first trimester biospecimen collection is critical for assessing longitudinal changes during pregnancy, as pregnancy induces many physiologic changes following conception and implantation. Thus, having two randomly selected groups of 'normal’ pregnant women who differ only in terms of infants' birth weight will allow us to characterize and quantify the exposome during pregnancy for each of these two samples of pregnant women. This strategy was a part of our initial work presented to the Division for FY13, but later restricted to only the former group in light of concerns about the integrity of the biospecimens for research purposes. We now demonstrate that the sample integrity is there, and variation can be quantified. Our second objective is to sample a third group of 'normal' pregnant women who are obese and who are most relevant given the increasing prevalence of obesity in contemporary obstetric populations.