EXPOSOME BIOCHEMICAL ANALYSIS FOR BIRTH WEIGHT/OBESITY

出生体重/肥胖的暴露生化分析

基本信息

批准号：
8933137
负责人：
MICHAEL TSAI
金额：
$ 30.32万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-29 至 2015-09-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8933137
关键词：
Albumins Aliquot Alkaline Phosphatase Amino Acids Antibodies Apolipoproteins B Bile Acids Bilirubin Biochemical Birth Weight C-Peptide CCL2 gene Cardiovascular Diseases Carotenoids Chemicals Cholecalciferol Cholesterol Chronic Disease Cohort Studies Collection Conceptions Creatinine Databases Development Discipline of obstetrics E-Selectin Elderly Endoglin Ensure Enzyme-Linked Immunosorbent Assay Estradiol Exposure to F2-Isoprostanes FABP4 gene Fatty Acids Ferritin First Pregnancy Trimester Gestational Age Glucose Goals High Density Lipoproteins Hippuric acid Homocysteine Homocystine Human Human Chorionic Gonadotropin Human Development Infant Insulin Insulin-Like Growth Factor Binding Protein 3 Intercellular adhesion molecule 1 Interleukin-10 Interleukin-6 Investigation Leptin Life Light Link Lipoprotein (a)Low-Density Lipoproteins Measures Methodology Morbidity - disease rate National Institute of Child Health and Human Development Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Nuclear Obesity Outcome Phospholipids Physiological Plasminogen Inactivators Population Positioning Attribute Pregnancy Pregnant Women Prevalence Prevention strategy Progesterone Proteins Published Comment Reproduction Research Research Design Research Personnel Resources Risk SHBG gene Sampling Serum Small for Gestational Age Infant Somatomedins TSH receptor antibody Testosterone Thyroglobulin Thyroglobulin antibody Tocopherols Transferrin Receptor Triglycerides Tumor Necrosis Factor-alpha Urea Nitrogen Uric Acid Urine Variant Vascular Cell Adhesion Molecule-1 Vascular Endothelial Growth Factors Very low density lipoprotein Vitamin D2 Woman Women&apos s Group Work acylcarnitine adiponectin analytical method cohort hepcidin high risk human IGFBP2 protein human TNF protein implantation improved inhibin B leptin receptor metabolomics mortality mullerian-inhibiting hormone nephrin obesity risk offspring oxidized low density lipoprotein podocalyxin population health post gamma-globulins prospective

项目摘要

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.

NICHD 校内人口健康研究部处于暴露组研究前沿的独特地位，因为其校内名称与高风险研究的进行相一致，许多前瞻性妊娠队列已生成丰富的数据库，并纵向收集（在不同程度上）可以获得人类发育敏感窗口期间的生物样本，并且该部门拥有具有开发适当分析方法所需专业水平的生物统计学家，这些资源为该部门的研究人员提供了在暴露组内设计研究计划的机会。范例。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过程中，目前该部门正在进行一项概念验证研究，以使用现有的正常结果的妊娠队列研究来表征和量化妊娠暴露组。本研究是在我们之前的工作基础上进行的，该工作的重点是正常妊娠暴露组的特征，通过将相同的方法扩展到婴儿在极端出生体重下出生的“正常”孕妇，即后代小于胎龄的妇女。 SGA）定义为出生体重< 10% 和大于胎龄 (LGA) 定义为出生体重 > 90% (Brenner, 1976) 被排除在先前的分析之外 [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相关。也已多次与晚年慢性疾病风险增加有关，例如心血管疾病和 2 型糖尿病 [21] 与出生体重相关的暴露组的全面调查可能会改善我们的健康状况。了解慢性疾病的早期生命决定因素，并帮助制定终生慢性疾病的早期预防策略。证据还表明，母亲肥胖的长期影响会增加肥胖风险和心脏代谢风险[22]。我们努力确保两组的抽样框架具有可比性，因为所有符合条件的女性都在妊娠 13 周内采集了初始生物样本，并且在每个妊娠期限制采集前三个月的生物样本对于评估妊娠期间的纵向变化至关重要。怀孕，因为怀孕会在受孕和着床后引起许多生理变化，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，这将使我们能够对每个人在怀孕期间的暴露组进行表征和量化。该策略是我们向该部门提交的 2013 财年初步工作的一部分，但出于对用于研究目的的生物样本完整性的担忧，后来仅限于前一组。样本完整性是存在的，并且我们的第二个目标是对第三组肥胖的“正常”孕妇进行抽样，考虑到当代产科人群肥胖的患病率日益增加，她们是最相关的。