Preterm Birth, Maternal and Cord Blood Metabolome, and Child Metabolic Risk

早产、母体和脐带血代谢组以及儿童代谢风险

• 批准号: 9125533
• 负责人: Frank B Hu
• 金额: $ 72.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-24 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125533
• 关键词: 15 year old; Address; Adult; Adverse effects; Affect; African American; Archives; Biological; Biological Markers; Birth; Blood Pressure; Blood specimen; Boston; Cardiovascular Diseases; Characteristics; Child; Child Development; Childhood; Chronic Disease; Clinical; Data Quality; Development; Diabetes Mellitus; Diet; Dietary Factors; Dose; Dyslipidemias; Environment; Epidemic; Fetal Growth Retardation; Funding; Future; Genetic; Genetic Markers; Glucose; Hypertension; Infant; Inflammatory; Insulin; Intervention; Investigation; Joints; Life; Life Cycle Stages; Light; Link; Lipids; Low income; Measures; Mediating; Metabolic; Metabolic Diseases; Metabolic Pathway; Minority; Mothers; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Pilot Projects; Population; Premature Birth; Public Health; Risk; Risk Factors; Sampling; Seminal; Technology; Term Birth; Testing; Umbilical Cord Blood; United States National Institutes of Health; Work; age group; cohort; cost; early childhood; effective intervention; epigenetic marker; fetal; follow-up; genome-wide; high risk; in utero; lifestyle factors; maternal hypertension; metabolome; metabolomics; novel; novel marker; offspring; premature; prospective; public health relevance; response

 DESCRIPTION (provided by applicant): Using a life-course framework, we propose to conduct a comprehensive and systemic investigation on preterm birth (PTB) and maternal and fetal metabolic characteristics in relation to child development of adverse metabolic outcomes. Seminal work by Barker and others has linked fetal growth restriction to adult chronic diseases including type 2 diabetes (T2D). The link between PTB and later metabolic risk is not well studied but of great clinical and public health importance. In the U.S., the rates of PTB are high, affecting 1 in 9 of all births and 1 in 6 African American births. Obesity and T2D have become epidemic, affecting all age groups including mothers and children, especially in poor minority populations. This proposal is motivated by our recent study in the Boston Birth Cohort (BBC), which demonstrated a significant dose-response relationship between degree of prematurity and elevated insulin levels that were detectable at birth and persistent through early childhood (Wang et al, JAMA, 2014). Our findings raise the possibility that PTB is an important early life risk factor of subsequent metabolic risk. We propose to study preterm and term mother-child pairs (n= 3,000 pairs for Aim 1 and 1,200 pairs for Aims 2 and 3) in the BBC, one of the largest NIH-funded urban low-income minority birth cohorts, to address three specific aims: Aim 1. We will test the hypothesis that PTB is associated with adverse child metabolic outcomes, including overweight or obesity, surrogates of total body and central adiposity, elevated insulin and glucose levels, abnormal lipid profiles, and elevated blood pressure and metabolic/inflammatory biomarkers during critical developmental windows from birth to age 15 years. Aim 2. We will examine the interrelationships between PTB and the maternal and cord blood metabolomes assessed at birth. We will also explore the impact of maternal factors such as lifestyle and dietary factors, obesity, diabetes, dyslipidemia, and hypertension on the maternal and cord blood metabolomes. Aim 3. We will test the hypothesis that PTB and unfavorable maternal and cord blood metabolome profiles can independently and jointly increase child metabolic risk; we further hypothesize that the cord blood metabolome may mediate, while the maternal metabolome may modify the adverse effect of PTB on child metabolic outcomes listed in Aim 1. We will focus on a panel of 300 well-developed and validated metabolites that have been implicated in obesity, diabetes, and metabolic risk. In addition, we will include non-targeted metabolites in our exploratory analyses. This would be the first large-scale study to integrate cutting-edge metabolomics with a prospective birth cohort to address critical questions about fetal origins of metabolic diseases in the context of preterm birth and in the setting of a U.S. high-risk, urban low-income, minority population. Findings from this project will shed new light on whether and how in-utero metabolic environments (maternal metabolome), prematurity, and the fetal metabolic state (cord blood metabolome) jointly influence future metabolic outcomes in children.

 描述（由应用程序提供）：使用生命过程框架，我们建议对早产（PTB）进行全面的系统投资以及与儿童发展不良代谢结果有关的孕产妇和胎儿代谢特征。 Barker等人的开创性工作将胎儿生长限制与包括2型糖尿病（T2D）在内的成人慢性疾病联系起来。 PTB与后来的代谢风险之间的联系不是很好，而是非常重要的临床和公共健康重要性。在美国，PTB的比率很高， 影响所有出生中的九分之一，而六个非裔美国人的出生中有1个。肥胖和T2D已成为流行病，影响了包括母亲和儿童在内的所有年龄段，尤其是在贫困少数群体中。这项提议是由我们最近在波士顿出生队列（BBC）进行的研究激发的，该研究表明，早产程度与胰岛素水平升高之间存在显着的剂量反应关系，这些关系在出生时可以在出生和童年时期持续检测到（Wang等，Jama，2014年）。我们的发现提出了PTB是随后的代谢风险的重要早期生活风险因素的可能性。我们建议在BBC中研究早产和学期的母子对（目标1和1,200对的目标2和1,200对），AIM 2和3）是NIH资助的NIH资助的城市低收入少数族裔出生队列之一，以解决三个具体的目标：AIM 1：我们将与PTB相关。中枢肥胖，胰岛素和葡萄糖水平升高，脂质异常，血压和代谢/炎症生物标志物在关键的发育窗口中从出生到15岁。 AIM 2。我们将检查PTB与出生时评估的孕产妇和脐带血代谢组之间的相互关系。我们还将探索诸如生活方式和饮食因素，肥胖，糖尿病，血脂异常以及高血压等遗物因素的影响。 AIM 3。我们将检验以下假设：PTB，不利的母体和脐带血代谢组轮廓可以独立并共同增加儿童代谢风险；我们进一步假设，脐带血代谢组可能会介导，而母体代谢组可能会改变PTB对AIM 1中列出的儿童代谢结果的不利影响。我们将重点关注一个300个经过良好发达和经过验证的代谢产物，这些小组已在肥胖，糖尿病和糖尿病和代谢风险中被浸入。此外，我们将在探索性分析中包括非靶向代谢产物。这将是首次将尖端代谢组学与前瞻性出生队列相结合的大规模研究，以解决在早产诞生的背景下以及在美国高风险，城市低收入，低收入的少数族裔的情况下，解决有关代谢疾病的胎儿起源的关键问题。该项目的发现将为未来的代谢环境（母体代谢组），早产和胎儿代谢状态（脐带血代谢组）共同影响儿童未来的代谢结果。