Prenatal Longitudinal Metabolomics Profiling for Early Childhood Growth Trajectories and Obesity Risk in a US Biracial Birth Cohort

美国混血出生队列中儿童早期生长轨迹和肥胖风险的产前纵向代谢组学分析

• 批准号: 10580910
• 负责人: Qi Zhao
• 金额: $ 75.61万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580910
• 关键词: 4 year old; Affect; African American; Age; Alcohol consumption; American; Beginning of Life; Biological; Biological Assay; Biological Process; Birth; Blood; Blood specimen; Cardiovascular Diseases; Child; Childhood; Clinical; Clinical Data; Collection; County; Development; Diet; Dietary Factors; Dietary Practices; Disease; Endogenous Factors; Energy Intake; Environmental Exposure; Epidemic; European; Exogenous Factors; Future; Gestational Diabetes; Goals; Growth; Health; High Prevalence; Individual; Intervention; Investigation; Learning; Life Cycle Stages; Life Style; Link; Live Birth; Longevity; Measurement; Measures; Mediation; Mendelian randomization; Methods; Molecular Weight; Morbidity - disease rate; Mothers; Neurocognitive; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity Epidemic; Outcome; Overweight; Participant; Physiological Processes; Plasma; Pregnancy; Pregnant Women; Prevention; Public Health; Race; Risk Factors; Sampling; Second Pregnancy Trimester; Smoking; Technology; Tennessee; Testing; Third Pregnancy Trimester; Time; Tissues; Translational Research; Umbilical Cord Blood; Umbilical cord structure; Validation; Visit; Weight Gain; adult obesity; adverse outcome; biracial; cohort; early childhood; early detection biomarkers; effective intervention; fetal; follow-up; gestational weight gain; innovation; insight; liquid chromatography mass spectrometry; maternal condition; metabolomics; modifiable risk; novel; novel marker; obesity in children; obesity risk; offspring; offspring obesity; overweight child; personalized intervention; predictive marker; prenatal; prenatal risk factor; prepregnancy obesity; prevent; psychologic; rapid growth; rapid weight gain; recruit; risk prediction; sex; tool

Childhood obesity remains one of the most serious public health challenges because of its persistent high prevalence and adverse health consequences. There is an urgent need for novel biomarkers which can predict and provide effective interventional targets for the early prevention of childhood obesity. Although a growing body of evidence strongly supports maternal conditions during pregnancy which reflect fetal intrauterine exposures are associated with obesity risk in offspring, it is still far from fully understanding prenatal programming for offspring obesity. The emerging metabolomics technology, a systematic profiling of low-molecular-weight metabolites in biofluids and tissues, provides a snapshot of ongoing physiological processes as well as external environmental exposures. Thus, prenatal metabolomics profiling will have the potential to represent biological processes of both endogenous and exogenous factors, providing biological mechanisms underlying prenatal programming of offspring health and early biomarkers for predicting child disease development. However, studies of prenatal metabolomic profiling for child obesity, especially longitudinal profiling which integrates measurements from multiple time points during pregnancy, are still scarce. The overall goal of the proposed study is to identify prenatal circulating metabolomic profiles which are associated with early childhood growth trajectories and overweight/obesity risk in offspring and to examine their associations with metabolomic profiles of cord blood (for mechanism investigation) and prenatal modifiable risk factors (for intervention method investigation). The proposed study will leverage a large and biracial contemporary birth cohort with repeated blood collection from the mothers during pregnancy, cord blood collection at birth, and annual anthropometric measurements of the children from birth to 4 years old. A total of 1,425 (953 black and 472 white) mother-child pairs will be included in this study. A two-stage liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach, including an untargeted analysis with relative quantification (for discovery), followed by a finding-driven targeted LC-MS analysis with absolute quantification (for validation) will be used to achieve the Specific Aims: Aim 1) To identify both gestation stage-specific and longitudinal changes in maternal metabolomic profiles during pregnancy which are associated with early childhood growth trajectories and overweight/obesity risk at age 4; Aim 2) To examine the associations between the childhood outcome-related prenatal metabolomic profiles identified in Aim 1 and the metabolomic profiles of cord blood; Aim 3) To examine the associations between prenatal modifiable risk factors (e.g., gestational weight gain, diet, and smoking) and the childhood outcome-related prenatal metabolomic profiles identified in Aim 1. This project will be the first study to identify prenatal longitudinal metabolomic profiles associated with early childhood growth outcomes. It will shed new light on the biological mechanisms of prenatal programming of childhood obesity and potentially provide personalized intervention methods to curb the huge public health burden of childhood obesity in the US.

儿童肥胖仍然是最严重的公共卫生挑战之一，因为它持续很高 患病率和不利的健康后果。迫切需要新颖的生物标志物，可以预测 并为早期预防儿童肥胖提供有效的介入目标。虽然增长 证据主体在怀孕期间强烈支持孕产妇状况，反映了胎儿内的胎儿 暴露与后代的肥胖风险有关，它仍然远非完全了解产前编程 对于后代肥胖。新兴的代谢组学技术，一种系统的低分子量分析 生物流体和组织中的代谢产物提供了正在进行的生理过程以及外部的快照 环境暴露。因此，产前代谢组学分析将有可能代表生物学 内源性和外源性因素的过程，提供产前生物学机制 为预测儿童疾病发展的后代健康和早期生物标志物编程。然而， 研究儿童肥胖症的产前代谢组分析，尤其是整合的纵向谱分析 怀孕期间多个时间点的测量仍然很少。拟议的总体目标 研究是为了确定与幼儿生长有关的产前循环代谢组谱 后代中的轨迹和超重/肥胖风险，并检查其与代谢概况的关联 脐带血（用于调查机制）和产前可修改的危险因素（用于干预方法 调查）。拟议的研究将利用一个重复的大型和混血儿的现代出生队列 怀孕期间，母亲的血液收集，出生时脐带血收集和年度人体测量学 从出生到4岁的孩子的测量。共有1,425（953个黑色和472个白色）母子 对将包括在本研究中。基于两阶段的液相色谱 - 质谱法（LC-MS） 代谢组学方法，包括具有相对量化的非目标分析（用于发现），然后是 具有绝对定量（用于验证）的发现驱动的靶向LC-MS分析将用于实现 具体目的：目标1）确定母亲妊娠期特异性和纵向变化 与儿童早期生长轨迹相关的怀孕期间的代谢组学特征和 4岁时超重/肥胖风险；目标2）检查儿童结局相关的关联 在AIM 1中鉴定出的产前代谢组谱和脐带血的代谢组谱；目标3）检查 产前可改变的危险因素（例如妊娠体重增加，饮食和吸烟）和 AIM 1中确定的与儿童结局相关的产前代谢组概况。该项目将是第一个研究 确定与幼儿生长结果相关的产前纵向代谢组谱。会 开发了有关儿童肥胖产前编程的生物学机制，并可能 提供个性化的干预方法来遏制美国儿童肥胖的巨大公共卫生负担。