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，因为其持续的高发病率 患病率和不良健康后果。迫切需要能够预测的新型生物标志物 为儿童肥胖的早期预防提供有效的干预目标。虽然正在成长 大量证据有力地支持了怀孕期间反映胎儿宫内情况的母体状况 暴露与后代肥胖风险相关，但目前还远未完全了解产前规划 对于后代肥胖。新兴的代谢组学技术，对低分子量的系统分析 生物体液和组织中的代谢物，提供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特征 内源性和外源性因素的过程，提供产前的生物学机制 对后代健康和预测儿童疾病发展的早期生物标志物进行规划。然而， 儿童肥胖的产前代谢组学分析研究，特别是整合了纵向分析 怀孕期间多个时间点的测量结果仍然很少。拟议的总体目标 研究旨在确定与儿童早期生长相关的产前循环代谢组学特征 后代的轨迹和超重/肥胖风险，并检查它们与代谢组学特征的关联 脐带血（用于机制研究）和产前可改变危险因素（用于干预方法） 调查）。拟议的研究将利用一个大型的、混血的当代出生队列，并重复进行 怀孕期间从母亲身上采集血液、出生时采集脐带血以及每年进行人体测量 测量儿童从出生到4岁的尺寸。共有 1,425 名（953 名黑人和 472 名白人）母子 本研究将包括对。基于两级液相色谱-质谱 (LC-MS) 的 代谢组学方法，包括具有相对定量的非针对性分析（用于发现），然后 将使用具有绝对定量（用于验证）的结果驱动的靶向 LC-MS 分析来实现 具体目标： 目标 1) 确定孕产妇妊娠阶段特定的变化和纵向变化 怀孕期间的代谢组学特征与儿童早期的生长轨迹相关 4岁时超重/肥胖的风险；目标 2) 检查儿童期结果相关之间的关联 目标 1 中确定的产前代谢组学概况和脐带血的代谢组学概况；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）与 目标 1 中确定的与儿童结局相关的产前代谢组学特征。该项目将是第一项研究 确定与儿童早期生长结果相关的产前纵向代谢组学特征。它将 揭示了儿童肥胖产前规划的生物学机制，并有可能 提供个性化干预方法，以遏制美国儿童肥胖带来的巨大公共健康负担。