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.

Childhood obesity is one of the most serious public health challenges because of its harmful consequences, such as type 2 diabetes, cardiovascular disease, and psychological problems. To identify risk factors for childhood obesity at the very beginning of life, we propose to use an innovative metabolomics approach (a high-throughput method for testing metabolites in biofluids) to systematically identify metabolites in the plasma of pregnant women which can predict the risk of childhood obesity. The study findings will significantly contribute to a better understanding of the biological mechanisms underlying the early origins of childhood obesity and the development of early and effective tools for preventing childhood obesity.