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.
