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Updated: Sep 11, 2025

Biochemical Measurement of Neonatal Hypoxia
Published on: August 24, 2011
Evaluating neonatal cord serum metabolome in association with adolescent cardiometabolic risk factors
Elvira S Fleury1, George D Papandonatos2, Katherine E Manz3
1Department of Epidemiology, Brown University, Providence, RI, US.
Insights
Fetal exposure to certain metabolic pathways may influence adolescent cardiometabolic risk. Neonatal metabolic features identified link to distinct adolescent risk factor groups, suggesting early-life origins for these conditions.
Area of Science:
- Metabolomics
- Developmental Origins of Health and Disease (DOHaD)
- Cardiometabolic Disease Research
Background:
- Cardiometabolic disease (CMD) risk factors may originate in fetal development.
- Biological pathways connecting gestational conditions to CMD risk are not fully understood.
Purpose of the Study:
- To investigate the association between neonatal metabolic features and adolescent CMD risk factors.
- To identify potential biological pathways linking early-life exposures to CMD development.
Main Methods:
- Analyzed 14,384 cord serum metabolic features from 145 mother-child dyads using liquid chromatography-high-resolution mass spectrometry.
- Measured adolescent CMD risk factors (visceral fat, lipids, glucose, insulin, blood pressure) at age 12.
- Utilized sparse Partial Least Squares Regression (sPLS-R) to model associations between neonatal metabolic features and adolescent CMD risk factors.
Main Results:
- Identified two distinct groups of adolescent CMD risk factors associated with neonatal metabolic profiles.
- The first group included visceral fat, triglycerides, HDL cholesterol, insulin, and leptin; the second included glucose and systolic blood pressure.
- 178 neonatal metabolic features were linked to these risk factor groups, enriched in 31 pathways including short-chain fatty acid, vitamin, and amino acid metabolism, as well as glycolysis and gluconeogenesis.
Conclusions:
- Discovered 31 biological pathways potentially mediating the link between fetal environmental exposures and adolescent CMD risk.
- Findings suggest distinct early-life cardiometabolic trajectories and adolescent subphenotypes based on neonatal metabolic profiles.
Background:
Risk factors for cardiometabolic disease may have fetal origins, but the biological pathways linking gestational conditions to these risk factors are only partially understood.
Methods:
Among 145 Cincinnati-based HOME Study mother-child dyads, we detected 14,384 cord serum metabolic features using liquid chromatography high-resolution mass spectrometry. We measured cardiometabolic risk factors, including visceral fat, serum triglyceride, high-density lipoprotein cholesterol (HDL), leptin, adiponectin, insulin concentration, glucose, and systolic blood pressure (SBP) at age 12 years. Using sparse Partial Least Squares Regression (sPLS-R), we simultaneously modeled the association of metabolic features with all 8 risk factors. We prioritized features with the highest sPLS-R-derived CM risk factor correlations for metabolic pathway enrichment analysis.
Results:
We identified two groups of cardiometabolic risk factors in adolescents maximally associated with neonatal metabolic features. The first was visceral fat, triglycerides, HDL, insulin, and leptin; the second was glucose and SBP. The 178 metabolic features with the highest sPLS-R-derived feature-outcome correlations were enriched in 31 pathways related to short-chain fatty acid, vitamins C and B3, and amino acid metabolism, as well as glycolysis and gluconeogenesis.
Conclusions:
We identified 31 pathways that may help elucidate underlying mechanisms between fetal environmental stressors and the development of cardiometabolic risk factors.
Impact:
Using non-targeted metabolomics, we identified neonatal metabolic features linked to two groups of cardiometabolic risk factors in adolescents, suggesting distinct early-life CM risk trajectories and adolescent subphenotypes. One cardiometabolic group was characterized by higher visceral fat, triglycerides, insulin, leptin, as well as lower HDL; the other group was related to elevated glucose and systolic blood pressure. Using a variable selection and data-dimension reduction technique, these two groups were associated with 178 metabolic features and 31 biological pathways related to short-chain fatty acid, vitamins C and B3, and amino acid metabolism, as well as glycolysis and gluconeogenesis.
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