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.

Pediatric Research
|August 16, 2025
PubMed

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.
Abstract

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