Perioperative Metabolomic Profiling in Neonatal Cardiac Surgery Identifies a High-Risk Phenotype for Adverse Outcomes

Area of Science:

• Neonatal physiology and cardiac surgery.
• Metabolomics and mass spectrometry.
• Biomarker discovery and risk stratification.

Background:

• Neonatal cardiac surgery carries significant risks of morbidity and mortality.
• Perioperative metabolic stress can lead to unique metabolic profiles.
• These metabolic phenotypes may correlate with adverse clinical outcomes.

Purpose of the Study:

• To identify perioperative metabolomic phenotypes in neonates undergoing cardiac surgery.
• To associate these phenotypes with adverse clinical outcomes.
• To investigate the role of cardiopulmonary bypass (CPB) in metabolic alterations.

Main Methods:

• Collected plasma samples from 230 neonates at multiple time points (preoperative, post-CPB, 24-hour).
• Utilized targeted metabolomics via mass spectrometry.
• Employed Boruta algorithm for feature selection and hierarchical clustering for phenotype identification.
• Defined primary endpoint as a composite of major morbidities and mortality.

Main Results:

• Identified 3 metabolomic phenotypes (intermediate-, low-, and high-risk) with varying composite outcome rates (40%, 6.1%, 58%).
• High-risk phenotype associated with elevated amino acid catabolism and inflammatory metabolites (tyrosine, alanine, proline, methionine).
• Low-risk phenotype linked to preserved redox balance and fatty acid oxidation (cystine, galactitol, acetylcarnitine).

Conclusions:

• Metabolomic profiling successfully identified distinct phenotypes associated with perioperative risk in neonatal cardiac surgery.
• Amino acid catabolism and inflammatory pathways are implicated in neonatal morbidity.
• Findings support metabolomic biomarkers for risk stratification and targeted interventions.