Discovery and validation of serum metabolic signature of neonatal sepsis

A more accurate diagnostic biosignature is crucial for neonatal sepsis. In this report, we identified a serum metabolite signature for diagnosing neonatal sepsis cases using mass spectrometry-based profiling of serum samples from two discovery cohorts (set-I/-II: n=71/269) of sepsis patients (culture positive/negative: CP/CN) and controls (no-sepsis: NS or healthy controls: HC). This signature was validated in both cross-sectional (n=60) and follow-up cohorts (n=100). The six-metabolite signature, which includes 1,5-anhydro-D-sorbitol, lactic acid, malic acid, myo-inositol, phenylalanine, and lysine, can distinguish CP and CN sepsis cases from HC. The deregulated serum metabolites returned to HC levels in neonates after completing antibiotic treatment. Additionally, a metabolic signature of PE (20:4(5Z,8Z,11Z,14Z)/0:0), 12-amino-dodecanoic acid, and 1,5-anhydro-D-sorbitol identified from a validation set-II (n=100) using LC-MS could differentiate CP and CN groups from NS groups. Translating this serum metabolite signature into a simple, deployable blood test for neonatal sepsis could enable faster and more accurate decision-making.