Survival of the littlest: Navigating sepsis diagnosis beyond inflammation in preterm neonates

ABSTRACT: Background Sepsis diagnosis in preterm neonates is challenging due to symptom overlap with non-infectious inflammatory conditions, and slow, unreliable diagnostic practices. This study aims to identify metabolic biomarkers to elucidate sepsis pathophysiology, and enable timely, accurate diagnosis, which is crucial for preventing rapid health deterioration and minimizing unnecessary antibiotic use. Methods Liquid chromatography-mass spectrometry was performed on 227 plasma samples, obtained from 94 preterm neonates (<32 week gestational age), to measure 317 metabolites encompassing amines and signaling lipids. Linear mixed-effect modeling, LASSO and logistic regression models were calculated to assess metabolic alterations across the control, systemic inflammation-no sepsis (SINS), and sepsis groups. Stratification by sex and pathogen type was performed to evaluate sex-specific responses and pathogen-driven variations in sepsis. Findings We identified metabolites that (i) were similarly altered in both SINS and sepsis, (ii) exhibited a trend from control to SINS to sepsis, and (iii) were exclusively altered in sepsis. Males exhibited a pro-inflammatory phenotype while females showed an anti-inflammatory phenotype. Gram-positive and gram-negative bacterial sepsis revealed distinct metabolic profiles. A diagnostic model comprising 5 metabolic features and IL6 distinguished SINS from sepsis with an AUC of 0.80. Interpretation Our findings elucidate common mechanisms underlying systemic inflammation irrespective of causative trigger, exaggerated immune responses in sepsis, and sepsis-specific anomalies. Metabolomics holds the potential for early, accurate sepsis diagnosis with personalized treatment strategies. Funding This research was supported by Medical Delta through the MOMETA and METABODELTA scientific programs, with partial funding from X-Omics (NWO Project 184.034.019), Exposome-Scan (NWO Project 175.2019.032), and the European Funds for Regional Development (Kansen voor West II: Phenomix Fieldlab).

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS10665 | MetaboLights | 2025-07-07

REPOSITORIES: MetaboLights