Abstract
Neonatal sepsis remains a leading cause of morbidity and mortality worldwide; however, timely and accurate diagnosis continues to present a significant clinical challenge. Current diagnostic methods, including blood culture and inflammatory markers, are limited by delayed turnaround times and a lack of specificity, often leading to overtreatment or missed opportunities for intervention. In recent years, metabolomics has emerged as a promising approach for discovering novel biomarkers that reflect the systemic metabolic disruptions characteristic of neonatal sepsis. This systematic review summarizes the existing evidence on changes in metabolites and metabolite classes associated with neonatal sepsis, with a focus on their potential as biomarkers. Eleven eligible studies were reviewed, covering various analytical techniques and biofluids, including serum, urine, and stool. Although a wide range of metabolite alterations was observed, particular attention was given to amino acid metabolism, energy substrates, and lipid derivatives. The findings emphasize both the potential and current limitations of metabolomics-based biomarker discovery in this area. The review identifies important gaps in the literature, including diverse study designs, small sample sizes, and inconsistent reporting, highlighting the need for rigorous, standardized research. The importance and clinical potential of metabolomics in neonatal sepsis are thoroughly discussed.