Serum biomarkers in the early detection of necrotizing enterocolitis: a systematic review

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease with high morbidity and mortality that predominantly affects preterm infants. Early diagnosis remains challenging due to nonspecific symptoms and delayed detection of radiological signs.

This systematic review provides an updated overview of the available evidence on serum biomarkers for early NEC detection, focusing on their diagnostic accuracy and clinical utility. A structured search was conducted in MEDLINE, Scopus, and web of science, identifying 40 studies evaluating biomarkers across various categories, including hematological indices, acute phase reactants, immunological markers, tissue damage and tissue repair markers, and metabolic markers.

Our findings highlight intestinal fatty acid-binding protein (I-FABP) as a promising biomarker for NEC prediction within the first 24 h of life. Ischemia-modified albumin (IMA) and certain multi-marker panels also showed high diagnostic accuracy. Despite these promising results, small sample sizes and heterogeneity in study design, biomarker thresholds, and patient populations limit immediate clinical implementation.

Future multicenter studies are essential to validate promising biomarkers, particularly I-FABP and IMA, and establish standardized cut-off values. Integrating biomarkers into multi-marker panels, alongside clinical and non-invasive approaches, may improve early NEC detection, enhance diagnostic accuracy, and guide timely interventions to optimize neonatal outcomes.