Necrotizing Enterocolitis: From Pathophysiology to Modern Prevention and Early Diagnostic Strategies

Background: Necrotizing enterocolitis (NEC) is a severe, multifactorial inflammatory disease and a leading cause of gastrointestinal mortality in preterm infants, particularly those with very low birth weight. Despite advances in neonatal care, its pathogenesis, early diagnosis, and effective prevention remain significant clinical challenges. Objective: This review aims to synthesize current knowledge (2018–2026) on the pathophysiology, diagnostic strategies, and preventive interventions in NEC, with a focus on improving early detection and clinical outcomes. Methodology: A narrative review of recent scientific literature was conducted, analyzing studies on molecular mechanisms, including immune dysregulation and gut microbiota, as well as advances in diagnostic tools and nutritional prevention strategies. Results: Contemporary evidence indicates that NEC arises from an exaggerated immune response mediated by Toll-like receptor 4 (TLR4) in the immature intestine, compounded by gut dysbiosis and hypoxic factors, as described in the “two-hit” hypothesis. Diagnostic approaches are shifting from reliance on the Bell classification toward multi-modal strategies integrating abdominal ultrasound and biomarkers such as C-reactive protein. Preventive measures, particularly the use of human milk, human milk oligosaccharides, probiotics, and standardized feeding protocols, significantly reduce disease incidence and severity. Conclusions: NEC management is evolving toward a proactive, precision-based model that integrates early diagnosis with targeted nutritional and microbiome-based interventions. These strategies offer substantial potential to reduce mortality and long term complications in this vulnerable population.