Exploring the Complex Pathophysiology of Necrotizing Enterocolitis in Preterm Neonates

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm neonates, with a mortality rate of 30-50% in advanced cases. Despite decades of research, its multifactorial pathophysiology remains incompletely understood. This review summarizes recent advances in NEC research and proposes an integrative theoretical framework for its pathogenesis. We examine key contributing factors, including intestinal vascular development, mucosal immunity, intestinal regeneration, the enteric nervous system, and the gut microbiome, highlighting how prematurity disrupts these processes and predisposes neonates to NEC. Furthermore, we propose a sequential model of NEC pathogenesis, hypothesizing that impaired intestinal microcirculation in preterm neonates compromises blood flow in response to enteral feeding, leading to localized ischemia. This initiates epithelial barrier dysfunction, exacerbates inflammatory responses, impairs intestinal regeneration, and disrupts enteric nervous system function, collectively driving NEC progression. By integrating experimental and clinical findings, we provide a comprehensive perspective on NEC initiation in preterm neonates and identify potential avenues for future research and therapeutic interventions.