Necrotizing enterocolitis in newborns: update in pathophysiology and newly emerging therapeutic strategies

Abstract

While the survival of extremely premature infants with respiratory distress syndrome has increased due to advanced respiratory care in recent years, necrotizing enterocolitis (NEC) remains the leading cause of neonatal mortality and morbidity. NEC is more prevalent in lower gestational age and lower birth weight groups. It is characterized by various degrees of mucosal or transmural necrosis of the intestine. Its exact pathogenesis remains unclear, but prematurity, enteral feeding, bacterial products, and intestinal ischemia have all been shown to cause activation of the inflammatory cascade, which is known as the final common pathway of intestinal injury. Awareness of the risk factors for NEC; practices to reduce the risk, including early trophic feeding with breast milk and following the established feeding guidelines; and administration of probiotics have been shown to reduce the incidence of NEC. Despite advancements in the knowledge and understanding of the pathophysiology of NEC, there is currently no universal prevention measure for this serious and often fatal disease. Therefore, new potential techniques to detect early biomarkers or factors specific to intestinal inflammation, as well as further strategies to prevent the activation of the inflammatory cascade, which is important for disease progression, should be investigated.

Keywords: Extremely premature infants; Necrotizing enterocolitis; Pathophysiology; Prevention; Risk factor.

Fig. 1

Role of Toll-like receptor 4 (TLR4) in epithelial injury and repair mechanisms. Many factors related to prematurity such as infections, inappropriate enteral nutrition, antibiotics use, microcirculatory dysfunction, and hypoxia can induce epithelial injury. Hyperactivation of TLR4 enhances translocation of pathological bacteria across the epithelial barrier. Modified from Terrin et al. Biomed Res Int 2014;2014:543765.