Understanding necrotizing enterocolitis—promising directions

The etiology of necrotizing enterocolitis remains elusive although intestinal barrier immaturity is the likely basic underlying, defect. Contributing to this barrier immaturity may be decreased mucus production, increased susceptibility to disruption of the epithelial cell layer, decreased repair capacity, decreased tissue antioxidant activity, immature regulation of intestinal blood flow and oxygenation, increased susceptibility to inflammatory mediators, dysfunctional immune response, and abnormal motility. It is likely a combination of these factors leads to mucosal injury that then progresses to necrotizing enterocolitis. Basic and clinical investigations have led to advances in our knowledge which may yield a better understanding of the etiology of necrotizing enterocolitis and thence on ways to prevent or ameliorate the disease. Based on currently available data as presented in this review, the most promising directions for future research to prevent necrotizing enterocolilis include investigation of (1) nitric oxide modulation of mucosal and vascular protective mechanisms in developing intestine, in particular the role of arginine supplementation of the diet of preterm infants; (2) platelet activating factor (PAF) receptor antagonists or recombinant PAF-acetylhydrolase in preterm infants; (3) alteration of the nutrient composition of preterm infant formula, in particular as relates to the lipid composition; (4) dietary supplementation with growth factors such as EGF, IGF, and glutamine; (5) antioxidant administration, especially glutathionc and vitamin E; (6) promotion of intestinal mucus production and addition of mucin to commercially-prepared infant formulas; and (7) enhancement of motility with feeding in all premature infants and possible utilization of erythromycin or other promotility agents in the older preterm infant.