Evidence-Based Approaches to Minimize the Risk of Developing Necrotizing Enterocolitis in Premature Infants

Purpose of the Review: The purpose of the current review is to identify evidence-based strategies for the prevention of necrotizing enterocolitis (NEC), a devastating disease of premature infants. Recent Findings: A growing body of evidence suggests that certain treatment strategies could decrease the incidence of NEC. These strategies include the administration of breast milk, the adoption of standardized feeding protocols, the administration of antenatal steroids, and the use of probiotics. Additional evidence suggests that the administration of immunonutrition based upon specific breast milk components—including immunoglobulins, lactoferrin, and human milk oligosaccharides—as well as essential amino acids including glutamine and arginine could also reduce NEC severity. The mechanism of action of these interventions is based in part upon their ability to inhibit the lipopolysaccharide receptor Toll-like receptor 4 (TLR4), whose activation is critical to NEC pathogenesis. Conclusion: Despite the high morbidity and mortality of NEC, strong evidence supports the adoption of risk-reduction strategies that can protect premature neonates from the development of this disease. Summary: Necrotizing enterocolitis (NEC) is a devastating surgical emergency that affects premature infants. NEC develops in part in response to the activation of the bacterial receptor Toll-like receptor 4 (TLR4) on the immature intestine by a dysbiotic microbiome in the setting of formula feeding. Given the rapid onset and often fulminant progression of NEC, prevention has the greatest potential to reduce its morbidity and mortality. Strong data suggests the utility of preventative strategies that include administration of a human milk-based diet, and standardized feeding strategies, while clinical evidence also supports the use of antenatal steroids and probiotics in certain circumstances. Pre-clinical and some clinical data support the administration of immunomodulatory compounds, including immunoglobulins, arginine, glutamine, and lactoferrin, which represent new directions for NEC prevention in vulnerable infants.