The Pathophysiology of Necrotizing Enterocolitis

Abstract

After completing this article, readers should be able to: 1. Describe the basic epidemiologic aspects of neonatal enterocolitis (NEC). 2. List the major risk factors that predispose neonates to NEC. 3. Delineate the current views on the mechanisms involved in the pathogenesis of NEC. 4. Discuss the various models used to study NEC. 5. List the major mediators believed to be involved in the pathogenesis of NEC. Despite many years of clinical observation and experimental investigation, the pathogenesis of neonatal enterocolitis (NEC) remains elusive. The multifactorial theory suggests that four key risk factors—prematurity, formula feeding, intestinal ischemia, and bacterial colonization—are important prerequisites to the initiation of intestinal injury in neonates (Figure⇓ ). Current hypotheses suggest that these risk factors stimulate activation of the inflammatory cascade that ultimately results in the final common pathway of bowel necrosis that is the hallmark of neonatal NEC. Figure 1. Schematic of NEC pathomechanism. Prematurity is the most consistent and important risk factor associated with neonatal NEC. The disease occurs in 10% of babies born in the United States who weigh less than 1,500 g, but it is extraordinarily infrequent among term newborns and almost never is diagnosed in older infants or children. Furthermore, data clearly show that the more preterm the infant, the higher the risk of NEC. Nonetheless, the specific reason(s) for this particular predisposition are not well understood. Evidence from animal and human studies have shown significant differences between term and preterm neonates in several aspects of intestinal development and function. The mucosal barrier matures throughout gestation and even remains deficient in the term neonate during the first few weeks of life. It is well known that several mucosal enzymes and gastrointestinal hormones are suppressed or deficient in preterm animals/humans. Many aspects of the intestinal host defense system, a complex and important cascade responsible for limiting the invasion …