Pathogenesis and prevention of necrotizing enterocolitis: a hypothesis based on personal observation and a review of the literature.

The hypothesis is, that necrotizing enterocolitis (NEC) of the neonate occurs by the coincidence of two of three pathologic events: (1) intestinal ischemia, (2) colonization by pathogenic bacteria, and (3) excess protein substrate in the intestinal lumen. NEC is more likely to appear following quantitative extremes, ie, severe ischemia highly pathogenic flora, or marked excess of substrate. NEC develops only if a threshold of injury, sufficient to initiate intestinal necrosis, is exceeded. The hypothesis is derived from previous theories by Santulli, which implicated all three events, and by Lawrence, in which a single event, abnormal bacterial colonization, was considered sufficient to induce NEC. This hypothesis may explain both typical occurrences of NEC among high-risk premature infants in neonatal intensive care units (NICUs), and atypical occurrences among infants considered at low-risk, eg, previously healthy term infants, infants fed breast milk exclusively, and infants never fed. It may further explain why NEC fails to develop in most high-risk infants in NICUs. Preventive measures might include: (1) pharmacologic stabilization of intestinal perfusion, (2) modification of the intestinal flora, or (3) feeding colostrum or other protective substances. Each theoretical benefit is accompanied by potential risks. The prevention of NEC may require favorable intervention in two of the three pathologic events.