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Necrotizing enterocolitis (NEC) is an ischemic and inflammatory necrosis of the bowel primarily affecting premature neonates after the initiation of enteral feeding.
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NEC is predominantly a disorder of preterm infants, with an incidence of 6–10% in infants weighing <1500 g, with the highest incidence in the most premature infants. NEC can also occur in term infants, many of whom have preexisting medical conditions.
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Multifactorial theory has been suggested in which several risk factors, including prematurity, formula feeds, ischemia, and bacterial colonization, interact to initiate mucosal damage via a final common pathway involving activation of an inflammatory cascade. Mucosal damage results in invasion of the bowel walls by gas-producing bacteria, resulting in intramural gas accumulation (pneumatosis intestinalis). This sequence of events may then progress to transmural necrosis or gangrene of the bowel wall and finally to perforation and peritonitis.
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Prematurity. There is an inverse relationship between gestational age and risk for developing NEC. While most preterm infants develop NEC at postmenstrual age (PMA) of 30–32 weeks, various factors resulting from premature birth places them at increased risk for NEC. These may involve immature mucosal barrier, mucosal enzymes, and various gastrointestinal (GI) hormones. Premature infants may have an imbalance between pro- and anti-inflammatory factors and thus have increased activation of inflammatory mediators and decreased inactivation of specific mediators like platelet activating factor (PAF), which has been linked to NEC. Abnormal toll-like receptor 4 (TLR 4) signaling in the premature intestine and increased activation of nuclear factor-κB may play a role in the pathogenesis of NEC. An inability to effectively regulate the intestinal microcirculation and differences in bacterial colonization may also make preterm infants more susceptible to NEC.
Microbial colonization. NEC has not been shown to occur in germ-free animals. While bacterial and viral pathogens including Escherichia coli, Klebsiella spp, Clostridium spp, Staphylococcus epidermidis, rotavirus, and enterovirus have been implicated, no single organism has been consistently associated with NEC. Blood cultures are positive in only 20–30% of cases. While colonization by normal gut flora supports the intestinal mucosa through toll-like receptors, pathological bacteria induce inflammation and apoptosis by signaling pathways such as nuclear factor-κB. The growth of these noncommensal bacteria may also result in endotoxin release, leading to mucosal damage.
Enteral feedings. NEC is rare in unfed infants, and 90–95% infants with NEC have received at least 1 enteral feed. Enteral feeding provides necessary substrate for proliferation of enteric pathogens. Hyperosmolar formula/medications may alter mucosal permeability and cause mucosal damage. Short-chain fatty acids produced as a result of colonic fermentation (due to deficient lactase activity in premature infants) may add to the damage.
Breast milk significantly lowers risk of NEC. It has the benefit of providing immunoprotective as well as local growth-promoting factors not available with commercially prepared formulas. Early initiation of small-volume feeds ...