DESCRIPTION

Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal (GI) emergency that occurs in the newborn period and consists of diffuse necrotic injury to the bowel, which can result in perforation or subserosal collections of gas. The entire GI tract is susceptible, but the most frequently involved areas are the distal small bowel and proximal colon. Lesions vary from being diffuse areas of patchy necrosis to more isolated focal disease. Systemic signs and symptoms related to the inflammatory GI injury are accompanied by characteristic radiographic findings of pneumatosis.

EPIDEMIOLOGY

• NEC typically has an onset at 2 to 5 weeks of life (3 to 20 days after the initiation of enteral feedings). The more premature the infant, the longer the child is at risk for developing NEC, with cases reported as late as 3 months of age.
• NEC affects mostly premature infants, but up to 10% of cases occur in term infants.
• The incidence of NEC is variable and ranges from 1% to 7% of all neonatal intensive care unit admissions or 1 to 3 per 1,000 live births.
• Preterm infants account for the vast majority of total NEC cases; the risk increases with decreasing gestational age and birth weight.
• Prevalence in very-low-birth-weight (VLBW) infants (birth weight <1,500 g) is 7%.
• Highest risk is in infants with birth weights between 500 and 750 g (15%).

RISK-FACTORS

The greatest risk factor for NEC is prematurity. Additional risk factors for both preterm and full-term infants include the following:

• Enteral feeding with formula
• Cardiovascular instability
• Respiratory compromise resulting in recurrent or prolonged hypoxia
• Cyanotic heart disease
• Polycythemia
• Exchange transfusions
• Gastroschisis
• Perinatal asphyxia
• Small size for gestational age
• Maternal preeclampsia
• Antenatal cocaine abuse
• Prolonged use of IV antibiotics
• Gastric acid suppression with H2 blockers

GENERAL-PREVENTION

• Exclusive maternal breast milk feeding has been advocated. When maternal breast milk is unavailable, use of donor milk may decrease the risk of developing NEC when compared to formula.
• Standardized feeding protocols with early initiation of trophic feeds (<10 mL/kg/24 h) for several days prior to advancing feeding volumes may stimulate maturation of the GI tract with resultant improvement in feeding tolerance. A rapid rate of feeding advancement (>20 mL/kg/24 h) may increase the risk of NEC in infants <1,500 g.
• Minimizing prolonged use of empiric antibiotics immediately after birth
• Specific probiotic strains may decrease the incidence for VLBW infants. Concern has been raised regarding lack of quality standards and an increased risk of sepsis when using probiotics.
• Immunonutrient supplementation with agents such as arginine, glutamine, lactoferrin, and omega-3 polyunsaturated fatty acids is being investigated, but there is currently insufficient evidence to make any recommendations for their use.

PATHOPHYSIOLOGY

• Exact mechanism of injury in NEC is unclear, but research suggests a multitude of factors in an immature host lead to activation of the inflammatory cascade with subsequent tissue injury and necrosis.
• Components of the innate immune system, such as toll-like receptors (TLRs), play a role.
  • Specifically, TLR type 4 (TLR4) activation by pathologic bacteria inhibits the body’s ability for intestinal repair and increases the release of inflammatory cytokines causing epithelial injury.
  • In preterm infants, expression of TLR4 is elevated leading to an increased risk for overactivation, intestinal injury, and NEC.
• The most common sites for NEC include the terminal ileum, ileocecal region, and ascending colon.
  • 50% of infants have both colonic and small intestine disease, with the other 50% divided between isolated ileal and colonic involvement.

ETIOLOGY

• The etiology of NEC is unknown but thought to be a multifactorial process.
• Various factors that cause direct and indirect mucosal disruption, which in turn may lead to an increased permeability in the gut of agents that lead to injury, include the following:
  • Hypoxia/ischemia leading to mucosal injury
  • GI tract immaturity
  • Immature host defense
  • Enteral feedings
  • Decreased diversity of bacteria within the GI lumen
  • It is noteworthy that each of these factors can increase expression of immune receptors including TLR4 in the gut.
• Enteral alimentation
  • Because 95% of infants who develop NEC have been enterally fed, initiation of feedings has been implicated as an important contributor to the etiology of NEC.
  • The composition of the formula (osmolarity), the rate of volume increase, and the immaturity of the mucosa have all been implicated as factors.
• Because of the frequent report of epidemic, cluster-type episodes, a variety of microorganisms has been implicated in the development of NEC, although there is no single causative organism.
  • Blood cultures may be positive in 20–30% of cases, often gram-negative organisms.
• Immaturity of the GI mucosal defense system, including factors such as reduced levels of defensins and impaired mucin production, may impair defense against invading organisms, leading to NEC.
• Medications may cause direct mucosal injury.