The incidence of NEC varies from center to center and from year to year within centers. There are endemic and epidemic occurrences. An estimated 0.3 to 2.4 cases occur in every 1,000 live births. In most centers, NEC occurs in 2% to 5% of all NICU admissions and 5% to 10% of very low birth weight (VLBW) infants. If VLBW infants who die early are excluded and only infants who have been fed included, the incidence is approximately 15%.

Sex, race, geography, climate, and season do not appear to play any determining role in the incidence or course of NEC.

Prematurity is the single greatest risk factor. Decreasing gestational age is associated with an increased risk of NEC. The mean gestational age of infants with NEC is 30 to 32 weeks, and the infants generally are weight appropriate for gestational age. Approximately 10% of infants with NEC are full term. The postnatal age at onset is inversely related to birth weight and gestational age, with a mean age at onset of 12 days.

Enteral feeding is perhaps the next greatest risk factor. More than 90% of infants have been fed before the onset of this disease. In the extremely premature infants, the risk is least with infants who are exclusively breast-fed, and any kind of exposure to bovine milk—based products may increase the risk of NEC.

Similar to the effect on the lungs, antenatal steroids have been shown to improve the maturity of the GI tract. Randomized controlled trials performed even before the widespread use of antenatal steroids have shown reduced incidence of NEC among the infants treated with antenatal steroids.

Infants exposed to cocaine have a 2.5 times increased risk of developing NEC. The vasoconstrictive and hemodynamic properties of cocaine may promote intestinal ischemia (see Chap. 12).

The overall mortality is 9% to 28% regardless of surgical or medical intervention. The mortality for infants weighing <1,500 g can be as high as 45%; for those weighing <750 g, it may be much higher. The introduction of standardized therapeutic protocols with criteria for medical management and surgical
intervention, a high index of suspicion for the disease, and general improvements in neonatal intensive care have decreased the mortality rate. Infants exposed to cocaine who develop NEC have a significantly higher incidence of massive gangrene, perforation, and mortality than do infants not exposed.

Case-controlled epidemiologic studies have revealed that almost all previously described risk factors for NEC, including maternal disorders (e.g., toxemia), the infant’s course (e.g., asphyxia, patent ductus arteriosus [PDA]), and the type of management (e.g., umbilical artery catheterization [UAC]), simply describe a population of high-risk neonates. Apart from prematurity, exposure to artificial formula feeds, and cocaine exposure, no maternal or neonatal factors are known to increase the risk of NEC. This suggests that immaturity of the GI tract is the greatest risk factor.

Although NEC is primarily a disease of preterm infants, term infants also are rarely affected. The incidence of NEC in term infants is 1 in 20,000 live births. Some authors believe that NEC in term infants is a different disease process compared to that in preterm infants, displaying a more definite association with splanchnic hypoperfusion. Those term infants in whom NEC develops commonly have other risk factors such as congenital heart disease, polycythemia, sepsis, hypotension, and asphyxia.

The pathogenesis of NEC is not well defined. NEC is a multifactorial disease resulting from complex interactions between immaturity, mucosal injury secondary to a variety of factors (including ischemia, luminal substrate, and infection), and poor host work response to injury.

The concept of a hypoxic or hemodynamic insult, resulting in splanchnic vasoconstriction and reduced mesenteric flow, inducing bowel mucosal hypoxia, and rendering the intestine susceptible to injury, has long been considered a contributing factor in the pathogenesis of NEC. The pathologic findings of NEC resemble those seen in older individuals with gut vascular compromise. However, in a significant number of cases, no hypoxic or ischemic problems can be identified, and the temporal sequence of events does not support an ischemic event alone.

Enteral feedings have been implicated in the pathogenesis of NEC, as almost all babies who develop NEC have been fed. Factors that have been considered include osmolality of formula, the lack of immunoprotective factors in formula, and the timing, volume, and rate of feeding. Breast milk has been shown to have protective factors. Although breast milk alone does not prevent development of NEC in extremely premature infants, exclusive human milk diet in contrast to a combination of mother’s milk and bovine-based products has shown to reduce the rates of NEC and surgical NEC. Some case control studies suggest judicious introduction of feedings and avoidance of large day-to-day volume increases may lower the incidence of NEC. However, the rate of daily feeding increment that may protect infants from developing NEC has not been identified, and the mechanism by which larger volumes may predispose to the development of NEC is not known. It has been shown that adoption of standardized feeding regimen, dictating the advance of feedings in the VLBW population, and strict adherence to it reduce the risk of NEC by up to 87% despite heterogeneity of the feeding regimens used.

The microbiologic flora involved in NEC is not unique but represents the predominant bowel organisms present in the infant at the time of onset.
Various bacterial and viral agents have been reported in the microbial picture that is sometimes associated with NEC, especially with epidemic NEC, but none has yet been proved to be causal. Most often, it simply represents the gut flora translocating the compromised gut barrier. Release of endotoxin and cytokines by proliferation of colonizing bacteria, and bacterial fermentation with gaseous distension, may play a role as well. Presence of bacteria is likely important in the pathogenesis of NEC, since antenatal intestinal ischemia when the gut is in a sterile environment results in stenosis and not NEC.

Evidence supports a critical role for inflammatory mediators. Platelet activating factor (PAF), endotoxin lipopolysaccharide (LPS), tumor necrosis factor a (TNF-a), interleukins, and nitric oxide are some of the inflammatory mediators that have been suspected to have a role in the pathophysiology of NEC. Both animal studies and samples from human infants demonstrate the association of elevated levels of PAF in infants with NEC compared with those without. In animal models, exogenous administration of PAF mimics NEC-like injury and PAF antagonists limit such injury. The discovery of the roles of several inflammatory mediators points to the multifactorial etiology of the disease and underlines the fact that not one but several strategies are necessary for the prevention of NEC. Improved understanding of the role inflammation and pro-inflammatory mediators play in the development of NEC is needed before devising strategies to either limit or prevent this inflammatory cascade.

Histopathologic examination of tissue after surgery or autopsy shows that the terminal ileum and ascending colon are the most frequently involved areas, but in the most severe cases, the entire bowel may be involved. This localization has implications for long-term sequelae (see IV.). The pathologic lesions consist of coagulation necrosis, bacterial overgrowth, inflammation, and reparative changes.

Use of H2 blockers have been implicated in a higher risk of NEC in extremely low birth weight (ELBW) infants, suggesting that an acidic GI environment may be protective.

Several studies have suggested a temporal association of packed red blood cell (PRBC) transfusions with the onset of NEC. Hypothesized mechanisms include T cell activation, immune-mediated hemolysis, and splanchnic vasoconstriction associated with the transfusion. However, a consistent description of risk factors such as gestation, severity of anemia, or the stability of the infant prior to the transfusion is lacking, thereby making it difficult to institute evidence-based transfusion guidelines.

Systemic signs. Respiratory distress, apnea and/or bradycardia, lethargy, temperature instability, irritability, poor feeding, hypotension (shock), decreased peripheral perfusion, acidosis, oliguria, or bleeding diathesis.

Abdominal (enteric) signs. Abdominal distension or tenderness, gastric aspirates (feeding residuals), vomiting (of bile, blood, or both), ileus (decreased or
absent bowel sounds), bloody stools, abdominal wall erythema or induration, persistent localized abdominal mass, or ascites.

The course of the disease varies among infants. Most frequently, it will appear (i) as a fulminant, rapidly progressive presentation of signs consistent with intestinal necrosis and sepsis or (ii) as a slow, paroxysmal presentation of abdominal distension, ileus, and possible infection. The latter course will vary with the rapidity of therapeutic intervention and require consistent monitoring and anticipatory evaluation (see III.).

Radiology studies. The abdominal radiograph will often reveal an abnormal gas pattern consistent with ileus. Both anteroposterior (AP) and cross-table lateral or left lateral decubitus views should be included. These films may reveal bowel wall edema, a fixed position loop on serial studies, the appearance of a mass, pneumatosis intestinalis (the radiologic hallmark used to confirm the diagnosis), portal or hepatic venous air, pneumobilia, or pneumoperitoneum taking the appearance of gas under the diaphragm. Isolated intestinal perforation (IP) may present with pneumoperitoneum without other clinical signs.

Blood and serum studies.

Stay updated, free articles. Join our Telegram channel

Join