Chapter 52 Necrotizing Enterocolitis
PATHOPHYSIOLOGY
Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal (GI) disease among sick newborns and is the single most common surgical emergency among newborns. It is a spectrum of illness that varies from a mild, self-limiting process to a severe disorder characterized by inflammation and diffuse or patchy necrosis in the mucosal and submucosal layers of the intestine. The cause of NEC has been the focus of research for over 30 years; although many theories have been proposed, however, the pathogenesis remains elusive and controversial. Most researchers agree that, regardless of the initiating event(s), the pathogenesis of NEC is multifactorial. At present, the etiology is thought to involve three major pathologic mechanisms occurring in combination to create a favorable disease environment: ischemic injury to the bowel, bacterial colonization of the bowel, and the presence of a substrate such as formula.
The hypoxic or ischemic injury causes a reduced blood flow to the bowel. Birth asphyxia, umbilical artery cannulation, persistence of a patent ductus arteriosus, respiratory distress syndrome, maternal cocaine abuse, and/or exchange transfusion may be the initiating factor(s). Intestinal hypoperfusion damages the intestinal mucosa, and the mucosal cells lining the bowel stop secreting protective enzymes. Bacteria, whose proliferation is aided by enteral feedings (substrate), invade the damaged intestinal mucosa. Bacterial invasion results in further intestinal damage because of the release of bacterial toxins and hydrogen gas. The gas initially dissects into the serosal and submucosal layers of the bowel (pneumatosis intestinalis). The gas may also rupture through the bowel into the mesenteric vascular bed, where it can be distributed to the venous system of the liver (portal venous air). The bacterial toxins in combination with ischemia result in necrosis. Full-thickness bowel necrosis results in perforation, with the resulting release of free air into the peritoneal cavity (pneumoperitoneum) and peritonitis. This chain of events is considered a surgical emergency.
INCIDENCE
The incidence of NEC varies considerably from nursery to nursery, both within a given geographic region and from region to region. These estimates may not accurately reflect the true incidence because of inconsistencies in definitions and in reporting of cases that are complicated by other confounding variables such as prematurity.
1. NEC occurs in 1% to 8% of all infants admitted to neonatal intensive care units.
2. NEC occurs in 6% to 10% of neonates with birth weights of less than 1500 g.
3. Seventy to 90% of cases occur in high-risk low birth weight infants.
4. Of infants who develop NEC, 10% to 25% are full-term. Many of these infants have specific risk factors such as asphyxia, intrauterine growth retardation (IUGR), umbilical vessel catheters, anatomic GI malformations, polycythemia, or other medical problems.
5. NEC is the third leading cause of neonatal death, with an overall mortality rate of 20% to 40%.
6. Extremely low birth weight infants (1000 grams) are particularly vulnerable, with reported mortality rates of 40% to 100%.
7. Mortality rates for term versus preterm infants are reported as 4.7% and 11.9%, respectively.
8. Of those who survive, approximately 23% experience long-term sequelae related to the GI tract.
9. There is a slightly increased prevalence in male infants.
10. In some studies, higher NEC rates are seen in African-American than in white or Hispanic neonates.
CLINICAL MANIFESTATIONS
The onset of NEC occurs most commonly between days 3 and 12 of life, but it can occur as early as the first 24 hours of life or as late as 90 days of age. The disease is characterized by a broad range of signs and symptoms that reflect the differences in severity, complications, and mortality of the disease. Typically, suspected NEC (stage I) consists of nonspecific clinical findings that represent physiologic instability and may resemble the findings of other common conditions in premature infants. These include the following:
3. Recurrent apnea and bradycardia
6. Increased pregavage gastric residuals
Proven NEC (stage II) consists of the aforementioned nonspecific clinical findings plus the following:
Advanced NEC (stage III) occurs when the infant becomes acutely ill with peritonitis and/or radiographic evidence of intestinal perforation. Associated signs and symptoms include the following:
