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Necrotizing Enterocolitis

By

William J. Cochran

, MD, Geisinger Clinic

Last full review/revision Aug 2021| Content last modified Aug 2021
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Necrotizing enterocolitis is an acquired disease, primarily of preterm or sick neonates, characterized by mucosal or even deeper intestinal necrosis. It is the most common gastrointestinal emergency among neonates. Symptoms and signs include feeding intolerance, lethargy, temperature instability, ileus, bloating, bilious emesis, hematochezia, reducing substances in the stool, apnea, and sometimes signs of sepsis. Diagnosis is clinical and is confirmed by imaging studies. Treatment is primarily supportive and includes nasogastric suction, parenteral fluids, total parenteral nutrition, antibiotics, isolation in cases of infection, and, sometimes, surgery.

Risk factors

Three intestinal factors are usually present:

  • A preceding ischemic insult

  • Bacterial colonization

  • Intraluminal substrate (ie, enteral feedings)

Etiology of NEC

The exact etiology of necrotizing enterocolitis is not clear. However, the increased permeability and immature immune function of the immature intestinal tract are predisposing factors. It is believed that an ischemic insult damages the intestinal lining, leading to increased intestinal permeability and leaving the intestine susceptible to bacterial invasion. NEC rarely occurs before enteral feedings have begun and is less common among breastfed infants. However, once feedings are begun, ample substrate is present for proliferation of luminal bacteria, which can penetrate the damaged intestinal wall, producing hydrogen gas. The gas may collect within the intestinal wall (pneumatosis intestinalis) or enter the portal veins. Dysbiosis (alteration of the intestinal microbiome), such as that which occurs after treatment with antibiotics or acid-suppressing drugs, may also be a contributing factor because it increases potentially pathogenic bacteria.

The initial ischemic insult may result from vasospasm of the mesenteric arteries, which can be caused by an anoxic insult triggering the primitive diving reflex that markedly diminishes intestinal blood flow. Intestinal ischemia may also result from low blood flow during an exchange transfusion, during sepsis, or from the use of hyperosmolar formulas. Similarly, congenital heart disease with reduced systemic blood flow or arterial oxygen desaturation may lead to intestinal hypoxia/ischemia and predispose to NEC.

NEC may occur as clusters of cases or as outbreaks in neonatal intensive care units. Some clusters appear to be associated with specific organisms (eg, Klebsiella, Escherichia coli, coagulase-negative staphylococci, Pseudomonas, Clostridioides difficile), but often no specific pathogen is identified.

Complications of necrotizing enterocolitis

Symptoms and Signs of NEC

Infants may present with feeding difficulties and bloody or bilious gastric residuals (after feedings) that may progress to bilious emesis, ileus manifested by abdominal distention, or gross blood in stool. Sepsis may be manifested by lethargy, temperature instability, increased apneic spells, and metabolic acidosis.

Diagnosis of NEC

  • Detection of blood in stool

  • Abdominal x-rays

  • Ultrasonography

Early x-rays may be nonspecific and reveal only ileus. However, a fixed, dilated intestinal loop (sentinel loop) that does not change on repeated x-rays is very concerning for NEC. X-ray signs diagnostic of NEC are pneumatosis intestinalis and portal vein gas. Pneumoperitoneum Pneumoperitoneum Pulmonary air-leak syndromes involve dissection of air out of the normal pulmonary airspaces. (See also Overview of Perinatal Respiratory Disorders.) Extensive physiologic changes accompany... read more indicates bowel perforation and an urgent need for surgery.

Ultrasonography is being used increasingly in cases of NEC. With ultrasonography, clinicians have the ability to look at bowel wall thickness, pneumatosis intestinalis, and blood flow. This technique, however, is very operator dependent, and plain x-rays are still more commonly used.

Treatment of NEC

  • Feedings stopped

  • Nasogastric suction

  • Fluid resuscitation

  • Broad-spectrum antibiotics

  • Total parenteral nutrition (TPN)

  • Sometimes surgery or percutaneous drainage

The mortality rate is 20 to 30%. Aggressive support and judicious timing of surgical intervention maximize the chance of survival.

Support

Nonsurgical support is sufficient in over 75% of cases. Feedings must be stopped immediately if NEC is suspected, and the intestine should be decompressed with a double-lumen nasogastric tube attached to intermittent suction. Appropriate colloid and crystalloid parenteral fluids must be given to support circulation, because extensive intestinal inflammation and peritonitis may lead to considerable 3rd-space fluid loss. TPN is needed for 10 to 14 days while the intestine heals.

Systemic antibiotics should be started at once with a beta-lactam antibiotic (eg, ampicillin) and an aminoglycoside (eg, gentamicin, amikacin). Additional anaerobic coverage (eg, clindamycin, metronidazole) may also be considered. Antibiotics should be continued for 10 to 14 days (for dosage, see Table: Recommended Dosages of Selected Parenteral Antibiotics for Neonates Recommended Dosages of Selected Parenteral Antibiotics for Neonates In neonates, the extracellular fluid (ECF) constitutes up to 45% of total body weight, requiring relatively larger doses of certain antibiotics (eg, aminoglycosides) compared with adults. Lower... read more ). Because some outbreaks may be infectious, patient isolation should be considered, particularly if several cases occur within a short time.

The infant requires close monitoring; frequent complete reevaluation (eg, at least every 12 hours); and serial abdominal x-rays, complete blood counts (CBCs), platelet counts, and blood gases. Intestinal strictures are the most common long-term complication of NEC, occurring in 10 to 36% of infants who survive the initial event. Strictures typically manifest within 2 to 3 months of an NEC episode. Strictures are most commonly noted in the colon, especially on the left side. Resection of the stricture is then required. Short bowel syndrome Short Bowel Syndrome Short bowel syndrome is malabsorption resulting from extensive resection of the small bowel (usually more than two thirds the length of the small intestine). Symptoms depend on the length and... read more develops in about 10% of infants with NEC.

Surgery

Surgical intervention is needed in < 25% of infants. Absolute indications are intestinal perforation (pneumoperitoneum), signs of peritonitis (absent intestinal sounds and diffuse guarding and tenderness or erythema and edema of the abdominal wall), or aspiration of purulent material from the peritoneal cavity by paracentesis. Surgery should be considered for an infant with NEC whose clinical and laboratory conditions worsen despite nonsurgical support.

Primary percutaneous peritoneal drainage is an option and can be done at the bedside. In this procedure, the surgeon makes an incision in the right lower quadrant through which the abdomen is irrigated with warm saline solution. A drain is then placed to allow continued drainage of the abdomen. When drainage has stopped, the drain can be pulled back a little each day and subsequently removed. This procedure is done more commonly in very sick, extremely low-birth-weight infants who would be at risk if taken to an operating room; however, it may be associated with a higher mortality.

For infants undergoing laparotomy, the gangrenous bowel is resected, and ostomies are created. (Primary reanastomosis may be done if the remaining intestine shows no signs of ischemia.) With resolution of sepsis and peritonitis, intestinal continuity can be reestablished several weeks or months later.

Prevention of NEC

At-risk infants Risk factors Necrotizing enterocolitis is an acquired disease, primarily of preterm or sick neonates, characterized by mucosal or even deeper intestinal necrosis. It is the most common gastrointestinal emergency... read more Risk factors should ideally be fed breast milk, and feedings should begin with small amounts that are gradually increased according to standardized protocols. (Preterm formula is an appropriate substitute if breast milk is not available.) Hypertonic formula, drugs, or contrast material should be avoided. Anemia, low oxygen saturations, and polycythemia Perinatal Polycythemia and Hyperviscosity Syndrome Polycythemia is an abnormal increase in red blood cell mass, defined in neonates as a venous hematocrit ≥ 65%; this increase can lead to hyperviscosity with sludging of blood within vessels... read more should be treated promptly. When possible, antibiotics and acid-supressing drugs should be avoided.

Probiotics (eg, Bifidus infantis, Lactobacillus acidophilus) help prevent NEC, but further studies to determine optimal dosing and appropriate strains are required before routine use (1 Prevention references Necrotizing enterocolitis is an acquired disease, primarily of preterm or sick neonates, characterized by mucosal or even deeper intestinal necrosis. It is the most common gastrointestinal emergency... read more Prevention references ).

Prevention references

  • 1. van den Akker CHP, van Goudoever JB, Shamir R, et al: Probiotics and preterm infants: A position paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr 70(5):664–680, 2020. doi: 10.1097/MPG.0000000000002655

  • 2. Xiong T, Maheshwari A, Neu J, et al: An overview of systematic reviews of randomized-controlled trials for preventing necrotizing enterocolitis in preterm infants. Neonatology 13:1–11, 2019. doi: 10.1159/000504371

Key Points

  • Necrotizing enterocolitis (NEC) is intestinal necrosis of uncertain etiology; it occurs mainly in preterm or sick neonates after enteral feedings have begun.

  • Complications include intestinal perforation (most often in the terminal ileum) and peritonitis; sepsis occurs in 20 to 30%, and death may occur in 20%.

  • Initial manifestations are feeding difficulties and bloody or bilious gastric residuals (after feedings) followed by bilious emesis, abdominal distention, and/or gross blood in stool.

  • Diagnose using plain x-rays.

  • Supportive treatment using fluid resuscitation, nasogastric suction, broad-spectrum antibiotics, and total parenteral nutrition is effective in > 75% of cases.

  • Surgery to resect gangrenous bowel and treat perforation is needed in < 25% of infants.

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