Over 90% of cases of necrotizing enterocolitis (NEC) occur in premature infants Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more . It occurs in about 1 to 8% of neonatal intensive care unit admissions.
General risk factors for necrotizing enterocolitis in addition to prematurity Preterm Infants An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more include
Alteration of the intestinal microbiome (dysbiosis)
Non-human milk feeding
Three intestinal factors are usually present:
A preceding ischemic insult
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
Necrosis begins in the mucosa and may progress to involve the full thickness of the intestinal wall, causing intestinal perforation Acute Perforation of the Gastrointestinal Tract Any part of the gastrointestinal tract may become perforated, releasing gastric or intestinal contents into the peritoneal space. Causes vary. Symptoms develop suddenly, with severe pain followed... read more with subsequent peritonitis Peritonitis Abdominal pain is common and often inconsequential. Acute and severe abdominal pain, however, is almost always a symptom of intra-abdominal disease. It may be the sole indicator of the need... read more and often free intra-abdominal air. Perforation occurs most commonly in the terminal ileum; the colon and the proximal small bowel are involved less frequently. Sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more occurs in 20 to 30% of infants with NEC, and death may occur in 20% of infants with NEC.
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
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
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.
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 ). 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.
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 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 ).
Corticosteroids may be given to pregnant women who are at risk of preterm birth to help prevent necrotizing enterocolitis (2 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 ).
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
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.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Garamycin, Genoptic, Genoptic SOP, Gentacidin, Gentafair, Gentak , Gentasol, Ocu-Mycin|
|Amikin, Amikin Pediatric, ARIKAYCE|
|Cleocin, Cleocin Ovules, Cleocin Pediatric, Cleocin T, CLIN, Clindacin ETZ, Clindacin-P, Clinda-Derm , Clindagel, ClindaMax, ClindaReach, Clindesse, Clindets, Evoclin, PledgaClin, XACIATO|
|First-Metronidazole 100 , Flagyl, Flagyl ER, Flagyl RTU, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol|
|Acidophilus, Acidophilus Gold Extra Strength, BioGaia, Culturelle, Culturelle Health & Wellness, Culturelle Health & Wellness Vegetarian, Culturelle Kids, Culturelle Kids Probiotic, Culturelle Kids Pro-well Probiotics, Culturelle Kids Purely Probiotic, Culturelle Kids Regularity, Culturelle Probiotics, Culturelle Probiotics Health & Wellness, Culturelle Probiotics Total Balance, Florajen, Floranex Granules, Lacto Freedom , Mega Probiotic, NewFlora, PROBACAP, Probiotic, Probiotic Acidophilus, REJUVAFLOR, RENEWAFLOR, UpSpring DUAL|