PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
First described over a century ago, necrotising enterocolitis (NEC) is now the most common gastrointestinal emergency occurring in neonates. Prematurity and low birth weight are the most important risk factors. This is particularly poignant because:
- It mainly affects premature infants who, having survived a difficult neonatal period, then confront a disease with high morbidity and mortality.
- With obstetric advances more infants of very low birth weight survive the neonatal period, increasing the population at risk of NEC.
NEC is rare in term babies as a whole; however, these account for 10% of cases. In term babies, the initiating events are different and it it often associated with underlying disorders.
Diagnosis and treatment remain very difficult and challenging.
- It is estimated that nearly 12% of infants born weighing less than 1500 g will develop NEC and about 30% of these infants will not survive.
- More than 85% of all NEC cases occur in infants of very low birth weight or in very premature infants. Full-term and near-term infants also develop the disease.
- Patent ductus arteriosus is a risk factor in premature babies, especially if conservative closure using indometacin has been attempted.
- In full-term infants, NEC is usually associated with predisposing or underlying disorders:
- Perinatal asphyxia.
- Respiratory distress.
- Congenital anomalies (myelomeningocele, congenital heart disease).
- Cow's milk protein-induced enterocolitis and glucose-6-phosphate dehydrogenase deficiency have been mooted as possible pathophysiological mechanisms.
- Antibiotic treatment for more than 10 days has been reported as an independent risk factor.
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Despite a lot of research over many years, the aetiology remains elusive. It involves serious intestinal injury following a combination of vascular, mucosal, toxic and possibly other insults to a relatively immature gut. A genetic predisposition may also play a part. Epidemic clusters have suggested an infective aetiology and viral, fungal and bacterial agents have all been isolated, although many infants have negative culture findings. The fact that organisms found in NEC babies are also found in healthy babies suggests that damage to the intestinal mucosa is the main underlying problem, resulting in spread of commensural organisms beyond their normal location. Colonisation by pathological organisms may also occur (eg, Escherichia coli, Klebsiella spp., Salmonella spp., Staphylococcus epidermidis).
NEC does not occur in utero. Colonisation of the gut with either commensal or pathogenic bacteria may affect maturation of the innate immune system (pattern recognition receptors and microbial-associated molecular patterns). Hyperactive inflammation in infants, caused by inadequate or altered colonisation of the gut, may cause deficiencies in dampening of bacterially mediated inflammatory pathways.
The classical form of NEC usually occurs in preterm neonates in the first two weeks of life.
In premature babies there is often a history of initially making progress on enteral feeding. There is an increase in incidence after blood transfusion for asymptomatic anaemia. Feeding difficulties may be noted by nursing staff and there may be concerns about vomiting or abdominal distension.
- Abdominal distension with increasing gastric aspirates.
- Visible intestinal loops.
- Altered stool pattern.
- Bloody mucoid stool and bilious vomiting.
- Decreased bowel sounds with erythema of the abdomen.
- Palpable abdominal mass or ascites.
- Associated features are bradycardia, lethargy, shock, apnoea, respiratory distress, temperature instability.
- Haemolytic disease of the newborn.
- Swallowed maternal blood.
- Pseudomembranous colitis.
- Stress ulcer.
- Meconium ileus.
- Metabolic or respiratory acidosis.
- Apnoea or prematurity.
- Coarctation of the aorta.
- Enteroviral infection.
- Gastro-oesophageal reflux.
- Hirschsprung's disease.
- Hospital-acquired infections.
- Hypoplastic left heart syndrome.
- Bacterial meningitis.
- Urinary tract infection.
- Focal intestinal perforation.
- Blood laboratory tests are nonspecific but cultures, FBC, blood gas and baseline biochemistry should be taken and lend support to the diagnosis:
- Severe or persistent thrombocytopenia, neutropenia, coagulopathy or acidosis indicate severe disease.
- Serial C-reactive protein may be useful, with persistently high levels associated with complications (stricture, abscess).
- Blood gases may assist in the diagnosis of respiratory distress or acute lactic acidosis.
- Diagnosis is confirmed by abdominal X-ray (AXR) - supine and decubitus/erect - and should be performed as soon as the diagnosis is suspected. Serial abdominal films are taken. Bowel wall thickening, persistent bowel loops that are filled with gas, and overall gaseous distention may suggest NEC but these X-ray findings are not specific.
- Ultrasound scanning may also be useful, particularly in identifying portal air, areas of walled-off perforation or ascites.
- Other imaging techniques being developed include contrast radiography, portal vein ultrasonography, MRI and radionuclide scanning.
- Newly developed biomarkers may prove helpful in achieving early diagnosis. These have been suggested as screening tests for at-risk babies.
- Various non-invasive methods are also being developed.
- Stage I - suspected NEC:
- Systemic: nonspecific signs such as temperature instability, lethargy, apnoea, bradycardia.
- Gastrointestinal tract (GIT): gastric residuals, occult blood in stool.
- AXR: normal/nonspecific changes.
- Stage IIA - definite and mild NEC:
- Systemic: nonspecific signs.
- GIT: abdominal distension ± tenderness, absent bowel sounds, frank blood in stool.
- AXR: ileus, focal pneumatosis intestinalis.
- Stage IIB - definite and moderate NEC.
- Systemic: mild acidosis, thrombocytopenia.
- GIT: abdominal wall oedema, tenderness ± mass.
- AXR: extensive pneumatosis intestinalis, early ascites, ± intrahepatic portal gas.
- Stage IIIA - advanced NEC:
- Systemic: respiratory/metabolic acidosis, apnoea, hypotension, decreasing urine output, leukopenia, disseminated intravascular coagulation (DIC).
- GIT: spreading oedema, erythema, induration of the abdomen.
- AXR: prominent ascites ± persistent sentinel loop, no perforation.
- Stage IIIB - advanced NEC:
- Systemic: deteriorating vital signs, shock, electrolyte imbalance.
- GIT and AXR: signs of perforation.
- Nil by mouth to rest the bowel.
- Nasogastric or orogastric tube to decompress the bowel with low intermittent orogastric suction.
- Intravenous (IV) fluids, total parenteral nutrition (TPN) and IV antibiotics for 10-14 days:
- Ampicillin/gentamicin or cefotaxime.
- Plus metronidazole or clindamycin.
- Antifungals should be considered for babies who have recently been on lengthy courses of antibiotics or are not responding to antibiotic treatment.
- Upper gastrointestinal small bowel follow-through is sometimes performed therapeutically in resolving NEC where intestinal obstruction develops as a result of a fibrous band or stricture.
- Paracentesis for ascites may be necessary.
- Treat shock, DIC, etc. Very ill babies may benefit from blood pressure support with vasopressors (eg, naloxone, dopamine).
- Surgery if a deteriorating or perforated/necrotic bowel is suspected (eg, free air on abdominal radiography). Up to 20% to 40% of infants with NEC will need surgical intervention at some point.
- Peritoneal drainage appears to be of equal effectiveness to laparotomy, although further research is needed.
- Intubation/ventilation for apnoea.
- Oral feeds can be restarted 7-10 days after pneumatosis clears.
Complications and prognosis
- Acquired short bowel syndrome (following surgery).
- Stoma-related complications.
- Sepsis and shock.
- Intestinal strictures (~30%).
- Enterocolic fistulae.
- Abscess formation.
- Recurrent NEC (rare)
- Iatrogenic complications - eg, central venous catheter-related thrombotic events and nosocomial infections, metabolic complications secondary to prolonged hyperalimentation (a nutrient mixture given to premature babies before giving milk).
- The overall survival rate is 75% but mortality varies considerably according to birthweight (10-44% in infants less than 1500 g, 0-20% in infants over 2500 g).
There is another NEC that affects older children and adults. It is known by different local names over the globe (for instance, 'Darmbrand' in Germany and 'pigbel' in Papua New Guinea).
- Occurring either sporadically or in epidemics, it is thought to be due to food contaminated with different strains of Clostridium perfringens (type A for most sporadic cases and probably type C for larger outbreaks).
- The disease course usually involves abdominal pain, vomiting, fever and bloody diarrhoea. In severe cases, shock follows and the mortality rates can be very high (30-100%).
- Treatment follows the same principles as the neonatal form (bowel rest, antibiotics +/- surgery) but would depend on available local medical and surgical services.
Feeding with human milk is known to be an effective intervention in the prevention of NEC. Other interventions have a limited evidence base but have focused on reducing the multiple contributing factors in a susceptible host.
Interventions that have been tried include:
- Factors relating to feeding:
- Correction of hypovolaemia, hyperviscosity and allowing adequate time for homeostatic mechanisms to mature before the enteral feeding challenge is begun.
- Starting feeds slowly using formulas of low volume.
- Small increments (20 ml/kg/day) when increasing feeds.
- Avoiding hyperosmolar medications and feeds.
- Conservative feeding.
- Trophic feeding rather than extended bowel rest.
- Some have suggested steroids for women in preterm labour.
- IgA supplementation (IV Ig prophylaxis of neonatal infections not protective).
- Arginine supplementation.
- Oral antibiotics.
- Implementation of strict infection-control measures to prevent faecal and oral spread of organisms.
Further reading & references
- Lahmiti S, Aboussad A; Neonatal necrotizing enterocolitis. ScientificWorldJournal. 2011 Mar 22;11:655-6.
- Neu J; Necrotizing enterocolitis. World Rev Nutr Diet. 2014;110:253-63. doi: 10.1159/000358474. Epub 2014 Apr 11.
- Lin PW, Stoll BJ; Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83.
- Gephart SM, McGrath JM, Effken JA, et al; Necrotizing enterocolitis risk: state of the science. Adv Neonatal Care. 2012 Apr;12(2):77-87; quiz 88-9. doi: 10.1097/ANC.0b013e31824cee94.
- Sharma R, Hudak ML; A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol. 2013 Mar;40(1):27-51. doi: 10.1016/j.clp.2012.12.012. Epub 2013 Jan 17.
- Alexander VN, Northrup V, Bizzarro MJ; Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr. 2011 Sep;159(3):392-7. Epub 2011 Apr 13.
- Terrin G, Scipione A, De Curtis M; Update in pathogenesis and prospective in treatment of necrotizing enterocolitis. Biomed Res Int. 2014;2014:543765. doi: 10.1155/2014/543765. Epub 2014 Jul 17.
- De Plaen IG; Inflammatory signaling in necrotizing enterocolitis. Clin Perinatol. 2013 Mar;40(1):109-24. doi: 10.1016/j.clp.2012.12.008. Epub 2013 Jan 17.
- Neu J; Necrotizing enterocolitis: the mystery goes on. Neonatology. 2014;106(4):289-95. doi: 10.1159/000365130. Epub 2014 Aug 20.
- Neu J, Mshvildadze M, Mai V; A roadmap for understanding and preventing necrotizing enterocolitis. Curr Gastroenterol Rep. 2008 Oct;10(5):450-7.
- Young C, Sharma R, Handfield M, et al; Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention? Pediatr Res. 2009 Jan 28.
- Ng PC, Ang IL, Chiu RW, et al; Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. J Clin Invest. 2010 Aug 2;120(8):2989-3000. doi: 10.1172/JCI40196. Epub 2010 Jul
- Oh S, Young C, Gravenstein N, et al; Monitoring technologies in the neonatal intensive care unit: implications for the detection of necrotizing enterocolitis. J Perinatol. 2010 Nov;30(11):701-8. Epub 2010 Mar 25.
- Gregory KE, Deforge CE, Natale KM, et al; Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation. Adv Neonatal Care. 2011 Jun;11(3):155-64; quiz 165-6. doi: 10.1097/ANC.0b013e31821baaf4.
- Niemarkt HJ, de Meij TG, van de Velde ME, et al; Necrotizing enterocolitis: a clinical review on diagnostic biomarkers and the role of the intestinal microbiota. Inflamm Bowel Dis. 2015 Feb;21(2):436-44. doi: 10.1097/MIB.0000000000000184.
- Rao SC, Basani L, Simmer K, et al; Peritoneal drainage versus laparotomy as initial surgical treatment for perforated necrotizing enterocolitis or spontaneous intestinal perforation in preterm low birth weight infants. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD006182.
- Clark RH, Gordon P, Walker WM, et al; Characteristics of patients who die of necrotizing enterocolitis. J Perinatol. 2011 May 19.
- Aguayo P, Fraser JD, Sharp S, et al; Stomal complications in the newborn with necrotizing enterocolitis. J Surg Res. 2009 Dec;157(2):275-8. Epub 2009 Jul 10.
- Zachariah SK; Adult necrotizing enterocolitis and non occlusive mesenteric ischemia. J Emerg Trauma Shock. 2011 Jul;4(3):430-2.
- Matsuda T, Okada Y, Inagi E, et al; Enteritis necroticans 'pigbel' in a Japanese diabetic adult. Pathol Int. 2007 Sep;57(9):622-6.
- Morgan JA, Young L, McGuire W; Pathogenesis and prevention of necrotizing enterocolitis. Curr Opin Infect Dis. 2011 Jun;24(3):183-9.
- Schurr P, Perkins EM; The relationship between feeding and necrotizing enterocolitis in very low birth weight infants. Neonatal Netw. 2008 Nov-Dec;27(6):397-407.
- Thompson AM, Bizzarro MJ; Necrotizing enterocolitis in newborns: pathogenesis, prevention and management. Drugs. 2008;68(9):1227-38.
- Frost BL, Caplan MS; Probiotics and prevention of neonatal necrotizing enterocolitis. Curr Opin Pediatr. 2011 Apr;23(2):151-5.
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Dr Richard Draper
Dr Colin Tidy
Dr Adrian Bonsall