Basics
Description
Necrotizing enterocolitis (NEC) is a severe acquired GI disorder that occurs in the newborn period and consists of diffuse necrotic injury to the bowel, which can result in perforation or subserosal collections of gas. The entire GI tract is susceptible, but the most frequently involved areas are the distal small bowel and proximal colon. Lesions vary from being diffuse areas of patchy necrosis to more isolated focal disease. Systemic signs and symptoms related to the inflammatory GI injury are accompanied by characteristic radiographic findings of pneumatosis.
Epidemiology
- NEC typically has an onset at 1 " 3 weeks of life (3 " 20 days) after the initiation of enteral feedings. The more premature the infant, the longer the child is at risk for developing NEC, with cases reported as late as 3 months of age.
- NEC affects mostly premature infants, but up to 10% of cases occur in term infants.
- The incidence of NEC is variable and ranges from 1 to 7% of all neonatal intensive care unit admissions or 1 " 3 per 1,000 live births.
- Preterm infants account for the vast majority of total NEC cases; the risk increases with decreasing gestational age and birth weight.
- Prevalence in very-low-birth-weight (VLBW) infants (birth weight <1,500 g) is 7%.
- Highest risk is in infants with birth weights between 500 and 750 g (15%).
Risk Factors
- The greatest risk factor for NEC is prematurity. Additional risk factors for both preterm and full-term infants include the following:
- Cardiovascular instability
- Respiratory compromise resulting in recurrent or prolonged hypoxia
- Cyanotic heart disease
- Polycythemia
- Exchange transfusions
- Bowel malformations
- Perinatal asphyxia
- Small size for gestational age
- Maternal preeclampsia
- Antenatal cocaine abuse
- Prolonged use of IV antibiotics
General Prevention
- The use of maternal breast milk exclusively has been advocated. Donor breast milk, when maternal breast milk is unavailable, has been shown to decrease the incidence of NEC.
- A rapid rate of feeding advancement (>20 mL/kg/day) may increase the risk of NEC in infants less than 1,500 g. Early initiation of trophic feeds (<10 mg/kg/day) for several days prior to advancing feeding volumes may stimulate maturation of the GI tract with resultant improvement in feeding tolerance.
- The use of probiotics has not been shown consistently to effectively decrease the incidence for VLBW infants. Concern has been raised of an increased risk of sepsis when using probiotics.
- Immunonutrient supplementation with agents such as arginine, glutamine, lactoferrin, and omega-3 polyunsaturated fatty acids is being investigated, but there is currently insufficient evidence to make any recommendations for their use.
Pathophysiology
- Varying degrees of inflammation early in the course cause superficial mucosal ulcerations and submucosal edema and hemorrhage, leading to transmural coagulation necrosis and perforation in the most severe cases.
- The most common sites for NEC include the terminal ileum, ileocecal region, and ascending colon.
- 50% of infants have both colonic and small intestine disease, with the other 50% divided between isolated ileal and colonic involvement.
Etiology
- The etiology of NEC is unknown but thought to be a multifactorial process.
- Various factors causing direct and indirect mucosal disruption, which in turn may lead to an increased permeability in the gut of agents that lead to injury, include the following:
- Hypoxia/ischemia leading to mucosal injury
- GI tract immaturity
- Immature host defense
- Enteral feedings
- Decreased diversity of bacteria within the GI lumen
- Enteral alimentation
- Because 95% of infants who develop NEC have been enterally fed, initiation of feedings has been implicated as an important contributor to the etiology of NEC.
- The composition of the formula (osmolarity), the rate of volume increase, and the immaturity of the mucosa have all been implicated as factors.
- Because of the frequent report of epidemic, cluster-type episodes, a variety of microorganisms has been implicated in the development of NEC, although there is no single causative organism.
- Blood cultures may be positive in 20 " 30% of cases, often gram-negative organisms.
- Immaturity of the GI mucosal defense system against invading organisms has been noted in NEC.
- Medications may have a direct mucosal injury.
Diagnosis
Alert
Delay in making the correct diagnosis of NEC and instituting appropriate therapy may lead to a rapid progression of symptoms and often a worse outcome.
Physical Exam
- The triad of abdominal distention, bloody stools, and feeding intolerance is frequently seen 8 " 10 days after initiating enteral feedings.
- The clinical spectrum varies dramatically from nonspecific symptoms of feeding intolerance to severe abdominal distention, sepsis, and shock. A staging system ranks the disease into 3 categories based on severity of the clinical signs and symptoms, aiding formulation of individual treatment plans.
- Stage I (suspected NEC)
- Temperature instability
- Apnea
- Bradycardia
- Lethargy
- Cyanosis
- Glucose instability
- Increased gastric residuals
- Emesis (may be bilious)
- Abdominal distention
- Heme-positive stools
- Stage II (definitive NEC): stage I plus
- Mild metabolic acidosis
- Mild thrombocytopenia
- Poor perfusion
- Severe abdominal distention
- Absent bowel sounds
- Abdominal tenderness
- Grossly bloody stools
- Possible abdominal wall cellulitis, fullness/mass
- Ascites
- Stage III (advanced NEC): stage I and II plus
- Shock/deterioration of vital signs
- Metabolic acidosis
- Thrombocytopenia
- Disseminated intravascular coagulation (DIC)
- Significant abdominal tenderness/peritonitis
- Respiratory compromise
- Neutropenia
Diagnostic Tests & Interpretation
Lab
No single laboratory feature is diagnostic of NEC. Obtaining a blood culture and monitoring serial complete blood counts (CBCs) and blood gases are essential for monitoring patients with NEC to assess for the following:
- Thrombocytopenia
- Acidosis, metabolic
- Anemia
- Neutropenia
- DIC
Imaging
Abdominal radiographs are essential for the diagnosis and staging of NEC:
- Stage I: mild dilatation of bowel loops
- Stage II
- Dilated loops, which may be fixed
- Pneumatosis intestinalis (presence of submucosal or subserosal air in the intestinal wall)
- Possible portal venous gas
- Stage III: likely pneumoperitoneum, free air
Differential Diagnosis
- Systemic
- Sepsis with ileus
- Pneumothorax causing a pneumoperitoneum
- Hemorrhagic disease of the newborn
- Swallowed maternal blood
- GI tract
- Volvulus
- Malrotation
- Hirschsprung colitis
- Intussusception
- Spontaneous bowel perforation
- Stress gastritis
- Meconium ileus
- Milk protein allergy
Treatment
The best therapy for NEC is prevention. When present, early recognition and rapid medical management of infants with NEC are critical to minimize the progression of this aggressive disease.
Additional Treatment
General Measures
- Length of therapy and reinstitution of feedings are based on the severity of the episode and on clinical, laboratory, and radiologic abnormalities.
- If there are no laboratory or radiographic abnormalities, feedings may be started 24 " 72 hours after the episode.
- If mild abnormalities are present and the infant is only mildly ill, a 7-day course of therapy is considered.
- When laboratory and radiologic abnormalities include pneumatosis intestinalis, acidosis, and/or thrombocytopenia, a 10- to 14-day course is indicated.
Surgery/Other Procedures
- First-line therapy for NEC is medical management and is successful in 50 " 75% of infants.
- Surgical intervention is required in 25 " 50% of all cases.
- Indications include the following:
- Pneumoperitoneum
- Cellulitis of the anterior abdominal wall, abdominal mass
- Suspicion of intestinal infarction with a fixed loop of dilated bowel on radiography
- Metabolic acidosis secondary to bowel necrosis unresponsive to medical therapy
- The goal of surgery is to remove all necrotic bowel and to preserve as much bowel length as possible. The most widely accepted procedure is laparotomy with resection of gangrenous intestine and exteriorization of all viable ends as stomas.
- Peritoneal drains placed at the bedside were developed as a palliative procedure to decrease surgical morbidity and mortality in infants weighing <1,000 g, decompressing the peritoneal cavity of gas, necrotic debris, and stool. This approach has a higher mortality rate and increased adverse neurodevelopmental outcome than initial laparotomy. However, the majority of pediatric surgeons in the United States believe there is role for peritoneal drainage as a bridge to the more definitive operation.
Inpatient Considerations
Initial Stabilization
- Therapy is based on the severity and progression of the symptoms.
- Initial management of all patients with suspected or proven NEC
- NPO status
- IV fluids
- Nasogastric (NG) tube placement for decompression
- IV antibiotics: broad spectrum
- Total parenteral nutrition (TPN) to ensure adequate nutrition and growth
- Severely ill patients may require hemodynamic support, acid " base regulation, and respiratory support as clinically appropriate.
- Evaluate every 6 hours to once a day, depending on the severity of the episode:
- Blood cultures
- CBC, electrolytes, and blood gas
- Fluid status
- Abdominal radiograph
Ongoing Care
Follow-up Recommendations
Despite early recognition and intervention, NEC is associated with a significant morbidity and mortality.
Diet
- During acute illness, NPO and TPN
- On resolution of illness, slow reintroduction of feeds is necessary, as the infant is at risk for recurrent NEC.
Prognosis
- Overall mortality for infants with NEC is between 20% and 40% but can be as high as 60% in patients with stage III NEC.
- Infants who survive the acute stage of NEC have a good long-term survival with 80 " 95% survival to discharge. However, hospitalization is 20 days longer on average than similar infants without NEC.
- Infants recovering from NEC have a 25% risk of microcephaly and serious neurodevelopmental delays.
Complications
- Acute complications that may occur with NEC include GI perforation, DIC, sepsis, shock, fluid and electrolyte imbalance, and respiratory failure.
- Long-term complications occur in 10 " 30% of infants and include the following:
- Intestinal strictures
- Acquired short bowel syndrome if the patient undergoes lengthy surgical resection of bowel
- Enterocolic fistulas or anastomotic leaks
- Malabsorption
- Cholestasis
- Failure to thrive
- Most common complication (10 " 35%) is intestinal stricture: occurs mainly in the left colon
Additional Reading
- Choo S, Papandria D, Zhang Y, et al. Outcomes analysis after percutaneous abdominal drainage and exploratory laparotomy for necrotizing enterocolitis in 4,657 infants. Pediatr Surg Int. 2011;27(7):747 " 753. [View Abstract]
- Gordon PV. Understanding intestinal vulnerability to perforation in the extremely low birth weight infant. Pediatr Res. 2009;65(2):138 " 144. [View Abstract]
- Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006;386(9543):1271 " 1283. [View Abstract]
- Neu J, Mihatsch WA, Zegarra J, et al. Intestinal mucosal defense system, part 1. Consensus recommendations for immunonutrients. J Pediatr. 2013;162(Suppl 3):S56 " S63. [View Abstract]
- Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011;364(3):255 " 264. [View Abstract]
Codes
ICD09
- 777.50 Necrotizing enterocolitis in newborn, unspecified
- 777.51 Stage I necrotizing enterocolitis in newborn
- 777.52 Stage II necrotizing enterocolitis in newborn
- 777.53 Stage III necrotizing enterocolitis in newborn
- 777.6 Perinatal intestinal perforation
ICD10
- P77.9 Necrotizing enterocolitis in newborn, unspecified
- P77.1 Stage 1 necrotizing enterocolitis in newborn
- P77.2 Stage 2 necrotizing enterocolitis in newborn
- P77.3 Stage 3 necrotizing enterocolitis in newborn
- P78.0 Perinatal intestinal perforation
SNOMED
- 2707005 necrotizing enterocolitis in fetus OR newborn (disorder)
- 206525008 neonatal necrotizing enterocolitis (disorder)
- 397729009 perinatal necrotizing enterocolitis (disorder)
- 65390006 Perinatal intestinal perforation (disorder)
FAQ
- Q: What are the most common complications of NEC?
- A: Mortality, poor growth, prolonged hospitalization, and the development of intestinal strictures
- Q: Is NEC preventable?
- A: The development of NEC is not clearly preventable, but cautious feedings in extremely premature infants with gradual advancement and use of breast milk decrease the risk of NEC.
- Q: Is NEC exclusively a process that occurs in the premature infant?
- A: Approximately 10% of cases occur in full-term infants with underlying risk factors.
- Q: How is spontaneous intestinal perforation (SIP) different from NEC?
- A: SIP represents a perforation not associated with pneumatosis, inflammation, or ischemia (all hallmarks of NEC) and occurs in infants that often have not yet been fed. Risk factors include extreme prematurity and early steroid use, particularly in combination with indomethacin in the first week of life.