What is neonatal necrotizing enterocolitis (NEC)?

Neonatal Necrotizing Enterocolitis: Comprehensive Overview

Definition and Epidemiology

Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal emergency characterized by inflammation and necrosis of the small bowel and colon, primarily affecting premature infants and representing the most common serious gastrointestinal disorder in neonatal intensive care units. 1, 2

• NEC predominantly affects premature infants (<37 weeks gestational age), though it can occasionally occur in term neonates 1, 3
• The disease carries an overall survival rate of approximately 95%, but when NEC involves the entire bowel (occurring in ~25% of cases), mortality increases dramatically to 40-90% 1, 4, 5
• Prematurity and low birth weight are the most consistent risk factors for disease development 2, 6

Pathophysiology

The pathogenesis of NEC involves a multifactorial process requiring three essential components 1:

Core Pathogenic Triad

• Substrate for bacterial growth: Enteral feedings provide the necessary substrate 1
• Infectious agent: Usually bacterial colonization, though no single organism has been definitively identified as causative 7
• Bowel injury event: Decreased blood flow to the bowel or bowel segment causing vascular compromise and mucosal injury 1

Contributing Mechanisms

• Intestinal ischemia: Alterations in blood flow, polycythemia, and hyperviscosity contribute to tissue damage 1, 6
• Microbiome alterations: Preterm infants experience delayed and altered microbial colonization patterns compared to term infants, with frequent clinical interventions (antibiotics, delayed enteral feeds, stress-inducing procedures) further disrupting normal gut microbiome development 1
• Inflammatory mediators: Eicosanoids (particularly thromboxane), platelet-activating factor, and leukotrienes are implicated as disease mediators 6
• Immature intestinal defense mechanisms: The premature infant's intestinal defense systems are insufficient, contributing to disease susceptibility 7

Pathological Progression

The disease evolves through distinct stages 6:

• Early phase: Mucosal ulcerations, hemorrhage, and thrombosis
• Intermediate phase: Inflammatory changes develop
• Advanced phase: Full-thickness necrosis, pneumatosis intestinalis, and potential perforation

Clinical Presentation

Timing of Onset

• In premature infants: Variable onset, typically after initiation of enteral feeds 1
• In term neonates: Earlier presentation, with 50% developing disease within the first 48 hours of life and 90% within the first 4 days 3

Clinical Signs and Symptoms

Gastrointestinal manifestations 1, 5:

• Abdominal distention (primary finding)
• Bloody stools (hematochezia)
• Bilious emesis
• Focal abdominal erythema

Systemic manifestations 1, 6:

• Increased episodes of apnea and bradycardia
• Signs of sepsis: thrombocytopenia and neutropenia
• Metabolic acidosis (particularly with bowel ischemia)
• Lethargy and temperature instability

Radiographic findings 1:

• Pneumatosis intestinalis (pathognomonic finding)
• Portal venous gas

Management

Immediate Initial Management

The American Academy of Pediatrics recommends immediate implementation of bowel rest, broad-spectrum antibiotics, fluid resuscitation, and nasogastric decompression, with surgical consultation if perforation or clinical deterioration occurs. 4, 5

Medical Management Components

Bowel rest and decompression 5:

• Immediately discontinue all enteral feeds
• Insert nasogastric tube for bowel decompression
• Maintain complete bowel rest until clinical improvement

Antibiotic therapy 5:

• Start broad-spectrum intravenous antibiotics immediately after obtaining blood cultures
• First-line regimens include:
  • Ampicillin + gentamicin + metronidazole
  • Ampicillin + cefotaxime + metronidazole
  • Meropenem as monotherapy

Fluid resuscitation and hemodynamic support 5:

• Initiate aggressive fluid resuscitation
• Monitor for signs of sepsis/septic shock
• Provide hemodynamic support as needed

Management of gastrointestinal bleeding 5:

• Consider blood transfusion for significant bleeding causing anemia or hemodynamic compromise
• Withhold enteral nutrition during and immediately after transfusion to reduce risk of transfusion-associated NEC (TANEC)

Nutritional Support During Acute Phase

Parenteral nutrition 4, 5:

• Provide parenteral nutrition during bowel rest period
• Ensure minimum amino acid intake of 1.0 g/kg/day to avoid negative nitrogen balance
• Provide minimum of 30-40 Kcal per 1g amino acids to guarantee amino acid utilization
• Include taurine in amino acid solutions (optimal dosing not well established)
• Monitor for parenteral nutrition-associated complications including cholestasis

Feeding reintroduction 4:

• Consider arginine supplementation when reintroducing feeds, as it may help prevent recurrence

Avoid glutamine supplementation: Not recommended for infants up to two years of age with NEC 4

Surgical Management

Indications for surgical intervention 1, 5:

• Bowel perforation (absolute indication)
• Peritonitis
• Clinical deterioration despite medical management
• Abdominal mass

Surgical options 1:

• Peritoneal drainage: May be used in very low birth weight neonates as either definitive treatment (when combined with antibiotics) or as temporizing measure before definitive surgery
• Exploratory laparotomy: Generally involves bowel resection with creation of stomas or reanastomosis

Disease distribution and surgical findings 3:

• In term neonates: Severe colonic disease predominates, with colonic perforation or full-thickness necrosis common
• Small bowel involvement is less frequent in term infants
• Subsequent intestinal continuity can be restored in surviving patients, though some require resection of additional NEC strictures

Success Rates

• Nonoperative management is successful in approximately 70% of cases 1, 5
• Surgical intervention required in remaining 30%

Prevention Strategies

Probiotic Supplementation

Probiotic supplementation initiated early in life is an effective prophylactic measure for preventing NEC, late-onset sepsis, and reducing all-cause mortality in preterm infants. 1, 5

• Recommended strains: Combinations of Lactobacillus spp. and Bifidobacterium spp. show the most benefit 4, 5
• Mechanism: Probiotics accelerate microbiome maturation to a state more comparable to term-born infants and facilitate health-promoting changes in immune and metabolic parameters 1
• Engraftment: Some probiotic strains successfully engraft into the preterm microbiome, potentially conferring long-lasting benefits beyond treatment cessation 1

Feeding Practices

• Human breast milk: Use of human breast milk is a key prevention strategy 2
• Standardized feeding regimens: Implementation of standardized feeding protocols reduces NEC incidence 2

Risk Factor Modification

Avoid or minimize 2:

• Early antibiotic exposure (when not medically necessary)
• Proton pump inhibitors (PPIs) and H2 receptor antagonists (alter microbiota and increase NEC risk)
• Unnecessary infections through strict infection control

Prognosis and Long-term Outcomes

Mortality

• Overall mortality: ~5% 4, 5
• Mortality with total bowel involvement: 40-90% 1, 4, 5
• Single mortality factor: Extent of bowel involvement is the primary determinant of survival

Morbidity

• Survivors may require multiple surgical interventions for stricture formation 3
• Long-term complications can include short bowel syndrome, feeding difficulties, and developmental delays
• Most surviving patients can achieve intestinal continuity restoration 3

Special Considerations

Term Neonates with NEC

Term infants with NEC present differently than premature infants 3:

• Earlier disease onset (within first 48-96 hours)
• Higher birth weights (typically >2.7 kg)
• Recognized risk factors (asphyxia, hypoglycemia, polycythemia, respiratory distress) absent in 60% of cases
• Predominantly colonic disease with higher rate of surgical intervention (70% vs. 30% in general NEC population)
• Better overall prognosis when managed appropriately

Critical Pitfalls to Avoid

• Delayed surgical consultation: Obtain surgical consultation early when perforation or clinical deterioration is suspected 4, 5
• Inadequate protein provision: Failure to provide minimum 1.0 g/kg/day amino acids leads to negative nitrogen balance 4
• Premature feeding reintroduction: Ensure adequate clinical improvement before restarting enteral feeds
• Transfusion-associated NEC: Withhold enteral nutrition during and immediately after blood transfusions 5