Necrotizing Enterocolitis Pathophysiology

Background An acquired disease of acute intestinal necrosis The most common medical/surgical emergency in neonates Associated with an increase in morbidity and mortality

Incidence Estimated 0.3-2.4 cases/1000 live births 2-5% of all NICU admissions 5-10% of VLBW infants; 11% in infants < 750 grams Approximately 90% of cases are in preterm infants Occurs in clusters and sporadically Incidence is increasing as preterm infant survival rate increases

Necrotizing Enterocolitis described as an inflammatory disease of the bowel

Risk Factors Single most important risk factor: Prematurity Decrease in gestational age = increase risk for NEC Cocaine exposure (2.5x increased risk) Excluding cocaine exposure, no maternal or neonatal factors other than prematurity are known.

Premature Infant Risk Factors Immature intestinal barrier Immature digestion and absorption Decreased intestinal motility Poor circulatory regulation Decreased immunologic factors in GI tract (secretory IgA) with exaggerated inflammatory response Decreased regenerative capabilities Increased gastric pH

Etiology Unclear & multifactorial Most likely a combination of factors: Intestinal ischemia Bacterial colonization of GI tract Enteral feedings with poor motility and unabsorbed nutrients leads to bacterial proliferation Advancing feeds > 20-30ml/kg/day Hyperosmolar formula Medications (xanthine derivatives, indomethacin, vitamin E)

Pathophysiology Impaired host intestinal defense system + immunological immaturity  colonization of GI tract with NICU flora Bacteria may migrate through mucosa  inflammatory reaction/cytokine release Enteric bacteria produces intraluminal gas

Pathophysiology Accumulation of gas in the submucosal layers of the bowel wall  necrosis Range of pathology: Mucosal injury  full thickness injury  perforation

Normal Bowel Wall

NEC Bowel Wall

Staging of NEC Clinical presentation varies among infants with NEC Ranges from slow and insidious to rapid and progressive Difficult for the clinician to diagnosis Dr. Martin Bell (1978) proposed original criteria for staging Subsequently modified as more became known and increasingly lower gestational ages

Bell Staging Criteria Stage IA and IB-suspected NEC Systemic signs Temp. instability, A/B’s, lethargy Intestinal signs Mild abdominal distention, residuals, emesis Bright red blood from rectum (Stage B) Radiological signs Normal or dilated, mild Ileus

Bell Staging Criteria Stage IIA-Definite NEC, mildly ill Systemic signs Temp. instability, A/B’s, lethargy Intestinal signs Same as IB, and decreased or absent BS with or without abdominal tenderness Radiological signs Intestinal dilation, Ileus, pneumotosis intestinalis

Bell Staging Criteria Stage IIB-Definite NEC, moderately ill Systemic signs Temp. instability, A/B’s, lethargy, mild acidosis, and mild thrombocytopenia Intestinal signs Same as IIA, and definite abdominal tenderness with or without abdominal cellulitis or RLQ mass, absent BS Radiological signs Same as IIA with or without portal vein gas, with or without ascites

Bell Staging Criteria Stage IIIA-Advanced NEC, severely ill, bowel intact Systemic signs Same as IIB, and hypotension, bradycardia, severe apnea, respiratory and metabolic acidosis, DIC, neutropenia, and anuria Intestinal signs Same as IIB, and signs of generalized peritonitis, marked tenderness, abdominal distension, abdominal wall erythema Radiological signs Same as IIB with definite ascites

Bell Staging Criteria Stage IIIB-Advanced NEC, severely ill, bowel perforation Systemic signs Same as IIIA Intestinal signs Radiological signs Same as IIB, and pneumoperitoneum

Bell Staging is Exhausting!

There’s more! Necessary to differentiate NEC from acquired neonatal intestinal diseases (ANIDs) Gordon et al propose reclassification for the <1250 gram infant to have 3 sub groups: Feeding intolerance of prematurity Medical ANIDs, preterm NEC or viral enteritis (VEI) Surgical ANIDs: spontaneous perforation (SIP), preterm NEC and VEI

Question: is it NEC or feeding intolerance? Symptoms are similar although not as severe: Abdominal distention, increase in residual (25 to 50% of feeding volume), emesis Bile stained emesis/residual – NEC?? Bloody stool??