1. Necrotizing Enterocolitis Priscilla Joe, MD
Children’s Hospital and Research Center Oakland

2. Incidence Most common GI emergency in premies
2-10% of VLBW infants < 1500 grams
Inverse relationship with gestational age
Males and females equally effected
Mean diagnosis 20 days (premies) vs. 7 days (term)
Jejunum, ileum, and colon most commonly affected
10% term infants (usually in those with pre-existing illness)

3. Clinical Findings Abdominal distension (70-98%)
Increased gastric residuals ( >70%)
Emesis (>70%)
Gross blood per rectum (25-63%)
Occult GI bleeding (22-59%)
Diarrhea (4-26%)
Lethargy, temperature instability, apnea/bradycardia, hypotension

4. Physical Findings Absent bowel sounds Abdominal tenderness
Abdominal wall erythema
Fixed abdominal mass (RLQ)

7. Pathophysiology Bacterial proliferation Ischemic mucosal damage
Transmural necrosis allowing bacterial translocation, increasing risk for perforation
Endotoxin activation of inflammatory cascade

8. Risk Factors Prematurity Feeding Circulatory Instability
Medications (vasoactive agents, indocin)
Bacterial Overgrowth/Infection

9. Prematurity
Deficient mucosal barrier (suppressed GI hormones and mucosal enzymes)
Dysfunctional intestinal host defense system
Decreased motility
Dysregulation of intestinal microcirculation (increased bacterial overgrowth)

10. Feeding and NEC 90% of babies receive enteral feedings
Disrupts mucosal integrity
Reduces gut motility
Alters GI blood flow
Abnormal bacterial colonization
-Formula: Enterobacter
-Breastmilk: Enterobacter and Bifidobacterium
Rate of feeding advancement
Hyperosmolar feeding

11. Intestinal Ischemia
Term infants (polycythemia, asphyxia, exchange transfusion, congenital heart disease, IUGR)
PDA
Indocin
Cocaine exposure in utero
UAC lines?
Gastroschisis

12. Bacterial Colonization
High risk infants susceptible to bacterial overgrowth
Breast milk (lactobacilli and facultative anaerobes)
Formula fed (potentially pathogenic gram-negative bacteria)

13. Work Up

14. Radiographic Findings
Intestinal ileus
Dilated and thickened bowel loops, air-fluid levels
Intramural gas (pneumatosis intestinalis); cystic and/or linear patterns, terminal ileum and proximal colon
Free air (football sign)
Portal venous gas
Fixed or persistent dilated loop of bowel (sentinel loop)
Gasless abdomen with ascites

20. Laboratory Findings CBC: Elevated CRP
Elevated or decreased WBCs
Thrombocytopenia
Low ANC = poor prognosis
Elevated CRP
Cultures (blood, +/- stool, +/- CSF)
Usually reveals enteric flora
Stool Analysis - heme +, check for C. diff toxin

21. Laboratory Findings Coagulopathy Electrolytes ABG/VBG Prolonged PT/PTT
Low fibrinogen
Elevated D-dimers
Electrolytes
Hypo- or hyperglycemia
Hyponatremia
Low bicarb
ABG/VBG
Metabolic acidosis

22. Differential Diagnosis
Sepsis with ileus
Bacterial enterocolitis: C. diff, other gram negatives
Mechanical bowel obstruction:
Hirschsprung
Ileal atresia
Volvulus
Meconium ileus
Intussusception
Isolated gastric perforation (indocin, steroids)

23. Mean Age at Presentation
Gestational age (weeks)
< 30
31-33 34
Full term
Age at onset (days) 20 14 5 2

24. Clinical Management
Medical Vs. Surgical

25. Medical Management Successfully treats ½ to 2/3 of patients
Consult surgery from the start
Bowel rest - NPO, gastric decompression, TPN
Broad spectrum antibiotics for 7-14 days
Cardiopulmonary support
Correction of metabolic acidosis and electrolyte abnormalities
Treatment of coagulopathy and/or thrombocytopenia
Serial exams, labs, and x-rays

26. Signs Of Ongoing Necrosis
Increasing distension
Persistent:
Metabolic acidosis
Thrombocytopenia
Hypotension from third spacing

27. Indications for Surgical Intervention
Severe peritonitis
Pneumoperitoneum
Intra-abdominal abscess
Positive paracentesis findings (bile & stool)
Portal venous gas seen on X-ray

28. Surgical Management 34-50% of patients
Laparotomy with resection, formation of enterostomy and mucous fistula
Patch, drain, and wait
Primary peritoneal drainage
Eventual reanastomosis

29. Potential Complications
Short bowel syndrome
TPN-associated cholestasis with liver cirrhosis and liver failure
Catheter related sepsis
Intestinal strictures and partial small bowel obstruction
Enterocolic fistulas
Developmental and growth delay (50%)

30. Long-term Outcome: What’s Important?
Length of residual bowel
Ileum vs. jejunum (better adaptation)
Presence of ileocecal valve
Presence of intact colon
Maturity of infant and general condition

31. Survival Without Transplantation
Patients with > 25cm of normal bowel who have an intact ileocecal valve
Normal bowel length:
Term infants cm
Preterm infants cm
Patients with >40cm of normal bowel who have no ileocecal valve

32. Short Bowel Syndrome Fluid & electrolyte losses
Bile acid and Vit B12 malabsorption
Gastric acid hypersecretion inactivates pancreatic enzymes and causes fat malabsorption
Secretory diarrhea
Bacterial overgrowth
- Increases malabsorption, lactic acidosis, colitis, Vit B12 deficiency
Gastric acid hypersecretion is common in patients with SBS. The degree of hypersecretion is proportional to the degree of bowel resected. Hypersecretion may contribute to malabsorption by inactivating pancreatic enzymes and, thus, interfering with fat absorption. The usual treatment is with either H2 blockers or proton pump inhibitors.
The absence of normal physiologic mechanisms that increase intestinal transit, including the ileocecal valve and colon, also shortens intestinal transit time. However, if the existing small bowel or colon shows signs of dysmotility due to fibrosis or surgical narrowing, stagnant bowel contents may aggravate an existing bacterial overgrowth, thereby worsening malabsorption and diarrhea.
Extensive jejunal resection leads to carbohydrate malabsorption. The undigested foods produce an osmotic diarrhea typical of most patients with SBS. The proximal small bowel also is important in the absorption of proteins, fat, and certain micronutrients, including copper.
Extensive resection of the ileum may lead to severe malabsorption of bile salt and vitamin B-12. Bile salt malabsorption produces a choleretic diarrhea. Furthermore, bile salt depletion affects fat absorption, thereby worsening steatorrhea and fat-soluble vitamin malabsorption. Ileal resection leads to the malabsorption of bile salts and an abnormal bile acid pool that leads to the formation of a lithogenic bile and cholelithiasis.

33. Malabsorption Fat: Bacterial deconjugation of bile salts and acids
Protein and carbohydrates: enzyme and transport deficiencies
Vit B12: bacterial uptake

34. Sites of Nutrient Absorption
Duodenum: iron
Jejunum: Carbohydrates, proteins, fats and vitamins, copper
Ileum: Bile acids, Vit B12
The ileocecal valve is important in preventing bacterial overgrowth. Problems associated with proximal small-bowel overgrowth include deconjugation of bile salts and depletion of bile salt stores. Bacteria often compete for vitamin B-12, which may facilitate a pernicious anemia. Bacteria overgrowth also leads to carbohydrate malabsorption, worsening of osmotic diarrhea, and the risk of metabolic acidosis and dehydration. Treatment is generally aimed at lessening the degree of bacterial overgrowth with antibiotic therapy, including administration of metronidazole alternating with either kanamycin or oral gentamicin.

35. Short Gut: Symptoms Distension Diarrhea Cramping Weight loss
Anemia (occult blood loss, Vit B12 deficiency)

36. Treatment of Short Gut Syndrome
Promotion of villous hyperplasia:
Drip feedings using elemental formulas
Long-chain fats stimulate intestinal adaptation
MCT diet bypasses need for bile acids
Hydrolyzed proteins absorbed rapidly
Cholestyramine (bile acid binder)
Trimethoprim-sulfa, metronidazole treats bacterial overgrowth
Proton pump inhibitors or H2 blockers

37. Formulas
Elemental:
Require minimal digestive function and cause less pancreatic secretion
Individual amino acids or short peptides
Glucose polymers
Low fat (long chain triglycerides)
MCT absorbed in absence of lipase or bile salts

38. Monitoring Stool output for fluid losses
Carbohydrate malabsorption (low stool pH or stool reducing substances)
Anticipate slow gut adaptation over years
Weight gain and growth

39. Lengthening Procedures

41. Prevention of NEC Prenatal steroids
Correction of hypovolemia and hyperviscosity
Slow, gradual advancement of feeds
Breastfeeding
Probiotics - Oral immunoglobulins and
bifidobacterium?
Oral antibiotics?
Acidification of feedings (avoidance of PPIs and H2 blockers)?
Glutamine or arginine supplemenation?
Probiotics work through a variety of mechanisms to produce several positive clinical effects (Table 3). These "good" microorganisms can produce antibiotic molecules that directly influence proliferation of pathologic organisms. They can prevent pathologic bacterial colonization by competing for the same sugar glycoconjugate on the epithelial surface, and they can metabolize nutrients into volatile fatty acid and chemically modified bile acids that, in turn, create a local environment that is generally unfavorable for the growth of many enteric pathogens. Their attachment to the intestinal epithelium can strengthen the host’s mucosal defenses through enhancement of secretory antibody responses, tightening of the mucosal physical barrier to microorganism translocation, and creation of a balance in T-helper cell response.

42. Trophic Feedings No increased risk of NEC Increases gut motility
Reduces cholestasis
Improves tolerance of subsequent feedings
May prevent gut atrophy, inflammation, and bacterial translocation