This document provides information on necrotizing enterocolitis (NEC), including:
- NEC is an acquired intestinal necrosis of unknown etiology that mainly affects premature infants.
- Risk factors include prematurity, formula feeding, and circulatory instability. The immature gut is more susceptible to infectious agents and inflammatory mediators that can lead to necrosis.
- Clinical presentation ranges from nonspecific symptoms to shock. Diagnosis involves lab tests and imaging showing findings like pneumatosis intestinalis. Treatment involves stopping feeds, antibiotics, and surgery for complications like perforation. Surgical interventions aim to remove necrotic bowel while preserving intestinal length.
3. Epidemiology:
Epidemiology
Incidence: 0.3-2.4 /1000 live births
2.5% of all NICU admissions
5-10% of VLBW infants
over 90 % of cases occur in preterm babies.
About 10 % occur in term newborns:essentially
limited to those having some underlying illness or
condition requiring NICU admission.
4. Epidemiology
Sporadic or epidemic clusters
Sex,race,geography,climate,season: no role
male VLBW infants are at a greater risk of death.
Black infants: increased Risk of NEC , and its
associated mortality.
5. Prematurity is the single greatest risk factor
The risk is inversely related to birth weight and
gestational age.
6. Familial
Twins
Gene polymorphism
VEGF( VASCULAR ENDOTHELIAL GROWTH
FACTOR): VEGF G + 450polymorphism might be
associated with a higher risk of preterm birth and
that VEGF C-2578A polymorphism may participate
in the development of perinatal complications
such as NEC and ARF.
7. G-6-PD deficiency
Indomethacin:
Metaanalysis 2007 showed that recent exposure
to indomethacin was associated with NEC.
Indomethacin in early life :associated withSIP.
DEXAMETHASONE
H2 BLOCKERS
Co –amoxiclav
Acyclovir
8. Maternal cocaine abuse:
It is very potent vasoconstrictor
Prenatal exposure increase risk of NEC by 2.5 times.
Greater need for surgical intervention(72%) , higher
incidence of gangrene(54%) , higher mortality(54%) in
infants with prenatal cocaine exposure.
9. A.Initiation of disease
1. Impaired gut barrier
2. Infectious agent
3. Circulatory instability
B.Progression of disease
10. A-initiation of disease
1-impaired gut barrier
Preterm GI tract is characterized by
Immature immunity
Increase permeability
Reduce gastric acid secretion
Reduce proteolytic enzyme
Decrease motility
Immaturity of intestinal epithelium and microivilli.
11. 2- infectious agents
Breast feed infant colonized predominantly with
bifidobacteria (gram+)
It control growth of (gram -) bacteria
Formula feed infants colonized with coliforms,
enterococci.
13. 3-Circulatory Instability
Hypoxic-ischemic injury
Due to
fetal distress,
perinatal asphyxia,
respiratory distress syndrome
Hypothermia
It causes
poor blood flow to the mesenteric vessels
local rebound hyperemia with re-perfusion
production of O2 radicals
16. On initiation of the pathologic process of NEC ,
cellular communication through inflammatory
mediator result in a multitude of events, cause
end -organ damage seen in NEC.
Inflammatory mediators involved in development
of bowel injury and sytemic side effects.
17. 1- Epidermal growth factor
Secreted by salivary glands , brunner gland of
duodenum , breast milk
It is protective and trophic factor for developing GI
tract
Reduced levels of EGF found in Premature infant
18. 2- Erythropoietin (Epo)
Produced by kidney
Found in breast milk
Trophic factor in developing GI tract
Decreased levels found in premature infants
Intraperitoneal injection of recombinant Epo resulted in
decreased mucosal inflammation and necrosis.
19. 3 -Cytokines
Proinflammatory cytokines
IL-1, IL-2, IL-6, IL-8, IL-12,
Anti-inflammatory
IL-4, IL-10, IL-11,
Produced by intestinal endothelial cells, mucosal fibroblasts,
enterocytes.
Higher levels of proinflammatory cytokines found in patients
of NEC
20. 4- Nitric Oxide
Produced from arginine by nitric oxide synthase
Functions of NO
Maintenance of mucosal integrity
Regulation of mucosal permeability and blood flow
Regulation of motility
Inhibition of leukocytes adhesion and activation
21. 5 -TNF-α
Proinflammatory effect
Neutrophil activation
Induction of leukocytes and endothelial adhesion
molecules
Induction of other cytokines
22. 6- LPS(endotoxin)
Bacterial product
Activation of cytokines
Produce hypotension, shock and intestinal necrosis
Mediated by PAF and TNF-α
23. 7- Cyclooxygenase (cox)
Two forms:
Constitutive form(cox-1) in GI tract have protective role
Inducible form(cox-2)
24. Onset varies with gestational age
VLBW – 14-20 days
Term - first week
Course of disease
Fulminant presentation
Slow, paroxysmal presentation
29. Sudden Onset:
1. Full term or preterm
infants
2. Acute deterioration
3. Respiratory
decompensation
4. Shock/acidosis
5. Marked abdominal
distension
6. Positive blood culture
Insidious Onset:
1. Usually preterm
2. Evolves during 1-2 days
3. Feeding intolerance
4. Change in stool pattern
5. Intermittent abdominal
distention
6. Occult blood in stools
30.
stage Systemic signs Intestinal signs Radiological signs
1 suspected
A
Temperature
instability,
bradycardia,apnoea
Elevated gastric
residuals,mild
abdominal
distension,occult
blood in stool
Normal or mild ileus
B
Same as 1A Same as 1A plus gross
blood in stool
same as 1A
2 definite
A mildly ill
same as 1A same as 1A plus
absent bowel sound
and abdominal
tenderness
ileus, pneumotosis
intestinalis
31. stage Systemic signs Intestinal signs Radiological signs
2
B – moderately
ill
Same as 1 plus
metabolic acidosis
mild
thrombocytopenia
same as1 plus absent
bowel sound,
abdominal
tenderness,abdominal
cellulitis, mass
Same as 2A plus
portal venous gas with
or without ascites
3 advanced
A- severely ill
bowel intact
Same as 2B plus
hypotension,bradycar
dia,metabolic
acidosis,DIC ,
neutropenia
Same as 2 plus
generalized
peritonitis,marked
tenderness,
abdominal distension
Same as 2B plus
Definite ascites
B- severely ill
bowel
perforated
same as 3A same as 3A Same as 2B plus
pneumoperitoneum
32. A high index of suspicion is required
Sometimes cannot be differentiated from sepsis
33. No lab test is specifiC for NEC
THE MOST COMMON TRIAD(!)
Thrombocytopenia
Persistent metabolic acidosis
Severe refractory hyponatremia
WBC-raised / decreased levels
Hyperkalemia
Stool:reducing substances, occult blood.
34. C-Reactive Protein
Early indicator of NEC
Sensitivity- 99%, Specificity- 81%
Level raises> 10 mg/l within 48 hrs of suspected
diagnosis.
Failure of CRP to return normal in 10 days is an
indicator of abscess, stricture, septicemia.
35. Abdominal X- ray:
AP supine
Left lateral decubitus
Suggestive findings
1. abnormal gas pattern, ileus
2. Bowel wall oedema
3. Pneumoperitoneum(left lateral decubitus)
4. Intrahepatic portal venous gas(in absence of UVC)
5. fixed configuration of bowel loops over serial
films(every 6 to 8 hour)for 24 to 36 hours.
38. portal venous gas (PVG)
• linear branching lucencies over liver
• more peripheral than biliary gas
• It represent the gas dispersed through
fine radicals of the portal venous system
• In 10 to 30% of cases
• Associated with poor prognosis
• 61% in pan necrosis
40. Pneumoperitoneum
free air in the peritoneal cavity secondary to
perforation
In 12% to 30% of cases
Best noted in left lateral view
Air on both sides of bowel wall(rigler sign or double wall
sign)
Outline of falciform ligament(football sign)
Surgical emergency
42. Intraperitoneal fluid
Grossly distended abdomen devoid of gas
Gas filled loops in center surrounded by opacity in
flanks
Increase haziness within the abdomen
Separation of bowel loops
In 11% cases
Associated with high mortality
43. DIAGNOSIS,RADIOLOGICAL STUDIES
ABDOMINAL Ultrasonography-
Used in case of distended and gasless abdomen
1. Thickened bowel loops
2. Increased or decreased vascularity
3. Intraperitoneal fluid
4. Portal venous air
5. Hypoechoic ring with central echogenic focus (target sign )
suggests abnormal bowel loop
6. Pericholecystic hyperechogenecity
44. CT scan
Not typically used for diagnosis
1. Bowel wall thickened with increased or decreased bowel
wall enhancement.
2. Pneumatosis, free air, PVG, ascites
45. Contrast studies
Upper GI contrast study
Use water soluble contrast agent
Barium should never be used
Contrast enema should never be performed –risk of
rectosigmoid perforation.
Finding
1. Bowel loops separated by edematous wall
2. An irregular mucosa with ill defined margins
3. Mucosal ulceration
4. Bowel wall spiculations
5. Pnuematosis intestinalis
46. Gross
Bowel is markedly distended with patchy areas of
thining.
Serosal surface red to gray
With frank gangrene serosal surface is black
Subserosal gas collection
Mucosal surface is ulcerated with areas of
epithelial sloughing
49. Microscopic
Acute and chronic inflammatory changes coexist in 60% of
cases
Coagulative necrosis of mucosa(89%)
Edema and hemorrhage of submucosa
Pneumatosis intestinalis in submucosa and muscularis and
subserosa later.
50. Bacteria in bowel lumen and wall in 40% of cases
Transmural necrosis in advancd cases
Granulation tissue with mucosal and submucosal
fibrosis
Small vessel thrombosis
51. Non operative
In the absence of necrosis or perforation the mainstay of
treatment is supportive.
Feedings are stopped (NPO)
Nasogastric tube decompression
i.v fluid
Central venous access for parenteral nutrition
Broad spectrum antibiotics for 7 to 14 days
52. Ampicillin(50mg/kg/day), gentamicin
(5mg/kg/day)and clindamycin(10mg/kg/day)
vancomycin (15mg/kg/day),third generation
cephalosporin (100mg/kg/day)with
metro(15mg/kg/day)
Close clinical observation
Frequent physical examination
Abdominal x-ray every 6 to 8 hour
53. Enteral feeding withheld for 10 to 14 days after
radiological evidence of disease has abated.
After resumption of feeding stools are tested for occult
blood and reducing substances
Feeding discontinued if result is positive
Feeding volume increase slowly
55. Indications of surgery
A- best indicator
1- pneumoperitoneum
2- positive paracentesis
3- portal venous gas
Specificity and positive predictive value about 100%
Aspiration of >o.5 ml brown or yellow fluids defined as
positive paracentesis
56. B- good indicator
1- fixed intestinal loop
2- erythema of abdominal wall
3- palpable abdominal mass
4- pneumatosis intestinalis
Specificity and PPV <100%
58. Operative methods
1- primary peritoneal drainage
For unstable patients >1500g
Use in patients <1500g with perforation
It allow resuscitation and stabilization before definitive
laparotomy.
Performed at bedside with local anesthesia
Placement of drain in right lower quadrant
59. 2- laparotomy
Incision- Rt transverse supraumblical
Sample of peritoneal fluid may be taken for culture.
Assess
extent of disease
Focal, multifocal (>50% viable) , pan necrosis(<25% viable)
Viability of bowel
60. 1 – focal disease
When a single area of bowel is necrotic or perforated
Proximal enterostomy and distal mucus fistula
Perforation repair
Resection and primary anastomosis in carefully selected
patients
A sharply localized disease
Undamaged remaining intestine
A good overall patient condition
61. 2- multifocal disease
A -Resection and anastomosis
B – a proximal jejunostomy created and distal bowel
spliced together
C – Moore described ‘ patch, drain and wait procedure
in 1989.
This involves-
Transverse single layer suture approximation of
perforation(patch)
Insertion of two drains in lower quadrant.
Long term parenteral nutrition
62. D-’clip and drop method’
Described by Vaughan et al.
Necrotic bowel removed and the cut ends are closed with
titanium clips or staples.
Re-exploration is performed 48 to 72 hour later
Clips removed and all segments are reanastomosed without
any stoma.
63. 3 – pan involvement (NEC totalis)
In 19% of patients
A- resection of all necrotic bowel with proximal or multiple
stomas.
B – proximal diversion without bowel resection with second
look procedure after 6 to 8 weeks.
64. Stoma closure
There is neither an ideal weight nor age for stoma
closure.
Enterostomy may be safely closed anytime after 4
weeks since last operation.
Before closure patency of distal end should be
confirmed by contrast study.
66. Long term Complication of NEC
Occurs in 50% of cases
1 – intestinal strictures
9% to 36% incidence
More frequent after nonoperative treatment
Colon (80%)
Terminal ileum(15%)
Splenic flexure – most common site.
Multiple strictures- 21%
Failure to thrive, rectal bleeding bowel obstruction after non
operative treatment suggest stricture
67. 2 – malabsorption and short bowel syndrome
-Occur in 23% cases
Due to
Decreased bowel length
Decreased mucosal area
Enzyme depletion
Gut hypermotility
Hypersecretion of gastric acid
Decreased intestinal transit time
Bacterial overgrowth
Vit. B 12 deficiency
68. 3 – cholestatic liver disease
4 – recurrent NEC-4% to 6% incidence
5 – anastomotic ulceration
Lower GI bleeding
Diagnosed by colonoscopy
Treatment-Ulcer resection
69. Prevention
1 – infection control measures in nursery
Proper hand washing
Use of gloves and long sleeved gown
Separate diaper and laundry bag for each patient
Isolation of confirmed cases
70. 2 – oral immunoglobulins
IgA deficient in premature gut
It act as an antiseptic paint by binding the bacteria and
prevent attachment to the intestinal mucosa
Enteral administration of IgA preparation decreases the
incidence of NEC
71. 3 – breast milk
breast milk may have a protective effect
IgA
macrophages, lymphocytes
complement components
lysozyme, lactoferrin
Acetylhydrolase
Interferon
EGF
Erytheropietin
Probiotics
72. 4 - Maternal glucocorticoid
Accelerate mucosal cell maturation
improve gut barrier function
Down regulation of inflammatory response
5 – feeding practices
For premature infants given a hypocaloric formula at a
slow rate
73. 6 – administration of probiotics
‘ live microbial supplements that colonize the gut to provide
benefit to host
Use of probiotics (bifidobactetria) decrease the incidence of
NEC
.