Necrotizing enterocolitis is an acquired intestinal disease of unknown etiology that commonly affects premature infants. The main risk factors are prematurity, genetic factors, maternal health conditions like cocaine use, medications like indomethacin and dexamethasone, and certain enteral feeding practices. The pathogenesis involves an initial hypoxic-ischemic insult to the intestine combined with microbial factors and an excessive inflammatory response that can lead to necrosis of the intestinal tissue. Timely diagnosis and management are important for improving outcomes.

1. NECROTIZING
ENTEROCOLITIS
By
AYMAN ABOU MEHREM, MD, CABP
Assistant Consultant
Department of pediatrics
King Abdulaziz Hospital, Al-Ahsa
November 25, 2007

2. Necrotizing Enterocolitis
Definitions
Epidemiology
Risk Factors
Pathogenesis
Pathophysiology
Clinical Presentation
Diagnosis
Management
Prognosis
Prevention

3. Definitions
Necrotizing Enterocolitis:
an acquired neonatal acute intestinal necrosis
of unknown etiology
NEC is neither a uniform nor a well-defined
disease entity.1
1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's
criteria?, J Perinatol. 2007 Nov;27(11):661-71.

4. Definitions
Isolated spontaneous intestinal perforation
(SIP): ill-defined clinical syndrome of undetermined
cause resembling NEC with less systemic involvement
and a less severe clinical course. It may present a variant
of classical NEC.
The National Institute of Child Health and Human
Development Neonatal Network (NICHD): intestinal
perforation without evidence of pneumatosis since 2002.1
1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's
criteria?, J Perinatol. 2007 Nov;27(11):661-71.

5. Definitions
Acquired neonatal intestinal diseases (ANIDs)1
Wider umbrella includes different pathologies affecting
gastrointestinal tract in preterm and term infants. Some
which do lead to the common final pathology of NEC and
some which do not.
Includes:
NEC
SIP
Viral enteritis of infancy
Cow’s milk protein allergy
1 Gordon PV et al, Emerging trends in acquired neonatal intestinal disease: is it time to abandon Bell's
criteria?, J Perinatol. 2007 Nov;27(11):661-71.

6. 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 that have some underlying illness or
condition requiring NICU admission.2
2 Lambert DK et al. Necrotizing enterocolitis in term neonates: data from a multihospital health-care
system . J Perinatol. 2007 Jul;27(7):437-43 .

7. Epidemiology
Sporadic or epidemic clusters
Sex, race, geography, climate, season: No role
Holman et al.3:
o Male VLBW infants are at greater risk of death.
o Black infants: increased risk of NEC, and its
associated mortality
3 HolmanRC et al. The epidemiology of necrotizing enterocolitis infant mortality in the United States.
Am J Public Health 1997; 87: 2026–31.

8. Risk Factors: Prematurity
Prematurity is the single greatest risk
factor
The risk is inversely related to birth
weight and gestational age.4
4 LinPW, Stoll BJ. Necrotizing enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83.
5 Czyrko C et al. Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival. J Pediatr
Surg. 1991 Apr;26(4):414-8; discussion 419-21.

9. Risk Factors: Genetics
Familial:
Fried and Vure (1974) reported a consanguineous Jewish
Ashkenazi family in which three of four children died
within a few weeks after birth from severe enterocolitis.5
Mégarbané and Sayad (2007) reported a Lebanese
consanguineous family where three term sibs presented
with severe early and lethal enterocolitis, all with delayed
meconium passage.6
5 FriedK, Vure E. A lethal autosomal recessive entero-colitis of early infancy. Clin Genet 1974 (6),
195-196.
6 Mégarbané A, Sayad R. Early lethal autosomal recessive enterocolitis: report of a second family. Clin
Genet. 2007 Jan;71(1):89-90.

10. Risk Factors: Genetics
Twins:
Bhandari et al, in a multicenter retrospective study of
450 twin pairs born at < or =32 weeks of gestation,
showed that intraventricular hemorrhage,
necrotizing enterocolitis, and bronchopulmonary
dysplasia are familial in origin.7
7 Bhandari et al. Familial and genetic susceptibility to major neonatal morbidities in preterm twins.
Pediatrics. 2006 Jun;117(6):1901-6.

11. Risk Factors: Gene Polymorphism
Vascular endothelial growth factor:
Bányász et al suggest that VEGF G+405C polymorphism 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.8
Carbamoyl phosphate synthetase:
Moonen et al suggested that the CPS1 T1405N polymorphism may
be associated with the risk of NEC in preterm infants.9
8 Bányász et al. Genetic polymorphisms for vascular endothelial growth factor in perinatal
complications. Eur Cytokine Netw. 2006 Dec;17(4):266-70.
9 Moonen RM et al. Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing
enterocolitis. Pediatr Res. 2007 Aug;62(2):188-90.

12. Risk Factors: G-6-PD Deficiency
Schutzman and Porat, in a retrospective study10, found:
G6PD deficiency was significantly higher (27.8%) in
infants with NEC compared with the 5.3% prevalence
among NICU admissions (odds ratio = 6.9; 95%
confidence interval = 2 to 23.5).
G6PD deficiency also was found to be a marker for more
severe NEC.
G6PD deficiency should be considered a risk factor for
NEC.
10 Schutzman DL, Porat R. Glucose-6-phosphate dehydrogenase deficiency: another risk factor for
necrotizing enterocolitis?. J Pediatr. 2007 Oct;151(4):435-7.

13. Risk Factors: Cocaine
Maternal cocaine abuse increases the risk by
2.5 folds (95% CI = 1.17 to 5.32, P = 0.02) 11
11 CzyrkoC et al. Maternal cocaine abuse and necrotizing enterocolitis: outcome and survival. J
Pediatr Surg. 1991 Apr;26(4):414-8; discussion 419-21.

14. Risk Factors: Indomethacin
Indomethacin for Tocolysis: Metaanalysis 2007
Recent exposure (within 48 hours of delivery) to
antenatal indomethacin was associated with
necrotizing enterocolitis (OR, 2.2; 95% CI; 1.1-4.2). 12
Some limitations.
12 AminSB et al. Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. Am J
Obstet Gynecol. 2007 Nov;197(5):486.e1-10.

15. Risk Factors: Indomethacin
Indomethacin in Early Life:
Associated with SIP 13
Prolonged versus Short Course of Indomethacin for the
treatment of PDA in preterm infants: Systematic Review 14
o The reduction of transient renal impairment does not outweigh the
increased risk of NEC associated with the prolonged course.
o Based on these results, a prolonged course of indomethacin cannot
be recommended for the routine treatment of PDA in preterm
infants.
13 Schmidt B et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.
N Engl J Med 2001; 344: 1966–1972.
14 Herrera C et al. Prolonged versus short course of indomethacin for the treatment of patent ductus
arteriosus in preterm infants. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD003480.

16. Risk Factors: Dexamethasone
Paquette et al showed that the combined use of
indomethacin and dexamethasone increases the
risk of SIP in VLBW neonates. 15
15 Paquette et al. Concurrent use of indomethacin and dexamethasone increases the risk of spontaneous
intestinal perforation in very low birth weight neonates. J Perinatol. 2006 Aug;26(8):486-92.

17. Risk Factors: H2-Blockers
Guillet et al, in large case control study using
NICHD Neonatal Research Network, showed
that “Antecedent H2-blocker use was associated
with an increased incidence of NEC.
(OR 1.71, 95% CI 1.34-2.19, P < .0001) 16
16 Guillet
R et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in
very low birth weight infants. Pediatrics. 2006 Feb;117(2):e137-42.

18. Risk Factors: Co-amoxiclav
Kenyon et al. in a Systematic Review:
Co-amoxiclav should be avoided in women at
risk of preterm delivery because of the increased
risk of neonatal necrotising enterocolitis. 17
(RR 4.60, 95% CI 1.98 to 10.72)
17 KenyonS et al. Antibiotics for preterm rupture of membranes . Cochrane Database Syst Rev.
2003;(2):CD001058 .

19. Risk Factors: Acyclovir
Montjaux-Régis et al, case report: 18
Term baby, developed NEC after receiving
prophylactic acyclovir.
Mother had herpes genitalis and pROM at 32 wks of
GA, treated with acyclovir until vaginal delivery.
Acyclovir treatment in utero and after birth is
discussed as a possible cause of necrotizing
enterocolitis in the infant.
18 Montjaux-RégisN et al. Necrotizing enterocolitis in a full-term infant. Is acyclovir involved?. Arch
Pediatr. 2007 Oct 10.

20. Risk Factors: Kayexalate
Rugolotto et al., case report: 19
Necrotizing enterocolitis in a 850 gram infant
receiving sorbitol-free sodium polystyrene sulfonate
Their case report shows that Kayexalate per se, and
not necessarily suspended in sorbitol, can lead to
gastrointestinal tract complications and NEC in
preterm infants.
19 RugolottoS et al. Necrotizing enterocolitis in a 850 gram infant receiving sorbitol-free sodium
polystyrene sulfonate (Kayexalate): clinical and histopathologic findings. J Perinatol. 2007
Apr;27(4):247-9.

21. Risk Factors: UAC
Rand et al. suggested that UAC cause a decrease in mesenteric blood
flow. Therefore, their use in hemodynamically unstable neonates or
in those with gastrointestinal disease should be very carefully
considered. 20
High vs. low UAC: necrotising enterocolitis are not more frequent
with high compared to low catheters. 21
Havranek et al.: Preprandial SMA BFV and postprandial SMA BFV
responses to minimal enteral feedings were not affected by the
presence of a UAC. 22
20 Rand T et al. Effects of umbilical arterial catheterization on mesenteric hemodynamics. Pediatr
Radiol. 1996 Jul;26(7):435-8.
21 Barrington KJ. Umbilical artery catheters in the newborn: effects of position of the catheter tip.
Cochrane Database Syst Rev. 2000;(2):CD000505.
22 Havranek T et al. Umbilical artery catheters do not affect intestinal blood flow responses to minimal
enteral feedings. J Perinatol. 2007 Jun;27(6):375-9.

22. Risk Factors: UVC
Butler-O'Hara et al. compared long-term (up to 28
days) and short-term (7-10 days) use of umbilical venous
catheters in premature infants with birth weights of less
than 1251 grams. 23
There were no differences in time to full feedings or to
regain birth weight or in the incidence of necrotizing
enterocolitis or death.
23 Butler-O'HaraM et al. A randomized trial comparing long-term and short-term use of umbilical
venous catheters in premature infants with birth weights of less than 1251 grams. Pediatrics. 2006
Jul;118(1):e25-35.

23. Risk Factors: PDA
Patole et al., in prospective observational study,
reported that: 24
No association between significant PDA and NEC.
The age at starting feed and full enteral feed was
significantly delayed in infants with significant PDA.
24 Patole
SK et al. Does patent ductus arteriosus affect feed tolerance in preterm neonates?. Arch Dis
Child Fetal Neonatal Ed. 2007 Jan;92(1):F53-5.

24. Risk Factors: in Term Babies
Limited to those that have some underlying
illness or condition requiring NICU admission.2
Congenital Heart Disease
Intrauterine growth restriction
Polycythemia
Hypoxic-ischemic events
2 Lambert DK et al. Necrotizing enterocolitis in term neonates: data from a multihospital health-care
system. J Perinatol. 2007 Jul;27(7):437-43.

25. Risk Factors: Exchange Transfusion
Dempsey and Barrington in a Systematic Review 25
showed:
There is no evidence of long term benefit from partial exchange
in polycythaemic infants.
The incidence of gastrointestinal injury is increased.
NEC (RR 8.68; 95% CI 1.06 to 71.1)
25 Dempsey EM, Barrington K. Short and long term outcomes following partial exchange transfusion in
the polycythaemic newborn: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2006
Jan;91(1):F2-6.

26. Pathogenesis

27. Pathophysiology
Hypoxic-Ischemic insult
Enteral Feeding
Microbiologic Flora
Cytokines and Inflammatory Mediators

28. Hypoxic-ischemic insult
Hypoxia-Reoxygenation.
Ischemia-Reperfusion.
Intramural microcirculation.
Balance between Endothelin-1 and Nitric Oxide.26
26 NowickiPT. Ischemia and necrotizing enterocolitis, Where, when, and how. Seminars in Pediatric
Surgery (2005) 14, 152-158.

29. Enteral Feeding
Formula vs. Donor Breast Milk: 27, 28
Formula is associated with higher risk of
NEC
27 Quigley M et al. Formula milk versus donor breast milk for feeding preterm or low birth weight
infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971.
28 Boyd CA et al. Donor breast milk versus infant formula for preterm infants: systematic review and
meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F169-75.

30. Enteral Feeding
Disadvantages of Formula:
Higher osmolality ±
Lack of immunoprotective factors
Lack of growth factors
Altering intestinal flora

31. Microbiologic Flora and Infection
Several organisms have been accused, but non has
been proven to be causative:
Enterobacteriaceae
Enterobacter sakazakii
Coagulase-negative staphylococci: SIP
Closrtidium perfringens
Candida species: SIP
Cytomegalovirus
Torovirus
HIV
Mucormycosis

32. Cytokines and Inflammatory Mediators
Platelet Activating Factor (PAF)
Tumor Necrosis Factor (TNF)
High-mobility group box 1 protein (HMGB 1)
Interferon-gamma (INF-gamma)
Interleukins (ILs)
Matrix metalloproteinases (MMPs)

33. Inflammatory cascade. The inflammatory cascade results in the secretion of multiple
proinflammatory and counterregulatory cytokines that eventually lead to the generation of
toxic metabolites and destruction of the intestinal mucosa.
29 Markel TA et al. Cytokines in necrotizing enterocolitis. Shock. 2006 Apr;25(4):329-37.

34. Pathophysiology, in summary
Ischemic or toxic mucosal Enteral feeding
damage
Loss of mucosal integrity Bacterial proliferation
Invasion of mucosa and submucosa
Intramural gas
Transmural necrosis
Perforation
Peritonitis

35. Pathology
Closeup of intestine of infant showing necrosis and
pneumatosis intestinalis. Autopsy

36. Pathology
Postmortem photograph of bowel involved with severe NEC. The arrows indicate areas of the bowel
wall where there has been so much necrosis and sloughing of the mucosa, submucosa, and muscularis
that only the serosa is intact.
30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with
pathologic correlation. RadioGraphics 2007; 27:285–305.

37. Pathology
NEC induced by an intravenous injection of
PAF in a rat model

38. Pathology
Microscopic images of (A) normal bowel and (B) characteristic findings of
NEC, which illustrates hemorrhagic necrosis, beginning in the mucosa and
extending to the muscular bowel wall, where the potential for perforation exists.
NEC frequently involves the terminal ileum. Reprinted with permission from
WebPath, courtesy of Edward C. Klatt, MD, Florida State University College of
Medicine, Tallahassee, FL (http://medlib.med.utah.edu/WebPath).

39. Pathology
Parietal ileal pneumatosis in neonatal necrotizing
enterocolitis

40. Clinical Presentation
Onset varies with gestational age
VLBW 14 – 20 days
Term first week
Course of the disease
Fulminant presentation
Slow, paroxysmal presentation

41. Clinical Presentation
Systemic signs:
Respiratory distress, apnea, bradycardia
Lethargy, irritability
Temp. instability
Poor feeding
Hypotension
Acidosis
Oligurea
Bleeding diathesis

42. Clinical Presentation
Abdominal (enteric) signs:
Distension
Tenderness
Gastric aspirate, vomiting
Ileus
Abdominal wall erythema, induration
Ascites
Abdominal mass
Bloody stool

43. Clinical Presentation

44. Diagnosis
A high index of suspicion is required
Sometimes cannot be differentiated from
sepsis

45. Diagnosis, Laboratory studies
No lab test is specific for NEC
The most common triad (!):
Thrombocytopenia
Persistent metabolic acidosis
Severe refractory hyponatremia
↑ WBC, ↓ WBC, ↓ PMN
Hyperkalemia
Stool: reducing substances, occult blood

46. Diagnosis, Radiologic studies
Abdominal X-ray:
Abnormal gas pattern, ileus
Bowel wall edema
Pneumatosis intestinalis
Fixed position loop
Intrahepatic portal venous gas ( in the absence of
UVC)
Pneumoperitonium, left lateral decubitus or cross-
table lateral views

47. Diagnosis, Radiologic studies
Supine radiograph of the
abdomen of a normal
neonate shows a normal
bowel gas pattern. Gas is
distributed throughout the
small and large bowel, and it
is difficult to differentiate the
small bowel from the large
bowel. Each loop causes
impressions on adjacent
loops, giving each loop a
multifaceted appearance; the
overall pattern resembles that
of a mosaic. The loops are
generally not rounded or
elongated.
30Epelman M et al. Necrotizing
enterocolitis, review of state-of-the-
art imaging findings with pathologic
correlation. RadioGraphics 2007;
27:285–305.

48. Diagnosis, Radiologic studies
Pneumatosis intestinalis.
Very obvious case.
Tremendous amount of
air in bowel walls
Reference:
Radiology Cases In Neonatology
Copyright 1996, Loren Yamamoto

49. Diagnosis, Radiologic studies
Pneumatosis intestinalis.
Note the air visible in
the bowel wall. The air
dissects the bowel wall
giving it a double lined
appearance (ie., railroad
tracks without the ties)
Reference:
Radiology Cases In Neonatology
Copyright 1996, Loren Yamamoto

50. Diagnosis, Radiologic studies
Pneumatosis intestinalis

51. Diagnosis, Radiologic studies
Supine AXR, The bowel is mildly dilated with gas, mainly on the left side. The bubbly pattern of
gas seen mainly in the right lower quadrant represents intramural gas.
30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with
pathologic correlation. RadioGraphics 2007; 27:285–305.

52. Diagnosis, Radiologic studies
Free intraperitoneal gas is present anteriorly (arrows)
30 Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with
pathologic correlation. RadioGraphics 2007; 27:285–305.

53. Diagnosis, Radiologic studies
NEC with perforation

54. Diagnosis, Radiologic studies
Left lateral decubitus radiograph shows free air
Ref: Necrotizing Enterocolitis, emidicine.com, Beverly P Wood, MD, MS, PhD

55. Diagnosis, Radiologic studies
Abdominal ultrasound:
Thick-walled loops of bowel with hypomotility.
Intraperitoneal fluid is often present.
Intramural gas can be identified in early-stage NEC 31
In the presence of pneumatosis intestinalis, gas is
identified in the portal venous circulation within the
liver.
Color Doppler US is more accurate than abdominal
radiography in depicting bowel necrosis in NEC. 32
31 Kim WY et al. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr
Radiol. 2005 Nov;35(11):1056-61.
32 Faingold R et al. Necrotizing Enterocolitis: Assessment of Bowel Viability with Color Doppler US,
Radiology 2005;235:587-594.

56. Diagnosis, Radiologic studies
Sonogram of a bowel loop shows differentiation of intraluminal gas from intramural gas.
The intraluminal gas (L) is surrounded by a thickened bowel wall. Within the bowel wall
are multiple hyperechoic foci (arrows), which represent intramural gas.
30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with
pathologic correlation. RadioGraphics 2007; 27:285–305.

57. Diagnosis, Radiologic studies
Sonogram shows a bowel loop with a large amount of intramural gas (arrows) in the more
dependent and vertically oriented parts of the loop. This gives the bowel wall a typical
granular appearance and causes a posterior artifact.
30Epelman M et al. Necrotizing enterocolitis, review of state-of-the-art imaging findings with
pathologic correlation. RadioGraphics 2007; 27:285–305.

58. Diagnosis, Radiologic studies
Abdominal Doppler ultrasound:
Murdoch et al., in a prospective cohort study,
concluded that neonates with high resistance patterns
of blood flow velocity in the superior mesenteric
artery on the first day of life are at increased risk of
developing necrotizing enterocolitis. 33
33 Murdoch EM et al. Doppler flow velocimetry in the superior mesenteric artery on the first day of life
in preterm infants and the risk of neonatal necrotizing enterocolitis. Pediatrics. 2006
Nov;118(5):1999-2003.

59. Modified Bell’s Staging Criteria
Stage I : Suspected NEC
Clinical signs and symptoms
No diagnostic radiograph

60. Modified Bell’s Staging Criteria
Stage II : Definite (confirmed) NEC
A: Mild NEC
• Sign & symptoms, absent B/S, gross blood in stool
• AXR: ileus, focal areas of pneumatosis intestinalis
B: Moderate NEC
• Systemically ill
• AXR: extensive pneumatosis intestinalis, early
ascites, possible intrahepatic portal venous gas

61. Modified Bell’s Staging Criteria
Stage III: Advanced NEC
A: Severe NEC without perforation
• Critically ill
• Abdominal wall induration, extensive erythema
• AXR: prominent ascites, paucity of bowel gas,
persistent fixed loop
B: Severe NEC with perforation

62. Differential Diagnosis
Systemic infection: sepsis, pneumonia
Surgical abdominal catastrophes
Infectious enterocolitis
Allergic collitis
Feeding intolerance

63. Management
The main principle of management of
confirmed NEC is to treat it as an acute
abdomen with impending or septic
peritonitis
Isolation: cohort isolation in case of
epidemic clusters

64. Management, Medical
Basic NEC protocol: for all stages
NPO
NGT with low pressure suction
Close monitoring of vital signs & abdominal girth
Remove UAC and UVC
Septic workup: blood, urine, and stool cultures
LP and CSF culture: controversial
Antibiotics: ampicillin + gentemicin or cefotaxime
add metronidazole or clindamycin if peritonitis or
perforation is suspected

65. Management, Medical
Basic NEC protocol …..continued
Monitor for GI bleeding
Fluid balance: maintain urine output 1-3 ml/kg/hr
Lab.: CBC, PLT, electrolytes q 8-12 hrs
PT, PTT, LFT’s as indicated
CRP 34
Radiology: serial AXR q 6-8 hrs in the first 2-3 days
Family support
34 Pourcyrous M et al. C-reactive protein in the diagnosis, management, and prognosis of neonatal
necrotizing enterocolitis. Pediatrics. 2005 Nov;116(5):1064-9.

66. Management, Medical
Stage I
Basic NEC protocol
If all cultures are negative, the infant improved
clinically, and AXR is normal, antibiotics can
be stopped after 2-3 days and feeding can be
resumed.

67. Management, Medical
Stage II
Basic NEC protocol
NPO for 14 days
TPN, 90-110 kcal/kg/day
Antibiotics for 14 days
Respiratory support
± Inotropic support
Surgical consultation

68. Management, Medical
Stage III
As stage II
Inotropic support
Treat anemia, thrombocytopenia,
coagulopathy
Surgical intervention

69. Management, Surgical
Early Surgical Consultation
Indications for surgery:
Perforation: 20-30 % of cases
12-48 hrs after onset
Full-thickness necrosis
Deterioration despite aggressive medical treatment

70. Management, Surgical
Surgical Approach:
Exploratory laparotomy
Peritoneal drainage

71. Management, Surgical
Exploratory laparotomy:
The most commonly used approach.
Intestinal resection with enterostomy.
Primary anastomosis. 35, 36
35 Hall NJ et al. Resection and primary anastomosis is a valid surgical option for infants with
necrotizing enterocolitis who weigh less than 1000 g. Arch Surg. 2005 Dec;140(12):1149-51.
36 Singh m et al. Surgery for intestinal perforation in preterm neonates: anastomosis vs stoma. J Pediatr
Surg. 2006 Apr;41(4):725-9.

72. Management, Surgical
Peritoneal drainage:
More conservative approach, Started in 1977
Insertion of a peritoneal draine local anaesthesia
Initially, used for very sick premature babies, with
weight ≤ 1000 g
Now, it is used more commonly with larger and more
stable babies
It is used as a definite treatment in some centers

73. Management, Surgical
Algorithm for the treatment of necrotizing enterocolitis
37 Xavier
Demestre et al Peritoneal drainage as primary management in necrotizing enterocolitis: A
prospective study, J Pediatr Surg. 2002 Nov • Volume 37 • Number 11 • p1534 to p1539.

74. Management, Surgical
Laparoscopy:
Clarck and Mackinaly reported the use of laparoscopy on day 30 of
life in the treatment of a VLBW infant (900 g) with perforated NEC.38
Tan et al.: 4 babies (500-1000 g)
Needlescopic diagnosis is feasible and appears to be safe, even in
critically ill micropremmies less than 1000 g. The technique can
provide useful information for surgical decision-making and allows
for precise placement of a microlaparotomy incision over the site of
perforation, thus minimizing the trauma from open surgery in this
special group of patients. 39
38 Clark C, Mackinlay GA. Laparoscopy as an adjunct to peritoneal drainage in perforated necrotizing
enterocolitis. J Laparoendosc Adv Surg Tech A. 2006 Aug;16(4):411-3.
39 Tan HL et al. The role of diagnostic laparoscopy in micropremmies with suspected necrotizing
enterocolitis. Surg Endosc. 2007 Mar;21(3):485-7.

75. Prognosis and Outcome
NEC with perforation: mortality 20-40 %
Recurrent NEC : rare complication, 4%
Subacute or intermittent symptoms of bowel obstruction:
strictures, 10-35 %
Short-gut syndrome: FTT, high mortality.
The type of operation (peritoneal drain vs. laparotomy)
performed for perforated NEC does not influence survival
or other clinically important early outcomes in preterm
infants. 40
40 Moss
RL et al. Laparotomy versus Peritoneal Drainage for Necrotizing Enterocolitis and Perforation.
N Engl J Med. 2006 May 25;354(21):2225-34.

76. Neurodevelopmental Outcome
Soraisham et al.: Preterm infants who develop
NEC are at a significantly higher risk for
developing neurodevelopmental disability. 41
41 SoraishamAS et al. Does necrotising enterocolitis impact the neurodevelopmental and growth
outcomes in preterm infants with birthweight < or =1250 g?. J Paediatr Child Health. 2006
Sep;42(9):499-504.

77. Neurodevelopmental Outcome
Rees et al. Systematic Review (UK):
NEC is associated with significantly worse
neurodevelopmental outcome than prematurity alone.
Presence of advanced NEC and need for surgery increase
the risk of neurological impairment. 42
Schulzke et al. Systematic Review (Australia):
Survivors of stage II or higher NEC are at risk for long-
term neurodevelopmental impairment, especially if they
require surgery for the illness. 43
42 Rees CM et al. Neurodevelopmental outcomes of neonates with medically and surgically treated
necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F193-8.
43 Schulzke SM et al. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing
enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007
Jun;161(6):583-90.

78. Neurodevelopmental Outcome
Adesanya et al. Retrospective Study:
Intestinal perforation caused by NEC, as compared to
SIP, is associated with worse neurodevelopmental
outcome at 1 year. 44
Blakely et al. Retrospective Study:
the risk-adjusted odds ratio favoring laparotomy for death
or impairment, indicate the need for a large, multicenter
clinical trial to assess the effect of the initial surgical
therapy on outcome at > or =18 months. 45
44 Adesanya OA et al. Intestinal perforation in very low birth weight infants: growth and
neurodevelopment at 1 year of age. J Perinatol. 2005 Sep;25(9):583-9.
45 Blakely ML et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated
intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted
age. 2006 Apr;117(4):e680-7.

79. Prevention
Breast milk
Antenatal Steroid therapy
Oral immunoglobulins
Oral antibiotics
Probiotics (Lactobacillus, Bifidobacterium)
Feeding strategies
Oral PAF antagonists
Glutamine
Arginine
Polyunsaturated fatty acids (PUFA)
Lactoferin
Pentoxifylline

80. Prevention: Breast Milk
Formula vs. Donor Breast Milk: 27, 28
Breast milk is associated with
lower risk of NEC
slower growth in the early postnatal period
27 Quigley M et al. Formula milk versus donor breast milk for feeding preterm or low birth weight
infants. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD002971.
28 Boyd CA et al. Donor breast milk versus infant formula for preterm infants: systematic review and
meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2007 May;92(3):F169-75.

81. Prevention: Antenatal Steroids
Antenatal corticosteroids for women at risk of
preterm birth: Systematic Review 46
Decreased risk of NEC
RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants
46 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at
risk of preterm birth. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004454.

82. Prevention: Oral Immunoglobulin
The evidence does not support the administration
of oral immunoglobulin for the prevention of
NEC. There are no randomised controlled trials
of oral IgA alone for the prevention of NEC. 47
47 Foster
J et al, Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-
weight neonates. Cochrane Database Syst Rev. 2004;(1):CD001816.

83. Prevention: Probiotics
Probiotics might reduce the risk of necrotising
enterocolitis in preterm neonates with less than 33 weeks'
gestation (relative risk 0.36, 95% CI 0.20-0.65)
the short-term and long-term safety of probiotics needs to
be assessed in large trials
Unanswered questions include the dose, duration, and
type of probiotic agents (species, strain, single or
combined, live or killed) used for supplementation. 48
48 Deshpande G et al. Probiotics for prevention of necrotising enterocolitis in preterm neonates with
very low birthweight: a systematic review of randomised controlled trials. Lancet. 2007 May
12;369(9573):1614-20 .

84. Prevention: Feeding Strategies
Pietz et al. reported 20-year experience, in
Fairview Hospital, Cleveland, Ohio, with 1239
very low birth weight infants suggests strongly
that the late-onset, slow, continuous drip feeding
protocol and avoidance of indomethacin and
early dexamethasone treatment contribute to the
prevention of necrotizing enterocolitis. 49
49 Pietz
J et al. Prevention of necrotizing enterocolitis in preterm infants: a 20-year experience.
Pediatrics. 2007 Jan;119(1):e164-70 .

85. Prevention: Glutamine
The available data from good quality randomised
controlled trials suggest that glutamine
supplementation does not confer clinically
significant benefits for preterm infants. The
narrow confidence intervals for the effect size
estimates suggest that a further trial of this
intervention is not a research priority. 50
50 Tubman TR et al, Dalziel S. Glutamine supplementation to prevent morbidity and mortality in preterm
infants. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001457.

86. Prevention: Arginine
The data are insufficient at present to support a
practice recommendation. A multicentre
randomized controlled study of arginine
supplementation in preterm neonates is needed,
focusing on the incidence of NEC, particularly
the more severe stages (2 or 3). 51
51 ShahP, Shah V., Arginine supplementation for prevention of necrotising enterocolitis in preterm
infants. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004339 .

87. References
Manual of Neonatal Care, Cloherty, 5th ed, 2004,
Lippincott Williams & Wilkins
Neonatology, Tricia Gomella, 5th ed, 2004,
McGraw Hill
A Manual of Neonatal Intensive Care, Rennie &
Roberton, 4th ed, 2002, Arnold