This document provides an overview of necrotizing enterocolitis (NEC), including its epidemiology, risk factors, pathophysiology, clinical features, management, outcomes, prevention and areas for further research. Some key points: - NEC most commonly affects very preterm infants, with a mortality rate around 13% that increases with lower birth weight. - Risk factors include prematurity, hypoxia, poor intestinal integrity, bacterial colonization and enteral feeding. - Clinically it presents with abdominal distension, bloody stools and vomiting. Diagnosis is confirmed via x-ray showing pneumatosis or free air. - Management involves stopping feeds, antibiotics, surgery for complications like perforation.

1. NECROTIZING
ENTEROCOLITIS
DR.KM PARAKRAMA
REGISTRAR
NICU-THK
24 JAN 2020

2. INTRODUCTION
• NEC is the most common life-threatening emergency of the GIT in
the new-born period.
• Characterized by various degrees of mucosal or transmural
necrosis of the intestine.
• Cause of NEC remains unclear but is most likely multifactorial.
• Incidence and case fatality rates increase with decreasing birth
weight and POA.

3. EPIDEMIOLOGY
• Incidence of NEC is 1-3 per 1000 live births.
• 2–5% of VLBW infants.
• In 1–8% of admissions to NICU.
• Mortality of NEC has now fallen to around 13%.
• Most affected are preterm
• 12% of infants with NEC are born at term.

4. • NEC occurs in 14% of infants under 26 weeks POA and in less than
1% after 32 weeks.
• Mortality ranges from 42% to 16% across a birthweight range of
500–1500 g.
• Onset of signs is most commonly in the second week
• There are no reliable seasonal, sexual or geographical patterns
with NEC.

6. RISK FACTORS
• Prematurity
• Intrauterine growth restriction
• Abruptio placentae
• Premature rupture of membranes
• Perinatal asphyxia
• Low Apgar score

7. • Non-human milk
• Hypertonic feeds
• Rapid introduction of enteral feeds
• Fluid overload
• Pathogenic bacteria
• Polycythaemia
• Thrombocytosis
• Anaemia
• Exchange transfusion
• Cyanotic congenital heart disease

8. • Umbilical catheterisation
• Hypoxia and shock
• Hypothermia
• Patent ductus arteriosus

9. PATHOPHYSIOLOGY
• NEC may affect any part of the gastrointestinal tract.
• In patients who undergo surgery, or die,
• Commonest sites are the terminal ileum, caecum and ascending
colon.
• It’s a transmural disease
• Bowel is purple and discoloured, distended with serosal damage.

10. • Pneumatosis is the most characteristic appearance at laparotomy,
histologically and radiographically.
• Produced by gas-forming bacteria.
• Earliest signs are coagulative necrosis of the mucosa with
microthrombus formation,
• Patchy mucosal ulceration, oedema and haemorrhage.
• In focal intestinal perforation,
• Haemorrhagic necrosis distinguishes from classical NEC.

11. • Cytokines play an important role in inflammation and damage in
NEC.
• Raised levels of interleukins-1, -3 and -6, TNF-α and platelet-
activating factor (PAF) relate to severity of the disease.
• PAF, the lipid-derived, proinflammatory cytokine, has a central
role.
• Imbalance in the pro- and anti-inflammatory balance with
increased proapoptotic protease activity.

12. AETIOLOGY
• Numerous potential risk factors have been explored
• But most important ones would be,
• Hypoxia ,
• Prematurity,
• Poor mucosal integrity,
• Bacterial flora and
• Presence of a metabolic substrate – milk – in the intestinal lumen

14. GUT HYPOXIA
• In term infant with NEC, risk factors for gut hypoxia are invariably
present.
• May follow severe generalised hypoxia, maternal cocaine abuse
and exchange transfusion.
• Adverse intrauterine environment leads to diversion of cardiac
output away from the gut.

15. • Absent or reversed end-diastolic flow on foetal Doppler studies
predispose to NEC.
• Reduction of gut blood flow is still evident after birth.
• Infants with abnormal foetal Doppler, IUGR, are considered at high
risk of NEC.
• Oligohydramnios and foetal echogenic bowel predict difficulties in
the introduction of milk.
• IUGR is an important risk factor for NEC in infants over 29 weeks’
gestation.

16. • The preterm infant is at particular risk of intestinal hypoxia.
• In the animal model, bacterial colonisation and excessive formula
feeding do not precipitate NEC unless hypoxia is also present.
• After feeds, intestinal oxygen use is increased but not blood flow.
• PDA diminishes superior mesenteric artery blood flow.
• Indometacin has long been said to predispose to NEC,
• Had been attributed to exchange transfusion after HDN, through
UVC.

17. • UAC has been attributed to reduced blood flow through
thrombosis and emboli.
• Studies done before 1980 ????.
• But early or late introduction of small volume feeds with a high or
low UAC does not predispose to NEC.
• UVC does not predispose to NEC.

18. MUCOSAL INTEGRITY
• Loss of mucosal integrity disrupts barrier function, allowing
macromolecular absorption,
• Bacterial translocation and interferes with digestion.
• Preterm gut has an immature microvillous membrane with relative
deficiency of mucus and secretory IgA
• Further mucosal damage increases permeability to
microorganisms and toxins.
• This process may initiate NEC

19. • Antenatal corticosteroid administration induces intestinal
maturation,
• Decreases permeability and protects against NEC.

20. MICROBIAL INFECTION
• Most NEC is not infectious.
• Presence of bacteria is probably necessary for NEC to occur,
• But is not sufficient without other risk factors.
• In epidemic NEC there may be an identified infectious agent.
• Infection with clostridia, occurs in epidemics and in Hirschsprung’s
enterocolitis.

21. • NEC during epidemics fare better than in sporadic disease.
• In sporadic disease, a large variety of microorganisms are
associated.
• Positive blood cultures are found in 10–50% and correlate with
isolates from stool or peritoneal fluid.
• proliferation of pathogenic species may occur,
• Bacterial translocation and absorption toxins, explaining the
increased risk of NEC in infants whose mothers were treated with
co-amoxiclav after PROM

22. ENTERAL NUTRITION
• All studies have demonstrated that most infants with NEC have
received milk.
• Intraluminal milk may simply promote bacterial proliferation or
increase bacterial endotoxin production by Gram-negative bacteria
• Results in gas formation and the production of short-chain fatty
acids.

23. • They are toxic to intestinal epithelium,
• Long-chain fats and undigested casein may contribute to
inflammation and injury.
• Lipid in milk increases mucosal permeability.
• Immature patterns of motility and decreased digestive capacity
predispose the preterm infant to NEC.
• In healthy infants without NEC, milk induces a cellular and humoral
inflammatory mucosal reaction with an increase in circulating
cytokines.

24. • Prolonged delay of oral feeding is not recommended.
• Aggressive enteral feeding with rapid increase in feed volume is
more causative.
• Hyperosmolar feeds, promote mucosal damage and NEC.
• Breast milk protects against NEC
• 7- 10 times less likely to suffer from NEC,
• Benefit is attenuated when breast milk is given with formula.

25. • Important factors in breast milk include,
• Immunoglobulins,
• lysozyme, complement, macrophages, growth factors,
• PAF-acetylhydrolase and
• Production of anti-inflammatory cytokines.
• Prebiotic oligosaccharides in breast milk are bifidogenic,
• Trophic feeding –does not increase the risk of NEC
• Trophic feeding prior to standard milk advancement may protect
against NEC

26. CLINICAL FEATURES
• Presentation may vary,
• From insidious deterioration with nonspecific signs, to a rapidly
progressive illness with shock, peritonitis and death.
• Early recognition of NEC requires a high index of suspicion.
• Clinically it’s similar to sepsis with pallor, skin mottling and often
jaundice

27. • Bleeding may be due to DIC.
• Increased volume of gastric residuals or emesis.
• Then develop classic triad of abdominal distension, bloody,
mucusy stools and bilestained vomit or aspirates.
• Careful review of a baby who consistently has more than 50% of
feed volume as a residual.

28. • The commonest abdominal sign is distension.
• Often, distended loops are palpable.
• An intra-abdominal mass may represent localised perforation.
• Blue abdominal discoloration suggests disease progression.
• Focal intestinal perforation occurs earlier in life,
• characteristically in infants of low gestation who are receiving full
intensive care,
• Associated with blue discoloration of the abdomen.

31. INVESTIGATIONS
• Immediate investigations include
• Hb, white cell and platelet counts,
• Coagulation studies,
• Urea, electrolytes
• Albumin
• Blood gas analysis

32. • Abdominal radiography is mandatory.
• Appearance varies from a gasless abdomen to dilated loops of
thick walled gut with fluid levels.
• Pathognomonic radiographic appearance is pneumatosis
intestinalis.
• Severe disease gas collects within the portal venous system.
• Only 2/3 of patients with perforation will have free air in x ray.
• A lateral horizontal beam shoot-through X-ray may allow easier
detection of anterior collection of gas.

33. • X-ray Showing Intraluminal Gas

34. • Free Gas Is Under The Diaphragm

35. • Shoot-through Horizontal Beam Film.

36. MANAGEMENT
• Aims of treatment are,
• Rest the gut,
• Control infection,
• Restore metabolic equilibrium
• With intensive or high dependency care,
• Maintain the infant in an optimal condition until the bowel heals

37. • Cessation of enteral feeding.
• Nasogastric drainage with suction.
• Monitoring of vitals.
• Plain abdominal radiography: repeated bd on day 1(high risk of
perforation)
• Peripheral venous access.
• Septic screening
• Volume replacement:

38. INTRAVENOUS ANTIBIOTICS
• Intravenous antibiotics: a triple-antibiotic regime is
• Gram-negative cover: gentamicin or a third-generation
cephalosporin (e.g. ceftazidime),
• Gram-positive cover: amoxicillin or vancomycin.
• should also include metronidazole..

39. • Regular blood gas analysis.
• Transfuse to maintain haemoglobin,
• Platelet transfusion is necessary if the count is Below 30 × 109/l or
below 70 × 109/l before surgery.
• Consider removal of umbilical cannulae.
• TPN
• Starvation for at least 7–10 days is needed
• Barrier nursing.

40. • Surgical,
• In all, 20–50% of infants with NEC require surgery
• Cardinal indications for surgery in NEC are:
• Failure to respond to medical management
• Formation of a mass
• Perforation.

41. • Commonest indication for surgery is clinical deterioration with
intestinal perforation
• 40–70% of infants who required surgery.
• Commonest site of perforation is the terminal ileum,

44. OUTCOME
• 5–10%, NEC relapses occurs
• Usually within a month of initial presentation.
• Overall survival after NEC is 70–90%
• Mortality is higher in infants of less than 28 weeks
• Survival rate is poor in <1000g

45. • Extensive disease, bacteraemia, DIC and persistent ascites are bad
prognostic indicators

47. PREVENTION
• Use of breast milk
• Minimal enteral feeding (0.5 ml/h) for 7 days before increasing
feeds
• Slow feed advancement
• Standardised feeding regimen
• Probiotics.

48. • Avoidance of perinatal asphyxia
• Maternal antenatal steroids reduce the risk of NEC
• Choice of antibiotic in preterm rupture of membranes is
important, and co-amoxiclav should be avoided.
• Maintenance of good tissue perfusion,
• Blood pressure and hydration
• Avoidance of hypotension,
• Unnecessary H2 receptor blockers, hypoxia and hypothermia.

49. • UAC should be removed if there is evidence of thrombosis or
reduced blood flow to buttocks or lower limbs.
• Breast milk should be given.
• Donor breast milk will reduce the risk of NEC fourfold compared
with formula.
• In the VLBW infant, most advise introduction of milk feeds at 20–
25 ml/kg/day,
• Increased by the same amount daily.
• Minimal enteral feeding promotes gut development.

50. • In IUGR with abnormal foetal Doppler studies, introduction of milk
on day 2 is safe,
• Advantage of earlier feed tolerance.
• Control of infection is essential in the management of epidemic
NEC
• Prophylactic use of systemic antibiotics is not advised
• Administration of probiotics or prebiotics looks promising
• Future possibilities include modification of cytokine activity and
treatment with growth factors.

51. RESEARCH

52. • Preterm neonates at high risk of NEC:
• Admitted to NICU within 3 days of birth at <32 weeks’
• Gestation or at 32–36 weeks’ gestation and of birth
• Weight <1500 g.
• Conclusions
• Administration of multispecies probiotics has been associated with a
significantly decreased risk of nec and late-onset sepsis
• No safety issues.

54. • SIGIRR is a major negative regulator of intestinal inflammation mediated
by TLRs.
• Conclusion-data provide novel insight into the probable causation of
NEC
• Support the hypothesis that inherited defects in genes that inhibit
intestinal innate immune signalling can contribute to NEC.

55. REFERENCES
• Rennie and Roberton’s textbook of neonatology 5th Edition
• Nelson Textbook of Paediatrics 21st Edition
• Joint Trust Guidelines for the Management of Necrotising
Enterocolitis in Neonates and Infants-NHS 2019
• Robertson C, Savva GM, Clapuci R, et al. Arch Dis Child Fetal
Neonatal Ed Epub “Incidence of necrotising enterocolitis before
and after introducing routine prophylactic Lactobacillus and
Bifidobacterium probiotics”

56. • Venkatesh Sampath, MDa, et al “SIGIRR Genetic Variants in
Premature Infants With Necrotizing Enterocolitis” PEDIATRICS
(ISSN Numbers: Print, 0031-4005; Online,1098-4275).

57. •THANK YOU!