Department of Pediatrics

15/01/2024
L.N. Medical College & Research Centre, 1
 NECROTISING ENTEROCOLITIS

MODERATOR –DR. KIRTI VISHWAKARMA

PRESENTATOR- DR. RAJENDER SINGH
 REFERENCE ARTICLES
• WOLTERS KLUWER
• Literature review current through: Dec 2019. | This topic last updated: Apr 16,
2019.

• LINKS-
• A)https://
www.uptodate.com/contents/neonatal-necrotizing-enterocolitis-clinical-features-
and-diagnosis/print?search=nec&source=search_result&s%E2%80%A6
• B)https://
www.uptodate.com/contents/neonatal-necrotizing-enterocolitis-management/pr
int?search=nec&source=search_result&selectedTitle=2~7%E2%80%A6
 TOPICS COVERED
DIAGNOSIS
A) ABDOMINAL RADIOGRAPHY
B) ABDOMINAL ULTRASONOGRAPHY
C) MODIFIED BELL’S STAGING
D) LABORATORY EVALUATION
E) DIFFERENTIAL DIAGNOSIS
MANAGEMENT
A) SUPPORTIVE CARE
B) EMPERICAL ANTIBIOTIC THERAPY
C) MONITORING TO THERAPY
PREVENTION
 DIAGNOSIS
• Diagnosis is made from either intestinal surgical or post mortem
specimens( intestinal inflammation, infarction, and necrosis).

CLINICAL DIAGNOSIS – FEATURES-

• Abdominal distention
• Bilious vomiting
• Gastric aspirate
• Rectal bleeding

ON ABDOMINAL IMAGING – FEATURES-

• Intramural gas (pneumatosis intestinalis),
• Pneumoperitoneum
 ABDOMINAL RADIOGRAPHY
Confirms the diagnosis of NEC and follow the progression of the
disease.

Often lack sensitivity and specificity.

Findings need to be interpreted in the context of the patient's other

clinical findings.

Not as sensitive in extremely preterm infants (gestational age [GA]

<28weeks) as radiologic findings vary by GA.
 RADIOGRAPHIC FEATURES
• An abnormal gas pattern with dilated loops of bowel that is consistent with ileus, and
is typically seen in the early stages of NEC. Nonspecific pattern that can also be seen
in other conditions such as septic ileus.

• Pneumatosis intestinalis, considered a hallmark of NEC, appears as bubbles of gas in

the small bowel wall, and is seen in most patients with Bell stages II and III NEC.
Pneumatosis in the preterm infant is indicative of NEC until proven otherwise.

• Pneumoperitoneum typically appears when bowel perforation occurs in patients with

IIIB NEC. A substantial amount of intraperitoneal air may result in the "football" sign
on a supine radiograph.

• Sentinel loops, a loop of bowel that remains in fixed position and that can be seen in
orthogonal views (anteroposterior and lateral), is suggestive of necrotic bowel and/or
perforation in the absence of pneumatosis intestinalis.
 Left panel: There is marked abdominal distention due in part to dilated bowel loops, and bubbles of gas in the
bowel wall due to extensive PNEUMATOSIS INTESTINALIS (arrow). An orogastric tube is in place. Right panel: There
is marked abdominal distention, pneumatosis intestinalis, and a suspicion of PORTAL VENOUS (ARROW) AND/OR
FREE INTRAPERITONEAL AIR.
 ABDOMINAL ULTRASONOGRAPHY
Abdominal ultrasonography is increasingly helpful in the diagnosis
and management of NEC.

Ultrasound is more sensitive in detecting fluid collections.

Doppler ultrasound is dynamic and permits real-time visualization of

bowel wall thickness, peristalsis, and perfusion.
 ULTRASONOGRAPHY FEATURES
Changes in bowel wall thickness – Bowel wall thickening and increased blood
flow are initial changes seen with increasing inflammation.

Thinning bowel wall with a central echogenic focus and a hypoechoic rim(the
pseudo-kidney sign) may indicate necrotic bowel and imminent perforation.

Increased bowel wall echogenicity is indicative of inflammation, swelling, and

increased perfusion of the affected bowel.

Ultrasonography also can detect intermittent gas bubbles in liver parenchyma

and the portal venous system that are not detected by radiographs.

Evidence of free air, bowel wall thickening, and complex ascites strongly indicate
(A) There is normal flow to normal bowel. The diagram shows NORMAL BOWEL WALL THICKNESS AND
PERFUSION.
(B) The changes of NEC are shown with BOWEL WALL THICKENING AND HYPEREMIA.
(C) The BOWEL WALL THICKENING persists, but the perfusion has diminished.
(D) As the process progresses in more severely affected neonates, the mucosa starts to slough, and the BOWEL
WALL BECOMES MUCH THINNER, although some perfusion persists.
(E) Sloughing continues, the BOWEL WALL BECOMES ASYMMETRICALLY THINNED, and blood flow ceases.
 IMPORTANT NOTE
• CONTRAST ENEMA — Contrast enemas are NOT recommended if NEC
is suspected, as it may result in bowel perforation with extravasation
of contrast material into the peritoneum.
 SEVERITY OF NEC
Modified Bell staging criteria-provide a uniform clinical definition of NEC based
upon the severity of systemic, intestinal, radiographic and laboratory findings.

 Most commonly used diagnostic and staging criteria in practice.

Bell staging criteria is the standard that is used in most neonatal intensive care
units (NICUs).

Each advancing stage includes the characteristics of the previous stage plus
additional findings due to increasing severity of the disease.
 THREE STAGES
SUSPECTED NEC, stage I

PROVEN NEC, stage II

ADVANCED NEC, stage III

 MODIFIED BELL STAGING CRITERIA
Mo d ifie d B e ll s t a g in g c rit e ria fo r n e c ro t iz in g e n t e ro c o lit is ( N EC) in n e o n a t e s

Sta g e Cla s s ific a t io n o f N EC S y s t e m ic s ig n s Ab d o m in a l s ig n s Ra d io g ra p h ic s ig n s

IA Suspected Temperature instability, Gastric retention, abdominal Normal or mild intestinal

apnea, bradycardia, distention, emesis, heme- dilation, mild ileus
lethargy positive stool

IB Suspected Same as above Grossly bloody stool Same as above

IIA Definite, mildly ill Same as above Same as above, plus absent Intestinal dilation, ileus,
bowel sounds with or pneumatosis intestinalis
without abdominal
tenderness

IIB Definite, moderately ill Same as above, plus mild
metabolic acidosis and
thrombocytopenia
Same as above, plus absent Same as IIA, plus ascites
bowel sounds, definite
tenderness, with or without
abdominal cellulitis or right
lower quadrant mass

IIIA Advanced, severely ill, intact Same as IIB, plus
bowel hypotension, bradycardia,
severe apnea, combined
respiratory and metabolic
acidosis, DIC, and
neutropenia
Same as above, plus signs Same as IIA, plus ascites
of peritonitis, marked
tenderness, and abdominal
distention

IIIB Advanced, severely ill, Same as IIIA Same as IIIA Same as above, plus
perforated bowel pneumoperitoneum
REF-AIIMS NICU PROTOCOL-2019
 TRIAD OF NECROTISING
ENTEROCOLITIS
• Most common triad-;

• A) Thrombocytopenia

• B) Persistent metabolic acidosis

• C) Severe refractory hyponatremia

 LABORATORY EVALUATION
Laboratory findings may support the diagnosis and staging of disease severity,
and aid in the management of infants with NEC.

COMPLETE BLOOD COUNT- An absolute neutrophil count of less

than1500/microL is more commonly observed in patients with NEC and is
associated with a poor prognosis.

Thrombocytopenia is a frequent finding and can result in significant bleeding.

Early course of NEC, declining platelet counts correlate with necrotic bowel and
worsening disease, whereas a subsequent rise in platelet counts often signals
improvement.
CONTINUED……………………
COAGULATION STUDIES-Done to see DIC, DIC is confirmed by a decreased
platelet count, prolonged prothrombin and partial thromboplastin times,
decreased serum factor V and fibrinogen concentrations, and increased fibrin
split products (D-dimer).

Patients with DIC and significant bleeding, replacement therapy is administered.

SERUM CHEMISTRIES-Serum electrolytes, blood urea nitrogen, creatinine, and

pH are routinely measured

Persistence of hyponatremia (serum sodiumlevels of less than 130 mEq/L),

increasing glucose levels, and metabolic acidosis are suggestive of necrotic bowel
or sepsis.
 OTHER TESTS
An ARTERIAL BLOOD GAS ANALYSIS is performed in infants with signs of respiratory compromise.

SERIAL LACTATE LEVELS may be used to follow metabolic acidosis as indicators of disease
progression and healing.

SEPSIS EVALUATION — A sepsis evaluation (blood culture, and if indicated, cerebral spinal fluid
culture) is performed when NEC is suspected because sepsis is a common concomitant finding or
one of the main differential diagnosis.

PERITONEAL CULTURE — A diagnostic abdominal paracentesis occasionally is performed to

obtain fluid for culture and Gram stain in infants with severe ascites or when peritonitis is
suspected.

STOOL TESTS: GENERALLY NOT USEFUL — Bedside stool tests (examination for occult blood and
reducing substances, and measurement of alpha-1 antitrypsin) have NOT been clinically helpful
as they are nonspecific findings.
CONTINUED…………………..
• POTENTIAL PREDICTIVE BIOMARKERS — Number of possible biomarkers that
may assist in early prediction of NEC, diagnosing NEC, and/or determining the
severity of NEC.

• EXAMPLE-
• C-reactive protein,
• Platelet activating factor or
• Cytokines such as interleukins (IL-6, IL-8), or
• Tumor necrosis factor-beta (TNF-beta).
• MicroRNAs

NOTE-However, none have been used in clinical practice or as part of a standard

definition.
 DIFFERENTIAL DIAGNOSIS
 Includes other conditions that cause RECTAL BLEEDING, ABDOMINAL
DISTENSION, GASTRIC RETENTION, or INTESTINAL PERFORATION.
 INFECTIOUS ENTERITIS-Pathogenic organisms, including Campylobacter,
Clostridioides (formerly Clostridium) difficile, Salmonella, and Shigella sometimes
cause infectious neonatal enterocolitis.
 Viral enteritis of infancy is characterized by frequent and sometimes bloody
stools, abdominal distension, and secondary sepsis.
 SPONTANEOUS INTESTINAL PERFORATION -of the newborn is a single intestinal
perforation that is typically found at the terminal ileum or colon. It occurs
primarily in very low birth weight (VLBW) infants (BW <1500 g) similar to NEC.
 Distinguished from NEC by the absence of pneumatosis intestinalis on abdominal
imaging and the clinical findings of hypotension and abdominal distension, along
with the classical bluish discoloration of the abdominal wall.
CONTINUED ……………………
 Hirschsprung disease, ileal atresia, volvulus, meconium ileus, and intussusception.
Abdominal radiography distinguishes these entities from NEC.
 ANAL FISSURES, condition usually is benign, although the diagnosis of NEC must be
strongly considered in any premature infant who has occult or gross blood in the
stools.
 NEONATAL APPENDICITIS, presentation may be the same as NEC and the diagnosis
may be made only at laparotomy.
 INFANTS WITH SEPSIS can have an ileus that is difficult to distinguish from early
signs of NEC (stage I).
 FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME (FPIES) can MIMIC NEC in
preterm infants, as both conditions may present with pneumatosis, low albumin,
anemia, and inflammatory marker elevations.
 Patients with NEC commonly (but not always) have leukopenia and
thrombocytopenia, whereas those with acute FPIES typically have thrombocytosis,
 MEDICAL MANAGEMENT
Components of medical care-:

● SUPPORTIVE CARE

● EMPIRICAL ANTIBIOTIC THERAPY

● SERIAL EXAMINATIONS AND CLOSE LABORATORY AND RADIOLOGIC

MONITORING
 SUPPORTIVE CARE
Bowel rest - discontinuation of enteral feedings, lessen the stress on the gut .
Duration of bowel rest parallels the antibiotic treatment course of 10 to 14 days.
Enteral feedings are resumed gradually as the infant's clinical condition improves.
Gastric decompression , NEC have a loss of gut motility (ileus) due to bowel
inflammation and bowel wall thickening, Nasogastric suction is continued until
the ileus resolves and pneumatosis is no longer seen on the abdominal
radiograph.
Total parenteral nutrition, administered until enteral feeds sufficiently provide
adequate caloric intake.
Fluid replacement to correct third space losses.
Assessment and support of both the cardiovascular & respiratory systems in
critically ill infant.
When necessary, correction of hematologic (eg, disseminated intravascular
coagulation) and metabolic abnormalities (eg, metabolic acidosis)
 ANTIBIOTIC THERAPY
• Administer BROAD-SPECTRUM ANTIBIOTICS after obtaining appropriate
specimens for culture.
• Empiric broad-spectrum antibiotics combinations used to treat NEC include, but
are not limited to, the following choices-;

● Ampicillin, gentamicin (or amikacin), and metronidazole

● Ampicillin, gentamicin (or amikacin), and clindamycin
● Ampicillin, cefotaxime (if available), and metronidazole (ceftazidime is an
alternative choice for cefotaxime)
● Piperacillin-tazobactam and gentamicin (or amikacin)
● Vancomycin, piperacillin-tazobactam, and gentamicin
● Meropenem
CONTINUED…………………..
VANCOMYCIN may be used instead of ampicillin in centers where there is a high
prevalence of methicillinresistant Staphylococcus aureus (MRSA) or ampicillin-resistant
enterococcal infections.

Antibiotic regimens are modified based upon the results of cultures of blood,
peritoneal fluid, or surgical specimens.

10- to 14-day course usually is sufficient unless the course is complicated by abdominal
abscess formation.

NOT recommend the use of ORAL AMINOGLYCOSIDES because this treatment has
significant toxicity, can result in the development of resistant bacterial strains.

FLUCONAZOLE OR AMPHOTERICIN B should be used when fungal infection is

 MONITORING RESPONSE TO
THERAPY
Help determine whether there is clinical improvement or deterioration
SERIAL PHYSICAL EXAMINATIONS-Recognizing changes in vital signs (increased
heart rate and respiratory rate, variability in blood pressure) and the abdominal
examination may assist in determining the severity and progression of illness and
prompt earlier radiologic and surgical assessment.

Changes that suggest possible bowel perforation, such as abdominal erythema or

bruising, marked abdominal distension, and increased tenderness lead to further
evaluation and therapeutic changes in management.

LABORATORY MONITORING- Depends upon the results of the initial evaluation

and the clinical condition of the infant. Complete blood count and differential,
platelet count, serum electrolyte and creatinine measurements, blood urea
nitrogen, and acid-base studies that include lactate levels every 12 to 24 hours
CONTINUED……………..
 Low platelet count, metabolic acidosis, low monocyte count, and increased blood glucose are
associated with NEC.

 RADIOGRAPHY — Abdominal radiographic monitoring is a relatively insensitive guide to the

diagnosis and progression of the disease.

 Obtain an abdominal radiograph in the supine position every 6 to 12 hours during the initial
phase of illness, and repeated if there are physical signs suggesting further clinical deterioration.

 Films in the lateral decubitus view with the infant's, left side down also are obtained in order to
visualize the presence of free air over the liver.

 ULTRASONOGRAPHY-Dynamic nature of bowel ultrasound can assess motility and perfusion,

which cannot be done by static imaging. As a result ultrasound may be useful to identify patients
with severe necrosis who are at risk for bowel perforation and are candidates for surgical
intervention.
 SURGICAL MANAGEMENT
• Surgical intervention is performed to control enteric spillage and
resect necrotic intestine while maximizing the length of viable
intestine

• INDICATIONS — only absolute indication for surgical interventions is

evidence of pneumoperitoneum detected by abdominal imaging,
which indicates intestinal perforation due to severe necrosis.

• PROCEDURES —either exploratory laparotomy with resection of the

affected intestinal region(s), or primary peritoneal drainage (PPD).
INTRAOPERATIVE PHOTOGRAPH OF THE BOWEL SHOWS THE NECROTIC BOWEL LOOP (ARROW)
 COMPLICATIONS
ACUTE COMPLICATIONS-Complications during the acute stage of the
disease and immediate post-recovery stage-;
● INFECTIOUS COMPLICATIONS – Sepsis, meningitis, peritonitis, and
abscess formation
● Disseminated intravascular coagulation, which contributes to
intestinal or extraintestinal bleeding
● RESPIRATORY AND CARDIOVASCULAR COMPLICATIONS –
Hypotension, shock, and respiratory failure
● METABOLIC COMPLICATIONS – Hypoglycemia and metabolic acidosis
CONTINUED……………………..
• LATE GASTROINTESTINAL COMPLICATIONS — Most common late
gastrointestinal complications of NEC are intestinal narrowing (ie, stricture
formation) and short bowel syndrome.

• In a review of the literature of gastrointestinal sequelae in 4260 patients surviving

surgery for NEC, the following findings and frequency were noted-;

● STRICTURES – 24 percent (95% CI 17-31 percent)

● INTESTINAL FAILURE – 13 percent (95% CI 3-15 percent)
● RECURRENT NEC – 8 percent (95% CI 7-19 percent)
● ADHESION ILEUS – 6 percent (95% CI 4-9 percent)
CONTINUED……………………..
In a multicenter prospective study, the RISK OF SHORT BOWEL SYNDROME in
infants following surgery for NEC was INCREASED by the following factors-;
 Parenteral antibiotics on the day NEC is diagnosed.
Birth weight (BW) <750 g.
Mechanical ventilation on the day NEC is diagnosed.
 Exposure to enteral feeds before the diagnosis of NEC.
Small bowel resection that exceeded a composite score based upon the actual
percentage of small bowel resected, whether a diverting jejunostomy was
created, and the duration of its use.

• RARE COMPLICATIONS — Rare complications of NEC include enterocele,

enterocolic fistula, and intra abdominal abscess.
 OUTCOME
MORTALITY-NEC accounts for approximately 10 percent of deaths of infants cared for in neonatal
intensive care units.

PRETERM INFANTS-Mortality increases with decreasing gestational age and for those who
undergo surgical intervention . Overall, mortality ranges from 20 to 30 percent of affected infants.

In addition to lower BW, earlier gestation, and surgical intervention, other reported risk factors
include mechanical ventilation, treatment with vasopressor agents, and black ethnicity.

TERM INFANTS — Retrospective data show a reported mortality rate of 11 percent for infants
with NEC and BWs >2500 g . Risk factors include major congenital anomalies, chromosomal
abnormalities, sepsis, and surgery for NEC.

LONG-TERM OUTCOME — Approximately one-half of survivors have no long-term sequelae.

However, in the remaining survivors, long-term morbidity include gastrointestinal complications
impaired growth and impaired neurodevelopmental outcome .
 PREVENTION
Efforts to minimize the frequency or severity of NEC are directed at
reducing exposure to risk factors and finding interventions that will
prevent the disorder.

NEC occurs almost exclusively in preterm infants, prevention of

preterm birth would have an impact on NEC incidence.
CONTINUED……………..
Antenatal corticosteroids should be given to all women at risk for preterm delivery within
seven days. Antenatal corticosteroids reduces the risk of neonatal respiratory distress
syndrome, mortality as well as NEC.

Human milk compared with intact bovine milk-formula is associated with a lower risk of
NEC. In preterm infants who are at risk for developing NEC,recommend initiation of enteral
feeds with mother's milk . If mother's milk is unavailable or its use contraindicated,
pasteurized donor human milk should be used.

Standardized feeding regiment be used when initiating feeds in very low birth weight
(VLBW) infants (BW <1500 g) . The use of a standardized protocol provides a consistent
approach to initiation of feedings, timing and rate of advancement of feeding, and criteria
when to withhold and restart feeds.
CONTINUED………………………
 Prolonged courses of antibiotics with sterile cultures be avoided to reduce the
incidence of NEC.
 It remains uncertain whether the risk of NEC is increased due to severe anemia
(hematocrit<25 percent) and/or to the subsequent red blood cell (RBC)
transfusions used to treat the anemia. Although data are insufficient, suggest
holding feeds during and after RBC transfusion to minimize the risk of NEC.
 PROBIOTICS-Probiotics, defined by the World Health Organization (WHO) as "live
microorganisms which, when administered in adequate amounts, confer a health
benefit on the host, "are one of the most studied preventive measures for NEC.
 Significant unanswered concerns remain that, until resolved, preclude their use in
routine care, including:-
 Inconsistent data including potential differences in benefit based on gestational
age (GA) and birth weight (BW). In particular, probiotics may not be as effective in
extremely low birth weight (ELBW) infants (BW <1000 g) who are most vulnerable
CONTINUED…………………..
 Lack of an established regimen of optimal strain, dosing, and timing of
administration.

 Absent quality control regulation to ensure consistency and safety of product,

which is required for any approved medication.

 Bacteremia from the bacterial probiotic strain or contamination of the probiotic

product is an uncommon but serious and potentially fatal adverse event.

 Lack of regulatory control – There is confusion regarding the classification of

probiotics, and hence their regulation.


CONTINUED……………………
• NUTRITIONAL SUPPLEMENTS —Recommend NOT to use nutritional
supplements including lactoferrin, arginine and glutamine, to prevent NEC in
preterm infants.
IMMUNOGLOBULINS-
Oral immunoglobulins may reduce NEC by inhibiting the release of
proinflammatory cytokines .

Meta-analysis of five trials reported that oral administration of IgG or IgG/IgA

combination did not reduce the incidence of definite NEC.

Immunoglobulin therapy should not be used because there is lack of evidence

demonstrating any benefit from this therapy