Necrotizing Enterocolitis and
A. Necrotizing enterocolitis (NEC) is an
acquired neonatal disorder representing an
end expression of serious intestinal injury after
a combination of vascular, mucosal, and
metabolic (and other unidentified) insults to a
relatively immature gut.
B. Spontaneous intestinal perforation is a
clinical syndrome of undetermined cause
resembling NEC with less systemic
involvement and a less severe clinical course.
It may represent a variant of classic NEC.
A. NEC is predominantly a disorder
of preterm infants
6-10% in <1.5 kg.
70% to 90% of cases high-risk LBW
10-25% in full-term
NEC: 2-5% of (NICU) admissions
B. NEC occurs sporadically or in
Currently, there is no single unifying theory for the
pathogenesis of NEC that satisfactorily explains all of
the clinical observations associated with this disorder.
loss of mucosal integrity( ischemic, toxic).
Then, (with feeding) bacterial proliferation
followed by invasion of the damaged intestinal mucosa
by gas-producing (methane and hydrogen) organisms
that cause intramural bowel gas (pneumatosis
This sequence of events may then progress to
transmural necrosis or gangrene of the bowel and
finally to perforation and peritonitis.
IV. Risk factors
B. Asphyxia and acute cardiopulmonary disease lead to low cardiac output and
diminished perfusion states, resulting in redistribution of cardiac output away from
the mesenteric circulation and causing episodic intestinal ischemia.
C. Enteral feedings. NEC is rare in unfed infants. About 90-95% of infants with
NEC have received at least one enteral feeding. The explanations for this include
1. Enteral feeding provides necessary substrate for proliferation of enteric
2. Hyperosmolar formula or medications cause altered mucosal
permeability and direct mucosal damage.
3. There is a loss or lack of immunoprotective factors in commercially
prepared formulas and in stored breast milk.
4. Breast-feeding significantly lowers the risk of NEC.
D. Polycythemia and hyperviscosity syndromes.
E. Exchange transfusions.
IV. Risk factors
F. Feeding volumes, timing of enteral
feeding, and rapid advancement in enteral
feedings. These appear to play a role, but
clinical evidence remains controversial.
G. Enteric pathogenic microorganisms.
Bacterial and viral pathogens, including
Escherichia coli, Klebsiella, Enterobacter,
Pseudomonas, Salmonella, Staphylococcus
epidermidis, Clostridium sp, coronaviruses,
rotaviruses, and enteroviruses, have been
implicated, either directly or indirectly, by
blood, stool, or peritoneal space cultures.
V. Clinical presentation.
The time of NEC onset varies inversely with gestational age.
In the (VLBW) group, onset invariably follows initiation of enteral
feedings and is usually diagnosed between 14 and 20 days of age.
In full-term infants, age of onset is within the first week of life.
The presentation may vary from abdominal distention (the most
frequent early sign, noted in 70% of cases), ileus, and increased
volume of gastric aspirate or bilious aspirate (two thirds of cases) to
frank signs of shock, bloody stools, peritonitis, and perforation. NEC may
also present insidiously with nonspecific signs such as labile
temperature, apnea, bradycardia, or other signs of suspect sepsis.
The clinical syndrome has been
classified into stages by Walsh and
Kliegman (1986) to include systemic,
intestinal, and radiographic findings
A. Stage I: suspected NEC
1. Systemic signs are nonspecific,
including apnea, bradycardia, lethargy,
and temperature instability.
2. Intestinal findings include
feeding intolerance, recurrent gastric
residuals, and guaiac-positive stools.
3. Radiographic findings are
normal or nonspecific.
B. Stage IIA: mild NEC
1. Systemic signs are similar to
those in stage I.
2. Intestinal findings include
prominent abdominal distention with or
without tenderness, absent bowel
sounds, and gross blood in the stools.
3. Radiographic findings include
ileus, with dilated loops with focal areas
of pneumatosis intestinalis.
C. Stage IIB: moderate NEC
1. Systemic signs include stage 1 signs
plus mild acidosis and thrombocytopenia.
2. Intestinal findings include increasing
distention, abdominal wall edema, and
tenderness with or without a palpable mass.
3. Radiographic findings include
extensive pneumatosis and early ascites.
Intrahepatic portal venous gas may be
D. Stage IIIA: advanced NEC
1. Systemic findings include respiratory
and metabolic acidosis, assisted ventilation for
apnea, decreasing blood pressure and urine
output, neutropenia, and coagulopathy.
2. Intestinal findings include spreading
edema, erythema or discoloration, and
induration of the abdominal wall.
3. Radiographic findings include
prominent ascites, paucity of bowel gas, and
possibly a persistent sentinel loop.
E. Stage IIIB: advanced NEC
1. Systemic findings reveal generalized
edema, deteriorating vital signs and laboratory
indices, refractory hypotension, shock
syndrome, disseminated intravascular
coagulation (DIC), and electrolyte imbalance.
2. Intestinal findings reveal a tense,
discolored abdomen and ascites.
3. Radiographic findings commonly
show absent bowel gas and often evidence of
intraperitoneal free air.
A. Clinical diagnosis. NEC is a tentative diagnosis in
any infant presenting with the
abdominal distention, and
grossly bloody stools
(hematochezia) or acute
change in stool character.
Alternatively, the earliest signs may be identical to those
of neonatal sepsis.
B. Laboratory studies. The following should be performed as baseline
studies. If there is clinical progression of disease or if these laboratory
tests are abnormal, the tests should be repeated every 8-12 h.
1. Complete blood cell count (CBC) with differential.
2. Platelet count. Thrombocytopenia is seen. 50%v of NEC Pts
3. Blood culture
4. Stool screening for occult blood.
5. Arterial blood gas measurements. Metabolic or combined
acidosis or hypoxia may be seen.
6. Electrolyte panel., particularly hypo- or hypernatremia, and
hyperkalemia are common.
7. Stool cultures for rotaviruses and enteroviruses should be
obtained if diarrhea is an epidemic in the nursery.
C. Radiologic studies
1. Flat plate x-ray studies of the abdomen
a. Supportive for NEC. Look for abnormal bowel gas
patterns, ileus, a fixed sentinel loop of bowel, or areas suspicious
for pneumatosis intestinalis.
b. Confirmatory of NEC. Look for (1) intramural bowel
gas (pneumatosis intestinalis) and (2) intrahepatic portal venous
gas (in the absence of an umbilical venous catheter).
2. Lateral decubitus and cross-table lateral studies of
the abdomen. These studies are more likely to demonstrate a
Perforation commonly occurs within 48-72 h
after pneumatosis or portal venous gas.
In the presence of pneumatosis intestinalis or
portal venous gas, flat plate and left lateral
decubitus or cross-table lateral x-ray studies of
the abdomen should be obtained every 6-8 h
to check for the development of
pneumoperitoneum, signaling intestinal
perforation. Serial x-ray studies may be
discontinued with clinical improvement, usually
after 48-72 h.
The main principle of management for
confirmed NEC is to treat it as an acute
abdomen with impending or septic peritonitis.
The goal is to prevent progression of disease,
intestinal perforation, and shock. If NEC
occurs in epidemic clusters, cohort isolation
has been shown to limit transmission. Signs to
watch closely for include progressive
distention and discoloration of the abdomen,
refractory metabolic acidosis, falling platelet
counts, and shock.
A. Basic NEC protocol. Any infant with suspected NEC should be managed
according to the following protocol:
1. Nothing by mouth
2. Use of a nasogastric tube
3. Close monitoring of vital signs and abdominal circumference.
4. Removal of the umbilical catheter and placement of peripheral venous and
arterial catheters, depending on severity of illness (controversial).
5. Antibiotics. Start ampicillin and gentamicin or cefotaxime intravenously.
Add anaerobic coverage (clindamycin or metronidazole [Flagyl]) if peritonitis or
perforation is suspected.
6. Monitoring for gastrointestinal bleeding.
7. Strict monitoring of fluid intake and output.
8. Removal of potassium from intravenous fluids in the presence of
hyperkalemia or anuria.
9. Laboratory monitoring. Check CBC, platelet count, and electrolyte panel
every 12-24 h until stable.
10. Septic workup L p ??
11. Radiologic studies.
B. Management of stage I.
Start the basic NEC protocol described in section VII,A. If all cultures are negative and the infant has improved clinically, antibiotics
can be stopped after 3 days. The infant may also be fed after 3 days if clinically improved.
C. Management of stages IIA and B
1. Basic NEC protocol, including antibiotics for 10 days (see section VII,A,5).
2. NPO for 2 weeks. Oral feedings may be started 7-10 days after radiographic resolution of pneumatosis.
3. Continue and advance TPN to achieve a caloric intake of ³90-110 cal/ kg/day.
4. Respiratory support. Appropriate level of ventilatory support to correct hypoxia and respiratory and metabolic acidosis and
maintain acceptable arterial blood gas parameters. Progressive abdominal distention causing loss of lung volume may increase the
need for positive-pressure ventilation.
5. Fluid and electrolyte management. Adjust total fluid intake, making allowance for third space losses, transfusion of blood
and blood products, and prerenal and renal failure. Hyperglycemia resulting from glucose intolerance frequently complicates fluid
and electrolyte management of the extremely low birth weight (ELBW) infant with NEC.
6. Surgical consultation is required.
7. Low-dose dopamine infusion. Low-dose dopamine infusion (2-4 mg/ kg/min) to improve intestinal blood and renal
perfusion in low-flow states. (This practice varies among institutions.)
D. Management of stages IIIA and IIIB
1. Basic NEC protocol, as described in section VII,A.
2. Plus stage II management, as described in section VII,C.
3. Blood pressure support. Refractory hypotension is common and multifactorial in origin. Treatment includes replacement of
ongoing fluid losses, volume expansion with colloids (see Chapter 46), and vasopressors such as dopamine (for dosage, see
Chapter 80). The goal is to maintain adequate mean blood pressure (see Appendix C) and urine output (1-3 mL/kg/h).
4. Progressive leukopenia, granulocytopenia, and thrombocytopenia usually parallel a deteriorating clinical status.
Granulocyte transfusion and granulocyte colony-stimulating factor (G-CSF) are not routinely indicated. Blood and platelet
transfusions are frequently needed.
E. Surgical management
1. Exploratory laparotomy is indicated if there is evidence
of intestinal perforation.
2. Peritoneal drainage. In selected cases in unstable (or
3. Deteriorating clinical condition with failure to respond to
appropriate medical management.
a. Evidence of a persistent, fixed sentinel loop over 24
4. Right lower quadrant mass.
5. Abdominal wall erythema
6. Spontaneous intestinal perforation in the VLBW infant.
Breast milk has been shown to decrease
the risk and incidence of NEC.
Studies with the use of immunoglobulins
and prophylactic enteral antibiotics to
prevent NEC remain largely
A. NEC with perforation is associated with a mortality of 20-
B. Recurrent NEC is a rare complication.
C. Subacute or intermittent symptoms of bowel
obstruction resulting from stenosis or strictures of the colon and,
less commonly, of the small bowel are seen in ~10-20% of cases.
A barium enema is usually confirmatory.
D. Infants undergoing extensive surgical resection require
long-term parenteral nutrition, enterostomy care, and
management of short-gut syndrome. Chronic electrolyte
imbalance and failure to thrive are common.
E. In the absence of short-gut syndrome, growth, nutrition,
and gastrointestinal function appear to catch up and are normal
by the end of the first year.