necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most common newborn surgical emergency and the leading surgical cause of death in the neonatal intensive care unit. Since NEC is typically a disease of premature infants, as neonatal therapies evolve pediatric surgeons are asked to assess and treat increasing numbers of these patients. Non-operative management is the initial approach with surgical intervention reserved for the treatment of the complications of the disease. A universal optimal surgical strategy for NEC remains elusive despite decades of experience with this disorder.

Opportunities exist in improving our prevention and treatment of NEC as well as elucidating its complex pathophysiology [1].

see also Spontaneous Intestinal Perforation and Necrotizing Enterocolitis Exploration

Content in this topic is referenced in SCORE Necrotizing Enterocolitis overview


Necrotizing enterocolitis is primarily a disease of prematurity.

Which patients are at risk for necrotizing enterocolitis?

The incidence of necrotizing enterocolitis (NEC) is between 0.7 to 1.1 cases for every one thousand live births. It appears that the functional maturity of the gastrointestinal tract plays a crucial role in determining the risk for the development of NEC with the overwhelming majority of cases occuring in premature infants. Only seven to thirteen percent of cases occur in full term infants.

In extremely low and very low birth weight (ELBW and VLBW) populations the incidence may be as high as ten percent with the greatest incidence being in smaller infants. The incidence decreases as birth weight and gestational age increase. Small for gestational age (SGA) infants are not at particularly increased risk for NEC [2]. Most affected infants have received enteral nutrition.

NEC that develops after one week of age tends to be in younger infants (average gestational age of 33 weeks). NEC that develops in the first week of life is more commonly associated with more mature infants (average gestational age of 36 weeks).

Approximately 4500 hospitalizations occur each year due to NEC. The highest incidence is in male non-Hispanic black VLBW newborns. Average length of hospital stay is fifty days with an overall mortality of twenty-five percent.

What are the other risk factors for necrotizing enterocolitis?

Peripartum events that are associated with NEC include absent or reversed end diastolic umbilical artery blood flow [3], maternal eclampsia, fetal distress and premature rupture of membranes. Postnatal risk factors include asphyxia, hypothermia, respiratory distress syndrome, apnea, congenital heart disease, persistent fetal circulation, persistent ductus arteriosus and sepsis. Infants with gastroschisis and Hirschsprung disease also have a higher incidence of NEC.


Necrotizing enterocolitis is the result of mucosal compromise in the presence of pathogenic bacteria that is often associated with the introduction of enteral feedings in a susceptible host. This leads to bowel injury and an inflammatory cascade.

What is the pathophysiology of necrotizing enterocolitis?

The complete pathophysiology of necrotizing enterocolitis (NEC) is multifactorial [4][5] and has yet to be fully elucidated (see Research and Future Directions). Failure of the intestinal barrier is crucial to the development of NEC. The normal intestinal barrier has several non-mechanical and mechanical components including motility, digestion, the mucus coat and tight junctions.

Various contributing factors have been implicated in the development of NEC including microcirculatory changes and inappropriate inflammatory responses. Disruption of the intestinal epithelium occurs which allows enteric bacteria to gain entry to the lymphatic and portal venous systems causing pneumatosis and portal venous gas. Gastrointestinal motility normally develops during the third trimester and continues to mature through the eighth month of gestation. Decreased motility in the premature infant increases the amount of time potential noxious agents may be in contact with the mucosa. The premature intestine also has an diminished ability to absorb nutrients which can lead to epithelial injury due to a decreased intestinal luminal pH.

Mucin is an important protective barrier for the intestinal mucosa. Mature mucin has an increased buffering ability, higher viscosity and greater resistance to bacterial breakdown. Premature infants have immature goblet cells leading to inadequate and immature mucin production. Deficient mucin production may decrease the resistance of the epithelial lining to bacterial invasion leading to the development of NEC.

Tight junctions are responsible for the semipermeable properties of intestinal epithelial cells. In the premature infant these junctions may be immature allowing increased mucosal permeability. Cytokines produced in response to bacteria and their byproducts such as lipopolysaccharide also cause increased permeability.

Some studies suggest that bile acid metabolism may play a role in NEC. Ileal bile acids may be increased in premature infants due to low levels of ileal bile acid binding proteins that are needed to transport bile acids into the portal circulation. Formula fed infants have more bile acids than those fed breast milk which may contribute to the development of NEC.

What growth factors and cytokines have been shown to be associated with either the prevention or development of necrotizing enterocolitis?

Growth factors and cytokines play a role in the pathophysiology of NEC. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are present in human breast milk and have been shown to be important in gastrointestinal tract development. These growth factors improve proliferation and differentiation of intestinal epithelial cells, decrease epithelial cell apoptosis and promote healing of damaged mucosa after injury. Decreased levels of these growth factors have been associated with the development of NEC [6]. Animal models suggest that administration of these growth factors may reduce the severity and incidence of NEC (see Research and Future Directions).

Interleukin-2 (IL-2) is a proinflammatory cytokine associated with shock, multiorgan failure and death. Platelet activating factor (PAF) causes vasoconstriction, capillary leakage and increases the permeability of the intestinal mucosa. Increased levels of IL-2 and PAF have been demonstrated in infants who develop NEC [7]. Erythropoietin is present in human breast milk. Classically associated with the regulation of red blood cell production it may also have a role in gastrointestinal tract development. Immunoglobulin-A is normally found in the mucin layer of the gut where it binds bacteria and viruses. Neonates deficient in Ig-A have an increased susceptibility to mucosal infections.

What differentiates spontaneous intestinal perforation (SIP) from classic necrotizing enterocolitis?

see Spontaneous Intestinal Perforation


Current evidence indicates that the use of human breast milk and probiotics decrease the risk of necrotizing enterocolitis.

Until the cellular, biochemical and molecular mechanisms of intestinal injury in necrotizing enterocolitis (NEC) are further elucidated, therapy directed at interrupting the disease process once it has begun will be elusive. Currently, medical therapy of NEC consists of antibiotics and supportive care (see Medical Treatment). Surgical therapy is essentially reserved for the treatment of complications such as perforation, smoldering sepsis and stricture (see Indications for Surgery).

Therefore neonatal management strategies that are shown to prevent NEC are likely to play the biggest role in improving outcomes [8]. The table lists the strategies that are corroborated by meta-analysis, randomized studies or retrospective cohort studies. Those strategies receiving the most current attention are the use of human breast milk, prophylactic probiotics and conservative enteral feeding.

Suggested strategies to prevent NEC

early human breast milk feeding with standardized advancement

minimize unnecessary antibiotic exposure

minimize acid blockade

remove central venous access as soon as possible

enteral nutrition fortification with human milk based fortifiers or elemental formula

avoid elective transfusions and extreme anemia

avoid traditional nasal CPAP

Does the use of human breast milk rather than formula prevent the development of necrotizing enterocolitis?

Human breast milk (HBM) includes many beneficial antimicrobial and anti-inflammatory factors such as secretory immunoglobulins, cytokines, lactoferrin, lysozyme and growth factors. The oligosaccharides in HBM help to colonize the intestine with beneficial flora.

Meta-analyses of smaller studies and a larger randomized trial [9][10][11] indicate that the use of HBM feeds reduces the relative risk of NEC, decreases the risk of death and decreases the risk of developing NEC that requires an operation when compared to formula feeding.

Formula feeding of premature and low birth weight infants does offer the advantage of better weight gain along with increased length and increased head circumference growth compared to HBM. The lack of available mother or donor breast milk and the frequent need for caloric supplementation with either formula or fortifier limit the exclusive use of HBM. ExPERT

Do prophylactic probiotics reduce the rate of necrotizing enterocolitis?

The character of the bacterial flora in the premature infant intestine likely plays a role in the pathogenesis of NEC with premature infants displaying a delay in colonization with beneficial bacteria. Probiotics are enteral supplements that contain viable microorganisms thought to be beneficial to the developing gut. In addition to promoting the colonization of commensal intestinal flora and decreasing the aberrant overgrowth of pathogenic bacteria, probiotics also promote intestinal host defenses, decrease bacterial translocation and decrease intestinal inflammation.

A meta-analysis indicates that probiotics significantly reduce the incidence of severe NEC in very low birth weight infants [12][13]. The best results were obtained with the use of two or more species administered for at least seven days. Patients receiving probiotics had reduced overall and NEC specific mortality, total hospitalization days and time to reach full enteral feeds. Days on total parenteral nutrition did not differ. There were no differences in long-term neurodevelopmental outcomes. ExPERT

Current widespread probiotic use is prevented by the broad range of doses (0.056 to 6 x 107 to 109 colony forming units/day) and bacterial strains (Bifodobacterium, Lactobacillus, Saccharomyces) used in the studies, the theoretical risk of sepsis and obstacles to regulatory approval for the use of probiotics as a supplement versus a drug. In the absence of specific evidence or recommendations, the use of probiotics in extremely low birth weight infants should be viewed cautiously (see Research and Future Directions).

Does the timing, rate of advancement or method of delivery of feeds affect the development of necrotizing enterocolitis?

Early enteral feeding of premature infants is beneficial in terms of promoting weight gain and decreasing the need for parenteral nutrition. Unfortunately, it also appears that the early and rapid provision of substrate may traumatize the immature gut and promote pathogenic bacterial growth leading to NEC.

The practice of minimal enteral nutrition (trophic feeding or gut priming) delivers 15 to 20 mL/kg/d of enteral nutrition initiated within one to three days of life and appears to not increase the rate of NEC compared to fasting. A meta-analysis indicates no detriment for a rapid systematic advancement of feeds (30 to 35 mL/kg/d) in very low birth weight infants [14]. Limited data exists to direct feeding strategies in extremely low birth weight infants. ExPERT

Because the maturation of sucking and swallowing mechanisms occurs at approximately 32 weeks of gestation, most very low birth weight infants require tube feeding. Intermittent bolus feeds may imitate normal feeding but continuous feeding may decrease feeding intolerance. A systematic review failed to identify a difference in the incidence of NEC between bolus and continuous feeds [15].


The modified Bell staging criteria provide a useful way to describe patients in order to guide therapy and compare outcomes[16].

What is the staging system for necrotizing enterocolitis?

Necrotizing enterocolitis (NEC) is an extremely variable disease with a broad spectrum of presentation and severity. In general, stage I patients have a clinical suspicion of NEC, stage II patients have definitive NEC and stage III patients have advanced NEC [17].

Stage I disease is treated non-operatively, Stage II disease may or may not require surgery and Stage III disease nearly always requires surgical intervention.

Modified Bell staging criteria


Systemic findings

Abdominal findings


IA (suspected)

perinatal stress, temperature instability, apnea, bradycardia, lethargy

feeding intolerance, distension, occult blood in stool

normal, intestinal dilation, mild ileus

IB (suspected)

same as above

gross blood in stool

same as above

IIA (definite, mildly ill)

same as above

absent bowel sounds, tenderness

pneumatosis intestinalis

IIB (definite, moderately ill)

metabolic acidosis, thrombocytopenia

cellulitis, mass

same as above plus ascites

IIIA (advanced, severely ill, intact bowel)

hypotension, bradycardia, respiratory/metabolic acidosis, DIC, neutropenia

same as above plus peritonitis

same as above

IIIB (advanced, severely ill, perforated bowel)

same as above

same as above



Infants with early necrotizing enterocolitis display nonspecific findings that become more definitive as the disease progresses. The diagnosis of necrotizing enterocolitis is usually confirmed with radiographs.

What are the presenting signs and symptoms of an infant with necrotizing enterocolitis?

Early signs of necrotizing enterocolitis (NEC) are those of systemic illness and sepsis including apnea, bradycardia, temperature instability, lethargy, feeding intolerance, hypoglycemia, hypotension and worsening respiratory failure. Abdominal distention, bilious emesis, blood in the stool or an ileus pattern on abdominal radiograph should lead to a suspicion of NEC.

As disease severity increases additional specific findings develop including abdominal tenderness, absent bowel sounds and pneumatosis intestinalis on radiograph.

Patients with advanced disease have evidence of intestinal perforation such as abdominal wall discoloration and edema, cellulitis, a palpable abdominal mass and pneumoperitoneum associated with signs of severe sepsis such as metabolic acidosis, thrombocytopenia, neutropenia and disseminated intravascular coagulation.

abdominal wall discoloration

Thrombocytopenia is present in 65-90% of infants with NEC and is due to gram negative sepsis with platelet binding by endotoxin. A low or rapid fall in platelet count tends to be associated with sicker infants and a poorer prognosis. Obtaining serial platelet counts may be helpful as a marker for progression of disease and assist in determining the need for and timing of operative intervention.

Infants with NEC may have either neutropenia or leukocytosis with counts lower than 6000 cells/mm3 associated with gram negative sepsis. Those with more significant neutropenia tend to have a poorer prognosis.

How is necrotizing enterocolitis or spontaneous intestinal perforation influenced by the administration of indomethacin?

Indomethacin used to treat patent ductus arteriosus (PDA) has been associated with both NEC and spontaneous intestinal perforation (SIP)[18]. The drug causes vasoconstriction by blocking prostaglandin synthetase and thus may increase vascular resistance thereby reducing local blood flow and tissue oxygenation. One study noted that indomethacin increased the incidence of NEC prior to 30 weeks gestational age but not after 32 weeks. Other studies have not corroborated that finding. A recent Cochrane review noted that ibuprofen may be as effective as indomethacin in closing a PDA while associated with a decreased incidence of NEC.

Although enteral feeds are often discontinued while treating with indomethacin due to concerns for NEC, continued feeding does not appear at raise the risk of NEC or SIP in those patients on indomethacin [19]. ExPERT

What other medical issues and treatments are associated with the development of necrotizing enterocolitis?

Maternal preeclampsia is predictive of NEC in premature infants with an odds ratio of 1.74 (95% confidence interval) [20].

Inhibitors of gastric acid secretion are associated with NEC (OR:1.78) as well as other infections such as sepsis, pneumonia and urinary tract infections in the very low birth weight (VLBW) population [21].

Transfusion associated necrotizing enterocolitis (TANEC) describes NEC that occurs within 48 hours of red cell transfusion. Evidence related to TANEC is limited to observational retrospective studies [22] while more recent case control studies did not show higher incidence of NEC in transfused patients. However, two studies do support holding feedings during transfusion and another study documented changes in mesenteric blood flow during red cell transfusion [23].

Prolonged initial empirical antibiotic treatment in patients with sterile cultures are associated with increased NEC. These antibiotics are thought to adversely alter the intestinal microbiome[24].

Which full term infants are at risk for necrotizing enterocolitis?

colonic pneumatosis

Colonic pneumatosis in a full term infant.

Approximately ten percent of NEC occurs in full term infants. These patients are more likely to have comorbid conditions such as congenital heart disease, polycythemia, sepsis or hypotension [25]. In more mature gestational infants the disease tends to present more commonly in the first week of life [26][27], although those full term infants who present at an age greater than one week have a worse prognosis [28]. Full term patients with NEC are more likely to have colonic involvement and require surgery.

The management of these infants is somewhat controversial as some studies suggest early intervention is best while others note that the indications for surgery are similar to those in the premature age group.

The evidence seems to indicate that NEC outcomes are similar for term and premature infants.ExPERT


Abdominal radiographs indicating pneumatosis are a common finding in necrotizing enterocolitis and pneumoperitoneum is an indication for surgical intervention.

What radiographic findings are associated with necrotizing enterocolitis?

pneumatosis intestinalis

Pneumatosis intestinalis is found on abdominal radiographs in 19 to 98% of infants with necrotizing enterocolitis (NEC) and may be either cystic or linear. Pneumatosis is pathognomonic but not specific to NEC and may be found in a variety of other conditions including malrotation with midgut volvulus, Hirschsprung disease, carbohydrate intolerance, inspissated milk syndrome and pyloric stenosis.

Portal venous gas is seen in ten to thirty percent of NEC patients and is likely a marker for more significant disease. It is seen in 61% of patients found to have less than twenty percent of viable bowel (NEC totalis). Portal gas is a fleeting finding and may be present more often than is thought. In some series portal gas has been considered an indication for surgery but other reports use it as only one data point in deciding when to operate. There are ample reports of infants with portal gas being successfully managed non-operatively.

Pneumoperitoneum, seen in twelve to thirty percent of NEC patients, may be noted on a decubitus film or may be present as outlining of the falciform ligament (the football sign). Lateral decubitus radiographs or cross table lateral films may be more sensitive in identifying free air. Pneumoperitoneum is present in only 63% of infants subsequently surgically proven to have perforation. Free air in the abdomen may also result from pneumomediastinum or pneumothorax in infants with pulmonary disease who are on high positive pressure ventilation.


Pneumoperitoneum on a supine anterior/posterior abdominal radiograph.

Plain abdominal radiographs revealing a persistent dilated fixed loop(s) of bowel over 24 to 36 hours may represent circumstantial evidence of full thickness necrosis. Some authors regard it as an indication for operation since intestinal necrosis requiring surgery occurs in nearly fifty percent of patients with a fixed loop. However there are reports of a significant number of these infants recovering without surgery.

What is the role of other imaging modalities in the management of necrotizing enterocolitis?

Additional radiographic studies have been evaluated such as ultrasound (US), computerized tomography and magnetic resonance imaging. US may be of some benefit as it can discern ascites, intestinal perfusion, vascular orientation and bowel wall thickness. It may also be able to identify pneumatosis and portal venous gas not seen on plain radiograph.

Although the role of US is not clearly defined in the diagnosis of NEC it seems most helpful in identifying patients with complex ascites associated with a gasless abdomen on radiograph and in directing paracentesis.

What is the role for paracentesis in managing necrotizing enterocolitis?

Paracentesis may be a very useful means of confirming intestinal perforation of any cause. Sonographic guidance assists in obtaining peritoneal fluid and avoiding aspirating contents from dilated loops of bowel. A positive aspirate (pus, free stool or a positive gram stain) is indicative of perforation and the need for operative intervention.


Necrotizing enterocolitis predominantly occurs in the small intestine.

What is the appearance of necrotizing enterocolitis affected bowel?

necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a variable disease. It can affect the entire bowel or just a single location but is usually patchy and seen in multiple segments of the small bowel with a predilection for the ileal-cecal region. NEC does not typically involve the stomach, duodenum, or the rectum and the first five to ten centimeters of proximal small bowel are often spared.

The appearance of the bowel also varies depending upon the degree of ischemia. Subserosal gas may be noted consistent with pneumatosis intestinalis with viable, non-perforated intestine visible below. The intestines are often distended, thin-walled and very susceptable to iatrogenic injury during exploration.

More severely affected areas can be divided into those that are ischemic, those with partial thickness necrosis and those with full thickness necrosis and perforation. Areas of ischemia may be gray or black and at times the bowel may appear to be white consistent with liquefactive necrosis compatible with impending perforation. Most comonly the histology shows inflammation and coagulation necrosis.

The pattern of spontaneous intestinal perforation and NEC are different than the more diffuse pattern seen in the setting of mesenteric ischemia associated with congenital heart disease.

What is necrotizing enterocolitis totalis?

The term NEC totalis is used to describe the operative findings in which at least eighty percent of the entire bowel is gangrenous. It is associated with a nearly one hundred percent mortality in patients less than 1000 g and all of the survivors will manifest severe short bowel syndrome. When found at exploration performing a proximal stoma and mucous fistula may allow the distal bowel to declare whether it is salvageable and even lead to healing. In addition, the potential ability to offer bowel transplantation to such patients has complicated the operative decision making. Nonetheless, the path for a premature patient considering transplantation following NEC totalis is one that is associated with high morbidity and mortality and many surgeons would suggest that aggressive operation and care should be avoided in the setting of NEC totalis.

Medical Treatment

The initial treatment of most patients with necrotizing enterocolitis is non-operative. Bowel rest and parenteral antibiotics are successful in fifty to seventy-five percent of patients.

What is the optimal medical management of necrotizing enterocolitis?

The process of tissue destruction has already begun by the time necrotizing enterocolitis (NEC) is clinically suspected. Medical management is intiated immediately including consists of bowel rest, sump orogastric decompression, intravenous fluid resuscitation, broad spectrum antibiotics and parenteral nutrition. A complete blood count, blood gas, C-reactive protein, serum electrolytes, blood cultures, abdominal radiographs and urine cultures are obtained.

For patients who require pulmonary support, endotracheal intubation and mechanical ventilation are preferred over nasal cannula or continuous positive airway pressure to avoid abdominal distention. Based on the condition of the patient, vasopressor support may be needed for hemodynamic instability and transfusions may be required to treat anemia, thrombocytopenia and coagulopathy. Parenteral pain medicine is usually required.

What antibiotics are used to treat necrotizing enterocolitis?

Broad spectrum antibiotics including anaerobic coverage are administered. Recommendations range from ampicillin, gentamicin and clindamycin to a third generation cephalosporin combined with metronidazole and also vancomycin if nosocomial flora include methicillin resistant staphylococcus [29][30]. Several studies have failed to identify a specific evidence-based antibiotic regimen or course [31]. Interestingly, the use of clindamycin may be associated with subsequent intestinal stricture formation [31][32]. ExPERT

Fungal therapy should be initiated if the course is prolonged as fungal sepsis is prevalent in patients who subsequently die from NEC.

How are medically treated patients with necrotizing enterocolitis followed?

Serial abdominal examinations, radiographs and laboratory studies are obtained every six to eight hours in order to monitor the patient’s response. A stable or improving patient can continue to be managed expectantly and the frequency of studies can be tapered accordingly. Clinical deterioration or worrisome radiographs should prompt surgical consultation.

Antibiotic therapy and total parenteral nutrition should continue for seven to fourteen days if NEC is strongly suspected. Enteral feedings can be restarted at that time if bowel function has returned.

Patients that are successfully managed medically presumably have intestinal necrosis that is less than full thickness. However, these patients remain at risk of developing intestinal strictures as healing and scarring occur. Patients that develop signs of an intestinal obstrution following non-operative management of NEC may require contrast studies (enema followed by upper intestinal with follow-through) to rule-out a stricture.

Indications for Surgery

Pneumoperitoneum or a positive paracentesis remain the only absolute indications for surgery in infants with necrotizing enterocolitis but are not always present in patients with full thickness intestinal gangrene or perforation. Additional clinical criteria combined with deterioration should prompt consideration for intervention.

Given that a majority of infants with necrotizing enterocolitis (NEC) will respond favorably to medical therapy (antibiotics, bowel rest and serial evaluations) it is important to determine which patients would benefit from a procedure and the optimal timing. Ideally the twenty to forty percent of patients who require surgical intervention would be identified prior to developing full thickness intestinal necrosis and perforation. At this time no criteria exist that uniformly predict the presence of intestinal gangrene with impending perforation.

What are the absolute indications for surgical intervention in necrotizing enterocolitis?

The absolute indications for surgical intervention are pneumoperitoneum and a positive paracentesis since they are indicative of intestinal perforation [33][34].

Since pneumoperitoneum is an indication for surgery, serial abdominal radiographs (see Medical Treatment) are integral to the medical management of infants with NEC. Unfortunately, one third of NEC patients with perforation will not display free air on radiograph.

Another surgical indication is a positive paracentesis containing intestinal contents such as stool, bile, cloudy fluid or bacteria on gram stain [35]. A negative paracentesis or the return of clear fluid does not rule out a localized or walled off perforation.

At times increasing distention, ascites and bowel edema may raise the infant’s intra-abdominal pressure sufficiently to cause abdominal compartment syndrome with compromised perfusion and deteriorating respiratory status. Urgent laparotomy and decompression with silo placement may be life-saving.

What are the relative indications for surgical intervention in necrotizing enterocolitis?

Many patients with full thickness intestinal necrosis related to NEC will not have pneumoperitoneum or a positive paracentesis. In these situations additional clinical findings may provide sufficient circumstantial evidence of necrosis or perforation to warrant surgery.

While not specific enough to be absolute indications for surgery the finding of abdominal wall cellulitis and edema, a palpable abdominal mass, or a dilated persistent fixed loop(s) on abdominal radiograph [36] are suspicious for full thickness intestinal necrosis. Clinical deterioration despite maximal medical management manifested by hemodynamic instability, increasing pressor and ventilatory requirements and worsening laboratory abnormalities (acidosis and thrombocytopenia) are also relative indications that the patient may benefit from surgical intervention [37].

Complex ascites on abdominal ultrasound correlates well with subsequent surgical findings of intestinal gangrene or perforation [38]. Paracentesis or ultrasound may be particularly useful in patients with a gasless abdomen and apparent ascites on radiograph.

Portal venous gas or extensive pneumatosis on radiograph has been used as an indication for operation by some surgeons but one prospective study noted that almost half of the patients with portal venous gas survived without operation [39].

Kosloske performed a probability analysis for many of the potential indications for intervention.

Probability analysis for potential indications for surgical intervention [34]


Sensitivity (%)

Specificity (%)

Positive predictive value (%)





portal venous gas




fixed loop




abdominal mass




abdominal wall erythema




positive paracentesis




severe pneumatosis




clinical deterioration




Surgical Decision Making

What is the role of primary peritoneal drainage for the treatment of necrotizing enterocolitis?

peritoneal drainage

In 1977 Ein et al described the effectiveness of peritoneal drainage in premature newborns with necrotizing enterocolitis (NEC): approximately one third of patients required exploration soon after drain placement, one third required an operation at some point later in their course and one third did not require further operative intervention [40]. In general, primary peritoneal drainage has become a consideration for premature newborns weighing less than 1500 gm. Although this approach remains controversial, the initial randomized controlled trial comparing peritoneal drainage with laparotomy suggested that the outcome is equivalent in terms of mortality, length of stay and dependence on parenteral nutrition [41].

A second randomized controlled trial suggested that laparotomy was required in 74% of patients managed initially with peritoneal drainage [42]. A systematic review has come to the same conclusion [43].

A prospective, albeit nonrandomized, cohort study also showed no significant difference in survival, intestinal strictures or intra-abdominal abscesses. However, this study did suggest improved long term neurodevelopmental outcomes with initial laparotomy in that 38% of survivors suffered neurodevelopmental impairment compared to 68% of those with initial peritoneal drainage [44]. ExPERT

This question is being subjected to further clinical trials that include longer term follow up of neurologic outcome.

In a propensity-matched cost analysis drainage alone and laparotomy alone had similar overall inpatient costs. Not surprisingly, drainage followed by laparotomy was the most expensive [45]. ExPERT

How is a peritoneal drainage procedure for necrotizing enterocolitis performed?

These are usually very ill infants on mechanical ventilation who should are likely already receiving parenteral pain medications. A site in the right lower quadrant is chosen and the area prepped and draped. A small amount of local anesthesia is infiltrated in the skin taking care not to pass the needle tip through the very thin abdominal wall. An eight to ten millimeter incision is created in the right lower quadrant. Cautery can be used to dissect through the fascia however the wall may be so thin that it can be safely opened with the tip of a hemostat. Often a large amount of fluid or enteric contents are encountered and appropriate cultures are obtained. The abdomen is irrigated with warmed saline until clear.

Multiple types of drains and techniques have been described. Most often a Penrose drain is passed through the right lower quadrant incision to the other side of the abdomen. Some surgeons choose to bring the Penrose drain out of a counter incision in another quadrant of the abdomen and to sew the drain to itself externally. Others prefer a single exit site and sew the drain to one of the skin edges along with placing a safety pin through the drain to prevent it from passing entirely into the abdominal cavity. At all times injury to the liver is avoided so as to not induce hemorrhage [46]. Once a drain is placed studies have suggested that a subsequent exploratory laparotomy will not alter the outcome. Peritoneal drainage would seem to be most effective in the setting of spontaneous intestinal perforation [47] but is still effective in patients with NEC [48].

How should a patient with necrotizing enterocolitis be managed when they don’t respond to peritoneal drainage?

The randomized study by Rees et al found that drainage alone was sufficient definitive treatment in only eleven percent [42] and a meta-analysis concluded that drainage alone may be associated with increased mortality [48]. Current data suggest that drainage and laparotomy are equivalent but it is often difficult to forgo definitive operation when a newborn does not respond to peritoneal drainage. Although controversial, consideration should be given to exploring patients whose condition does not improve following peritoneal drainage in order to identify undrained sources of sepsis, remove necrotic intestine or identify NEC totalis.ExPERT

Preoperative Preparation

Patients with necrotizing enterocolitis who require surgery should be resuscitated and receive antibiotics.

How should necrotizing enterocolitis patients be prepared for surgery?

The preoperative approach to the newborn with necrotizing enterocolitis (NEC) is similar to any newborn with sepsis. Once the need for operation is clear, resuscitation is guided by peripheral perfusion and urine output. Ventilatory support is provided as required. Over resuscitation should be avoided because it may be associated with hepatic and pulmonary congestion. Anemia, thrombocytopenia and coagulopathy are corrected prior to surgery.

If not already being given for the medical treatment of NEC or sepsis, Vitamin K and broad spectrum antibiotics should be administered. Adequate venous access is mandatory and arterial access should be obtained if it will not significantly delay the procedure. A central venous catheter is often appropriate since the newborn will likely require prolonged fluid, nutritional and antibiotic support.

While the exploratory laparotomy is best performed in the operating room, the inability to transport the patient safely may require an operation in the newborn intensive care unit under as close to sterile operating room conditions as possible.

What is the best hospital environment for infants with surgical necrotizing enterocolitis?

The effect of the deregionalization of neonatal intensive care unit care on NEC survival has been studied. High level and high volume care centers achieved the lowest risk adjusted mortality from NEC. Interestingly, infants initially treated at a neonatal intensive care unit (NICU) with no surgical capability (Level II) had the shortest initial length of stay and the highest rate of acute transfer to facilities with the highest level of care (Level IIIC) with risk-adjusted mortality rates comparable to those born into Level IIIB/IIIC high-volume NICU [49]. ExPERT

Steps of the Procedure

see Necrotizing Enterocolitis Exploration

How is a peritoneal drainage procedure for necrotizing enterocolitis performed?

see Surgical Decision Making

Intraoperative Decision Making

see Necrotizing Enterocolitis Exploration

Postoperative Care

Postoperative support is typical for a patient with a gastrointestinal source of sepsis including orogastric decompression and parenteral nutrition. Most practitioners maintain the patient on antibiotics for seven to fourteen days. At that point enteral nutrition can be slowly restarted once bowel function returns. The success of enteral feedings is typically limited by the amount and quality of remaining intestine. Administration of medications to decrease stool output, such as pectin, or refeeding of stomal contents into a distal mucus fistula may enhance enteral feeding capabilities.

Stoma management in these small patients can be challenging. The early involvement of an experienced stoma therapy team is frequently beneficial to the nursing staff and family.


Given the critically ill patients who develop necrotizing enterocolitis, it should not be surprising that up to half of the surviving patients will have a complication.

The most frequent surgical complications are related to the wound (infection, dehiscence) and the stoma (stricture, necrosis, prolapse, retraction) [50]. The high rate of stoma complications should be anticipated given that one of the goals at surgery is often to exteriorize questionable intestinal segments in an effort to preserve length[51][52]. Patients who undergo primary peritoneal drainage are at risk for enterocutaneous fistula formation and hernia formation.

A rare but serious complication following resection and ileocolic anastomosis for necrotizing enterocolitis (NEC) is anastomotic ulcer [53]. Patients may present years later with lower gastrointestinal bleeding from an ulcer identified at colonoscopy. Although resection is recommended in patients with symptoms, the rate of ulcer recurrence is high.

What is the likelihood of intestinal stricture formation after an episode of necrotizing necrotizing enterocolitis?

Intestinal strictures result from fibrotic healing and scarring in an area of ischemia. Following an episode of NEC the reported rate of stricture formation varies widely from nine to 57% which reflects the heterogeneity of the disease and variable institutional biases in the management of NEC. Patients managed medically have a higher incidence of strictures than those who undergo surgery with resection [54]. More severe disease, as evidenced by systemic illness, a prolonged course, extensive pneumatosis and higher C-reactive protein levels are associated with subsequent stricture formation [55]. As many as one third of patients with a NEC-related stricture will have multiple strictures owing to the diffuse nature of the disease.

A stricture may become clinically significant six weeks or longer after the acute ischemic insult [56]. Up to three quarters of strictures identified early in the course of healing will resolve spontaneously.

Contrast study interrogation of defunctionalized intestinal segments must be performed prior to re-establishing continuity [57]. Despite this, strictures may be identified at the time of stoma closure or later when feeding intolerance develops.

Whether or not to prospectively study all medically treated patients with NEC to evaluate for stricture formation is controversial. Patients with a history of NEC who develop feeding intolerance, rectal bleeding or clinical signs of intestinal obstruction should be studied. Because the highest incidence of stricture formation is in the colon (80%) and ileum (15%), contrast enema should be the initial study. Strictures discovered in this fashion should undergo resection.

What is the risk of recurrent necrotizing enterocolitis?

Up to ten percent of patients with NEC will develop recurrent disease [58]. It can develop weeks to months after the initial episode, often in response to additional stress such as a cardiac surgical procedure or hypotension. Neither feeding strategies nor antibiotic choice seems to effect the development of recurrent NEC.

Similar to primary NEC, three quarters of patients with recurrent NEC will respond to nonoperative medical management [59].

What is the risk of intestinal failure associated liver disease and short bowel syndrome in patients surgically treated for necrotizing enterocolitis?

Seventy percent of surgically treated patients will develop signs of intestinal failure associated liver disease (IFALD). Those with prolonged exposure to parenteral nutrition, extensive small intestinal resection and proximal jejunostomy are most at risk [60]. Use of an early postoperative enteral feeding schedule has been shown to decrease the rate of IFALD by forty percent [61].

Unfortunately, extensive intestinal resection of necrotic bowel is occasionally required [62]. Twenty-three percent of surviving surgically treated patients will manifest signs of SBS with NEC being responsible for half of the cases of SBS in children. The historic prediction that at least forty centimeters of small intestine are required for eventual transition to full enteral feeding is likely too simplistic. The health, function and location of the remaining intestine are more important than the absolute length or the presence of the ileocecal valve[63]. Given the poor adaptability of the jejunum, patients with extensive ileal resections fare worse. Conversely, due to the ability of the ileum to adapt, patients with resections limited to the jejunum tend to do better.


The mortality from necrotizing enterocolitis is related to birth weight, gestational age and the need for surgery [64]. Short bowel syndrome and neurodevelopmental abnormalities are long-term issues.

What is the mortality rate for patients with necrotizing enterocolitis?

The overall mortality rate for neonates with necrotizing enterocolitis (NEC) is 25 to 30%. For those treated non-operatively the mortality varies directly with birth weight and gestational age, ranging from approximately fifteen percent for infants weighting 1250 to 1500 gm to over forty percent for infants weighing less than 750 gm [65].

The distinction of medically versus surgically treated NEC is critical because the requirement for surgery correlates with the rate of complications, length of stay and mortality (up to fifty percent). Interestingly, mortality in neonates with NEC undergoing surgery is less linked to birth weight in the higher birth weight groups, perhaps related to the greater disease severity in surgically treated NEC [66].

A significant fraction of the mortality in surgically treated patients accrues from those with NEC totalis or panintestinal involvement.

What are the long-term growth and neurodevelopmental issues for neonates with necrotizing enterocolitis?

Short bowel syndrome (SBS) is the most common long-term gastrointestinal complication. Long-term growth and development issues are present even in the absence of clinically apparent SBS and survivors are likely to remain below the fiftieth percentile for height and weight for years. Likewise, neurodevelopmental dysfunction is common including speech, motor and intellectual delay [67][68].

Research and Future Directions

As our understanding of the precise mechanisms of necrotizing enterocolitis pathophysiology improve, preventive and therapeutic strategies that are earlier, more focused and more effective will be possible. The following areas of research are being actively pursued in an effort to reduce the burden of this disease.

How does the intestinal microcirculation impact the development of necrotizing enterocolitis?

Animal models of necrotizing enterocolitis (NEC), as well as human specimens from infants with NEC, confirm that dysregulation of intestinal microcirculation plays an important role in the development of NEC [69]. This dysregulation results largely from an imbalance between endothelin-1 (ET-1), the primary vasoconstrictor in neonates, and nitric oxide (NO), the primary vasodilator in neonates [70].

ET-1 production has been shown to be upregulated in the face of hypoxia and various inflammatory cytokines[70]. Alternatively, sodium nitrate found in breast milk has been shown to increase NO production and improve intestinal microcirculation [71]. Active research is ongoing to better understand the complex opposing mechanisms controlling the intestinal microcirculation since modifying these mechanisms may represent a promising strategy for the prevention or treatment of NEC.

Measuring regional tissue oxygen uptake with near infrared spectroscopy (NIRS) represents a novel potential modality to detect NEC. NIRS can be used to measure mesenteric oxygenation in real time [72]. Although normative data for premature infants is sparse, NIRS may hold promise in identifying infants with poor intestinal perfusion.

What role does an infant’s innate immunity play in necrotizing enterocolitis progression?

Toll-like receptors (TLRs) are a vital component of the innate immune system. They stimulate the production of pro-inflammatory cytokines involved in host defense. Activation of TLRs, especially TLR4, has been linked to the development and progression of NEC. Up regulation of TLR4 produces NEC in animal models of disease while mice with mutated TLR4 are resistant to the development of NEC.

Potential therapeutic strategies are being investigated that exploit the relationship of TLRs and NEC. TLR4 inhibitors such as HSP70 may attenuate the development of NEC. CpG-DNA, which activates TLR9 and reduces TLR4 signaling is another potential treatment strategy. An increased understanding of the role of TLRs, and their potential as therapeutic strategies, is the subject of intense research and may play a central role in the treatment of NEC in the future [73].

Can probiotics be used to prevent necrotizing enterocolitis?

An altered intestinal microbiome has been linked to the development of neonatal NEC. Unlike adults, neonates have been shown to have a rapidly changing microbiome composed of a small number of bacterial species at any given time. Intestinal microbiomes also vary widely between neonates. Pathogenic bacterial colonization in premature infants has been implicated as a central factor in NEC development [74][75].

The use of probiotics represent a leading area of NEC research. The goal of probiotic use is to promote the formation of a beneficial and protective intestinal microbiome. Animal models have demonstrated attenuated inflammation and a reduced incidence of NEC with the administration of probiotics[76]. Human trials have shown that probiotic administration to very low birth weight premature infants reduces the incidence of severe NEC and mortality [12][13]. However, the risk of bacteremia from the introduction of live bacteria to premature babies with immature immune systems is a concern with probiotic administration. Questions that still remain regarding probiotic use include which strains of probiotics are most effective and which method of probiotic administration is superior [77]. In addition, strategies that produce longstanding beneficial alterations in the microbiome (rather than transient benefits) are being actively pursued.

What role does the enteric nervous system have in the development of necrotizing enterocolitis?

The enteric nervous system (ENS) is vital for intestinal motility and function. But it is not fully developed in premature infants and it is believed that this immaturity may contribute to the development of NEC. Also NEC induces significant damage to the neural and glial cells of the ENS resulting in worsened intestinal motility and increased morbidity. This ENS damage persists even after the resolution of acute NEC and is still present months later at the time of stoma closure in human infants. Therapeutic modalities aimed at improving intestinal motility may be beneficial in the prevention of NEC [78].

What role does stem cell therapy have in the management of necrotizing enterocolitis?

Administration of neural stem cells (NSCs) can protect the ENS from damage in experimental NEC. This preservation of the ENS results in improved intestinal motility, increased intestinal integrity and decreased mortality [79]. Other studies have shown that the administration of amniotic fluid-derived mesenchymal stem cells in animal models of NEC reduces inflammation and apoptosis, increases enterocyte proliferation and reduces the incidence and severity of NEC [80][81]. Active research is underway to better understand the mechanisms utilized by stem cells in protecting the intestines from NEC and how stem cell therapy can be incorporated into future treatment strategies for NEC.

Can growth factors be useful in the therapy for necrotizing enterocolitis?

Much attention has been directed at the administration of growth factors to prevent or treat NEC. Growth factors are naturally occurring proteins that stimulate cells to proliferate and to migrate which are very important components of restitution, the earliest component of wound healing of the intestine. In animal models of NEC, the addition of growth factors to the feeds delivered to pups results in protection from NEC. In addition, administration of feeds in conjunction with stem cell therapy, or genetic alteration of stem cells so that they over-express certain growth factors, confers even better protection from the disease. Growth factors that have been most frequently examined in this capacity include epidermal growth factor (EGF)[82] and heparin-binding EGF (HB-EGF)[83].

How can high risk patients be identified prior to the onset of necrotizing enterocolitis?

Given the nonspecific clinical findings of early NEC, and the fact that intestinal damage is often already severe by the time the diagnosis is made, early diagnosis and detection of patients at risk of developing the disease is a critical area of study [84].

Identification of serum or urine biomarkers which indicate a genetic predisposition to NEC, or which can distinguish early NEC from sepsis and medical NEC from surgical NEC, are desperately needed. Recently a number of urine proteins (A2ML1, CD14, CST3, FGA, PEDF, RET4, and VASN) were identified that provide accurate prognostic and diagnostic abilities in infants with suspected NEC [85]. Integration of these urine biomarkers with clinical parameters has been used to create an algorithm to predict NEC outcomes [86]. Refinement of this type of analysis may be very helpful in identifying those at risk of developing the disease in the future [87].

Since the development of NEC depends on the intestinal microbiome, it is not surprising that previous antibiotic use increases an infant’s risk of NEC. (see Presentation) Monitoring of the microbiome by fecal volatile organic compound analysis holds promise for identifying patients with NEC prior to the development of clinical symptoms [88]. ExPERT

Perspectives and Commentary

To submit comments about this topic please contact the editors at

Invited commentary from R. Lawrence Moss (January, 2015)

I congratulate the authors on a very thoughtful, concise, yet also comprehensive review of this complex topic. From a personal perspective, I believe necrotizing enterocolitis (NEC) is one of the few disorders in children’s surgery in which we have made no significant progress in improving patient outcomes over the twenty years of my career. While there have been important advances in our understanding of pathophysiology and the impact of various treatments, there is little evidence to suggest that babies with NEC are faring better than they did decades ago. This is colored by the fact that the population of infants with NEC is markedly different than it was years ago. We have made tremendous advances in neonatal care. Therefore babies that would have previously succumbed to other problems are now surviving to become “candidates” for the development of NEC. As care of the premature infant becomes increasingly refined, it is likely that the importance of NEC will only increase.

I hope the reader will not interpret these opinions as pessimistic. Rather, I hope they will be interpreted in the context of what a tremendous opportunity this disease represents for young pediatric surgeons committed to making meaningful advances that will improve our field and reduce suffering and death for our patients. NEC is a high impact, high mortality disease that occurs at the very beginning of life. Even a modest reduction in morbidity and mortality will have a significant impact. A large proportion of infants who get NEC would be able to live full and productive lives if we could prevent or ameliorate the disease. It is my personal bias that this is an area that deserves strong focus by the upcoming generation of researchers in pediatric surgery.

There is nothing in this excellent review with which I significantly disagree. I’ll offer personal comments in a few areas in order to amplify the text. What follows reflects my personal opinion and interpretation of available information. I ask the reader to consider my comments in this context and understand that others may have markedly different and equally or more valid viewpoints.

Risk factors and clinical studies

With respect to risk factors for NEC, the literature is replete with extensive epidemiologic studies examining the correlation between numerous factors with NEC. Many are retrospective; some are prospective. Most correctly utilize multiple regression analyses and other advanced statistical techniques. The bottom line, in my opinion, is that the only demonstrable meaningful risk factor for NEC is prematurity. Nothing else. This was true thirty years ago and it remains true today. Some investigators have gone as far as to argue that it is not even possible that clinical variables will ever be able to predict who will get NEC. In my view, the absence of identifiable risk factors is at the core of why we have not made meaningful advances in the care of these patients.

The NICU is full of premature infants. We have no idea which ones will get NEC, which of these will develop surgical NEC, and which of these will die. Given the low incidence of NEC the inability to risk stratify patients makes meaningful study of drugs and other interventions virtually impossible. A study of any potential intervention must be applied to every premature baby in the NICU since they are essentially all at risk. Even if the intervention is moderately effective, the adverse consequences that might occur in the over ninety percent of patients who aren’t going to get NEC would likely exceed the benefit. Thus, these studies never get started. Pharmaceutical companies are well aware that adverse event rates for virtually anything are very high in premature infants. If the disease of interest cannot even be risk stratified in this fragile population, it’s nearly impossible to design a study that is justified in terms of patient risk. For this reason, I believe it is crucial that current research focus on developing a means to risk stratify premature infants for NEC. I am especially intrigued by ongoing work looking at biomarkers and genetic information identified via high-throughput molecular techniques. In full disclosure, I have been personally involved with some of this work.

Laparotomy vs peritoneal drainage

There has been much written regarding the choice between laparotomy and primary peritoneal drainage (PPD) for perforated NEC. This is well covered in the topic content. I will add my personal view of the available evidence. The preponderance of evidence suggests that the choice of operation for perforated NEC does not affect the outcome. It doesn’t matter. It doesn’t matter. It doesn’t matter. I have heard numerous experienced and highly skilled surgeons argue a myriad of nuances to suggest why he or she believes that in a certain population or a certain setting or a certain gestational age, or a certain weight etc. that one of these operations is better than the other. I disagree with this. As much as we surgeons would sincerely like to believe otherwise, a large amount of evidence suggests that, “it doesn’t matter.” Until newer evidence refutes this, I encourage the practicing surgeon to accept this. There may be social, ethical, or even religious reasons to choose one treatment over the other. This is fine, but there is no reason to think that outcome will be affected.

I am particularly convinced of this because of the marked difference in randomized trial design between the US and UK multicenter trials on this topic. Despite wide variation in design both found no difference in outcome between the treatments. The US trial was conducted in major referral centers, protocols were rigorous and adhered to, postoperative care was uniform, there were no patients from the developing world, laparotomy following drainage was not allowed and rarely performed and the trial included patients up to 1500 gm. The UK trial was conducted in all types of clinical environments representing the spectrum of NEC in the world, care was determined locally without constraints of protocol, postoperative care varied widely, there were many patients from the developing world, laparotomy following drainage was encouraged and widely performed and the trial included only patients up to 1000 gm. The results of the two trials were strikingly similar. The choice of operation did not affect the outcome. My belief that this is the correct interpretation of the evidence is at the heart of why I believe that developing the knowledge to risk stratify premature infants is so critical to making an impact on NEC. I believe that once NEC has evolved to the point where surgical treatment is indicated the chance of impacting patient outcome is remote. I await the results of an ongoing study to see whether long term neurodevelopmental outcome is affected by choice of operation.

This relates to the issue of whether laparotomy after peritoneal drainage is beneficial. Can a patient who undergoes PPD and is not doing well (remember up to one half of all patients with surgical NEC are going to die) be salvaged with subsequent laparotomy? My interpretation of the available evidence is that they cannot. There is some evidence in the literature that patients who are doing poorly after PPD and undergo “salvage laparotomy” actually fare even worse than if laparotomy is not done. Further support that laparotomy after PPD will not alter outcome comes from the two randomized studies, one of which prohibited it while the other encouraged it. The findings from these studies did not differ.

NEC-related strictures

I have a personal comment regarding post-NEC strictures that comes only from my anecdotal experience for which I have no evidence to support. I believe that the evolutionary process of post-NEC intestinal stricture takes roughly six weeks. I do not believe in operating on these strictures earlier than six weeks regardless of the size and weight of the infant. As the chapter points out many of these strictures will resolve spontaneously and therefore operation might be unnecessary. On the other hand, I have observed multiple cases where a stricture was resected only to have it recur a few weeks later or have a new stricture develop in another area in the early postoperative period. In my opinion, this happens because an evolving process was occurring at the time of operation that could not be reflected in the preoperative radiographs. A second operation can be avoided by letting the process evolve to conclusion before the first operation.


Finally, with respect to long-term outcomes I believe it is important to recognize that the outcome of age matched premature infants to infants with medical NEC is virtually identical. Virtually all of the significant morbidity and mortality from NEC occurs in the surgical group. This justifies significant attention specifically to this group. It justifies research efforts to determine which patients are at greatest risk of this extent of disease, efforts to better understand the pathophysiology at this stage and trials to test new therapies in this population. While the choice of surgical procedure is not relevant to the outcome, the surgeon remains exceedingly relevant and obligated to develop new knowledge that will improve the care of these patients. I appreciate the privilege of reviewing this work.

Residents and Students

Problem: Abdominal distention, intolerance of feeds, bilious vomiting, bloody stools in a newborn

Likely diagnosis: necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is one of the most devastating diseases to affect infants in the neonatal intensive care unit and a leading cause of morbidity and mortality. It is an acquired inflammatory disease of the intestine of neonates. It is the most common newborn surgical emergency.

NEC has a multifactorial etiology of intestinal mucosal compromise, pathogenic bacteria and enteral feedings in a susceptible host leading to bowel injury and the initiation of the inflammatory cascade. The most consistent risk factors include prematurity and enteral formula feeds. The highest risk is in infants less than 1000 g and less than 28 wk gestation.

NEC primarily affects the vascular watershed regions and is in a single area in half of patients. The most commonly affected areas are the terminal ileum followed by the colon. Forty-four percent of patients with have multiple discontinuous regions of intestine with both small and large intestine affected

NEC totalis is the most fulminant form of NEC with necrosis of at least 75% of the intestine.

Bell Classification

Stage I – clinical findings suspicious for NEC but no definitive criteria

Stage II – definitive NEC without indication for surgical intervention (e.g. abdominal radiograph with with pneumatosis intestinalis)

Stage III – evidence of pneumoperitoneum (i.e. free air) or irreversible tissue damage with perforation

Key history points

The presentation can vary but a common scenario is a consult in a premature baby who was previously tolerating enteral feeds and develops physiologic instability with apnea, bradycardia, lethargy, temperature instability, hypoglycemia and shock who became distended, developed green emesis, abdominal distention and/or bloody stools.

Key physical exam findings

The exam may be noteworthy for unstable vital signs, poor perfusion, decreased capillary refill and abdominal distension. Abdominal wall discoloration (i.e. erythema or a bluish discoloration) can indicate perforation.

The inguinal rings and scrotum should be evaluated for a bluish discoloration as meconium can travel to these areas through a patent processus vaginalis.

Differential diagnosis

A similar condition, spontaneous intestinal perforation (SIP) also occurs in premature infants although the babies are usually not as ill appearing, generally present much earlier in life and usually have not been fed.


Flat and right side up lateral decubitus or cross table lateral abdominal radiographs are obtained to look for pneumatosis, portal venous gas or free air. Serial radiographs may show a fixed loop.

Indications for surgery

In the absence of an indication for surgery, infants are treated with supportive care such as intravenous fluid resuscitation, NPO with gastric decompression and broad spectrum antibiotics. Serial evaluation includes abdominal exams, two view abdominal radiographs, WBC and platelets and blood gases.

Evidence of intestinal necrosis or perforation is an indication for surgical intervention. Progression of the disease (e.g. abnormal blood work, thrombocytopenia, neutropenia and metabolic acidosis), a fixed loop indicating necrotic bowel and abdominal compartment syndrome are also indications for surgery. If abdominal compartment syndrome is present there may be a need to place a silo or leave the abdomen open.

The procedure may be either exploratory laparotomy or peritoneal drain placement depending on the weight and condition of the baby. Peritoneal drain placement may be appropriate in infants less than 1000 g or those with poor physiologic reserve and inability to handle the stress of surgery

Operative consent points

The goal of laparotomy is to resect necrotic bowel, preserve intestinal length. Theconsent should include exploratory laparotomy, bowel resection, likely ostomy and possible temporary abdominal wall closure (i.e. silo). The discussion should also include the possibility of short gut syndrome, that the infant may get sicker before getting better and blood product transfusions may be required.

A second look operation 48 to 72 hr later may be needed. if applicable given the clinical condition, a senior or attending should discuss the possibility of NEC totalis.


Complications include abdominal compartment syndrome, sepsis, death, short gut syndrome, intestinal stricture (common in the ileum and colon although this is more common after medical management).

Postoperative care

Overall survival depends on weight and age of infant, severity of NEC and amount of remaining bowel. NEC may be a risk factor in abnormal neurodevelopment.

When to call next level

This consult should prompt an early assessment and quick call to senior even though not all the workup is done - especially if there is evidence of free air on radiograph.

Author: Grace, Mak, MD

Editor: Marjorie Arca, MD and Joseph A. Iocono, MD, MBA

Additional Resources

APSA Standardized Toolbox of Education for Pediatric Surgery (STEPS) Necrotizing Enterocolitis

APSA parent and patient education materials on Necrotizing Enterocolitis (NEC)

Stay Current in Pediatric Surgery podcast Necrotizing Enterocolitis

Discussion Questions and Cases

To submit interesting or controversial cases which display thoughtful patient management please contact the editors at

A two week old premature infant has abdominal tenderness and feeding intolerance. An abdominal radiograph reveals pneumatosis.

What are the next best steps in management?

A premature infant with necrotizing enterocolitis (NEC) has been treated medically for five days. The abdominal radiograph is gasless and he requires repeated transfusions for thrombocytopenia.

Is surgical intervention indicated?

A 1000 g infant being medically managed for NEC develops pneumoperitoneum on abdominal radiograph.

Which is more appropriate: laparotomy or peritoneal drainage?

Additonal questions are in SCORE Necrotizing Enterocolitis conference prep


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Last updated: August 8, 2017