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Necrotizing Enterocolitis Workup

  • Author: Shelley C Springer, JD, MD, MSc, MBA, FAAP; Chief Editor: Ted Rosenkrantz, MD  more...
 
Updated: Jan 02, 2016
 

Approach Considerations

Initial presentation of necrotizing enterocolitis (NEC) usually includes subtle signs of feeding intolerance, such as gastric residuals, abdominal distention, and/or grossly bloody stools. Abdominal imaging studies are crucial at this stage. In fact, radiographic studies should be obtained if any concern about NEC is present.

Laboratory studies are pursued, especially if the abdominal study findings are worrisome or the baby is manifesting any systemic signs. Laboratory values can give insight into the severity of the disease and can aid in the provision of appropriate therapy.

However, although all of the initial laboratory studies taken together may aid in the diagnosis of NEC, they do not substitute for an appropriate appreciation of the clinical presentation and appearance of the infant.

Complete blood count

A complete blood count (CBC), with manual differential to evaluate the white blood cell (WBC), hematocrit, and platelet count, is usually repeated at least every 6 hours if the patient's clinical status continues to deteriorate.

White blood cell count

Marked elevation may be worrisome, but leukopenia is even more concerning. Although elevated mature and/or immature neutrophil counts may not be good indicators of neonatal sepsis after the first 3 days of life, moderate to profound neutropenia (absolute neutrophil count [ANC] < 1500/μL) strongly suggests established sepsis.

Red blood cell count

Premature infants are prone to anemia due to iatrogenic blood draws, as well as anemia of prematurity; however, blood loss from hematochezia and/or a developing consumptive coagulopathy can manifest as an acute decrease in hematocrit.

An elevated hemoglobin level and hematocrit may mark hemoconcentration due to notable accumulation of extravascular fluid.

Platelet count

Platelets are an acute phase reactant, and thrombocytosis can represent physiologic stress to an infant, but acute NEC is more commonly associated with thrombocytopenia (< 100,000/μL). Thrombocytopenia may become more profound in severe cases that become complicated with consumption coagulopathy. Consumption coagulopathy is characterized by prolonged prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and decreasing fibrinogen and increasing fibrin degradation products concentrations

Thrombocytopenia appears to be a reaction to gram-negative organisms and endotoxins. Platelet counts of less than 50,000 warrant platelet transfusion.

Blood culture

Obtaining a blood culture is recommended before beginning antibiotics in any patient presenting with any signs or symptoms of sepsis or NEC. Although blood cultures do not grow any organisms in most cases of NEC, sepsis is one of the major conditions that mimics the disease and should be considered in the differential diagnosis. Therefore, identification of a specific organism can aid and guide further therapy.

Serum electrolytes

Serum electrolytes can show some characteristic abnormalities. Obtain basic electrolytes (Na+, K+, and Cl-) during the initial evaluation, followed serially at least every 6 hours depending on the acuity of the patient's condition.

Serum sodium

Hyponatremia is a worrisome sign that is consistent with capillary leak and "third spacing" of fluid within the bowel and peritoneal space. Depending on the baby's age and feeding regimen, baseline sodium levels may be low normal or subnormal, but an acute decrease (< 130 mEq/dL) is alarming, and heightened vigilance is warranted.

Metabolic acidosis

Low serum bicarbonate (< 20) in a baby with a previously normal acid-base status is also concerning. It is seen in conjunction with poor tissue perfusion, sepsis, and bowel necrosis.

Other tests

Reducing substances may be identified in the stool of formula-fed infants because poorly digested carbohydrates are fermented in the colon and excreted in stool. Similarly, results from a breath hydrogen test may be positive with increased carbohydrate fermentation. While early diagnosis is one of the most important ways to minimize morbidity and mortality, the lack of early biomarkers has hampered the clinician's ability to reliably distinguish early NEC from benign feeding intolerance. Results from a cohort of 119 premature infants, 85 of whom had NEC, recently published in the Journal of Pediatrics is encouraging for the possible identification of 7 urine protein biomarkers.[25]

Imaging techniques

Reports from outside of the United States suggest that imaging techniques such as contrast radiography, magnetic resonance imaging (MRI), and radionuclide scanning may play a role in diagnosis the diagnosis of NEC. These techniques are not currently in common use.

GI tonometry is an infrequently used technique that may be helpful in distinguishing benign feeding intolerance from early NEC. The use of radiography and ultrasonography in the diagnosis of NEC is discussed in detail below.

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Arterial Blood Gases

Depending on presentation acuity, hypoventilation and frank apnea are seen in necrotizing enterocolitis (NEC). Arterial blood gas (ABG) can aid in the determination of the infant's need for respiratory support. The ABG can also provide information of the acid-base status.

Acute acidosis is worrisome. Lactic acidosis results from decreased cardiac output (as in cardiovascular collapse and shock), leading to poor perfusion of peripheral tissues. Tissue necrosis may also add to the observed metabolic acidosis.

An arterial blood sample is a convenient way to simultaneously obtain a blood culture, CBC, serum electrolytes, and ABG for the initial evaluation (note that arterial blood has a lower yield for demonstrating bacteremia than does venous blood). Depending on presentation acuity, inserting a peripheral arterial line while peripheral perfusion and intravascular volume are still within the reference range may be prudent. This peripheral arterial line facilitates serial blood sampling and invasive blood pressure monitoring that is essential if the baby's condition deteriorates.

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Abdominal Radiography

The mainstay of diagnostic imaging is abdominal radiography. An anteroposterior (AP) abdominal radiograph and a left lateral decubitus radiograph (left-side down) are essential for initially evaluating any baby with abdominal signs. Perform abdominal radiography serially at 6-hour or greater intervals, depending on presentation acuity and clinical course.

Characteristic findings on an AP abdominal radiograph include an abnormal gas pattern, dilated loops, and thickened bowel walls (suggesting edema/inflammation). Serial radiographs help to assess disease progression. A fixed and dilated loop that persists over several examinations is especially worrisome.

Radiographs can sometimes reveal scarce or absent intestinal gas, which is more worrisome than diffuse distention that changes over time.

Pneumatosis intestinalis

Pneumatosis intestinalis is a radiologic sign pathognomonic of necrotizing enterocolitis (NEC). It appears as a characteristic train-track lucency configuration within the bowel wall. Intramural air bubbles represent gas produced by bacteria within the wall of the bowel. Analysis of gas aspirated from these air bubbles reveals that it consists primarily of hydrogen, suggesting that the bubbles are caused by bacterial fermentation. Carbohydrate (often lactose) fermentation by intestinal flora yields hydrogen and carbon dioxide and a series of short-chain organic acids, which can promote inflammation.

Pneumatosis is present in 70%-80% of patients with NEC, although it may be fleeting or intermittent and is often an early finding. The extent of gas is not correlated with the severity of disease, nor is it specific to NEC. Pneumatosis is also seen in Hirschsprung disease, severe diarrhea, carbohydrate intolerance, and inspissated milk syndrome. (See the images below.)

Pneumatosis intestinalis. Photo courtesy of Loren Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Extensive pneumatosis intestinalis. Extensive pneumatosis intestinalis.
Necrotizing enterocolitis totalis. Pneumatosis int Necrotizing enterocolitis totalis. Pneumatosis intestinalis and multiple areas of perforation were seen.
Pneumatosis intestinalis. Pneumatosis intestinalis.

Free air

Abdominal free air is ominous and usually requires emergency surgical intervention. The presence of abdominal free air can be difficult to discern on a flat radiograph, which is why decubitus radiographs are recommended at every evaluation. A subtle, oblong lucency over the liver and abdominal contents is characteristic of intraperitoneal air on a flat plate. It represents the air bubble that has risen to the most anterior aspect of the abdomen in a baby lying in a supine position. The free air can be difficult to differentiate from intraluminal air.

For this reason, left-side down (left lateral) decubitus radiography is essential and allows the detection of intraperitoneal air, which rises above the liver shadow (right-side up) and can be visualized more easily than it can be on other views. Obtain this view with every AP examination until progressive disease is no longer a concern.

Although free air typically indicates intestinal perforation, other causes include dissecting mediastinal air from barotrauma in a ventilated neonate, gastric perforation (most commonly due to a nasogastric tube), and Hirschsprung disease. Free air is seen in only 50-63% of infants who have intestinal perforation identified at surgery.

Portal gas

Portal gas appears as linear, branching areas of decreased density over the liver shadow and represents air present in the portal venous system. Its presence is considered to be a poor prognostic sign. Portal gas is much more dramatically observed on ultrasonography.

Although once heralded as an ominous sign in NEC, portal gas is now believed to be less so. It is caused by gas produced by bacteria in the portal veins or by the transmigration of gas from the bowel wall to mesenteric veins and into the portal vein. It is frequently a transient finding; the pattern is demonstrated in only 9-20% of infants with NEC.

Loop distention

Distended loops of small bowel are one of the most common, although nonspecific, radiographic findings in NEC. Air-fluid levels and bowel wall edema may also develop. Serial radiographic studies are important to monitor the degree of distention and to observe for any fixed or dilated loops of bowel persistent in nature and location for 24 hours. Some series have shown that intestinal necrosis requiring operative management develops in approximately 50% of infants with bowel loops.

Intraperitoneal fluid

Intraperitoneal free fluid is indicated by a generalized opacification of the abdomen and often by a gasless abdomen or medial displacement of bowel loops with opacification peripherally and increased distance between bowel loops. The finding of ascites may indicate intestinal fluid leakage from perforation and is an indication for paracentesis.

Ascites is a late finding that usually develops when peritonitis is present or after bowel perforation. Ascites is observed on an AP radiograph as centralized bowel loops that appear to be floating on a background of density. It is better appreciated on ultrasonography.

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Abdominal Ultrasonography

Abdominal ultrasonography can be helpful when suspected necrotizing enterocolitis (NEC) in neonates is evaluated. Advantages include the following:

  • Available at bedside
  • Noninvasive imagery of intra-abdominal structures

Disadvantages of ultrasonography include the following:

  • Limited availability at some medical centers
  • Requires extensive training to discern subtle ultrasonographic appearance of some pathologies
  • Abdominal air (easily observed on ultrasonography and in grossly distended patients) can interfere with assessing intra-abdominal structures.

With abdominal ultrasonography, a skilled clinician can identify a larger amount of diagnostic information faster and with less risk to the baby than with the current standard evaluation methods.

Ultrasonography can be used to identify areas of loculation and/or abscess consistent with a walled-off perforation when patients with indolent NEC have scarce gas or a fixed area of radiographic density. Ultrasonography is also excellent for identifying and quantifying ascites. Serial examinations can be used to monitor the progression of ascites as a marker for the disease course.

In addition, ultrasonography can be used to visualize portal air, which can easily be seen as bubbles present in the venous system. Moreover, abdominal ultrasonography has been reported to be more sensitive than plain radiography in the detection of pneumatosis intestinalis. This modality offers the ability to confirm findings of traditional radiographs (ie, pneumatosis intestinalis, portal venous air) with the added ability to better assess the integrity of the intestinal walls, decreased peristalsis, and bowel wall perfusion. Despite its benefits, however, integration of the additional information provided by this modality into clinical decision-making has been slow.[26]

Ultrasonographic assessment of major splanchnic vasculature can help in the differential diagnosis of NEC from other disorders that are either more benign or emergent.

The orientation of the superior mesenteric artery in relationship to the superior mesenteric vein can provide information regarding the possibility of a malrotation with a subsequent volvulus. If a volvulus is present, the artery and vein are twisted and, at some point in their courses, their orientation switches. This abnormality can be detected, even if the rotation is 360⁰, if the full path of the vessels can be observed.

Doppler study of the splanchnic arteries early in the course of NEC can help to distinguish developing NEC from benign feeding intolerance in a mildly symptomatic baby.

A clinical study from Europe and a small series in the United States demonstrated markedly increased peak flow velocity (>1) of arterial blood flow in the celiac and superior mesenteric arteries in early NEC.[27] Such a finding at the presentation of symptoms can further aid in diagnosis and therapy, potentially sparing those individuals at low risk for NEC from unnecessary interventions.

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Upper GI Series

Upper GI with or without small bowel follow-through is performed acutely only when a diagnosis other than necrotizing enterocolitis (NEC), such as bowel obstruction, is being considered because of bilious vomiting, abdominal distention, or other symptoms. This procedure is commonly performed in infants with resolved NEC who develop a picture of GI obstruction, usually due to a stricture or fibrous band. Perform this before contrast enema because the presence of contrast in the colon can obscure pertinent findings.

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Paracentesis

Ascites can develop during fulminant necrotizing enterocolitis and can compromise respiratory function. Paracentesis may be considered. This is most safely performed using ultrasonographic guidance. However, paracentesis is not without risks and should not be performed until a pediatric surgical consultation has been performed.

A positive finding on paracentesis with the free flow of at least 0.5 mL of brownish fluid that contains bacteria on Gram staining is highly specific for intestinal necrosis. A negative finding on paracentesis is uncommon with intestinal necrosis but may occur in the setting of a localized and walled-off perforation.

If no peritoneal fluid is aspirated, peritoneal lavage is performed with 30 mL/kg of isotonic sodium chloride solution, and the fluid is then suctioned.

Place an intra-abdominal drain as an alternative to laparotomy if the baby is not a surgical candidate (eg, in cases of extreme prematurity or cardiovascular collapse and shock).

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Histologic Findings

With NEC, the areas most commonly affected are the terminal ileum and the proximal ascending colon. The pattern of disease may involve a single isolated area or multiple discontinuous lesions. The most common histologic findings are associated with mucosal injury. These include coagulation necrosis of the mucosa with active and chronic inflammation, mucosal ulceration, edema, hemorrhage, and pneumatosis of the submucosa.

Advanced disease may result in full-thickness necrosis of the intestinal wall. Regenerative changes with epithelial regeneration, granulation tissue formation, and fibrosis are seen in as many as two thirds of patients. This indicates an inflammatory process lasting several days, with concurrent areas of continuing injury and healing. (See the images below.)

Micrograph of mucosal section showing transmural n Micrograph of mucosal section showing transmural necrosis. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Histologic section of mucosal wall demonstrating p Histologic section of mucosal wall demonstrating pneumatosis. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Histologic section of bowel mucosa showing regener Histologic section of bowel mucosa showing regeneration of normal cellular architecture. Photo courtesy of the Department of Pathology, Cornell University Medical College.
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Staging of NEC

The Bell system is the staging system most commonly used to describe necrotizing enterocolitis (NEC).

Bell stage I ̶ suspected disease

Stage IA characteristics are as follows:

  • Mild, nonspecific systemic signs such as apnea, bradycardia, and temperature instability are present
  • Mild intestinal signs such as increased gastric residuals and mild abdominal distention are present
  • Radiographic findings can be normal or can show some mild nonspecific distention.

Stage IB diagnosis is the same as stage IA, with the addition of grossly bloody stool.

Bell stage II ̶ definite disease

Stage IIA characteristics are as follows:

  • Patient is mildly ill.
  • Diagnostic signs include the mild systemic signs present in stage IA
  • Intestinal signs include all of the signs present in stage I, with the addition of absent bowel sounds and abdominal tenderness
  • Radiographic findings show ileus and/or pneumatosis intestinalis

This diagnosis is sometimes referred to as "medical" necrotizing enterocolitis as surgical intervention is not needed to successfully treat the patient.

Stage IIB characteristics are as follows:

  • Patient is moderately ill
  • Diagnosis requires all of stage I signs plus the systemic signs of moderate illness, such as mild metabolic acidosis and mild thrombocytopenia
  • Abdominal examination reveals definite tenderness, perhaps some erythema or other discoloration, and/or right lower quadrant mass
  • Radiographs show portal venous gas with or without ascites

Bell stage III ̶ advanced disease

This stage represents advanced, severe NEC that has a high likelihood of progressing to surgical intervention.

Stage IIIA characteristics are as follows:

  • Patient has severe NEC with an intact bowel
  • Diagnosis requires all of the above conditions, with the addition of hypotension, bradycardia, respiratory failure, severe metabolic acidosis, coagulopathy, and/or neutropenia
  • Abdominal examination shows marked distention with signs of generalized peritonitis
  • Radiographic examination reveals definitive evidence of ascites

Stage IIIB designation is reserved for the severely ill infant with perforated bowel observed on radiograph in addition to the findings for IIIA.

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Contributor Information and Disclosures
Author

Shelley C Springer, JD, MD, MSc, MBA, FAAP Professor, University of Medicine and Health Sciences, St Kitts, West Indies; Clinical Instructor, Department of Pediatrics, University of Vermont College of Medicine; Clinical Instructor, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health

Shelley C Springer, JD, MD, MSc, MBA, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

David J Annibale, MD Professor of Pediatrics, Director of Neonatology, Director of Fellowship Training Program in Neonatal-Perinatal Medicine, Department of Pediatrics, Medical University of South Carolina

David J Annibale, MD is a member of the following medical societies: American Academy of Pediatrics, National Perinatal Association

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Robert S Bloss, MD Clinical Associate Professor of Surgery and Pediatrics, University of Texas Medical School; Clinical Assistant Professor, Department of Surgery, Baylor College of Medicine; Consulting Staff, Houston Pediatric Surgeons

Robert S Bloss, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, Southwestern Surgical Congress, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Li Ern Chen, MD Fellow, Pediatric Surgery, Children's Hospital of Wisconsin, Medical College of Wisconsin

Li Ern Chen, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, and Sigma Xi

Disclosure: Nothing to disclose.

David A Clark, MD Chairman, Professor, Department of Pediatrics, Albany Medical College

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical & Dental Society, Medical Society of the State of New York, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Diana Farmer, MD Associate Professor, Departments of Clinical Surgery, Pediatrics, Obstetrics, Gynecology and Reproductive Services, Division of Pediatric Surgery and the Fetal Treatment Center, University of California at San Francisco

Diana Farmer, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, and American Pediatric Surgical Association

Disclosure: Nothing to disclose.

Philip Glick, MD, MBA Professor, Departments of Surgery, Pediatrics, and Gynecology and Obstetrics, Vice-Chairperson for Finance and Development, Department of Surgery, State University of New York at Buffalo

Philip Glick, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, American Thoracic Society, Association for Academic Surgery, Association for Surgical Education, Central Surgical Association, Federation of American Societies for Experimental Biology, Medical Society of the State of New York, Phi Beta Kappa, Physicians for Social Responsibility, Royal College of Surgeons of England, Sigma Xi, Society for Pediatric Research, Society for Surgery of the Alimentary Tract, Society of Critical Care Medicine, and Society of University Surgeons

Disclosure: Nothing to disclose.

Andre Hebra, MD Chief, Division of Pediatric Surgery, Medical University of South Carolina; Professor of Surgery and Pediatrics, Medical University of South Carolina

Andre Hebra, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, Association for Academic Surgery, Society of Laparoendoscopic Surgeons, South Carolina Medical Association, Southeastern Surgical Congress, and Southern Medical Association

Disclosure: Nothing to disclose.

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, and American Heart Association

Disclosure: Nothing to disclose.

Robert K Minkes, MD, PhD Professor of Surgery, University of Texas Southwestern; Chief of Surgical Services, Children's Medical Center of Dallas-Legacy

Robert K Minkes, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Tapash K Palit, MD Assistant Professor of Surgery, Louisiana State University Health Sciences Center, New Orleans

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, Medscape Reference

Disclosure: Nothing to disclose.

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Normal (top) versus necrotic section of bowel. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumatosis intestinalis. Photo courtesy of Loren G Yamamoto, MD, MPH, Kapiolani Medical Center for Women & Children, University of Hawaii, with permission.
Pneumoperitoneum. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Resected portion of necrotic bowel. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Micrograph of mucosal section showing transmural necrosis. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Histologic section of mucosal wall demonstrating pneumatosis. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Histologic section of bowel mucosa showing regeneration of normal cellular architecture. Photo courtesy of the Department of Pathology, Cornell University Medical College.
Extensive pneumatosis intestinalis.
Necrotizing enterocolitis totalis. Pneumatosis intestinalis and multiple areas of perforation were seen.
Pneumatosis intestinalis.
 
 
 
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