Risk Factors for Development of Pneumatosis Intestinalis after Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Case-Control Study.

The significance of pneumatosis intestinalis (PI) in pediatric patients following hematopoietic stem cell transplantation (HSCT) is poorly understood. A knowledge gap remains with respect to the etiology, risk factors, and evidence-based treatment of these patients. As a result, management is frequently based on each center's clinical practice, without standardization across treatment centers. In this single-center trial, we aimed to validate both previously proposed and additional risk factors for the development of PI and to examine our management and outcomes for these patients. We performed a retrospective case-control study examining risk factors for the development of PI in pediatric HSCT patients at a single tertiary referral children's hospital. We used univariate and multivariable conditional logistic regression analysis to explore differences in pharmacologic and other transplantation-specific risk factors. Between 2012 and 2019, PI was diagnosed in 212 patients at our pediatric hospital, of whom 42 were HSCT recipients. The majority of patients (88%; n = 37 of 42) with PI were diagnosed by X-ray. Eighteen patients (43%) were asymptomatic and diagnosed incidentally after imaging was obtained for standard post-transplantation surveillance or other nonrelated indications. All patients with PI were hospitalized and placed on strict bowel rest while receiving parenteral nutrition and antibiotics. Recurrence of PI occurred in 4 patients (10%) following their initial diagnosis. Increased doses of steroid exposure within 30 days of PI diagnosis (odds ratio [OR], 5.7; 95% confidence interval [CI], 2.1 to 15.3; P = .0006), presence of grade II-IV gastrointestinal acute graft-versus-host disease (GVHD) (OR, 5.3; 95% CI, 1.0 to 28.1; P = .05), and receipt of >50% of total daily nutrition by nasogastric (NG) tube feeds (OR, 22.0; 95% CI, 1.3 to 370.2; P = .03) were identified as independent risk factors for the development of PI. Intensity of the conditioning regimen, exposure to total body irradiation, stem cell source, donor type, HLA matching, use of mycophenolate mofetil, and presence of bacterial or viral infection at the time of PI diagnosis were not demonstrably associated with the development of PI in our study. We conclude that development of asymptomatic PI is a benign condition following HSCT, and that the risk for PI is increased in patients with gastrointestinal GVHD, patients receiving steroid therapy, and patients relying on supplemental NG tube feeds for at least one-half of their total daily nutrition.

Multicenter epidemiological survey of pneumatosis intestinalis in Japan.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare condition characterized by gas collection in the intestinal wall. We aimed to determine the etiology and affected segments associated with complications, treatment, and outcome. METHODS: We conducted a multicenter epidemiological survey using a standardized data collection sheet in Japan. Complicating PI was defined as strangulation or bowel necrosis, bowel obstruction, adynamic ileus, sepsis, shock, and massive gastrointestinal bleeding requiring blood transfusion. RESULTS: We enrolled 167 patients from 48 facilities. Multivariate analysis revealed that older age (adjusted OR, 1.05 and 95% confidence intervals [CI], 1.02-1.09, P = 0.0053) and chronic kidney disease (adjusted OR, 13.19 and 95% CI 1.04-167.62, P = 0.0468) were independent predictors of the small-bowel-involved type. Complicating PI was associated with the small-bowel-involved combined type (adjusted OR, 27.02 and 95% CI 4.80-152.01, P = 0.0002), the small-bowel-only type (adjusted OR, 3.94 and 95% CI 1.02-15.27, P = 0.0472), and symptomatic PI (adjusted OR, 16.24 and 95% CI 1.82-145.24, P = 0.0126). Oxygen therapy was performed in patients with a past history of bowel obstruction (adjusted OR, 13.77 and 95% CI 1.31-144.56, P = 0.0288) and surgery was performed in patients with complicating PI (adjusted OR, 8.93 and 95% CI 1.10-72.78, P = 0.0408). Antihypertensives (adjusted OR, 12.28 and 95% CI 1.07-140.79, P = 0.0439) and complicating PI (adjusted OR, 11.77 and 95% CI 1.053-131.526; P = 0.0453) were associated with exacerbation of PI. The complicating PI was the only indicator of death (adjusted OR, 14.40 and 95% CI 1.09-189.48, P = 0.0425). DISCUSSION: Small-bowel-involved type and symptomatic PI were associated with complications which were indicators of poor prognosis.

[Diagnosis and treatment of pneumatosis cystoides intestinalis].

Pneumatosis cystoides intestinalis (PCI) is a rare disease, which is characterized by the accumulation of gas cysts located in the submucosa or subserosa of the gastrointestinal tract. It can occur in the whole or part of the gastrointestinal tract from the esophagus to the rectum, but clinically the main involved sites are the colon and small intestine. PCI can also appear in other sites such as mesentery, the greater omentum and the hepatogastric ligament. In recent years, with the renewal of imaging method, the detection rate of PCI has been on the rise. Most patients with PCI have no obvious symptoms or only non-specific symptoms of the digestive tract like abdominal distension, abdominal pain, diarrhea, hematochezia, etc. The atypical clinical symptoms of PCI can easily lead to missed diagnosis or misdiagnosis. A small amount of patients would have complications like peritonitis and even perforation of the digestive tract. The therapeutic principle for these patients is different from that for patients with acute abdomen. The prognosis of PCI depends on its severity and comorbidities. In this article, a literature review would be conducted on the epidemiological characteristics, etiology and pathogenesis, clinical manifestations, diagnosis and treatment of PCI, which might help clinical doctors with diagnosis and treatment of the disease.

Pneumatosis Intestinalis and Its Association With Lung Transplant: Alberta Experience.

OBJECTIVES: We evaluated the incidence, clinical presentation, laboratory findings, possible causes, and outcomes associated with pneumatosis intestinalis in the setting of lung transplant. MATERIALS AND METHODS: A departmental database showed that, between October 2002 and August 2013, our institution performed 373 lung transplants. The database was queried for all patients who had pneumatosis intestinalis and/or pneumoperitoneum after lung transplant at our institution. For this retrospective chart review, information collected included demographics, baseline variables, symptoms, signs, laboratory parameters, radiologic work-up, medications, including immunosuppressants at presentation, progress and time to resolution, length of hospital stay, and postoperative complications, as well as short-term and midterm outcomes (up to 1 year). RESULTS: The incidence of pneumatosis intestinalis was 2.68% (10/373 patients). Mean age of patients was 52.2 years (range, 34.9-67.9 y). Mean time for development of pneumatosis intestinalis after transplant was 352.8 days (range, 5-2495 d). Abdominal symptoms and signs were present in 6 patients (60%). The large bowel was the site of involvement in all but 1 patient, with predilection for ascending colon (80%) and transverse colon (90%) in most patients. High serum lactate levels were found in 2 patients, and both underwent bowel resection, with surgical specimens revealing evidence of ischemic changes in the gut. Mean dose of prednisone was 22 mg at the time of presentation (range, 0-60 mg). Mean hospital length of stay was 16.9 days (range, 0-40 d). Short-term survival was 100%. Midterm survival at the end of 1 year was 80%. Mean time for pneumatosis to resolve was 18 days (range, 14-35 d). CONCLUSIONS: Pneumatosis intestinalis in bilateral lung transplant recipients can be treated with a minimal amount of imaging, and most patients can be treated conservatively. Survival outcomes are quite good, with 100% during the short term and 80% at 1 year in our series.

Pneumatosis Intestinalis Predictive Evaluation Study: A multicenter epidemiologic study of the American Association for the Surgery of Trauma.

BACKGROUND: Our group has previously published a retrospective review defining variables predictive of transmural bowel ischemia in the setting of pneumatosis intestinalis (PI). We hypothesize this prospective study will confirm the findings of the retrospective review, enhancing legitimacy to the predictive factors for pathologic PI previously highlighted. METHODS: Data were collected using the Research Electronic Data Capture. Forward logistic regression was utilized to identify independent predictors for pathologic PI. Statistical significance was defined as p ≤ 0.05. RESULTS: During the 3-year study period, 127 patients with PI were identified. Of these, 79 had benign disease, and 49 pathologic PI defined by the presence of transmural ischemia during surgical exploration or autopsy. Laboratory values such as elevated international normalized ratio (INR), decreased hemoglobin, and a lactate value of greater than 2.0 mmol/L were predictive of pathologic PI, as well as clinical factors including adynamic ileus, peritoneal signs on physical examination, sepsis, and hypotension. The location was also a significant factor, as patients with small bowel PI had a higher incidence of transmural ischemia than colonic PI. On multiple logistic regression, lactate value of greater than 2.0 mmol/L (odds ratio, 5.1, 1.3-19.5; p = 0.018), elevated INR (odds ratio, 3.2, 1.1-9.6; p = 0.031), peritonitis (15.0, 2.9-78; p = 0.001), and decreased hemoglobin (0.70, 0.50-0.97, 0.031) remained significant predictors of transmural ischemia (area under the curve, 0.90; 0.83-0.97). A lactate value of 2.0 mmol/L or greater and peritonitis are common factors between the retrospective review and this prospective study. CONCLUSIONS: We recommend surgical exploration to be strongly considered for those PI patients presenting also with a lactate greater than 2 mmol/L and/or peritonitis. We suggest strong suspicion for necrosis in those patient with PI and small bowel involvement, ascites on computed tomography scan, adynamic ileus, anemia, and a high INR. LEVEL OF EVIDENCE: Prognostic study, level II; therapeutic study, level II.

Benign pneumatosis intestinalis in a pediatric patient with multiple risk factors including granulomatosis with polyangiitis: a case report and review of the literature.

OBJECTIVE: To describe the first reported case of pneumatosis intestinalis (PI) in a pediatric patient with granulomatosis with polyangiitis (GPA) and multiple other risk factors and review the literature for PI in adult and pediatric rheumatologic conditions. METHODS: A PubMed search was completed using the search phrase "pneumatosis intestinalis." Searches were limited to humans and the English language, and remaining articles involving patients with rheumatologic diagnoses were identified and included in our discussion. RESULTS: This is the first reported of case of PI in a patient with underlying GPA or antineutrophil cytoplasmic antibody-associated vasculitides. Out of 90 previously reported cases of PI in patients with rheumatologic conditions, 79 cases were in adults and 11 in children. There were 30 patients with systemic sclerosis, 18 with MCTD/overlap syndrome, 18 with dermatomyositis or polymyositis, 16 with SLE, and 8 with other diagnoses. Overall, 81% of the patients were on corticosteroids or other immunosuppressants prior to development of PI. The most common presenting symptom was abdominal pain, and 51% of patients had associated pneumoperitoneum. CONCLUSIONS: PI can be associated with a broad spectrum of rheumatic diseases, including GPA, and should be included in the differential diagnosis of patients with rheumatologic conditions and nonspecific gastrointestinal symptoms.

A systematic analysis of pneumatosis cystoids intestinalis.

AIM: To increase the understanding, diagnosis and treatment of pneumatosis cystoides intestinalis (PCI) and to find the characteristics and potential cause of the disease in China. METHODS: We report here one case of PCI in a 70-year-old male patient who received a variety of treatment methods. Then, we systematically searched the PCI eligible literature published from an available Chinese database from May 2002 to May 2012, including CBM, CBMDisc, CMCC, VIP, Wanfang, and CNKI. The key words were pneumatosis cystoides intestinalis, pneumatosis, pneumatosis intestinalis, pneumatosis coli and mucosal gas. The patients' information, histories, therapies, courses, and outcomes were reviewed. RESULTS: The study group consisted of 239 PCI cases (male:female = 2.4:1) from 77 reported incidents. The mean age was 45.3 ± 15.6 years, and the median illness course was 6 mo. One hundred and sixty patients (66.9%) were in high altitude areas. In addition, 43.5% (104/239) of the patients had potential PCI-related disease, and 16.3% had complications with intestinal obstruction and perforation. The most common symptom was abdominal pain (53.9%), followed by diarrhea (53.0%), distention (42.4%), nausea and vomiting (14.3%), bloody stool (12.9%), mucous stool (12.0%) and constipation (7.8%). Most multiple pneumocysts developed in the submucosa of the colon (69.9%). The efficacy of the treatments by combined modalities, surgery, endoscopic treatment, conservative approach, oxygen, and antibiotics were 100%, 100%, 100%, 93.3%, 68.3% and 26.3%, respectively. CONCLUSION: PCI can be safely managed by conservative treatments, presents more frequently in males, in the large bowel and submucosa, than in females, in the small intestine and subserosa. High altitude residence maybe associated with the PCI etiology.

Pneumatosis and portal venous gas: do CT findings reassure?

BACKGROUND: Small, single-institution studies have suggested risk factors for bowel ischemia/necrosis (I/N) in patients with computed tomography (CT) findings of pneumatosis (PN) and portal venous gas (PVG). Here, analysis has been expanded in a large, multicenter study. MATERIALS & METHODS: Logistic regression models and receiver operating characteristic curves were used to construct a scoring system for I/N in cases of PN/PVG. RESULTS: Of 265 patients with PN/PVG identified, 209 had adequate data. In unadjusted analyses the following variables were significantly associated with I/N: age, peritoneal signs, ascites, the presence of both PVG and PN, blood urea nitrogen (BUN), CO2, albumin, and a history of hypertension, myocardial infarction, or stroke. In contrast, the CT findings of mesenteric stranding, bowel-wall thickening, and type of PN were not associated with I/N. In adjusted analyses, three variables were significantly associated with I/N: age ≥60 y (odds ratio = 2.51, 95% confidence interval: 1.26-4.97), peritoneal signs (10.58, 4.23-26.4), and BUN >25 mg/dL (3.08, 1.54-6.17), whereas presence of both PN and PVG (versus only one) was associated with an increase (but not statistically significant increase) in odds (2.01, 0.94-4.36). Although several ad hoc models were used to maximize diagnostic ability, with maximal odds ratio = 174, the areas of receiver operating characteristic curves were all below 0.80, revealing suboptimal accuracy to diagnose I/N. CONCLUSIONS: Older age, peritoneal signs, and high BUN are associated with I/N, suggesting an ability to predict which patients need operation. CT findings traditionally suggestive of ischemic PN/PVG, however, do not diagnose I/N accurately enough to reliably identify patients needing operation.

Pneumatosis Intestinalis Predictive Evaluation Study (PIPES): a multicenter epidemiologic study of the Eastern Association for the Surgery of Trauma.

BACKGROUND: Pneumatosis intestinalis (PI) is associated with numerous adult conditions, ranging from benign to life threatening. To date, series of PI outcomes consist of case reports and small retrospective series. METHODS: We conducted a retrospective multicenter study, involving eight centers, of PI from January 2001 to December 2010. Demographics, medical history, clinical presentation, and outcomes were collected. Primary outcome was the presence of pathologic PI defined as confirmed transmural ischemia at surgery or the withdrawal of clinical care and subsequent mortality. Forward logistic regression and a regression tree analysis was used to generate a clinical prediction rule for pathologic PI. RESULTS: During the 10-year study period, 500 patients with PI were identified. Of this number, 299 (60%) had benign disease, and 201 (40%) had pathologic PI. A wide variety of variables were statistically significant predictors of pathologic PI on univariate comparison. In the regression model, a lactate of 2.0 or greater was the strongest independent predictor of pathologic PI, with hypotension or vasopressor need, peritonitis, acute renal failure, active mechanical ventilation, and absent bowel sounds also demonstrating significance. Classification and regression tree analysis was used to create a clinical prediction rule. In this tree, the presence of a lactate value of 2.0 or greater and hypotension/vasopressor use had a predictive probability of 93.2%. CONCLUSION: Discerning the clinical significance of PI remains a challenge. We identified the independent predictors of pathologic PI in the largest population to date and developed of a basic predictive model for clinical use. Prospective validation is warranted. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Pneumatosis in post-Whipple patients.

Pneumatosis intestinalis (PI) is the finding of air in the wall of the intestine. Clinical significance ranges from an incidental radiologic finding to an indicator of life-threatening disease requiring surgical intervention. We report the incidence and consequence of PI in a 7-year, single-surgeon, retrospective review. Data from demographics, imaging, and outcomes were analyzed. Two-tailed Fisher's exact test was performed to analyze the difference between groups. A total of 214 patients underwent a Whipple procedure with a routinely placed feeding tube during this period. Most had a gastrojejunal feeding tube, 80.4 per cent. Thirteen patients developed PI. Overall reoperation rate was nine of 201 versus four of 13 in the PI group (P<0.02). Three patients taken back to the operating room with peritonitis and PI had a necrotic bowel. A fourth patient was taken to surgery for unrelenting upper gastrointestinal bleeding. The remaining nine were managed nonoperatively with resolution of PI. The 90-day death rate in those without PI was 2.9 per cent versus 23.3 per cent with PI (P<0.02). Isolated PI can be managed nonoperatively; however, in the presence of peritonitis, it is a strong predictor of lethal complications.

Tension pneumoperitoneum in a child resulting from high-frequency oscillatory ventilation: a case report and review of the literature.

An 18-month-old male infant was placed on high-frequency oscillatory ventilation for profound hypoxemia and subsequently developed tension pneumoperitoneum. He underwent a bedside exploratory laparotomy for suspected perforated viscus. No intestinal perforation was identified, and a diagnosis of tension pneumoperitoneum secondary to pneumatosis cystoides intestinalis was made. To our knowledge, this is the only report of a pediatric patient developing tension pneumoperitoneum from high-frequency oscillatory ventilation. A review of the literature examines the differential diagnosis, physiology, and treatment of tension pneumoperitoneum.

Pneumatosis intestinalis in children with acute lymphoblastic leukemia and acute myeloid leukemia.

PURPOSE: To describe symptoms, diagnostic features, treatments, and outcomes of pneumatosis intestinalis (PI) in pediatric patients being treated for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS: This retrospective chart review included 514 patients ≤ 18 years of age diagnosed with ALL or AML between January 1999 and December 2007. PI episodes were identified by radiology report reviews. RESULTS: Twenty patients with ALL and four patients with AML presented 31 PI episodes. The median time between diagnoses of leukemia and PI was 1.0 month (interquartile range 0.8-6.4 months). Plain radiographs diagnosed all PI episodes. Computerized tomography (CT) and ultrasound were performed in 6 and 13 episodes, respectively. All CT and three ultrasounds demonstrated PI. Thirty episodes occurred exclusively in the colon, most commonly in the ascending (n = 26) and transverse (n = 18) segments. Treatment included complete bowel rest in 27 (87.1%) and intravenous broad-spectrum antibiotics in 29 (93.5%). One case required colectomy. Two episodes were untreated. There were no fatalities associated with PI. CONCLUSIONS: PI is uncommon in children with ALL or AML. Ultrasound is less sensitive than plain radiographs for diagnosis. PI occurred almost exclusively in the colon. With conservative management, most patients had excellent outcome.

Gastrointestinal and hepatic manifestations of systemic lupus erythematosus.

In this review of the gastrointestinal (GI) and hepatic manifestations of systemic lupus erythematosus (SLE), 180 articles from the English literature, found using a medline search from January 1965 to December 2010, were examined. Vasculitis may cause ulcerations, bleeding, stricture formation, and perforation from ischemia and infarction. Otherwise, GI symptoms, occurring in about 50% of patients, are usually mild. Esophageal dysmotility may result in heartburn, regurgitation, and dysphagia. Occasionally, pneumatosis cystoides intestinalis may develop, sometimes associated with benign pneumoperitoneum. Patients are prone to salmonella bacteremia, presenting more commonly with fever and abdominal pain than with diarrhea. Intestinal pseudoobstruction usually is found with active lupus serology, preferentially involving small rather than the large bowel. Protein-losing enteropathy, characterized by diarrhea, edema, and hypoalbuminemia, can be the initial presentation of SLE. Malabsorption with a prevalence of 9.5% is occasionally associated with celiac disease. Pancreatitis, with an annual incidence of 0.4 to 1/1000, has an overall mortality of 27% that is decreased with corticosteroid therapy. Acute and chronic ascites may be due to lupus peritonitis or to associated diseases, such as pancreatitis, nephrotic syndrome, heart failure, or infections. Abnormal liver function tests may be due to steatosis from lupus or from corticosteroid therapy. Only about 10% of patients with autoimmune hepatitis have lupus. Up to 4.7% of patients with SLE have chronic active hepatitis correlating strongly with the presence of antibody to ribosomal P protein. SLE can involve the entire GI tract and the liver. Treatment with corticosteroids, cytotoxic agents, and/or immunosuppressants is often successful.

Clinical and CT features of benign pneumatosis intestinalis in pediatric hematopoietic stem cell transplant and oncology patients.

BACKGROUND: Pneumatosis intestinalis in children is associated with a wide variety of underlying conditions and often has a benign course. The CT features of this condition have not been systematically investigated. OBJECTIVE: Defining benign pneumatosis intestinalis as pneumatosis intestinalis that resolved with medical management alone, we sought to: (1) determine whether the incidence of benign pneumatosis intestinalis had increased at our pediatric cancer hospital; (2) characterize CT features of benign pneumatosis intestinalis; and (3) determine the relationship between imaging features and clinical course of benign pneumatosis intestinalis in this cohort. MATERIALS AND METHODS: Radiology reports from November 1994 to December 2006 were searched for "pneumatosis intestinalis," "free intraperitoneal air," and "portal venous air or gas." Corresponding imaging was reviewed by two radiologists who confirmed pneumatosis intestinalis and recorded the presence of extraluminal free air, degree of intramural gaseous distension, number of involved bowel segments, and time to pneumatosis resolution. RESULTS: The search revealed 12 boys and 4 girls with pneumatosis intestinalis; 11 were hematopoietic stem cell transplant recipients. The annual incidences of benign pneumatosis have not changed at our institution. Increases in intramural distension marginally correlated with the number of bowel segments involved (P=0.08). Three patients had free air and longer times to resolution of pneumatosis (P=0.03). CONCLUSION: Male children may be at increased risk of benign pneumatosis intestinalis. The incidence of benign pneumatosis at our institution is proportional to the number of hematopoietic stem cell transplants. The degree of intramural distension may correlate with the number of bowel segments involved. Patients with free air have a longer time to resolution of benign pneumatosis.

Asymptomatic pneumatosis at CT colonography: a benign self-limited imaging finding distinct from perforation.

OBJECTIVE: The purpose of our study was to report the prevalence and clinical course of colonic pneumatosis at CT colonography (CTC). MATERIALS AND METHODS: The study population consisted of 5,368 adults (mean age, 57.4 years; 2,807 women, 2,561 men) undergoing CTC. Pertinent medical history, CTC imaging studies, and clinic course were reviewed for all cases in which pneumatosis (i.e., air in the bowel wall) was prospectively identified. RESULTS: Colonic pneumatosis was seen in six (0.11%) of 5,368 total CTC studies. No cases of small-bowel pneumatosis were identified. There were no cases of frank colonic perforation in this series. All six cases of pneumatosis involved the use of automated carbon dioxide for colonic distention (0.17%; six of 3,451 cases). Pneumatosis was not seen in 1,917 cases with manual room air insufflation (p = 0.095). The right colon was involved in all cases, typically revealing a thin curvilinear configuration with variable circumferential extension. In one of the six cases, a frankly cystic appearance (pneumatosis cystoides intestinalis) was seen in the left colon. No free intraperitoneal gas, portomesenteric venous gas, or distant extraperitoneal gas was present in any case. No unexpected abdominal symptoms developed during the CTC examination, and all six patients were asymptomatic after the procedure. None of the patients required any treatment or intervention. CONCLUSION: Asymptomatic right-sided colonic pneumatosis is a rare self-limited condition associated with carbon dioxide delivery at CTC. This benign imaging finding should not be confused with symptomatic perforation.

Pneumatosis intestinalis and diarrhea in a child following renal transplantation.

Pneumatosis intestinalis is an uncommon finding beyond the neonatal period, but it has been reported in immunocompromized pediatric patients. The association of pneumatosis intestinalis in children following renal transplantation has to the best of our knowledge been only reported once in children. We describe a 4-year-old female who developed intermittent emesis, weight loss, and intermittently loose bloody stools after cadaveric renal transplantation at age 3.5 years. An abdominal x-ray demonstrated extensive pneumatosis in the colon. The infectious work-up was negative. Histologically, she had increased eosinophils throughout the lamina propria in the rectum. A glucose breath test was suggestive of small bowel bacterial overgrowth. She was treated with 10 days of metronidazole with resolution of the diarrhea and occult blood in stools. One month after the treatment she had radiologic resolution of her pneumatosis. Based on this report, pneumatosis intestinalis should be considered in the differential diagnosis of children after organ transplant suffering from diarrhea, abdominal pain, or blood in the stool.

Frequency of and risk factors for necrotizing enterocolitis in infants born before 33 weeks of gestation.

AIM: To investigate the frequency of and risk factors for necrotizing enterocolitis (NEC) among infants of <33 wk of gestation. METHODS: Prospective follow-up of 140 inpatients. RESULTS: 26 (18.6%) subjects developed NEC stage I-III and 12 (8.6%) severe NEC (stage II-III). Breast milk fortifier and duration of morphine infusion emerged as the statistically significant factors associated with NEC stage I-III, but only the latter had a significant association with severe NEC. CONCLUSION: Future studies are needed to be established whether morphine is a causative factor in NEC.