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[Factors associated with necrotizing enterocolitis].

OBJECTIVE: To evaluate the features of clinical presentation of neonatal necrotizing enterocolitis and its associated factors. METHODS: Retrospective study of the cases of neonatal necrotizing enterocolitis (n = 56) diagnosed at Neonatal Intensive Care Unit Lagoa (NICU), between December 1986 and July 1992. Diagnosis and stages of the disease followed the modified Bell's criteria. Diagnosis and follow-up of all cases were evaluated. The cases of enterocolitis - degrees II and III (n = 44) - were subsequently selected and compared to a case-control group (n = 44), selected according to birthweight (+/- 250 g) and hospitalization period (+/- 2 weeks). The statistically significant analysis was considered as p < 0.05. RESULTS: Out of 2,447 newborns admitted to the NICU, 56 (2.3%) presented enterocolitis. Mean weight was 1908.5 g; mean gestational age was 35 weeks and 1 day; mean period for diagnosis was 10.7 days; 51 (91.1%) patients were fed before diagnosis; 18 (32.1%) needed urgent surgery; nine (16.9%) hemocultures were positive; 10 (17.8%) patients died. Four clinical standards were observed: fulminant, acute with pneumatosis, insidious and suspect. Comparatively to the case-control group, three factors were significantly associated with enterocolitis: apnea (p = 0.045), rapid increase of food intake (< 20 ml/kg/day) - (p = 0.048) and presence of infectious agent (p = 0.000). CONCLUSIONS: Significant factors associated with enterocolitis were occurrence of apnea, rapid increase of food intake and identification of the infectious agent.

Enterocolitis, Necrotizing↗
PubMed2005

Lactoferrin-enhanced anoikis: a defense against neonatal necrotizing enterocolitis.

Enteral nutrition with human milk lowers the incidence of necrotizing enterocolitis in preterm human infants. Lactoferrin, the major whey protein in human milk, has many functions related to host defense against bacterial infection. Here, we hypothesize that lactoferrin also helps terminate bacterial invasion of enterocytes via a detachment-induced apoptosis called anoikis. Death of infected epithelia by anoikis prevents local spread of bacterial pathogens because the bacteria are trapped within the cell. Such infected, apoptotic and sloughed epithelia also cannot infect the lower gastrointestinal tract, and the epithelia exit the body in the stool. Currently, anoikis is a phenomenon related to the renewal of enterocytes, and it is not recognized as an anti-bacterial host defense. We suggest that anoikis of infected enterocytes is a process in which lactoferrin plays an important role. In a pilot study in which neonatal rats were pre-treated with intra-gastric recombinant human lactoferrin, we found evidence of epithelia with anoikis in ileal fluid after enteric infection. This finding was rarely seen in infected neonatal rats without pre-treatment with lactoferrin. Quantitative analysis of intestinal lavage specimens and quantitative stereology of apoptotic epithelia in this model will be required to verify the theory. We propose that oral use of recombinant human lactoferrin might have these hypothesized and other anti-bacterial effects in preterm infants, and hence, this protein might prevent necrotizing enterocolitis in preterm infants who cannot take human milk.

Animals↗
PubMed2005

Platelet transfusions in infants with necrotizing enterocolitis do not lower mortality but may increase morbidity.

OBJECTIVE: Necrotizing enterocolitis (NEC), a serious multisystemic inflammatory disease most commonly seen in premature neonates, is often associated with thrombocytopenia. Infants with severe forms of NEC commonly have platelet counts of less than 50,000/mm(3), occasionally less than 10,000/mm(3). Despite an absence of data to support the practice, platelet transfusions are commonly used to maintain a certain arbitrary platelet count in an effort to prevent bleeding. As platelet transfusions contain a variety of bioactive factors including pro-inflammatory cytokines, we hypothesized that a higher number and volume of platelet transfusions would not be associated with an improvement in mortality or morbidity. STUDY DESIGN: A retrospective cohort analysis was conducted of the medical records of all infants between 1997 and 2001 with Bell's Stage 2 or 3 NEC associated with platelet counts of <100,000/mm(3). The medical records were evaluated for the following variables: platelet counts, number and volume of platelet transfusions, symptoms of bleeding, and hospital course. Mortality and development of short bowel syndrome and/or cholestasis were correlated to the total number and volume (total ml and ml/kg) of platelet transfusions. Differences between the outcome groups were compared using the independent t-test, Fisher's exact test and Mann-Whitney tests. RESULTS: A total of 46 infants met the study criteria (gestational age 28+/-4 weeks and birth weight 1166+/-756 g, mean+/-SD). There were a total of 406 platelet transfusions administered to the study population. Of these, 151 (37.2%) were given in the presence of active bleeding, with 62% of these resulting in the cessation of bleeding within 24 hours. Other listed indications for platelet transfusions were hypovolemia and severe thrombocytopenia. On analysis of the entire cohort, there was no statistical improvement in either mortality or morbidity (short bowel syndrome and cholestasis) with greater number and/or volume of platelet transfusions. Furthermore, we found that infants who developed short bowel syndrome and/or cholestasis had been given a significantly higher number and volume of platelet transfusions when compared to those who did not have these adverse outcomes [median (minimum - maximum) - number of transfusions : 9 (0 to 33) vs 1.5 (0 to 20), p=0.010; volume of transfusions (ml/kg): 121.5 (0 to 476.6) vs 33.2 (0 to 224.3), p=0.013]. CONCLUSION: This retrospective analysis suggests that greater number and volume of platelet transfusions in infants with necrotizing enterocolitis are associated with greater morbidity in the form of short bowel syndrome and/or cholestasis without the benefit of lower mortality.

Cholestasis↗
PubMed1986

A mouse model for the study of necrotizing enterocolitis.

A mouse model for the study of necrotizing enterocolitis is presented. It is a model of temporary intestinal ischemia and consists of occluding both superior mesenteric vessels with a bulldog clamp for varying periods of time. The resultant lesions resemble the intestinal lesions seen in necrotizing enterocolitis in respect to the gradual development of the necrotizing lesions and their patchy distribution. We also studied the effect of intravenous saline and low molecular weight dextran in preventing the development of these ischemic lesions. In moderate ischemia, saline and dextran show a similar protective effect, and in severe ischemia, both show a protective effect, with dextran being more effective than saline.

Animals↗
PubMed2003

Necrotizing enterocolitis in full-term infants.

OBJECTIVES: Although necrotizing enterocolitis (NEC) is primarily a disease of prematurity, full-term infants account for approximately 10% of cases. Previous studies have reported conflicting results regarding NEC in full-term (FT) versus preterm (PT) infants. A review of all infants diagnosed with NEC at our institution over the past 3 decades was performed to identify factors associated with this disease in full-term neonates. METHODS: The charts of all infants with definitive NEC from January 1, 1972 through January 1, 2001 were reviewed. Two hundred seventy-seven patients made up the study group: 251 PT and 26 FT infants. Data regarding demographics, clinical presentation, management, outcome, and other variables were collected. FT and PT infants were compared. RESULTS: Mean gestational age and birth weight in the FT group were 39.3 weeks and 3,132 g versus 30.2 weeks and 1,396 g for PT infants. Apgar scores were similar. Mean age at diagnosis was 5 days in FT versus 13 days in PT neonates (P <.001). Enteral nutrition was initiated earlier in FT infants (1.6 days v 3.1 days; P <.001), and FT infants were discharged an average of 14 days earlier than PT infants (P value not significant). Factors predisposing to NEC were found in 62% (16 of 26) of patients-heart disease in 6 infants and other conditions in 10 patients. Cardiac disease was found significantly more often (23% v 10%; P =.027) in FT infants. Survival rate was 65% (17 of 26) in the FT group versus 69% (173 of 251) in the PT infants (P value not significant). CONCLUSIONS: FT infants with NEC differ from their PT counterparts in several distinct ways. FT neonates had NEC at a significantly earlier age, perhaps owing to earlier initiation of feeding. There was a correlation between age at which feeding was begun and age of onset of NEC. Additionally, an association between cardiac disease and development of NEC in term infants was shown. Predisposing factors were present in a majority of FT infants. In contrast to other reports, the outcome of NEC in full-term infants was no better than for PT infants.

Age of Onset↗
PubMed2000

Necrotizing enterocolitis in infants with very low birth weight.

Necrotizing enterocolitis (NEC) is a disease in which the primary risk factor is prematurity. Despite, and partially as a result of, the tremendous strides neonatal care has taken, it is a major cause of morbidity and mortality of the newborn. The infant with very low birth weight is particularly susceptible, and the management of the condition in this group differs somewhat from other neonates. The outcomes continue to improve, but there are significant sequelae. Prevention, which would be the best "cure," is elusive, in no small part because of the multifactorial nature of the etiology of NEC.

Enterocolitis, Necrotizing↗
PubMed2003

Surgical treatments of infants with necrotizing enterocolitis.

With the improvements in neonatal intensive care, necrotizing enterocolitis (NEC) has become the most common gastrointestinal emergency amongst infants in neonatal intensive care units. The incidence of NEC varies between 1 and 8% of neonatal intensive care unit admissions and the disease has a mortality rate between 20 and 40%. There are a number of surgical options available to the paediatric surgeon depending on the clinical condition of the infant and the extent of the disease. However owing to a paucity of prospective data in this field and a lack of randomized controlled trials there is little consensus as to which is the most appropriate. Primary peritoneal drainage has become very popular in North America and Europe for the treatment of perforated NEC in very low-birthweight infants. It is a useful manoeuvre in the resuscitation of critically ill infants and in some of these infants, further operation may be avoided completely by inserting a peritoneal drain. Others however remain too unwell to undergo laparotomy and may die. Two randomized controlled trials are currently underway to determine the real benefit of peritoneal drainage. Laparotomy in very small neonates has become safer with improvements in anaesthesia and intensive care management. Resection and primary anastomosis has been proposed as a valid treatment modality in neonates with both focal and multifocal disease. The advantage of resection and primary anastomosis over stoma formation is still controversial. Different surgical techniques such as diverting jejunostomy or 'clip and drop' have been described to deal with extensive disease and avoid massive small bowel resection. Prospective studies and randomized controlled trials are needed to define the best operative treatment for neonates with severe NEC.

Emergency Treatment↗
PubMed2000

A regional study of underlying congenital diseases in term neonates with necrotizing enterocolitis.

AIM OF THE STUDY: The aetiology of necrotizing enterocolitis (NEC) remains poorly understood in infants of all gestation, particularly when it occurs at term. We hypothesize that NEC in term infants is rare but often associated with underlying congenital illnesses. METHOD: Records of all term infants hospitalized with radiologically or surgically proven NEC in the 10 tertiary centres of two geographical regions of Australia during a 6.5-y period were reviewed. Regional birth data were obtained and a special care nursery survey was conducted. RESULTS: Twenty-nine infants had proven NEC giving a population incidence of 0.05 per 1000 live births. Nineteen (66%) of them had underlying congenital diseases. Five (17%) infants had endocrine disorders, which included panhypopituitarism, hypothyroidism, hypoparathyroidism and congenital adrenal hyperplasia. Ten infants had congenital heart disease, eight being cyanotic. Six of them developed NEC prior to any invasive cardiac procedures. Seven of the other nine infants without any congenital diseases had perinatal risk factors associated with NEC. The severity of illness was not different amongst the three groups. All infants, except two, survived. CONCLUSION: NEC in term infants is commonly secondary to or preceded by underlying congenital diseases. A considerable proportion of NEC cases had co-existing endocrine illnesses.

Birth Weight↗
PubMed2003

Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or antiinflammatory interleukin-10. METHODS: Newborn rats were artificially fed with either growth-factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold stress. Cytokine expression and localization were assessed using reverse-transcription real-time polymerase chain reaction and immunohistology/confocal microscopy. RESULTS: Enteral administration of EGF (RMS + EGF) decreased overproduction of interleukin-18 and increased interleukin-10 production in the ileum. Furthermore, increased interleukin-10 production was associated with up-regulation of the transcription factor Sp1 in RMS + EGF rats. CONCLUSIONS: These data suggest that EGF may reduce NEC via increased interleukin-10 and decreased interleukin-18 and that EGF-mediated up-regulation of Sp1 may account for the increased interleukin-10.

Animals↗
PubMed2004

Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units.

OBJECTIVES: Necrotizing enterocolitis (NEC) is the most common acquired intestinal disease of neonates. Previous reports on incidence have generally examined small cohorts of extremely low-birth-weight infants and have not examined risk-adjusted variations among neonatal intensive care units (NICUs). The authors examined risk-adjusted variations in the incidence of NEC in a large group of Canadian NICUs and explored possible therapy-related risks. METHODS: The authors obtained data on 18,234 infants admitted to 17 tertiary level Canadian NICUs from January 1996 to October 1997. They used multivariate logistic regression analysis to examine the inter-NICU variation in incidence of NEC, with adjustment for population risk factors and admission illness severity, and explored therapy-related variables. RESULTS: The incidence of NEC was 6.6% (n = 238) among 3,628 infants with birth weight < or = 1,500 g (VLBW), and 0.7% (n = 98) among 14,606 infants with birth weight > 1,500 g (HBW). Multivariate logistic regression analysis showed that for VLBW infants, NEC was associated with lower gestational age and treatment for hypotension and patent ductus arteriosus. Among HBW infants, NEC was associated with lower gestational age, presence of congenital anomalies (cardiovascular, digestive, musculoskeletal, multiple systems) and need for assisted ventilation. There was no significant variation in the risk-adjusted incidence of NEC among NICUs, with the exception of one NICU reporting no cases of NEC. CONCLUSIONS: Risk factors for NEC were different in VLBW and HBW infants. There was no significant variation in the risk-adjusted incidence of NEC among Canadian NICUs, with one possible exception.

Birth Weight↗
PubMed2005

Necrotizing enterocolitis in acute lymphoblastic leukemia patients: department experience.

Necrotizing enterocolitis is a severe complication of high-dose chemotherapy in patients with hematopoietic malignancies. Some patients with severe mucositis may develop necrosis of the intestine, leading to typhlitis and perforation of the intestinal tract. The patients have few obvious symptoms; thus, early diagnosis and prompt treatment of intestinal necrosis or bowel perforation seem critical for a good overall treatment outcome. We present 5 cases of intraabdominal complications in patients with acute lymphoblastic leukemia. All patients who underwent surgery survived the postoperative period. We also present a suggested algorithm for treatment of acute abdomen complications in leukemic patients.

Adult↗
PubMed1984

Left ventricular outflow obstruction and necrotizing enterocolitis.

Two neonates had unusually rapid development of necrotizing enterocolitis within 24 hours of birth. Both patients had decreased systemic perfusion secondary to aortic atresia. Onset of either clinical or radiographic manifestations of necrotizing enterocolitis in the first day of life should alert one to the possible presence of severe left ventricular outflow obstruction.

Aorta↗
PubMed1979

Changes in the incidence of necrotizing enterocolitis associated with variation of the gastrointestinal microflora in neonates.

The incidence of necrotizing enterocolitis was noted to vary in association with significant variation in the gastrointestinal microflora cultured from infants in the neonatal intensive care unit. Increased colonization with E. coli and K. pneumoniae was associated with an increased incidence of necrotizing enterocolitis, which suggests that these organisms are related to the pathogenesis of necrotizing enterocolitis.

Digestive System↗
PubMed1978

Spontaneous resolution of colonic strictures caused by necrotizing enterocolitis: therapeutic implications.

Colonic strictures are now a well recognized complication in infants surviving necrotizing enterocolitis. We describe the clinical course of seven infants with colonic strictures after necrotizing enterocolitis. Only two demonstrated the finding of fixed fibrotic stricture described in the literature, while the remaining five showed atypical radiographic and pathologic features. Two of the five showed partial or spontaneous resolution of post-necrotizing enterocolitis colonic stenoses on follow-up barium enema studies. In three of four patients with colonic resections, the histopathologic examination revealed a surprising absence of irreversible fibrosis or cicatrix formation. Current surgical practice dictates elective resection of these narrowed colonic segments. The radiologic and pathologic findings in our series of patients suggest surgical resection may be unnecessary in selected cases.

Colon↗
PubMed2004

Gemcitabine associated vasculitis leading to necrotizing enterocolitis and death in women undergoing primary treatment for epithelial ovarian/peritoneal cancer.

We present two patients who developed necrotizing enterocolitis following their first cycle of chemotherapy for epithelial ovarian/peritoneal cancer. After optimal cytoreductive surgery, both women received gemcitabine as part of a chemotherapy protocol. One patient developed necrotizing enterocolitis, 1 day after chemotherapy and the other 8 days after chemotherapy. The first patient succumbed to the enterocolitis despite aggressive supportive care. The second patient succumbed despite both aggressive supportive care and surgical intervention. Pathologic review for both patients revealed a drug induced vasculitis causing necrotizing enterocolitis.

Aged↗
PubMed1976

Early diagnosis of necrotizing enterocolitis.

This study demonstrates that the diagnosis of necrotizing enterocolitis can sometimes be made before the full-blown clinical and radiographic findings are manifest. Of 12 infants with films available prior to diagnosis of the disease, nine had early selective dilatation of small bowel and little or no air in the colon. Necrotizing enterocolitis should be foremost in the differential diagnosis when this finding is coupled with signs such as abdominal distention, acidosis, and diarrhea.

Enterocolitis, Pseudomembranous↗
PubMed1980

Interobserver variability in the radiographic diagnosis of necrotizing enterocolitis.

A total of 17 radiographs from seven babies with clinical evidence of necrotizing enterocolitis were examined by six pediatric radiologist and four neonatologists from the Southern California area. The participants were asked to interpret each radiograph as to the presence or absence of necrotizing enterocolitis and to indicate whether pneumoperitoneum was present. A substantial degree of interobserver variability was observed, with only one of the 17 films yielding universal agreement. We propose that this interobserver variability in interpreting abdominal films of neonates with clinically suspected necrotizing enterocolitis may in fact contribute to the reported difference in incidence of this disease among centers.

Diagnostic Errors↗
PubMed1986

Early enteral feeding does not affect the incidence of necrotizing enterocolitis.

To begin to determine the optimal time for initiating enteral feedings, 34 sick, very low birth weight infants were prospectively selected from all neonates of less than 1,500 g (N = 116) and randomly divided into two groups. Infants were fed either on day 1 (early) or 7 (late) of life, according to a feeding protocol which included parenteral nutrition and a scheduled progression from sterile water to 2.5% dextrose, half-strength, and finally full-strength formula over seven days. The incidence of necrotizing enterocolitis and subsequent hospital course were compared. Initiating enteral feedings on day 1 did not significantly increase the incidence of necrotizing enterocolitis, produce a clustering of cases, or induce an earlier onset of necrotizing enterocolitis. The overall incidence of necrotizing enterocolitis in sick, very low birth weight neonates was 29% (5/17) and 35% (6/17) in the early and late groups, respectively, compared with 4.2% (2/47) in minimally sick, very low birth weight neonates. No significant differences between groups were seen in obstetrical complications, birth weight, gestational age, Apgar scores, presence of patent ductus arteriosus or intraventricular hemorrhage, use of umbilical catheterization, and respiratory or oxygen requirements. Infants fed enterally from day 1 did show a significantly higher energy and protein intake during the second week of life. These data show that providing dilute, early enteral calories does not adversely affect the incidence of necrotizing enterocolitis.

Enteral Nutrition↗