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Sonographic demonstration of portal venous gas in necrotizing enterocolitis.

Portal vein gas embolism was demonstrated by ultrasound in a preterm infant with necrotizing enterocolitis. This sign could not be detected radiographically. It is speculated that portal venous gas occurs more frequently than hitherto inferred from radiological studies. This observation points to the value of ultrasonography in providing early objective evidence in support of the diagnosis of NEC. The favourable outcome for the patient proves that portal venous gas embolism is not necessarily associated with a fulminant course of enterocolitis.

Embolism, Air↗

The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis.

Enteric alimentation has been one of several factors implicated in the development of necrotizing enterocolitis (NEC). To examine this relationship further, the alimentation records of 19 patients who developed NEC were each compared with two matched patients controlled for birthweight and time of admission to the intensive care nursery. Parameters compared included total fluids provided, rate of enteral feed volume advancement, milk selection, and medications given. In addition, because there were no marked day-to-day differences between the mean values of most parameters and because we noted a marked fluctuation of formula intake and volume increments, we analyzed the maximum differences between the two groups. Maximum total fluids intake occurred on day 5 of life for the NEC patients and was 180.7 +/- 44 ml/kg. The control group on this same day received 149.7 +/- 35 ml/kg (p less than 0.01). Maximum enteral intake occurred on day 8 for the NEC patients at 124.3 +/- 5.7 ml/kg, whereas the control group had consumed only 83.5 +/- 60 ml/kg (p less than 0.05) on this matched day. The feed increment rate from initiation of feeds to day of maximum feeds was 27.8 +/- 16 ml/kg/day for the NEC patients and 16.8 +/- 11 for the control patients (p less than 0.0005). Furthermore, during the entire study period patients who developed NEC had the greatest 1 day increment compared with the controls (56.7 +/- 19.4 vs 44.6 +/- 26.2 ml/kg, p less than 0.05). Very rapid advancement of enteral feedings and excessive fluid volumes may predispose premature infants to the development of NEC and should be discouraged.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗

The anti-inflammatory effect of an oral immunoglobulin (IgA-IgG) preparation and its possible relevance for the prevention of necrotizing enterocolitis.

An exaggerated release of inflammatory mediators has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). Oral administration of a human immunoglobulin preparation (serum IgA-IgG) has been demonstrated to be an effective prophylaxis for NEC. The aim of the present study was to examine the regulatory effect of a human IgA-IgG preparation on the release of inflammatory cytokines in human monocytes. Our results indicate that the immunoglobulin preparation inhibits TNF-alpha and IL-6 release in monocytes following stimulation with heat-inactivated Hib in a dose-dependent manner. This might have a biological relevance in infants receiving oral immunoglobulin prophylaxis for NEC, since modulation of the release of inflammatory mediators at the level of the gastrointestinal mucosa could interfere with the development of noxious sequelae of acute and/or chronic inflammation initiated by microbial pathogens or their toxins that finally lead to the pathologic changes associated with NEC.

Administration, Oral↗

Surgical treatment of necrotizing enterocolitis: when? how?

In 10 years (1981-1990) 28 out of 54 neonates (51.8%) with definite necrotizing enterocolitis (NEC) underwent surgery. Operation was performed at 13.5 +/- 8.8 (range 3-38) days of life, after 1.7 +/- 1.5 (range 1-6) days from the onset of symptoms. Aiming to perform laparotomy before the occurrence of perforation, surgery was liberally indicated in stage IIIa, according to Walsh-Kliegman. Explorative laparotomy (+peritoneal drainage in 2 cases) was performed in 4 patients with massive intestinal necrosis: all died within 3 days of surgery. In one neonate, only pneumatosis was present and resection was not considered mandatory. Intestinal resection and enterostomy was performed in 17 neonates, 5 of them with perforation; three developed an intestinal stenosis. Enterostomy was closed after 116.2 +/- 61.8 days (range 26-193); 11 patients (64.7%) are long-term survivors. Intestinal resection and primary anastomosis was performed in 6 babies, 3 of them with perforation. Postoperatively, 2 dehiscences and 1 stenosis were recorded, but all children survived. In our opinion, resection followed by primary anastomosis seems to be the most satisfactory surgical option.

Anastomosis, Surgical↗

Neonatal necrotizing enterocolitis in Lagos.

The records of 14 infants in whom the diagnosis of Neonatal Necrotizing Enterocolitis was made between 1978 and 1984 were studied. The distance appeared in the second week of life of the majority (57%) of the babies, and was equally prevalent in preterm and term babies. Infections seemed to be the predisposing factor in all cases although no transmissable pathogens were identified. Abdominal distention (57%), rectal bleeding (21%) and bowel perforation (14%) were the main presenting features. The only three survivors were among the babies treated medically including intravenous metronidazole. The only baby that survived bowel resection succumbed three months later to jejunostomy diarrhoea. Extended medical management including intravenous metronidazole is being suggested as the treatment for acute NNEC in developing countries while surgical treatment is reserved only for perforation and uncontrollable rectal bleeding.

Enterocolitis, Pseudomembranous↗

Relationship of birth weight to the pathogenesis of necrotizing enterocolitis in the neonatal piglet.

The relationship between birth weight and the development of necrotizing enterocolitis (NEC) was studied in the term-delivered neonatal piglet. Hypoxia (pO2 less than 30% for 1 h) coupled with hyperviscosity (hematocrit more than 75%), with and without splenectomy, resulted in a high frequency and severity of NEC. This effect was most pronounced in low birth weight (LBW) animals. A statistically significant inverse relationship was found between birth weight and the number and severity of lesions. Splenectomy increased the incidence and severity of lesions particularly in LBW animals. A predominance of lesions was found in the distal ileum with occasional occurrences elsewhere in the small bowel and in the proximal colon. The neonatal piglet is capable of producing the full spectrum of NEC under acceptable experimental conditions. LBW is a significant predisposing factor in the pathogenesis of NEC.

Animals↗

The significance of portal vein gas in necrotizing enterocolitis.

To assess the significance of the presence of portal vein gas (PVG) in necrotizing enterocolitis (NEC), a retrospective study of all cases of NEC seen at Grady Memorial Hospital between July 1980 and June 1984 was conducted. Infants with PVG were compared with those without PVG with respect to clinical presentation, treatment, and outcome. There was no significant difference between the two groups in birth weight, Apgar scores, or the age of onset of NEC. All patients received standard medical therapy unless they developed pneumoperitoneum, had a positive paracentesis, or deteriorated in spite of maximal medical treatment, in which case they had surgery. Of 97 infants with "definite" NEC, 55 (56%) required surgery. Twenty-one patients (22% of the total) had PVG and 17 (81%) of them required surgery. Seventy-six patients (78% of total) did not have PVG and only 38 (50%) of them required surgery (P = 0.011). Five (29%) of 17 infants with PVG had nearly total intestinal necrosis compared with only five (13%, P = 0.25) of 38 infants without PVG. Patients with PVG had a lower overall survival rate (62% vs 88%, P = 0.009), medical survival rate (75% vs 97%, P = 0.184), and surgical survival rate (59% vs 79%, P = 0.19) than patients without PVG. Infants weighing less than 1000 grams fared worse regardless of the presence or absence of PVG. Portal vein gas is an ominous prognostic sign. It signals a greater likelihood for surgical intervention, a more extensive bowel involvement, and a significantly lower survival when compared to patients with NEC who do not have PVG.

Enterocolitis, Pseudomembranous↗

Inflammatory cytokine mRNAs in surgical specimens of necrotizing enterocolitis and normal newborn intestine.

Coagulation necrosis, inflammation, and hemorrhage are pathologic hallmarks of necrotizing enterocolitis (NEC). Because cytokines are peptides that mediate inflammatory cell recruitment and amplify the immune response, several of the inflammatory cytokines have been implicated in NEC. We hypothesized that mRNA levels for the interrelated cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and the neutrophil chemotactic factor IL-8 would be increased in NEC and would be associated with the presence of inflammation. In this study, we determined the relative levels and localization of mRNA for these cytokines in surgical pathology archival intestinal tissue from 29 premature infants with acute NEC and 15 control infants with congenital intestinal malformations using a novel quantitative in situ hybridization technique. Compared with controls, there were higher IL-1 beta mRNA levels in full-thickness sections and higher TNF-alpha mRNA levels in full-thickness and mucosa sections of acute NEC samples, suggesting a potential role for these cytokines in the pathogenesis of local inflammation in NEC. IL-6 and IL-8 mRNA levels were similar in samples of control and acute NEC cases. Analysis of covariance including all subjects showed that the presence of acute inflammation was associated with increased IL-1 beta mRNA levels in mucosa (P = .035) and increased IL-8 in full-thickness sections (P = .005) and mucosa (P = .01). In four of five NEC cases in which intestinal specimens were available from reanastomosis surgery, cytokine mRNA levels decreased to low or undetectable levels. These data suggest that the inflammatory cytokines are involved in neutrophil recruitment and augmentation of the inflammatory response in neonatal intestine.

Cytokines↗

P-selectin expression, neutrophil infiltration, and histologic injury in neonates with necrotizing enterocolitis.

BACKGROUND/PURPOSE: P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC). METHODS: Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades. RESULTS: Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578). CONCLUSIONS: Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue.

Enterocolitis, Necrotizing↗

Intestinal stenosis following successful medical management of necrotizing enterocolitis.

In the past decade, increased clinical awareness and better medical and surgical management of necrotizing enterocolitis (NEC) has resulted in improved survival. With an increase in the number of infants surviving the acute stages of NEC the sequelae, including intestinal stenosis, have become more apparent. In the past 5.5 yr, 62 patients with NEC have been treated at our institution. Of the 28 survivors of medical management for NEC seven patients developed intestinal stenosis. An average of 23 days elapsed between the recovery from NEC and the diagnosis of colonic stenosis. Only three patients manifested symptoms of intestinal obstruction. Two patients had blood in their stools and two patients were asymptomatic. Five infants were managed by primary or staged resection of the intestinal stenosis. The remaining two patients were treated nonoperatively. Our data suggests a high incidence of intestinal stenosis (25%) following medical management of NEC. There is a marked preference for the stenosis to occur on the left side of the colon. Colon stenoses can exist without symptoms and radiographically proven areas of stenosis can resolve. We recommend that all infants following medical management of NEC have a barium enema prior to hospital discharge. In selected cases asymptomatic patients with colonic stenosis may not require operative intervention.

Barium Sulfate↗

Peritoneal drainage under local anesthesia for necrotizing enterocolitis (NEC) perforation: a second look.

Between 1974 and 1979, 15 extremely ill neonates with necrotizing enterocolitis (NEC) were initially treated with peritoneal drainage under local anesthesia for intestinal perforation. They weighed 600 to 3040 g with half less than 1000 g. Most had other serious illnesses (RDS, PDA, jaundice, CNS abnormalities). There were no immediate complications such as hemorrhage or bowel evisceration from the local drainage procedures. Seven of the 15 (46%) survived. Three (20%) died because of unrelated problems (CNS, liver failure) with an intact gastrointestinal tract, while another 8 (34%) died from intestinal sepsis. Seven (87%) of the neonates weighing less than 1000 g had an adequately functioning GI tract after this drainage procedure. Half of the neonates requiring additional surgery within 24 hr of initial peritoneal drainage survived and half of the neonates requiring subsequent surgery survived. Five of 15 infants developed strictures one died before excision. This technique is contrary to standard practice and was employed in less than 10% of the neonates with NEC treated at our institution. These results indicate that this method is effective in possibly temporizing the very ill neonate with NEC. An added bonus, however, is that 40% of the neonates treated in this fashion had complete resolution of their disease without residual scarring of the gastrointestinal tract requiring further surgery. It is our continued conclusion that this form of peritoneal drainage under local anesthesia is warranted in certain carefully selected instances.

Anesthesia, Local↗

Prediction of outcome following necrotizing enterocolitis in a neonatal surgical unit.

Retrospective analysis of 27 factors in 80 neonates with necrotizing enterocolitis has enabled us to identify three factors that appear to be of prognostic statistical significance, namely blood pH, platelet count, and the presence of congenital defects. All three factors may be assessed objectively at the time of admission of the patient. Using these factors we have estimated a "probability of death" score for each patient and a high-risk group of neonates has been identified.

Blood Chemical Analysis↗

Long-term follow-up after surgical management of necrotizing enterocolitis: sixty-three cases.

One hundred twenty-five infants underwent surgical intervention for necrotizing enterocolitis between 1972 and 1984. Sixty-three infants, who survived more than 30 days postoperatively, were evaluated for long-term complications. There were 28 girls and 35 boys (mean birth weight 1,725 +/- 890 g; gestational age 32 +/- 4 weeks). Associated problems included hyaline membrane disease (43), cardiac anomalies (25), and trisomy 21(2). Thirty-six survivors required long-term ventilatory support. Fifty-nine infants underwent bowel resection and enterostomy, 3 decompressing enterostomies without resection, and 1, exploratory laparotomy only. Enterostomies were closed at four months. Twenty four had short bowel syndrome. Fifteen infants subsequently died for a late mortality rate of 23%. Mortality was related to sepsis (3), respiratory failure (5), cardiac anomalies (3), cardio-respiratory arrest (2), and TPN related liver failure (2), and was common with gestational age less than 31 weeks and birth weight less than 1,000 g. Medical problems included cholestasis (17), TPN induced cirrhosis (3), meningitis (3), seizures (8), and nutritional rickets (6). Significant developmental and intellectual delays were observed.

Adolescent↗

The development of necrotizing enterocolitis following repair of gastroschisis: a surprisingly high incidence.

We recently observed the development of necrotizing enterocolitis (NEC) in two consecutive newborn infants after gastroschisis repair. Because this association was unexpected, a retrospective review of our 11-year experience was performed using a multivariant computer analysis. The cohort consisted of 54 newborns with gastroschisis. All infants with omphalocele were excluded. Ten of 54 infants (18.5%) developed NEC as defined by classical clinical findings and pneumatosis intestinalis. Twenty-one distinct episodes of NEC occurred with up to three episodes (mean, 2.1) per patient. Twenty of the 21 episodes were successfully treated nonoperatively. Two infants developed pneumoperitoneum, one of whom underwent laparotomy upon which no perforation or intestinal infarction was found. Eight of the ten patients survived--a survival rate no different than for the remainder of the study group. Neither of the two deaths was attributable to NEC. The NEC was atypical in that no significant relationship was established with known predisposing conditions such as prematurity or low Apgar scores. Suspected risk factors such as time of feeding, type of closure, type of formula, total parenteral nutrition (TPN), and composition of TPN were not statistically related. Significant associations included concurrent TPN associated cholestatic liver disease in nine of the ten infants, antecedent intestinal surgery other than abdominal wall closure in five of the ten infants, and delay in initiation of enteral feedings (greater than 30 days) in eight of ten infants. In addition, the NEC occurred significantly later (range, 32 to 79 days; mean, 52 days) in the clinical course than usual; in fact, three of ten infants were rehospitalized with NEC following discharge. We conclude that a relationship exists between NEC and gastroschisis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

The incidence of meningitis in neonates with necrotizing enterocolitis.

Although meningitis is common among patients with neonatal sepsis, review of the literature on necrotizing enterocolitis (NEC) reveals a paucity of information on the association of NEC and meningitis. We report four patients who had meningitis during the course of illness among 238 patients with documented NEC. We recommend that all patients with suspected NEC have a lumbar puncture as part of the diagnostic work-up, as meningitis may require different and prolonged therapy, and will necessitate more specific follow-up for neurodevelopmental problems.

Enterocolitis, Pseudomembranous↗

Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging.

A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded intervention. For Stage I infants, vigorous diagnostic and supportive measures are appropriate. Stage II infants are treated medically, including parenteral and gavage aminoglycoside antibiotic, and Stage III patients require operation. All Stage I patients survived, and 32 of 38 Stage II and III patients (85%) survived the acute episode of NEC. Bacteriologic evaluation of the gastrointestinal microflora in these neonates has revealed a wide range of enteric organisms including anaerobes. Enteric organisms were cultured from the blood of four infants dying of NEC. Sequential cultures of enteric organisms reveal an alteration of flora during gavage antibiotic therapy. These studies support the use of combination antimicrobial therapy in the treatment of infants with NEC.

Anti-Bacterial Agents↗

Late intestinal strictures following successful treatment of necrotizing enterocolitis.

Between 1975 and 1992, in 16 infants (14%) out of 113 neonates with previous necrotizing enterocolitis (NEC) a total of 25 intestinal strictures had to be treated. Four (16%) were found in the ileum and 21 (84%) in the colon, and in 50% multiple strictures were present. In these 16 patients initial treatment for acute NEC included conservative treatment in 5, primary resection and enterostomies in 6 and proximal diverting enterostomies in 5. Therefore, the incidence of late strictures was 11% after conservative therapy, 11% after primary resection and 55% after primary proximal diverting enterostomies. An average of 49 days elapses between the recovery from NEC and the diagnosis of late strictures in conservatively treated patients. After initial surgical treatment, late strictures were detected on contrast studies on an average of 80 days. In pathologic specimens, marked fibrosis in the submucosa was consistently present in all strictures, whereas inflammatory changes in the mucosa, disruption or hypertrophy of the muscle layers or absence of ganglion cells were seen less frequently. All strictures were resected and primary end-to-end anastomosis was performed. But despite the development of late intestinal strictures, bowel preservation was improved after initial restrictive surgical therapy and aggressive medical treatment.

Constriction, Pathologic↗

[Necrotizing enterocolitis and cytomegalovirus infection (author's transl)].

During an 18-month period, 11 cases of necrotizing enterocolitis (NEC) were diagnosed in infants treated in Neonate Department. This represents 1% of total admissions. Six cases occurred during hospitalization. Clinically, the disease took three different forms: surgical form, medical form responding well to exclusive parenteral feeding and isolated haemorrhagic form, which deserves discussion. Seven of these infants had cytomegalovirus (CMV) infection. NEC accounted for 22% of clinical symptoms in CMV infection. These data suggest that the cytomegalovirus may act as aggravating factor in NEC.

Cytomegalovirus Infections↗