Gut hormone concentrations in preterm infants with necrotizing enterocolitis

Abstract Blood levels of gastrin, neurotensin and vasoactive peptide (VIP) were estimated in 14 premature infants with necrotizing enterocolitis (NEC) and in 12 controls. In comparison to the control group, infants with NEC had (a) significantly lower gastrin levels both before [9.3 (7.8) versus 33.7 (27.1)] and after [52.4 (48.1) versus 100.8 (50.9)] the development of NEC; (b) significantly lower neurotensin levels only after the development of NEC [37.8 (10.4) versus 54.5 (20.6)]; and (c) no significant difference in VIP values [25.4 (9.7) versus 18.9 (9.9) and 24.5 (15.7) versus 26.1 (19.1)]. It is concluded that NEC can adversely affect gastrin and neurotensin concentrations in the blood.     

极早产儿输血相关性坏死性小肠结肠炎危险因素分析

目的 探讨极早产儿发生输血相关性坏死性小肠结肠炎(TA-NEC)的危险因素。方法 选择2013年4月至2021年4月新生儿重症监护室收治的接受输注红细胞的极早产儿为研究对象。符合TA-NEC组纳入标准的极早产儿为TA-NEC组;按1:2比例匹配同期同性别、胎龄(±3d)、出生体重(±200g)、输血日龄(±3d)的非NEC极早产儿作为对照组。比较两组间临床特点差异,探讨TA-NEC发生的危险因素。结果 共纳入204例极早产儿,男138例、女66例,平均胎龄(29.0±1.5)周,中位出生体重1 100.0(951.0～1 200.0)g。TA-NEC组68例,对照组136例。多因素条件logistic回归分析结果显示,宫内窘迫、绒毛膜羊膜炎、晚发型败血症是极早产儿发生TA-NEC的独立危险因素(P<0.05),完全经口喂养是其独立保护因素(P<0.05)。结论 患有宫内窘迫、绒毛膜羊膜炎和/或晚发型败血症的极早产儿在输注红细胞后48 h内更容易发生NEC。预防围生期缺氧和败血症,在安全前提下完成到完全经口喂养的过渡,对降低极早产儿TA-NEC的发生率有积极作用。     

Role of platelet-activating factor in the pathophysiology of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal illness that affects predominantly preterm infants. Treatment options are limited and NEC remains a significant cause of morbidity and mortality. The precise aetiology of NEC remains unclear but evidence strongly suggests that the cause is multifactorial and there are four main aetiological factors: prematurity, hypoxia, enteral feeding and bacterial colonization. The presence of similar intestinal lesions, regardless of aetiological trigger, strongly implicates a final common pathway in the pathogenesis. There is now a substantial body of evidence to indicate that endogenous inflammatory mediators, particularly platelet-activating factor (PAF), play a vital role in this final pathway. CONCLUSION: The use of agents that antagonize PAF may provide therapeutic options in the management of NEC.     

血小板活化因子在新生儿坏死性小肠结肠炎发病中的作用

坏死性小肠结肠炎是新生儿,尤其是早产儿或极低出生体重儿最常见的胃肠道急症,至今仍是早产儿发病和死亡最常见的原因.大量流行病学、动物实验模型及临床研究发现NEC是与早产、配方奶喂养、肠缺血缺氧、细菌异常增殖等多种因素相互作用的结果,但其确切的发病机制尚不完全清楚.目前有研究者通过模拟上述因素建立NEC动物模型,发现模型鼠中NEC组回肠中血小板活化因子水平较对照组明显升高,予以PAF拮抗剂预处理后NEC的发病率显著降低,表明PAF在NEC发病中有关键作用.PAF通过与其受体特异性结合后,可激活多条信号传导通路,导致多种炎症介质合成与释放增加;肠道黏膜屏障受损,大量毒素吸收,进一步增加内源性PAF合成;通过依赖线粒体途径凋亡肠上皮细胞;激活核因子NF-κB通路放大级联炎症反应;诱导活性氧产生,引起细胞凋亡导致肠管坏死.     

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??Necrotizing enterocolitis??NEC?? is considered to be the most common gastrointestinal emergency among neonates. Although the pathogenesis of NEC is incompletely understood??there are several established risk factors??including prematurity??altered intestinal blood flow/oxygen delivery??formula feeding and bacterial infection. Recently??a large number of studies showed that intestinal flora imbalance had been implicated as key risk factor in the pathogenesis of NEC. After birth??the neonatal gut must acquire a healthy complement of commensal bacteria??which leads to deficient or abnormal microbial colonization of the gut??may protect the immature gut from inflammation and injury. Providing a healthy complement of commensal bacteria can maintain the intestinal microflora balance??shift the balance of intestinal microbiota from a pathegenic to protective complement of bacteria??protect the gut from inflammation and subsequent injury??and prevent NEC. We review the relationship between intestinal microbiota and NEC in preterm infants??the mechanism of probiotics in preventing NEC??and the efficacy and safety of probiotics in preterm infants.     

Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis

The pathogenesis of necrotizing enterocolitis (NEC) is poorly understood. We have established several animal models of NEC by using a combination of various stimuli and stress, including endotoxin, PAF, TNF, and hypoxia. We discuss the mechanism of their actions and the possible roles of these factors in the pathogenesis of human NEC.     

Plasma cytokine levels in necrotizing enterocolitis

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (>10pg/ml) in 71% samples with a mean of 48pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage HI (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.     

Epidemiology of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a worldwide problem that has emerged in the past 25 years as the most common gastrointestinal emergency in neonatal intensive care units (NICU). In the United States the incidence ranges from 1 to 7.7% of NICU admissions. Ninety percent of the patients are premature infants. Mucosal injury, bacterial colonization and formula feeding are the three major pathogenetic factors that have been documented in most infants who have developed NEC. However, NEC may develop only if a threshold of injury, imposed by the coincidence of at least two of three events (intestinal ischemia, pathogenic bacteria, and excess of protein substrate) is exceeded. Immunological immaturity of the gut in premature babies may represent the crucial risk factor.     

Spontaneous intestinal perforation and Candida peritonitis presenting as extensive necrotizing enterocolitis

Spontaneous intestinal perforation (SIP) has been increasingly reported in very-low-birthweight (VLBW) infants, although it is still less common than necrotizing enterocolitis (NEC). In around one-third of cases, SIP is associated with systemic candidiasis. We describe a case of SIP and Candida peritonitis in a VLBW infant, which was mistakenly diagnosed as NEC during the infant's short life. At laparotomy, the bowel surface was black and thought to be necrotic. As the infant was thought to have whole-bowel necrosis due to NEC, her condition was deemed incompatible with survival. At postmortem, however, the bowel wall was found to be healthy apart from a very localized patch of necrosis associated with a single perforation. The bowel was covered by a thick, black, serosal exudate consisting of fungal elements from Candida albicans. CONCLUSION: This case reinforces the fact that a markedly discoloured bowel is not necessarily necrotic and that the discoloration can potentially recover.     

新生儿坏死性小肠结肠炎发病机制及防治研究进展

新生儿坏死性小肠结肠炎(necrotizing enterocolitis of newborn,NEC)在新生儿期发病率及致死率均较高,其发病的病理生理学机制尚未完全阐明,治疗上主要限于对症支持治疗.近年来,较多研究发现大量炎症因子及其介导的信号途径在NEC发生发展过程中具有重要作用;另外,在蛋白质组学、肠道微生态等领域的研究也取得了一些进展.在NEC的防治上,提倡早期母乳喂养和应用微生态制剂.本文就上述领域的研究作一综述,为探讨NEC发病机制及防治奠定基础.     

炎症介质在坏死性小肠结肠炎发病机制中的作用

坏死性小肠结肠炎( necrotizing enterocolitis,NEC)是新生儿常见的危急重症,严重威胁新生儿的健康。凋亡信号传导途径可以分为外源性凋亡途径、内源性凋亡途径和内质网途径。新生儿发生NEC时炎症介质可通过以上三种途径诱导肠上皮细胞凋亡,在NEC的发生发展过程中起着重要的作用,是导致NEC发病的重要机制。     

新生儿坏死性小肠结肠炎遗传多态性研究进展

新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis,NEC)仍是新生儿期发病率和病死率较高的疾病,其病因目前尚不十分明确.炎症级联反应、先天性免疫及肠道血流动力学改变等在NEC发病机制中有重要作用.单核苷酸多态性是指DNA序列中单个碱基发生的变异,它可能通过改变转录效率或其所编码的分子的结构而与疾病相关联.该文就NEC相关因子如炎症因子、Toll样受体信号通路、甘露糖结合凝集素、血管内皮生长因子、氨甲酰磷酸合成酶、血管紧张素转换酶等的单核苷酸多态性研究作一综述.     

Late onset bowel stenoses after neonatal necrotizing enterocolitis

Abstract In 14 cases of bowel stenoses occurring after neonatal necrotizing enterocolitis (NEC), eight cases presented early, within 8 weeks from the onset of NEC and three beyond 4 months. In the other three cases the stenoses occurred in defunctionalized loops. The late onset stenoses remained undiagnosed until they presented with acute, life-threatening complications, and one of these patients died. We draw attention to these late onset stenoses which could be missed in early contrast studies, and recommend a study at 4 months rather than at 4 weeks, as previously recommended. Those presenting early should not be missed, as all of our cases presented with acute and obvious intestinal obstructions, and they were all still in hospital or undergoing frequent review.     

Surgical procedures in colonic strictures after necrotizing enterocolitis

Between 1982 and 1992, 22 patients were treated with colonic strictures in the course of necrotizing enterocolitis (NEC). Fourteen newborns in whom a primary enterostomy and, when necessary, resection of necrotic bowel was performed developed strictures in the diverted colon. The strictures were detected by colon contrast enema study performed on average 3 months after the first intervention. Eight additional children suffered from an ileus due to primary strictures after conservatively treated NEC, which was surgically managed by enterostomy. Closure of the enterostomy and resection of the stenotic part of the colon was performed thereafter in all 22 children as a single stage procedure. There was no insufficiency of the anastomosis nor any late stricture at follow-up 2.7 years after NEC in our patients. It is concluded therefore that reanastomosis of the enterostomy and resection of an intestinal stricture can be performed as a single stage procedure without any risk after an interval of 3 months between onset of acute NEC and reevaluation. During this interval, a close monitoring and an appropriate management of adequate supplement of electrolytes and bicarbonates is necessary. Most of our babies could be nursed at home and showed a good weight gain during this period, despite the enterostomy.     

Problems of ileostomy in necrotizing enterocolitis

Exteriorization of the intestine and resection of the gangrenous bowel are major therapeutic regimens for necrotizing enterocolitis (NEC). Ileostomy associated complications are well known, therefore the time of ileostomy closure is a matter for discussion. Between 1975 and 1992, 84 patients with NEC were treated surgically. Ileostomies were performed in 37 children (44%). Of these 37 neonates, 9 (7M, 2F) died. In the remaining 28 patients (16M, 12F) with a mean gestational age of 35.8 weeks and a mean birth weight of 2412 g, ileostomies were performed between the 2nd and 11th days after birth. On average, the stomies were in function for 91 days, and within this period the average weekly weight gain was 153 g. Nineteen patients of this group did not show any problems attributable to the ileostomy. In 9 patients (32%) complications occurred, requiring a preplanned closure of the stoma. Postinflammatory strictures of bowel were diagnosed in 9 patients and resection of the stenotic intestine was performed at the same time as stoma closure. In conclusion, an appropriate weight gain can be achieved in patients with an ileostomy with an adequate feeding regimen. In otherwise uncomplicated cases, ileostomy closure can be delayed by up to 10 weeks when simultaneous surgical correction of additional intestinal strictures is possible. In one-third of patients with an ileostomy, however, complications may occur and urge a preplanned closure of the stoma.     

Genetic variants of the tumour necrosis factor-alpha promoter gene do not influence the development of necrotizing enterocolitis

Previous studies indicated that elevated tumour necrosis factor-alpha (TNF-alpha) levels may play a role in the development of necrotizing enterocolitis (NEC). The A(-308) and A(-238) variants of the promoter region of the TNF-alpha gene are reportedly associated with altered TNF-alpha production. The aim of our study was to determine the impact of these gene polymorphisms on the development and course of NEC in very-low-birthweight (VLBW) infants. Dried blood samples from 46 VLBW neonates with NEC were analysed using the method of restriction fragment length polymorphism. Samples from 90 VLBW neonates without NEC were used as controls. The prevalence of alleles with guanine-adenine transition in the -308 and -238 positions was the same in NEC and control subjects (12% vs 10% and 3% vs 4%, respectively). CONCLUSION: The investigated genetic variants of the TNF-alpha gene promoter region have no influence on the risk and course of NEC in VLBW infants.     

早产极低出生体质量儿羊水胎粪污染与坏死性小肠结肠炎发病的相关性

目的探究早产极低出生体质量儿羊水胎粪污染(MSAF)与新生儿坏死性小肠结肠炎(NEC)的相关性以及NEC发生的危险因素。方法以2010年1月至2016年10月住院的胎龄34周、出生体质量1 500 g的新生儿为研究对象,按照胎龄相差3天内、出生体质量相差130 g内的标准,1:5配对收集MSAF及非MSAF新生儿,回顾分析两组新生儿母孕期基本特征及围生期并发症。结果共收集460例早产极低出生体质量儿,其中41例(8.9%)合并有MSAF,最终纳入MSAF组30例、非MSAF组150例。MSAF组的NEC发生率为26.7%,高于非MSAF组的10.0%,差异有统计学意义(P=0.028)。Logistic回归分析显示,MSAF(OR=3. 39,95%CI=1. 35～8. 49,P=0. 009)和败血症(OR=3. 54,95%CI=1. 44～8. 68,P=0. 011)是NEC发生的独立危险因素。结论 MSAF和败血症是早产极低出生体质量儿NEC发生的危险因素。     

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.     

The surgical management of neonatal necrotizing enterocolitis, 1975–1984

A review was conducted of 202 neonates with necrotizing enterocolitis (NEC) seen at the Royal Children's Hospital, Melbourne, over a 10-year period. The study population was biased towards the more severe cases and those requiring surgical intervention for complications. Most cases had one or more obstetric or perinatal stress factors present. Radiology was important in confirming the diagnosis and identifying those who required surgery. The indications for surgical intervention and the selection of the appropriate surgical procedure are discussed. Surgery was required for acute disease in 72 cases. In most of these, necrotic bowel was excised and temporary ostomies constructed. During the period of study the overall mortality decreased from 41% to 24%. Post-NEC strictures occurred in 18 patients, of whom 6 presented with bowel obstruction. The transverse and left colon seemed particularly susceptible to stricture formation. The diagnosis and management are described in detail. Offprints request to: A. W. Auldist at the above address