早产儿肠道因素对新生儿坏死性小肠结肠炎发病机制的影响

新生儿坏死性小肠结肠炎（necrotizing Enterocolitis,NEC）是新生儿期一种肠道炎症性疾病,好发于早产儿、低出生体重儿.近年来由于肺表面活性物质的应用及医疗水平的提高,未成熟儿的存活率增加,NEC的发病率不降反升.早产、肠道缺氧缺血、细菌感染以及肠道喂养是发生NEC的基本条件.早产儿肠道细菌定植模式改变、肠道屏障功能异常以及细胞因子表达异常等对NEC发生发展有重要影响,本文就上述方面研究进展做一综述.     

坏死性肠结肠炎并发肠套迭

肠套迭是新生儿期的罕见病,在早产儿中也极为罕见。坏死性肠结肠炎(NEC)主要是早产、应激婴儿的疾病。此两病有共同症状:腹胀、呕吐或胃潴留、和胃肠道出血。故在早产儿中对此两病的鉴别可能发生困难。本文报告2例NEC早产儿并发肠套迭。     

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.     

新生儿感染与新生儿坏死性小肠结肠炎

新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)是新生儿时期比较常见的消化系统危重症,严重者甚至可能危及新生儿生命.NEC的发生机制具有复杂性和不确定性,新生儿期的感染是其中重要的环节.早产儿肠道屏障结构和功能未成熟,肠道固有免疫存在缺陷以及异常的肠道细菌定植均会导致早产儿NEC的高发生率.目前明确有效的特异性治疗措施是有限的,对已经发现的风险因素采取有效的预防措施对于减少NEC发生是有益的.     

早产儿坏死性小肠结肠炎影响因素分析

目的 探讨早产儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)发生的影响因素.方法 回顾性分析我科2007年10月至2010年3月住院期间103例早产儿NEC患儿病史、一般情况、喂养情况、有无并发症、有无预防应用谷氨酰胺及孕母妊娠期患病状况等.采用Logistic多元回归法进行统计学分析.结果 胎龄、围生期窒息、宫内窘迫、缺氧缺血性脑病、脑出血、败血症是早产儿NEC发生的危险因素,谷氨酰胺应用为保护因素,均具有统计学意义(P＜0.05);而与性别、孕母妊娠并发症等无关,均无统计学意义(P＞0.05).结论 避免NEC的危险因素,预防应用谷氨酰胺能够降低早产儿NEC的发病率.     

肠屏障功能障碍与新生儿坏死性小肠结肠炎

坏死性小肠结肠炎( necrotizing enterocolitis,NEC)是严重危及新生儿生命的消化系统疾病,是导致新生儿,尤其是早产儿死亡的重要病因之一。新生儿,尤其是早产儿维持肠屏障功能的作用元件发育不成熟,极易受损,不能有效形成上皮细胞间的紧密连接,无法早期形成正常肠道蠕动以及分泌型IgA的减少,因此各种致病因素极易诱发肠屏障功能障碍,导致菌群移位和败血症,造成严重的肠道损害甚至并发症。缺氧缺血、炎症反应、病原体感染均可造成肠机械屏障损害,微生态屏障建立延迟、免疫屏障发育的不成熟以及病理情况下的肠微循环障碍均参与NEC的发生。此外,miRNA在肠上皮细胞的分化、结构和屏障功能调控中也发挥重要作用。 NEC的组织病理改变是肠屏障功能障碍的结果,而肠屏障功能的损害则加重NEC的病理改变。因此,认识肠屏障功能障碍在 NEC发病过程中的作用,对于防治NEC意义重大。     

新生儿坏死性小肠结肠炎研究进展

坏死性小肠结肠炎（NEC）是由多种因素导致的新生儿,尤其是早产儿的灾难性疾病。严重的NEC病死率高,幸存者多面临短期及长期不良预后。与NEC有关的危险因素包括早产、非母乳喂养、消化道内微生物异常、缺血再灌注损伤等。高分辨腹腔超声检查有助于NEC的早期诊断。通过营养干预保护肠黏膜、干扰肠道损伤信号、改变肠道微生态环境及早期微量喂养有助于预防NEC。该病进展迅速,目前尚无有效措施,以支持治疗为主,严重者需外科治疗,雷公藤红素、脂多糖结合蛋白、粪便移植可能有助于治疗NEC,但仍有待于进一步研究。     

维生素D缺乏与早产儿坏死性小肠结肠炎的相关性

目的 评估维生素D水平对早产儿坏死性小肠结肠炎（NEC）的影响。方法 选取2016年1~12月于生后2 h内入新生儿科住院治疗的胎龄 < 36周的早产儿429例为研究对象,依据患儿是否发生NEC,将429例患儿分为NEC组（n=22）和非NEC组（n=407）。采集早产儿及其母亲入院时外周静脉血进行25-羟基维生素D（25-OHD）水平检测,比较两组早产儿和母亲血清25-OHD水平,Pearson相关分析早产儿和母亲血清25-OHD水平相关性,比较两组早产儿维生素D缺乏情况,单因素logistic回归分析早产儿NEC影响因素。结果 NEC组母亲和早产儿血清25-OHD水平均显著低于非NEC组（P < 0.001）。两组母亲和早产儿之间血清25-OHD水平均呈正向关（P < 0.001）。非NEC组与NEC组早产儿维生素D水平在正常、不足、缺乏、严重缺乏等状况的分布上比较差异有统计学意义（P < 0.001）。单因素logistic回归分析结果显示：胎龄、出生体重、母亲和早产儿25-OHD水平、机械通气持续时间、用氧持续时间和住院时间可能是NEC发生的影响因素（P < 0.05）。结论 母亲和早产儿低血清25-OHD水平与早产儿NEC的发生可能具有相关性,提示母孕期补充维生素D对于预防早产儿NEC的发生有重要意义。     

坏死性小肠结肠炎早产儿病因及微生态制剂预防作用

目的探讨新生儿坏死性小肠结肠炎(NEC)病因及应用微生态制剂(培菲康)预防早产儿NEC的有效性及对体质量的影响。方法早产儿524例,随机分为预防组276例与非预防组248例。预防组予培菲康口服,0.5包/次,2次/d;非预防组仅予原发病治疗。观察二组NEC的发生情况及体质量变化。确诊NEC20例患儿为病例组,非NEC80例早产儿为对照组,对二组进行对照研究。结果预防组发生NEC5例,每日体质量增加(8.114±8.137)g;非预防组发生NEC17例,每日体质量增加(6.595±5.337)g。二组NEC发生率比较有显著差异(χ2=7.57P<0.01);二组每日体质量增加量比较有显著差异(t=2.497P<0.05)。Logistic多元回归分析提示:胎龄、HIE、败血症及病情危重症程度是NEC发生的危险因素,应用微生态制剂及免疫球蛋白(IVIG)是保护因素。结论避免NEC的危险因素,应用IVIG和微生态制剂能减少早产儿NEC的发生和促进体质量增长。     

新生儿坏死性小肠结肠炎的临床研究进展

新生儿坏死性小肠结肠炎(NEC)目前仍然是新生儿病死率增加的主要原因,也是导致早产儿死亡的主要疾病之一。至今对其确切的发病机制仍不清楚。目前认为肠黏膜损伤、肠道内细菌作用及肠道喂养是发生NEC的基本条件,并在一些重要的危险因素如早产、缺氧缺血性损伤、致病菌过度生长、高渗奶方喂养、胃肠道免疫屏障功能低下等综合影响下,导致NEC的发生。临床多采用修正的贝尔NEC分级标准进行诊断,当前仍然缺乏有效的预防与治疗策略,但近年对该病的研究提出了许多新的观点。本文就近年有关NEC临床研究的进展作一综述。     

新生儿坏死性小肠结肠炎发病原因及预后研究进展

新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis,NEC)是一种常见的胃肠道急症,属于新生儿期严重危及生命的疾病之一.其发病原因尚不完全明确,主要有早产、喂养不当、肠道感染和菌群失调、缺氧缺血及再灌注损伤等.疾病的临床分期、呼吸衰竭等严重并发症、治疗方法等多种因素均会影响NEC患儿的预后.该文就近期相关研究展开综述,为NEC的早期诊断、临床观察及治疗提供线索.     

早产儿坏死性小肠结肠炎临床流行病学特点

目的 对上海市早产儿中心近10年间NEC临床流行病学特点进行分析，旨在加强对本病的进一步认识，早期诊断，早期干预，进一步提高早产儿存活率。方法 调查1993年1月1日-2002年12月31日出生的1869例早产儿，对确诊NEC的59例临床资料进行比较分析，寻找引起。NEC可能的相关因素。结果 早产儿NEC发生率为3．16％。胎龄小、体重低、胃肠道动力功能差及局部免疫应答能力低下、感染仍是NEC发病重要的影响因素。临床分度与预后密切相关。结论 减少早产儿发生率是降低NEC发病率的最好办法。加强早产儿的护理，实施正确喂养方案，促进胃肠蠕动功能，及时发现和控制感染是十分重要的预防措施。何时恢复喂养需谨慎判断。     

Role of Asphyxia and Feeding in a Neonatal Rat Model of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a common gastrointestinal disorder affecting premature infants. To investigate critically the importance of the purported risk factors of NEC (formula feeding, asphyxia, bacteria, and prematurity), we developed a neonatal rat model that closely mimics the human disease. Full-term and premature newborn rats were stressed with formula feeding, asphyxia, and/or exogenous bacterial colonization and subsequently evaluated grossly and histologically for the development of intestinal injury. We found that most animals treated with asphyxia, formula feeding, and bacteria developed NEC (77%) and died (86%) by 96 h. All maternally fed animals treated with asphyxia and bacterial colonization survived and had normal intestinal histology. Furthermore, asphyxia was a critical instigating factor, because formula and bacterial exposure without asphyxia resulted in normal intestine and minimal mortality (12%). Enteral bacterial colonization was not a significant determinant of NEC in this model. We conclude that the neonatal rat model is an excellent test system for the study of NEC. As in the human disease, asphyxia and formula feeding play an important role in the pathophysiology of experimental NEC.     

Prevention of necrotizing enterocolitis in premature infants – an updated review

Necrotizing enterocolitis (NEC) is among the most common and devastating diseases encountered in premature infants, yet the true etiology continues to be poorly understood despite decades of research. Recently, gut bacterial dysbiosis has been proposed as a risk factor for the development of NEC. Based on this theory, several best clinical practices designed to reduce the risk of NEC have been proposed and/or implemented. This review summarizes the results of recent clinical trials and meta-analyses that support some of the existing clinical practices for reducing the risk of NEC in premature infants. It is evident that human milk feeding can reduce the incidence of NEC. While most of the studies demonstrated that probiotic supplementation can significantly reduce the incidence of NEC in premature infants, there are still some concerns regarding the quality, safety, optimal dosage, and treatment duration of probiotic preparations. Antibiotic prophylaxis does not reduce the incidence of NEC, and prolonged initial empirical use of antibiotics might in fact increase the risk of NEC for high-risk premature infants. Lastly, standardized feeding protocols are strongly recommended, both for prevention of postnatal growth restriction and NEC.     

Pathogenesis and prevention of necrotizing enterocolitis: a hypothesis based on personal observation and a review of the literature

The hypothesis is, that necrotizing enterocolitis (NEC) of the neonate occurs by the coincidence of two of three pathologic events: (1) intestinal ischemia, (2) colonization by pathogenic bacteria, and (3) excess protein substrate in the intestinal lumen. NEC is more likely to appear following quantitative extremes, ie, severe ischemia highly pathogenic flora, or marked excess of substrate. NEC develops only if a threshold of injury, sufficient to initiate intestinal necrosis, is exceeded. The hypothesis is derived from previous theories by Santulli, which implicated all three events, and by Lawrence, in which a single event, abnormal bacterial colonization, was considered sufficient to induce NEC. This hypothesis may explain both typical occurrences of NEC among high-risk premature infants in neonatal intensive care units (NICUs), and atypical occurrences among infants considered at low-risk, eg, previously healthy term infants, infants fed breast milk exclusively, and infants never fed. It may further explain why NEC fails to develop in most high-risk infants in NICUs. Preventive measures might include: (1) pharmacologic stabilization of intestinal perfusion, (2) modification of the intestinal flora, or (3) feeding colostrum or other protective substances. Each theoretical benefit is accompanied by potential risks. The prevention of NEC may require favorable intervention in two of the three pathologic events.     

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.     

What next in necrotizing enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants, with a mortality rate of 10-50%. It is uncommon in term infants and in premature infants who have not yet been fed. Most commonly NEC develops suddenly in a preterm infant who was otherwise well, with initial symptoms of abdominal distention, bilious or bloody emesis or gastric aspirates, hematochezia, and pneumatosis intestinalis, and sometimes progresses quickly to include bowel perforation, acidosis, shock, and death. Trigger factors (i.e. perinatal hypoxia, mild infection or formula feeding) cause focal mild intestinal mucosal injury. In the presence of proliferation of commensal bacteria, local breakdown of mucosal barrier may cause entry of bacterial products (e.g. lipopolysaccharides, platelet-activating factor). Endothelial platelet-activating factor and/or tumor necrotizing factor and/or direct stimulating effects of polymorphonuclear leukocytes cause proinflammatory cascade and focal necrosis, which increase the entry of large amounts of bacterial toxins, and then severe NEC, sepsis, and shock develop. Therapies for the prevention of NEC that appear to have some benefit are breastfeeding and antenatal steroids, and probably probiotics. Enteral immunoglobulin, polyunsaturated fatty acids, and arginine or glutamine supplementation are therapies for the prevention of NEC that do not appear to be of benefit. Enteral erythropoietin and enteral granulocyte colony-stimulating factor are promising novel therapies. Treatment options are limited to gut rest, parenteral nutrition, broad-spectrum antibiotics, and surgical interventions for enteral perforation. Two commonly used methods for NEC with intestinal perforation are laparotomy or primary peritoneal drainage ("patch, drain and wait"); however, the preferred method is controversial.     

Peritoneal needle suction for intestinal perforation in the preterm neonate.

A few years ago, most intestinal perforations in the premature newborn appeared within the clinical context of necrotising enterocolitis (NEC). Since then, we have observed an increase in the number of isolated perforations appearing outside typical NEC. The fact that the perforations are more often isolated, and the healing capabilities of the premature intestine, led us to propose peritoneal needle suction (PNS) alone as first treatment for intestinal perforations in the premature neonate. MATERIALS AND METHOD: The charts of 6 consecutive premature infants presenting with intestinal perforations treated initially by PNS alone were reviewed. RESULTS: The patients' median birth weight was 1030 g, with a median gestational age of 27 weeks. In 5 out of 6 infants (83 %), PNS achieved complete exsufflation without recurrence of the pneumoperitoneum and complete intestinal healing, allowing complete enteral feeding 30 to 71 days after perforation. One infant with recurrent pneumoperitoneum after 3 PNS and peritoneal drainage was operated. All infants survived. CONCLUSION: We believe that for early perforations of the premature neonate, the poor diffusion of the infection and the frequent capacity of the perforation to close and subsequently heal without scars, favour a minimally invasive management using PNS.