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.     

影响新生儿坏死性小肠结肠炎预后的危险因素分析

目的探讨影响新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis,NEC)预后的危险因素.方法对1990年4月至2003年4月收治156例NEC患儿进行回顾性分析.结果早产儿41例,足月儿110例,过期产儿5例.发病时间≤3d 94例,>3d 62例.治愈66例(42.3%),好转39例(25%),放弃14例(9%),死亡37例(23.7%).单因素分析发现NEC患儿病死组较治愈组合并或并发败血症、硬肿症、呼吸衰竭、全腹膜炎、颅内出血、代谢性酸中毒、低钠血症、肺出血、全心衰、肾功能衰竭、休克、中毒性脑病者发生率高,P<0.05.治愈组白细胞≤5×109/L或≥20×109/L为21.2%(14/66),病死组为45.9%(17/37),χ2=6.894,P<0.01.治愈组血小板计数(PLT)≤100×109/L发生率为18.2%(12/66),病死组为59.5%(22/37),χ2=18.268,P<0.001.治愈组腹部X线Ⅰ、Ⅱ、Ⅲ期表现发生率分别为74.2%、18.2%、7.6%,病死组分别为40.5%、24.3%、35.1%,χ2=15.077,P<0.0017.回归方程Logistic(NEC)=-2.1452+1.2971X2+1.6557X7+1.7707X10+1.7825X12+3.2555X15(χ2=24.5953,P<0.001).Logistic回归分析显示全腹膜炎、新生儿硬肿症、低钠血症、PLT≤100×109/L、呼吸衰竭的OR值分别为3.659、5.237、5.875、5.981、25.933(P<0.05).结论全腹膜炎、新生儿硬肿症、低钠血症、PLT≤100×109/L、呼吸衰竭为影响NEC预后的危险因素,积极防治NEC各种合并症及并发症,有助于降低其病死率.     

肠道微生态和新生儿坏死性小肠结肠炎

肠道微生态是由体内有益菌及有害菌共同构成的生态环境,是人体最大、最复杂的微生态系统.研究表明,适当的肠道微生物定植过程有助于肠道结构和功能发育以及免疫系统成熟,它决定了之后肠道发生疾病的风险.肠道微生态或益生菌与新生儿坏死性小肠结肠炎（neonatal necrotizing enterocolitis,NEC）的关系已越来越受到关注.该文就新生儿肠道微生态的构成及作用、肠道微生态在NEC发生中的作用及机制、益生菌对NEC的防治作用等研究进展作一综述.     

新生儿坏死性小肠结肠炎血浆肠脂肪酸结合蛋白水平变化的意义

目的 探讨血浆肠脂肪酸结合蛋白（I-FABP）水平变化在指导新生儿坏死性小肠结肠炎（NEC）诊断及治疗中的意义.方法 选择2011年5月至2012年12月我院新生儿科收治的患儿,按入院先后顺序,以明确诊断NEC的50例新生儿为NEC组,其中NECⅡ期30例,NECⅢ期20例,以非NEC新生儿50例为对照组.NEC组在确诊后24 h内、对照组在相应日龄取血,采用酶联免疫吸附法（ELISA）检测血浆I-FABP水平,根据NEC患儿病情转归分为存活组及病死组,按治疗方法分为保守治疗组和手术治疗组,比较不同组间血浆I-FABP水平、新生儿危重病例评分（NCIS）分值、脓毒症的发生率及病死率.结果 NECⅡ期组、NECⅢ期组和对照组血浆I-FABP水平分别为（95.6±18.5） μmol/L、（151.2±10.8）μmol/L和（1.2±2.3）μmol/L,组间比较差异有统计学意义（P＜0.05）;NECⅡ期组和NECⅢ期组NCIS评分明显低于对照组,脓毒症发生率和病死率均高于对照组,差异有统计学意义（P＜0.05）,NECⅡ期组和NECⅢ期组差异无统计学意义（P＞0.05）.病死组血浆I-FABP水平、脓毒症发生率高于存活组,NCIS评分低于存活组;保守治疗组I-FABP水平低于手术治疗组,NCIS评分高于手术治疗组,差异均有统计学意义（P＜0.05）.结论 血浆I-FABP水平可较敏感地反映NEC患儿的病情变化,可作为预测NEC病情严重程度及指导采取内外科治疗的指标之一.     

Surgical outcome of necrotizing enterocolitis

Forty-six neonates were treated for necrotizing enterocolitis (NEC) between 1982 and 1987. The mean gestational age was 33.6 weeks and the mean birth weight was 1865 g. Birth weight less than 1500 g and gestational age less than 32 weeks had an adverse effect on survival. Neonates less than or equal to 30 week's gestation developed symptoms at a mean age of 10.8 days while those greater than 30 weeks developed symptoms at a mean age of 1.7 days. All infants who never had enteral feedings survived; 20 were cured with medical treatment only. Three patients underwent peritoneal lavage (2 of these survived). Twenty-two patients required surgery; the operative mortality was 9%. Four patients underwent elective surgery for primary strictures. The remaining 18 presented with acute perforation (11), obstruction (5), deterioration with medical therapy (1), or peritonitis (1). The most frequent site of perforation was the terminal ileum, while the most common site of stricture was the left colon. Seven patients were found to have strictures after prior emergency surgery. In 6 of the patients who underwent primary enterostomy, the strictures were located in the defunctionalized bowel segment. Evidence of progression of the disease, which most frequently involved the right and transverse colon, necessitated extensive resection. When performing a proximal ileostomy for acute NEC, the surgeon must be aware that the chances of conservation of the defunctionalized distal bowel segment are minimal because of progression of the disease. Complications related to resection of the ileocecal valve have been negligible. Our results with peritoneal lavage are encouraging, and our overall mortality of 13% in contrast with higher rates in earlier series reflects improvement in the management of these neonates. Offprint requests to: S. Yazbeck     

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。     

微生态制剂防治新生儿坏死性小肠结肠炎病例对照研究

目的：探讨新生儿坏死性小肠结肠炎(NEC)的危险因素及应用微生态制剂(培菲康)预防NEC发生的有效性。方法：对2002年1月至2005年5月住院治疗的2528例新生儿分为微生态制剂预防组与非预防组,观察两组NEC的发病率;以确诊NEC的患儿为病例组,非NEC新生儿为对照组进行病例对照研究。结果：预防组1182例中6例诊断为NEC,发病率0.51%;非预防组1346例中19例发生NEC,发病率为1.41%,两组差异具有显著性(P<0.05)。条件Logistic回归分析提示:胎龄、新生儿缺氧缺血性脑病、败血症及病情危重程度是危险因素;微生态制剂的应用是保护因素。结论：避免NEC的危险因素,预防性应用微生态制剂能够降低NEC发病率。     

A scoring system in predicting the risk of intestinal stricture in necrotizing enterocolitis

Of 46 infants with a diagnosis of necrotizing enterocolitis (NEC) admitted to the neonatal intensive care unit over the period 1981–1985, 40 have been followed from 2 to 6 years after the acute episode. A contrast enema (CE) to look for intestinal strictures (IS) was performed either during the first months in surgically managed patients, or between 2 and 6 years in asymptomatic patients. Clinical, laboratory and radiology parameters collected during the 7 days following NEC were used to establish a score which was correlated with radiological data obtained after CE. Of the 40 infants, 17 developed symptomatic or asymptomatic IS and 16 of these 17 infants has a score 7. Nineteen of the 23 patients without IS had a score <7. We conclude that the proposed score established on day 8 after onset of NEC helps to identify infants at higher risk of developing IS and for whom closer follow up appears necessary.     

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.     

A case control study of necrotizing enterocolitis occurring over 8 years in a neonatal intensive care unit

The perinatal histories of 27 newborn infants with NEC were compared to those of 54 infants of equivalent birth weight who did not have NEC during an 8-year study period to see if possible predisposing factors were independent of the confounding effect of birth weight. No differences were observed in gestational age, degree of intrauterine growth retardation, premature rupture of membranes, perinatal asphyxia, skin temperature at admission, haematocrit, presence or absence of respiratory distress syndrome, umbilical catheter placement, start and type of feeding or presence of positive blood cultures. Prematurity is the greatest risk factor predisposing to the development of NEC and the perinatal problems which precede the onset of NEC are common among all premature infants.Abbreviation NEC necrotizing enterocolitis     

Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment

AIM: The incidence of necrotizing enterocolitis (NEC) strongly increased in an neonatal intensive care unit (NICU) in 1997 and 1998 compared with previous years, which coincided with increased incidence of nosocomial sepsis. Specific risk factors related to this NICU and a possible relationship between NEC and nosocomial sepsis were studied retrospectively, including all patients with NEC since 1990 and matched controls. METHODS: Clinical and bacteriological data from the period before the development of NEC and a similar period for the controls were collected retrospectively and corrected for birthweight and gestational age. Statistical analysis was performed by a stepwise regression model. RESULTS: Data of 104 neonates with NEC and matched controls were analysed. The median day of onset of NEC was 12 d (range 1-63 d). Significant risk factors for NEC were: insertion of a peripheral artery catheter [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.3-3.9] and a central venous catheter (OR 5.6, 95% CI 3.1-10.1), colonization with Klebsiella sp. (OR 3.4, 95% CI 1.5-7.5) and Escherichia coli (OR 2.1, 95% CI 1.0-4.5), and the occurrence of sepsis, in particular due to coagulase-negative staphylococci (OR 2.6, 95% CI 1.4-5.1). The risk for NEC was decreased after the early use (< 48 h after birth) of amoxicillin-clavulanate and gentamicin (OR 0.3, 95% CI 0.2-0.6). CONCLUSION: Insertion of central venous and peripheral arterial catheters is positively associated with NEC, as is colonization with the Gram-negative bacilli Klebsiella and E. coli and the occurrence of sepsis, particularly due to coagulase-negative staphylococci. Early treatment with amoxicillin-clavulanate and gentamicin is negatively associated with NEC and may be protective against NEC.     

Pathogenesis of neonatal necrotizing enterocolitis: a study of the role of intraluminal pressure, age and bacterial concentration

The pathogenesis of neonatal necrotizing enterocolitis (NEC) is unknown. Intestinal dilatation and preferred occurrence of NEC at sites of bacterial overgrowth (colon and ileum) are common findings. The study attempted to produce NEC with increasing intraluminal pressures and bacterial concentrations in two different aged groups of rats. First, 10-cm terminal ileum segments were isolated with intact vascular pedicles in 1-and 3-month-old rats, and a dose of 10¹¹ E. coli in 1 ml was injected into each segment. Intraluminal pressure was sustained for 1 h at 150, 100, 50 and 0 cmH₂0, respectively, in four experimental groups (n=6). The isolated loop was then returned to the abdominal cavity and assessed grossly for NEC after 24 h. Histological examination was performed by a pathologist (KWC) who was blinded to the procedures. Second, the procedure was repeated with doses of 10⁸, 10⁵ and 0 bacteria/ml (n=6) at intraluminal pressure of 100 cmH₂0 in 1-month-old rats. Third, in another experimental group, oxygenation of the pedicled loop was assessed by oximetry as the intraluminal pressure increased and the findings were correlated with aortic blood pressure. The blood pressures (mean±SD) for 3- and 1-month-old rats were 110±6 and 72±4 mmHg, respectively. Hypoxia (<50% oxygen saturation) of the bowel was detected when the intraluminal pressure exceeded the mean blood pressure. The relative incidences of NEC in the bowel with intraluminal pressure above and below mean blood pressure were 100% (6/6) vs. 4% (1/24; P<0.05) in 3-month-old rats, and 100% (12/12) vs. 11% (2/18; P<0.05) in 1-month-old rats. There was no occurrence of NEC in bowel injected with 10⁵ E. coli/ml and less at 100 cm intraluminal pressure. Increased intraluminal pressure results in bowel hypoxia and in the presence of adequate bacterial concentration predisposes to the development of NEC. Young age is associated with a lower threshold for increased intraluminal pressure leading to NEC.     

Neonatal necrotizing enterocolitis: An update

Necrotizing enterocolitis (NEC) is a leading cause of mortality and morbidity in neonatal intensive care units. Here we review selected manifestations of NEC, risk factors involved in its pathophysiology as well as putative mechanisms associated with how an immature gut might be more susceptible to NEC. Treatment and potential preventive strategies are discussed.     

Spontaneous biliary perforation and necrotizing enterocolitis

A case of spontaneous bile-duct perforation in a 5-month-old boy with a history of necrotizing enterocolitis in his 1st week of life is reported. To our knowledge, this is the second case reported with such an antecedent, supporting a vascular etiology for some cases of spontaneous biliary perforation. Accepted: 7 July 1998     

Rectal involvement in necrotizing enterocolitis

Although necrotizing enterocolitis (NEC) is a common cause of neonatal intestinal disease, rectal involvement has not previously been reported. We describe five children with NEC involving the rectum. In four infants pancolorectal disease occurred; in the fifth the ascending colon was spared. A Swenson-type abdomino-perineal resection was performed in four cases. No definitive cause for the extension of the disease into the distal rectum was noted. There were no immediate postoperative complications. Long-term follow-up showed normal anorectal function and a normal-appearing perineum. Possible rectal involvement should be considered in all neonates with colonic NEC. Contrast studies visualizing the rectum are advised prior to closing colostomies performed in newborns with NEC. Ileorectal anastomosis after resection produces a satisfactory result. Offprint requests to: S. Z. Rubin     

姜黄素对新生大鼠坏死性小肠结肠炎的保护作用

目的：通过研究姜黄素对新生大鼠坏死性小肠结肠炎(NEC)肠组织病理改变,环氧合酶-2(COX-2)表达,肿瘤坏死因子α(TNF-α)及白细胞介素-10 (IL-10)生成的影响,探讨姜黄素对NEC是否有保护作用。方法：40只新生大鼠随机分为4组：正常对照组,溶剂对照组,NEC模型组,姜黄素干预组,每组10只。每日定时观察各组大鼠的一般情况,连续3 d并于第4天处死,取肠道组织检测病理改变,TNF-α、IL-10含量及COX-2的表达。结果：姜黄素能改善NEC模型大鼠一般情况及病理组织学征象;与正常对照组、溶剂对照组比较,NEC模型组,姜黄素干预组TNF-α、IL-10浓度显著增高(P<0.05);姜黄素干预组TNF-α浓度较NEC模型组显著下降(P<0.05)、IL-10浓度较NEC模型组显著升高(P<0.05);姜黄素干预组COX-2表达量显著低于NEC模型组。结论：姜黄素对NEC大鼠具有保护作用,其机制可能与姜黄素抑制COX-2的表达,减少TNF-α的含量、增加 IL-10的含量有关。［中国当代儿科杂志,2010,12（2）：132-136］     

粪便钙卫蛋白对新生儿坏死性小肠结肠炎诊断作用的Meta分析

目的 通过Meta分析的方法探讨粪便钙卫蛋白（FC）对新生儿坏死性小肠结肠炎（NEC）的诊断作用。方法 检索Web of Science、Cochrane Library,PubMed、Embase、中国知网（CNKI）、维普期刊数据库、万方数据库、中国生物医学文献数据库,并结合手动检索作为补充,搜索时间为建库至2020年5月。采用QUADAS标准评估纳入文献的质量;采用Meta-Disc 1.4和Stata 15.0软件行Meta分析,包括评价特异度、敏感度、似然比和诊断比值比,进行敏感性分析及异质性测试,绘制综合受试者工作特征（SROC）曲线及Fagan图。结果 共纳入15篇文献,包括1 719例新生儿。其中,低质量文献4篇,高质量文献2篇,其余均为中等质量。纳入研究间异质性较高,不存在阈值效应及发表偏倚。应用随机效应模型分析结果显示：FC对NEC诊断的汇总特异度、灵敏度分别为0.80（95% CI：0.78~0.82）、0.86（95% CI：0.83~0.89）,阴性似然比、阳性似然比、诊断比值比分别为0.19（95% CI：0.14~0.26）、4.71（95% CI：3.57~6.23）、29.56（95% CI：17.98~48.61）。SROC曲线下面积为0.9131,Q^*指数为0.8456。Fagan图显示FC不增高时NEC发生概率为13%,FC增高时NEC发生概率提高为86%。Meta回归分析发现异质性来源于其他非协变量因素。结论 FC对NEC的早期诊断具有较高的潜力及效能。FC测定可用于NEC的诊断,但应与临床表现及其他相关实验室检查相结合。     

维生素D调节坏死性小肠结肠炎新生大鼠肠道上皮occludin蛋白表达的研究

目的：检测坏死性小肠结肠炎(necrotizing enterocolitis,NEC)新生大鼠肠道上皮occludin蛋白的定位及表达情况,探索维生素D处理对NEC新生大鼠的保护作用及对occludin蛋白表达的影响。方法 SPF级不同窝别新生48 h的Wistar大鼠60只,采用随机数字表法随机分为4组：母乳喂养＋对照组10只,母乳喂养＋维生素D组10只,NEC＋对照组20只,NEC＋维生素D组20只。 NEC模型：将生后48 h的仔鼠与母鼠隔离,采用鼠乳代乳品人工喂养＋缺氧＋寒冷刺激处理;维生素D处理：分别于NEC造模前30 min,造模后1 d、2 d腹腔注射活性维生素D(帕立骨化醇)。各组大鼠分别在实验72 h后处死取材,选取回肠组织采用HE染色观察肠腔结构改变并做Nadler病理评分,采用免疫荧光染色观察occludin蛋白在肠上皮的定位和表达情况,采用Western blot方法检测肠道黏膜组织occludin蛋白的表达量并做统计学分析。结果 HE染色可见NEC大鼠的肠腔组织结构破坏,黏膜下或肌层分离,部分绒毛脱落,甚至肠绒毛消失,肠上皮脱落伴肠坏死,Nadler病理评分为(2.90±0.23)分;维生素D处理的NEC大鼠上述病理表现较NEC大鼠减轻,Nadler病理评分为(1.70±0.21)分,两者比较差异有统计学意义(P<0.01)。免疫荧光显示NEC大鼠肠道上皮细胞间occludin表达明显减少、稀疏,呈现不连续或点状表达,维生素D处理的NEC大鼠肠道上皮细胞间occludin表达较NEC对照组大鼠明显增多,基本呈均匀、连续的表达。 Western blot显示NEC大鼠肠道黏膜组织的occludin表达明显减少,维生素D处理可以明显增加 occludin的表达( P <0.01)。结论 NEC 模型大鼠肠道上皮紧密连接相关蛋白occludin表达明显降低,维生素D处理可以通过上调肠道上皮occludin的表达来抑制NEC的发生发展。     

Neonatal necrotizing enterocolitis: a retrospective and multicentric review of 331 cases

The authors retrospectively review 331 cases of necrotizing enterocolitis from 13 different departments of pediatric surgery; 184 cases were treated only medically at the acute stage (47 of whom developed intestinal stricture) and 147 cases were operated on at the acute stage. The different procedures of acute surgical intervention are reported and the results of two surgical procedures are compared. The first is a classical one comprising a laparotomy with exploration of the intestinal tract and resection of the necrotic segments followed by enterostomy above the resected area. The other procedure comprises a minimal laparotomy in the right lower quadrant with ileostomy above necrotic areas, without resection of necrotic segments associated with peritoneal drainage. The results are assessed using the postoperative mortality rate and the number of secondary intestinal strictures. Mortality during the first postoperative month occurred in 27.9% of cases, and intestinal strictures were noted in 31.3% of cases after acute surgical procedure.     

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。