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。     

乳铁蛋白与早产儿坏死性小肠结肠炎

坏死性小肠结肠炎是早产儿常见主要并发症之一,具有较高的病死率和发病率,可以导致多种远期并发症,如短肠综合征、全身感染、眼部疾病、营养不良和神经系统发育障碍等.乳铁蛋白是母乳中的一种成分,具有抗细菌、抗病毒、抗真菌、增强免疫力等多种作用.新近许多研究评估了乳铁蛋白防治坏死性小肠结肠炎的效果和安全性.应用乳铁蛋白预防和治疗坏死性小肠结肠炎对于提高早产儿的预后具有很重要作用.     

新生儿坏死性小肠结肠炎伴发败血症的危险因素研究

目的 探讨新生儿坏死性小肠结肠炎 （NEC） 伴发败血症的危险因素。方法 回顾性研究273例NEC患儿的临床资料,分析伴发败血症的危险因素。结果 NEC伴发败血症的几率为32.2% （88/273）。Ⅲ期NEC伴发败血症的几率高于Ⅱ期 （69.0% vs 15.9%,P < 0.05）。62.5%的败血症发生在NEC诊断后3d内,37.5%发生在3d后。伴发败血症的NEC患儿与未伴发者相比,出生胎龄更小,出生体重更低 （P < 0.05）。硬肿症 （OR：9.75,95% CI：2.84~33.52,P < 0.001）、Ⅲ期NEC （OR：12.94,95% CI：6.82~24.55,P < 0.001） 及胃肠减压 （OR：2.27,95% CI：1.14~4.5,P=0.02） 为NEC伴发败血症的独立危险因素。结论 硬肿症、Ⅲ期NEC及胃肠减压为NEC伴发败血症的独立危险因素。     

Prevention and treatment of necrotising enterocolitis in preterm neonates

Prevention and treatment of NEC has become an area of priority for research due to the increasing number of preterm survivors at risk, and the significant mortality and morbidity related to the illness. Probiotic supplementation appears to be a promising option for primary prevention of NEC but further large trials are necessary for documenting their safety in terms of sepsis as well as long-term neurodevelopmental outcomes and immune function. As new frontiers including immunomodulating agents like pentoxifylline continue to be explored, the impact of well-established simple strategies like antenatal glucocorticoid therapy, and early and preferential use of breast milk must not be forgotten. Clinical research on manifestations of ileus of prematurity, and feeding in the presence of common risk factors such as IUGR is needed. Safety of minimal enteral feeds in terms of NEC and benefits of standardised feeding regimens need to be confirmed. Association of common clinical practices such as red cell transfusions, H2 receptor blockade, and thickening of feeds with NEC warrants attention. An approach utilising a package of potentially better practices seems to be the most appropriate strategy for the prevention and treatment of NEC.     

预防性使用益生菌对降低极低出生体重早产儿坏死性小肠结肠炎发病率和病死率的Meta分析

目的 运用循证医学方法,评价益生菌在降低极低出生体重(VLBW)早产儿坏死性小肠结肠炎(NEC)的发病率和病死率方面的安全性和有效性。方法 系统检索PubMed、EMBASE、Cochrane 临床对照试验资料库(CENTRAL)、the ISI Web of Knowledge Databases、中国生物医学文献数据库(CBM)、中文期刊全文数据库(CNKI)和维普中文科技期刊数据库(VIP)、万方数据库,检索时间均为建库至2014年3月,查找所有研究预防性使用益生菌对降低VLBW早产儿NEC的发病率和病死率的随机对照试验。按纳入排除标准进行RCT的筛选、资料提取和质量评价,应用RevMan 5.1软件进行Meta分析。结果 共纳入21项研究(4 607例VLBW早产儿),Meta分析发现预防性使用益生菌能显著降低VLBW早产儿NEC的发病率[RR=0.47;95%CI(0.35~0.62);PRR=0.63;95%CI(0.51~0.78),PRR=0.87;95%CI(0.72~1.06);P=0.17]及NEC相关病死率[RR=0.68;95%CI(0.31~1.48),P=0.33]差异无统计学意义。结论 预防性使用益生菌能降低VLBW早产儿NEC的发病率和病死率,但其对早产儿的长期影响仍需大量的临床研究来评估。     

The prognosis of very-low-birth-weight neonates operated upon for necrotizing enterocolitis

Thirteen neonates with necrotizing enterocolitis weighing less than 1,500 g (650 – 1,500 g) were operated upon over a 7-year period. The overall survival was 62%, for those without preoperative perforation 80%. A very low Apgar score predicts severe disease with high mortality. In the group below 1,000 g mortalily was extremely high, if there was a preoperative weight loss. These babies might have benefited from earlier surgery.     

新生儿输血相关性坏死性小肠结肠炎危险因素分析

目的探讨新生儿输血相关性坏死性小肠结肠炎(transfusion associated necrotizing enterocolitis,TANEC)发生的临床相关危险因素,以期减少新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)的发病率。方法收集2017年1月至2018年6月于兰州大学第一医院收治并接受输血治疗的新生儿的临床相关资料,包括围生期因素、患儿基本情况、合并症,根据输血后48 h内NEC发生与否分为TANEC组和非TANEC组,对两组患儿的临床资料进行分析。结果单因素分析结果显示:两组患儿在分娩方式、胎龄、出生体重、新生儿败血症、动脉导管未闭(patent ductus arteriosus,PDA)、新生儿呼吸窘迫综合征(neonatal respiratory distress syndrome,NRDS)和贫血严重程度上的差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,胎龄(P<0.05,OR=0.772,95%CI:0.684~0.871)、出生体重(P<0.05,OR=0.236,95%CI:0.079~0.711)是TANEC的保护因素,贫血程度(模型1中P<0.05,OR=3.129,95%CI:1.003~9.756;模型2中P<0.05,OR=3.449,95%CI:1.024~11.609)及新生儿败血症(模型1中P<0.05,OR=6.327,95%CI:1.732~23.720;模型2中P<0.05,OR=8.154,95%CI:2.122~31.336)是TANEC的危险因素。结论导致TANEC发生的因素是多方面的,输血时,胎龄越大,出生体重越高,发生NEC的风险越小;而合并新生儿败血症、贫血程度越重,发生TANEC的风险越高。临床上需采取综合措施预防新生儿贫血,并根据患儿的具体情况及贫血的程度制定合理的临床策略,尽量避免输血以减少TANEC的发病率,改善患儿预后。     

Plasma citrulline levels in preterm neonates with necrotizing enterocolitis

Background and aim

Citrulline is a non-protein amino acid synthesized in the small intestine. In children with short-bowel syndrome, citrulline has served as a reliable marker of the residual bowel length and parenteral nutrition (PN) independence. In the present study we aim to assess the value of citrulline measurement in preterm neonates developing necrotizing enterocolitis (NEC).

Methods

Plasma citrulline levels were measured prospectively in 17 preterm neonates with NEC stage II during the entire course of the disease. Serial citrulline determinations in 24 healthy preterm neonates on 2, 7, 14, 21 and 28 days of life (DOL), served as reference values.

Results

In healthy preterm neonates plasma citrulline levels showed a progressive increase in relation to age. In neonates presenting with NEC, mean citrulline levels were significantly lower as compared to controls' citrulline levels of the most approximate day of life (DOL 7: 16.85 ± 4.2 vs 20.5 ± 4.5 μmol/L, p < 0.05; DOL 14: 18 ± 4.2 vs 23.5 ± 4.3 μmol/L, p < 0.01; DOL 21: 17 ± 2.5 vs 30 ± 5.7 μmol/L, p < 0.01). The optimal citrulline cut-off distinguishing NEC patient from controls was 17.75 μmol/L (sensitivity 76%, specificity 87%). Plasma citrulline at presentation correlated inversely with the duration of parenteral nutrition (r = − 0.49, p < 0.05). Consecutive citrulline determinations revealed that plasma citrulline increased during reintroduction and gradual increase of enteral nutrition.

Conclusions

Our findings provide preliminary evidence that citrulline levels that are reduced in preterm neonates with NEC in comparison to age-matched controls and serial citrulline determinations could help to monitor improvement of functional enterocyte mass during the course and resolution of NEC.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

口服益生菌预防早产儿严重坏死性小肠结肠炎疗效和安全性的Meta分析

目的评价口服益生菌预防早产儿严重坏死性小肠结肠炎（NEC）的疗效和安全性。方法制定原始文献的纳入标准、排除标准及检索策略,检索PubMed、EMBASE、 Ovid、Springer、中国期刊全文数据库、万方数据库、维普中文科技期刊数据库 及中国生物医学文献光盘数据库等。应用Cochrane协作网推荐的方法评价文献质 量。采用RevMan 4.22软件对满足纳入标准的有关口服益生菌预防早产儿严重NEC （Ⅱ期及以上）的RCT研究进行Meta分析。主要观察指标为严重NEC的发生率、总 病死率、NEC相关病死率和院内感染导致脓毒症的发生率。结果共检索到107篇文献,符合纳入标准的10项RCT研究（共2 117 例早产儿）进 入Meta分析,文献质量评价8篇为A级,1篇为B级,1篇为C级。各研究间的基线水 平差异较大,出生体重,胎龄,益生菌应用的种类、剂量、开始应用时间和治疗 持续时间等均有差异。Meta分析结果表明,益生菌组可显著降低严重NEC的发生率 和总病死率,OR分别为0.34(95%CI：0.22~0.55,P<0.000 1)和0.36(95%CI： 0.22~0.58,P<0.000 1)。无证据表明预防性口服益生菌可减少院内感染导致脓毒 症的发生率和NEC相关的病死率,OR分别为0.94(95%CI：0.62~1.42)和0.48(95%CI ：0.16~1.47)。所有研究均未见口服益生菌导致相应菌株全身感染的发生。结论预防性口服益生菌可显著降低早产儿严重NEC的发生率和总病死率。对低出生 体重儿可给予口服益生菌预防NEC的发生。现有的研究尚不能证实预防性口服益生 菌对超低出生体重儿的疗效和安全性。有关超低出生体重儿预防性口服益生菌的 安全性和疗效仍有待大规模的临床多中心RCT研究予以明确。     

Surgical intervention in necrotizing enterocolitis in neonates with symptomatic congenital heart disease

The commonly accepted indication for surgical intervention in necrotizing enterocolitis (NEC) is perforation of the bowel. In this study, the indication and role of surgery was assessed in neonates born with symptomatic congenital heart disease (CHD). Records of neonates admitted to a single institution in Hong Kong between January 1981 and December 1997 with symptomatic CHD who subsequently developed NEC were reviewed. The patients were categorized into cyanotic and acyanotic groups. Of 850 neonates with CHD admitted during the period, 30 developed NEC (3.5%); 17 had cyanotic and 13 had acyanotic heart disease. The average Apgar scores at 1 and 5 min were 7.5 and 8.6, respectively. The mean gestational age was 37.7 weeks and the mean birth weight was 2.5 kg. The mean age at which NEC developed was 16 days. The overall mortality in the proven cases of NEC was 57%. After excluding the suspected NEC cases (stage I), it was found that surgery in the proven NEC cases without perforation, i.e., stages II and IIIA, resulted in higher survival than in those managed medically (75% vs 44%). The cyanotic patients had higher mortality than the acyanotic group (71% vs 39%). Neonates with CHD who develop NEC belong to a unique group of mature babies with reasonable birth weights and Apgar scores, unlike the common NEC patient population. The mortality of these patients is extremely high, and a modified management approach is required. Surgical intervention may be indicated at a much earlier stage of proven NEC before gut perforation occurs. Accepted: 3 February 1999     

Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis

In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25–34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0–24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487–10000 pg/ml), IL-10 (median 113 pg/ml, range 70–196 pg/ml), CRP (median 22 mg/l, range 4–80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747–8000 pg/ml, IL-10 (median 84 pg/ml, range 76–92 pg/ml), CRP (median 10 mg/l, range 8–33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595–7950 pg/ml), IL-10 (median 80 pg/ml, range 61–147 pg/ml), CRP (median 3 mg/l, range 2.8–8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198–349 pg/ml; IL-10 median 36 pg/ml, range 19–50 pg/ml; CRP median <2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r=0.65; P=0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422–753 pg/ml; CRP median 123 mg/l, range 20–219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61–143 pg/ml; CRP median 8 mg/l range 3–46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538–800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53–161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r=0.45; P=0.05). Conclusion Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis. Received: 21 November 2000 / Accepted: 23 January 2001     

新生儿坏死性小肠结肠炎患儿的远期预后

目的 了解新生儿坏死性小肠结肠炎（NEC）患儿的远期预后。方法 将2014年12月至2016年9月存活出院的83例NEC早产儿分为手术组（n=57）和非手术组（n=26）。手术组Ⅰ期、Ⅱ期、Ⅲ期NEC患儿分别有0、33、24例,非手术组分别有7、19、0例。对患儿出院后体格发育、神经系统发育等情况进行随访分析。结果 83例患儿随访结束时平均纠正年龄为21±6个月。31例（37%）体重落后,其中手术组体重落后率高于非手术组（P < 0.05）;22例（27%）身长落后;14例（17%）头围落后。运动发育落后/发育障碍患儿共18例（22%）,其中手术组发生率高于非手术组（28% vs 8%,P < 0.05）。共有5例（6%）患儿诊断为脑瘫,其中手术组4例,非手术组1例。结论 NEC会影响患儿的远期体格发育及神经系统发育等,尤其对病情严重需接受手术治疗的患儿影响更大,应对NEC患儿进行长期随访。     

谷氨酰胺预防早产儿坏死性小肠结肠炎的临床研究

目的 评估谷氨酰胺(glutamine,Gln)预防早产儿坏死性小肠结肠炎(necrotizing enterocolits,NEC)的临床疗效.方法 将我科2007年10月至2010年3月收治的2717例早产儿分为Gln预防组(1389例)和非Gln预防组(1328例),观察两组患儿NEC的发病率.结果 Gln预防组与非Gln预防组患儿在性别,胎龄,出生体质量,有无窒息史,是否合并肺炎、败血症、脑出血等方面比较,差异无统计学意义(P＞0.05).Gln预防组1389例患儿中35例诊断为NEC,发病率为2.52%;非Gln预防组1328例患儿中68例诊断为NEC,发病率为5.12%,两组患儿发病率比较差异有统计学意义(x2=12.590,P＜0.01).结论 预防性应用Gln能降低早产儿NEC的发病率.     

前白蛋白对重症坏死性小肠结肠炎的诊断价值

目的 了解重症新生儿坏死性小肠结肠炎(NEC)的临床特点,探究前白蛋白(PA)对于重症NEC的诊断价值。方法 对40例NEC新生儿(Ⅱ期29例、Ⅱ期11例)的临床资料及血常规、血生化结果进行研究,采用多因素logistic回归分析以及ROC曲线判断PA在重症NEC诊断中的价值。结果 多因素logistic回归分析发现PA对于重症NEC(≥Ⅱ B期)的诊断具有参考价值。ROC曲线分析显示在重症NEC(≥Ⅱ B期)的诊断中,PA拥有较高的灵敏度(0.870)及特异度(0.647)。结论 PA对重症NEC(≥Ⅱ B期)具有较高的诊断价值。     

新生儿坏死性小肠结肠炎手术介入治疗的临床分析

目的：评价新生儿坏死性小肠结肠炎（NEC）手术介入治疗的高危因素、预后因素及手术时机。方法：选取2001年10月至2011年10月10年间入住新生儿重症监护室的62例NEC早产儿患者。根据患儿是否需要手术治疗分为手术组（n=20）和非手术组（n=42）。比较两组患儿的一般资料、合并症、临床症状、实验室检查、治疗方法、预后等各因素。结果：呼吸窘迫综合征发生率、肠鸣音消失比例、CRP及血小板水平、血培养阳性比例、X线表现为气腹和固定肠绊及机械通气比例在两组间差异有统计学意义（P<0.05）。手术组患儿预后因素分析显示治愈患儿多处穿孔率及循环衰竭率显著低于死亡患儿,差异有统计学意义（P<0.05）。手术组20例患儿中,19例（95％）在NEC诊断后1周进行手术,15例顺利完成手术。结论：NEC手术介入治疗的高危因素是多因素的;手术的预后与肠道病变及是否循环衰竭有关。NEC手术时间一般在NEC诊断后1周内。     

Probiotics for the prevention of necrotising enterocolitis in very low‐birth‐weight infants: a meta‐analysis and systematic review

We performed an updated meta‐analysis incorporating the results of recent randomised controlled trials (RCTs) to measure the effectiveness of probiotic supplementation in preventing necrotising enterocolitis (NEC) and death in very low‐birth‐weight (VLBW) infants, and to investigate any differences in efficacy by probiotic agent. Using meta‐regression analysis, we assessed the contribution of other measured variables on the overall effect size and between‐study variability. Conclusion: Overall, probiotics lead to significant reductions in NEC incidence and mortality in VLBW infants. Differences in probiotic agents and the influence of prenatal steroids and feeding regimens may explain the differences in outcomes between studies.     

早产儿坏死性小肠结肠炎影响因素分析及发病预测模型的构建

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,制定一个可以预测NEC发生并指导预防的评分表。 方法 回顾性收集2011年1月至2020年12月吉林大学白求恩第一医院新生儿科收治的早产儿的临床资料,分为NEC组（Bell Ⅱ期及以上）（n=298）和非NEC组（n=300）,对NEC影响因素进行单因素及多因素统计分析,明确NEC的独立影响因素,并根据影响因素构建预测NEC的列线图,用受试者工作特征曲线及一致性指数（C指数）测量列线图的预测性能。 结果 多因素logistic回归分析显示：Ⅱ度及以上颅内出血、经外周静脉穿刺中心静脉置管、使用母乳强化剂、输红细胞悬液、红细胞比容>49.65%、平均红细胞体积>114.35 fL、平均血小板体积>10.95 fL是NEC的独立危险因素（P<0.05）;使用肺表面活性物质、使用益生菌、血小板分布宽度>11.8 fL是NEC的保护因素（P<0.05）。列线图预测NEC风险的准确性良好,bootstrap校正的C指数为0.844。预测有无NEC的列线图总分最佳截断值为171.02分,灵敏度、特异度分别为74.7%、80.5%。 结论 NEC发病风险预估列线图在指导NEC的早期预判及有针对性的预防及早期干预方面有一定的临床价值。