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.     

Maternal preeclampsia is associated with increased risk of necrotizing enterocolitis in preterm infants

Background

Necrotizing enterocolitis (NEC) is an important cause of mortality and morbidity in preterm infants.

Aims

To evaluate the effect of maternal preeclampsia on the development and severity of NEC in premature infants.

Study design

Prospective observational study in a tertiary neonatal intensive care unit.

Subjects

The preterm infants of ≤ 37 gestational age who were consecutively hospitalized were enrolled. The study group contained preterm infants born to a preeclamptic mother and the comparison group contained preterm infants born to a normotensive mother.

Outcome measures

The primary outcome was to determine the association between preeclampsia and NEC.

Results

A total of 88 infants had NEC diagnosis. The incidence of NEC in infants born to preeclamptic mothers (22.9%) was significantly higher compared with those born to normotensive mothers (14.6%). According to NEC stages, NEC was more advanced in preeclamptic mother infants. NEC developed significantly earlier in infants with NEC in the study group. The duration of NEC was also significantly longer in infants born to preeclamptic mothers. In multiple logistic regression model, preeclampsia was found to be predictive of NEC with an odds ratio of 1.74 (95% confidence interval 0.64–0.92).

Conclusions

Maternal preeclampsia may be an important risk factor for the development of NEC in premature infants as NEC incidence and severity of NEC were found to be significantly higher in premature infants born to preeclamptic mothers. The onset of NEC was significantly earlier and duration of NEC was longer in these infants.     

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。     

Challenging diagnosis between intussusception and necrotizing enterocolitis in premature infants

Although necrotizing enterocolitis (NEC) is a frequently encountered entity in premature infants in the neonatal intensive care unit, intussusception is extremely rare. Abdominal distension, bilious/non‐bilious gastric residuals and bloody stool are the common clinical findings of both entities. Here we present three cases of intussusception misdiagnosed as NEC, two of which were complicated with intestinal perforation. Similar clinical findings of NEC and intussusception leads to misdiagnosis and delay in treatment, particularly in premature infants with intussusception.     

肠道局部组织氧饱和度和C-反应蛋白在诊断早产儿坏死性小肠结肠炎中的价值

目的 探讨肠道局部组织氧饱和度(regional oxygen saturation,rSO₂)和C-反应蛋白(C-reactive protein,CRP)在早产儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)诊断中的临床价值。方法 采用前瞻性观察性方法,选取2020年10月—2021年12月安徽医科大学附属省儿童医院住院的早产儿为研究对象,其中NEC组22例,非NEC组35例。NEC组在NEC确诊后24 h内监测肠道r SO₂,并于抗感染治疗前检测血清CRP水平;非NEC组对应时间点进行肠道rSO₂监测和血清CRP检测。比较2组肠道rSO₂和血清CRP水平的差异,并采用受试者工作特征曲线分析肠道rSO₂、血清CRP单独及二者联合诊断早产儿NEC的价值。结果 NEC组的肠道rSO₂低于非NEC组(P<0.05),血清CRP水平高于非NEC组(P<0.05)。受试者工作特征曲线分析显示：肠道rSO₂     

Brainstem auditory response findings in preterm infants after necrotizing enterocolitis

Aim: To examine brainstem auditory function and detect any abnormality at term in preterm infants after neonatal necrotizing enterocolitis (NEC). Methods: Brainstem auditory evoked response (BAER) was recorded at 21/sec and 60 dB nHL in 37 preterm infants who had NEC. The data obtained at term equivalent age were analyzed and compared with those in normal term infants. Results: The threshold of BAER in infants after NEC, though slightly elevated, did not differ significantly from that in the controls. The latencies of waves I and III were slightly longer than in the controls, without any statistical significance. However, wave V latency was prolonged and differed significantly from the controls (p < 0.01). I-V interpeak interval was also prolonged (p < 0.05). The data point distribution of wave V latency and I-V interval was higher in the infants after NEC than in the controls. The amplitudes of BAER wave components in the infants after NEC did not differ significantly from those in the controls. Conclusion: Preterm infants after NEC have no major abnormality in peripheral auditory function. However, neural conduction in the brainstem auditory pathway is abnormal, suggesting that NEC adversely affects brainstem auditory conduction.     

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.     

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.     

小剂量多巴胺辅助治疗对坏死性小肠结肠炎早产儿炎症因子及预后的影响

目的 探讨小剂量多巴胺辅助治疗对坏死性小肠结肠炎（NEC）早产儿炎症因子及预后的影响。方法 将2017年6月至2019年6月住院治疗的NEC早产儿100例,依据随机数字表法分为多巴胺治疗组（多巴胺组）和常规治疗组（常规组）,每组50例。常规组给予常规对症治疗,多巴胺组在常规治疗基础上给予小剂量多巴胺辅助治疗。ELISA法检测两组C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）、白介素-8（IL-8）水平;观察并记录两组患儿临床症状缓解时间、禁食时间、治疗疗效、预后及不良反应。结果 多巴胺组和常规组治疗后CRP、TNF-α、IL-8水平均明显低于治疗前,多巴胺组治疗后CRP、TNF-α、IL-8水平均明显低于常规组（P < 0.05）;多巴胺组大便改善时间、腹胀及腹泻缓解时间、禁食时间均明显短于常规组（P < 0.05）;多巴胺组治疗有效率明显高于常规组,手术率明显低于常规组（P < 0.05）;两组病死率、不良反应发生率比较差异无统计学意义（P > 0.05）。结论 小剂量多巴胺辅助治疗可有效改善NEC早产儿炎症因子水平及临床症状,有利于提高患儿治疗疗效,且安全性好,值得临床推广。     

益生菌在早产儿的应用进展

早产儿的消化道结构、功能和机体免疫发育不成熟,且消化道微生物定植异常,易发生各种消化道疾病。益生菌能调节消化道微生物的构成,改善消化道屏障功能,减轻消化道炎症反应并调节机体免疫。目前主要益生菌用于防治坏死性小肠结肠炎、晚发败血症及喂养不耐受等。但益生菌在早产儿中应用的有效性和安全性仍存在争议。     

早产儿坏死性小肠结肠炎危险因素的Meta分析北大核心CSCD

目的 系统评价早产儿发生坏死性小肠结肠炎(necrotizing enterocolitis,NEC)的危险因素。方法 计算机检索PubMed、Embase、Cochrane Library、中国知网和万方数据库,检索时限均为建库起至2021年12月。收集关于早产儿发生NEC的危险因素的病例对照研究和队列研究,采用RevMan 5.3软件进行Meta分析。结果 共纳入38项研究,其中病例对照研究28项,队列研究10项。Meta分析结果显示:母妊娠糖尿病(OR=2.96,P<0.001)、孕期肝内胆汁淤积症(OR=2.53,P<0.001)、子痫前期(OR=1.73,P=0.020),以及新生儿窒息史(OR=2.13,P<0.001)、低胎龄(OR=1.23,P=0.010)、败血症(OR=5.32,P<0.001)、动脉导管未闭(OR=1.57,P=0.001)、先天性心脏病(OR=3.78,P<0.001)、机械通气(OR=2.23,P=0.020)、抗生素应用史(OR=1.07,P<0.001)、使用血管加压药(OR=2.34,P=0.040)、禁食(OR=1.08,P<0.001)是早产儿发生NEC的危险因素;而剖宫产出生(OR=0.73,P=0.004)、使用肺表面活性剂(OR=0.43,P=0.008)、母乳喂养(OR=0.24,P=0.020)是早产儿发生NEC的保护因素。结论 母妊娠糖尿病、孕期肝内胆汁淤积症、子痫前期、低胎龄、禁食、败血症、动脉导管未闭、先天性心脏病、窒息史、机械通气史、抗生素应用史、血管加压药应用史可增加早产儿发生NEC的风险;而剖宫产出生、使用肺表面活性剂、母乳喂养可降低早产儿发生NEC的风险。[中国当代儿科杂志,2022,24 (8):908-916]     

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。     

Prevention of necrotizing enterocolitis in extremely low birth weight infants by IgG feeding?

Oral immunoglobulin has been described as preventing necrotizing enterocolitis(NEC) in preterm infants. To prevent NEC in extremely low birth weight infants (ELBW), we have carried out oral IgG prophylaxis since April 1991. The efficacy of this prophylaxis was examined in a study comparing historical cohorts. ELBW infants delivered in the Department of Obstetrics and Gynaecology of the University of Ulm and treated until day 28 in the level III intensive care nursery, Division of Neonatology, University of Ulm were included. Cohort 1, born between 1.1.1988 and 31.3.1991, received no oral IgG and served as a control [n=84, gestational age: median 26 weeks, range 24–34; birth weight: 811 g, 490–990], cohort 2, born between 1.4.1991 and 31.12.1995 [n=137, gestational age: 26 weeks, 22–32; birth weight: 760 g, 362–995], received 6 × 100 mg/kg human IgG (Beriglobin) orally on days 1–28. NEC, stage 2a and higher according to the modified classification of Bell, was observed in 9 of 84 (10.7%) infants of cohort 1 and in 11 of 137 (8%) infants of cohort 2 until day 28. The difference did not reach statistical significance (P=0.63 Fisher's exact test). Conclusion In this historical cohort study, ELBW infants were not protected against NEC by oral IgG. The present published evidence does not allow recommendation of oral human IgG administration in preterm infants as a prophylactic measure against NEC. Received: 8 June 1997 / Accepted in revised form: 1 January 1998