人乳源外泌体对新生儿坏死性小肠结肠炎治疗潜力的研究进展

新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis, NEC)是新生儿死亡的重要原因之一, 目前尚缺乏有效的治疗药物, 而母乳喂养是NEC安全有效的预防措施。人乳源外泌体是母乳中的膜性囊泡, 有抑制炎症反应、抗氧化应激、调节免疫应答、促进肠上皮增殖与迁移、维持肠道上皮紧密连接等功能, 在维持肠道屏障完整性和促进肠道上皮损伤修复方面发挥重要作用。     

新生儿坏死性小肠结肠炎的诊断与治疗

坏死性小肠结肠炎是新生儿常见的腹部急症之一,严重时甚至需要外科手术治疗的介入。多发生于早产儿,常常在早产儿早期可能的合并症趋于稳定时,突然出现坏死性小肠结肠炎的前趋征兆,有时病情进展迅速让人措手不及。足月儿亦有可能发生,约占所有坏死性小肠结肠炎个案的5%至25%。本文针对坏死性小肠结肠炎的流行病学、病理生理机转、诊断、治疗及预后作一简单的介绍。     

小肠细菌过度生长在婴幼儿腹泻中的临床分析

目的 研究小肠细菌过度生长(SIBO)在婴幼儿迁延性和慢性腹泻中的患病率,同时分析婴幼儿SIBO的临床特点及治疗转归.方法 回顾性研究2017年4月11日至2019年4月10日我院住院部消化内科收治的迁延性和慢性腹泻婴幼儿110例.应用乳糖氢呼气试验作为SIBO的诊断方法.结果 乳糖氢呼气试验阳性率为9.09％(10例...     

腹泻病婴幼儿艰难梭菌定植与感染情况分析

目的了解腹泻病婴幼儿艰难梭菌定植与感染情况并探讨其检测方法。方法收集2014~2015年儿科消化门诊腹泻婴幼儿的临床资料及粪便,通过厌氧培养、毒素A和B PCR扩增法和酶联免疫法检测粪便中艰难梭菌和毒素。结果 65份标本中,厌氧培养阳性19例(29.23%),19例经PCR扩增,A/B毒素阳性5例(7.69%);酶联免疫法检测抗原阳性22例(33.85%),与厌氧培养比较,差异无统计学意义(P0.05),毒素A/B阳性5例(7.69%)与PCR扩增法比较,差异无统计学意义(P0.05)。结论婴幼儿有较高的艰难梭菌定植率,其中多为非产毒株,并不致病;酶联免疫法检测艰难梭菌抗原和毒素可以用于临床筛检。     

血浆D-乳酸水平与新生儿坏死性小肠结肠炎预后的关系

目的 探讨血浆D-乳酸水平与新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)预后的关系.方法 采用病例对照研究方法.选择2007年1月至2010年10月入住本院新生儿重症监护病房诊断为NECⅡ、Ⅲ期的早产儿104例(NEC组);同期因其他疾病入院的早产非NEC患儿104例(对照组),与NEC组匹配纠正胎龄、性别和出生体重,按1∶1比例进行配对.NEC组患儿于NEC确诊后24 h内,对照组患儿于相应日龄取血,采用酶联免疫吸附试验检测血浆D-乳酸水平,采用受试者工作特性曲线确定D-乳酸阳性标准.根据此标准将NEC组分为D-乳酸升高组与D-乳酸正常组,x2检验比较组间并发症及病死率.根据患儿病情转归将NEC组分为死亡组和存活组,t检验比较不同组间D-乳酸水平差异.结果 NEC组104例患儿中,NECⅡ期63例(60.6％),NECⅢ期41例(39.4％);存活88例(84.6％),死亡16例(15.4％).NECⅢ期组D-乳酸水平最高,为(35.4±29.1)μg/ml,其次是NECⅡ期组,为(29.5±16.2)μg/ml,对照组最低[(3.7±18.4)μg/ml],差异均有统计学意义(F=5.97,P＜0.05).受试者工作特性曲线分析显示,D-乳酸水平≥6 μg/ml为阳性标准,按此标准,NEC组血浆D-乳酸水平升高者87例(83.7％,87/104).D-乳酸水平升高者新生儿危重病例评分明显低于正常者[(80.9±22.6)分与(95.8±20.5)分,t=2.417,P＜0.05],而合并新生儿败血症的比例[48.3％(42/87)与5.9％(1/17),x2=11.538,P＜0.05]及病死率[27.6％(24/87)与5.9％(1/17),x2=7.146,P＜0.05]较高.NEC组死亡患儿与存活患儿D-乳酸水平[(43.2±13.5) μg/ml与(21.9±22.9) μg/ml,t=4.572,P＜0.05]、新生儿危重病例评分[(82.4±29.1)分与(90.6±21.3)分,t=2.409,P＜0.05]以及合并败血症的比例[68.8％(11/16)与38.6％ (34/88),x2=3.445,P＜0.05]差异均有统计学意义.结论 血浆D-乳酸水平与NEC预后相关,能较好地反映NEC患儿的病情及预后.     

婴幼儿腹泻食疗与外治选方

婴幼儿腹泻好发于2岁以下,婴儿期发病者占多数。根据病因的不同,本病可分为感染性和非感染性两类。临床上感染性腹泻多见,病情也相对较重。     

Toll样受体4信号通路靶点抑制与新生儿坏死性小肠结肠炎的关系

新生儿坏死性小肠结肠炎（necrotizing enterocolitis,NEC）发生机制尚不清楚,肠上皮细胞Toll样受体4（toll-like receptor 4,TLR4）介导的TLR4信号通路被认为是激活NEC炎症风暴的关键因素。本文围绕TLR4信号通路及其上、下游信号靶点抑制,以及部分关键模式识别受体和特...     

胎儿炎症反应综合征研究进展

胎儿炎症反应综合征（fetal inflammatory response syndrome，FIRS）是胎儿固有免疫系统被激活的一种亚临床状态，是全身炎症反应综合征（systemic inflammation response syndrome，SIRS）在胎儿期的特殊表现。宫内感染及胎儿宫内慢性缺氧是导致FIRS的两个重要原因。感染或缺氧所致的“失控”的全身性炎症反应是FIRS发生的主要机制。FIRS与早产、支气管肺发育不良、新生儿早发型败血症、新生儿脑损伤、新生儿坏死性小肠结肠炎等新生儿严重并发症密切相关。FIRS宫内表现通常不典型，极易忽视，如不及时干预，新生儿期可能出现脑瘫、多器官功能衰竭、死亡等严重后果。本文就近年FIRS的临床诊断、发病机制和危害等方面的研究进展进行综述。     

Human milk is the feeding strategy to prevent necrotizing enterocolitis!

Human milk is the preferred diet for preterm infants as it protects against a multitude of NICU challenges, specifically necrotizing enterocolitis. Infants who receive greater than 50% of mother’s own milk (MOM) in the 2 weeks after birth have a significantly decreased risk of NEC. An additional factor in the recent declining rates of NEC is the increased utilization of donor human milk (DHM). This creates a bridge until MOM is readily available, thus decreasing the exposure to cow milk protein. Preterm infants are susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in many ways such as lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability, and altering the composition of bacterial flora. Ideally, preterm infants should be fed human milk and avoid bovine protein. A diet consisting of human milk-based human milk fortifier is one way to provide the additional nutritional supplements necessary for adequate growth while receiving the protective benefits of a human milk diet.     

The human milk oligosaccharides are not affected by pasteurization and freeze-drying

Objectives: Human milk oligosaccharides (HMOs) are known as important factors in neurologic and immunologic development of neonates. Moreover, freeze-drying seems to be a promising storage method to improve the processes of human milk banks. However, the effects of pasteurization and freeze-drying on HMOs were not evaluated yet. The purpose of this study is to analyze and compare the HMOs profiles of human milk collected before and after the pasteurization and freeze-drying.

Methods: Totally nine fresh human milk samples were collected from three healthy mothers at the first, second, and third week after delivery. The samples were treated with Holder pasteurization and freeze-drying. HMOs profiles were analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry and compared between samples collected before and after the treatments.

Results: Human milk samples showed significantly different HMO patterns between mothers. However, HMOs were not affected by lactation periods within 3 weeks after delivery (r²?=?0.972–0.999, p?r²?=?0.989–0.999, p?Conclusion: HMO patterns were found not to be affected by pasteurization and freeze-drying of donor milks. We hope that introducing freeze-drying to the human milk banks would be encouraged by the present study. However, the storage length without composition changes of HMOs after freeze-drying needs to be evaluated in the further studies.     

Sharing the science on human milk feedings with mothers of very-low-birth-weight infants

Mother's milk provides protection from serious and costly morbidity for very-low-birth-weight infants (<1500 g), including enteral feeding intolerance, nosocomial infection, and necrotizing enterocolitis. However, NICU and maternity nurses may be hesitant to encourage mothers to initiate lactation because of a reluctance to make mothers feel guilty or coerced. This article reviews the evidence for the health outcomes of mothers' milk feeding in very-low-birth-weight infants and provides examples of ways to share this science with mothers so that they can make an informed feeding decision.     

Solely human milk diets for preterm infants

Human milk provides not only ideal nutrition for infant development but also immunologic factors to protect from infection and inflammation. For the newborn preterm infant, the natural delivery of milk is not attainable, and instead pumped maternal milk, donor human milk, and human milk fortification are mainstays of clinical care. Current research demonstrates a decreased risk of necrotizing enterocolitis with maternal milk and donor human milk when individually compared to formula and with a complete human milk diet of maternal milk supplemented with donor human milk. The incidence of severe retinopathy of prematurity is decreased with an exclusive human milk diet, and this decrease is more pronounced with human milk-based compared to bovine milk-based human milk fortifier. The incidence of other morbidities such as late-onset sepsis and bronchopulmonary dysplasia is decreased with higher dose of human milk though significant differences are not apparent in exclusive human milk diet studies.     

Breast milk oligosaccharides: effects of 2′-fucosyllactose and 6′-sialyllactose on the adhesion of Escherichia coli and Salmonella fyris to Caco-2 cells

Background: It is well known that human milk oligosaccharides play an important role as prebiotics, anti-inflammatory, and anti-infective agents. In the last few years, several studies have been performed using specific oligosaccharides, such as 2′-fucosyllactose and 6′-sialylactose, to evaluate their biological functions.

Objectives: The aim of the present study is to evaluate the anti-adhesive effect of the above oligosaccharides on Escherichia coli and Salmonella fyris.

Methods: Adhesion experiments were performed in the presence of 2′-fucosyllactose and 6′-sialyllactose as potential inhibitors of Escherichia coli and Salmonella fyris adhesion to Caco-2 cells. The oligosaccharides were used at different concentrations and the adhesion experiments were performed in triplicate and repeated at least three times.

Results: A significant reduction of Escherichia coli adhesion was observed in the presence of 2′-fucosyllactose and 6′-sialyllactose at the human milk concentration. On the contrary, no positive effects were observed in both oligosaccharides on Salmonella firis.

Conclusions: Our results suggest that the supplementation in infant formulas of 2′-fucosyllactose and 6′-sialyllactose, actually commercially available and absent in cow milk, could play positive effects in artificially fed infants.     

Impact of probiotics on necrotizing enterocolitis

A large number of randomized placebo-controlled clinical trials and cohort studies have demonstrated a decrease in the incidence of necrotizing enterocolitis with administration of probiotic microbes. These studies have prompted many neonatologists to adopt routine prophylactic administration of probiotics while others await more definitive studies and/or probiotic products with demonstrated purity and stable numbers of live organisms. Cross-contamination and inadequate sample size limit the value of further traditional placebo-controlled randomized controlled trials. Key areas for future research include mechanisms of protection, optimum probiotic species or strains (or combinations thereof) and duration of treatment, interactions between diet and the administered probiotic, and the influence of genetic polymorphisms in the mother and infant on probiotic response. Next generation probiotics selected based on bacterial genetics rather than ease of production and large cluster-randomized clinical trials hold great promise for NEC prevention.     

Using quality improvement to increase human milk use for preterm infants

This review will provide an overview of quality improvement methods that have been used to improve human milk use (mother’s own milk and donor milk) for very low-birth-weight infants in the hospital setting in the last decade. We will review the following: (1) evidence-based practices known to increase mother’s own milk for very low-birth-weight infants; (2) individual hospitals with exemplary lactation programs and past and current US-based statewide quality improvement collaboratives focused on increasing mother’s own milk; and (3) existing quality metrics for human milk and gaps in metrics. Finally, we will provide practical examples of key driver diagrams and change concepts that may be used to inform quality improvement for mother’s own milk for very low-birth-weight infants.     

Improved outcomes of feeding low birth weight infants with predominantly raw human milk versus donor banked milk and formula

Objectives: To investigate the benefits of treating low birth weight infants predominantly with mother’s own raw milk and early initiation of breastfeeding (raw human milk/breast-fed infants), in comparison to feeding only with donor banked milk (until the third week of life) and afterwards a preterm formula until hospital discharge (donor banked/formula-fed infants).

Methods: One hundred and ninety-two predominantly raw human milk-fed infants (70% of raw and 30% of donor milk) were matched to 192 donor/formula-fed ones (on 1:1 ratio). Aggressive nutrition policy and targeted fortification of human milk were implemented in both groups.

Results: The two groups show similar demographic and perinatal characteristics. Predominantly raw milk-fed infants regained earlier their birth weight, suffered less episodes of feeding intolerance and presented a higher body length and head circumference at discharge (p?<?0.001). Those treated mainly with their mothers’ milk were able to initiate breastfeeding almost 2 weeks earlier compared to those fed with donor milk who achieved to be bottle-fed later on post-conceptual age (p?<?0.001). Infants being breastfed until the 8th month of life conducted less visits for a viral infection to a pediatrician compared to those in the other group (p?<?0.001).

Conclusions: Feeding predominantly with mother’s raw milk seems to result in optimal neonatal outcomes.