AlFaleh Khalid, Anabrees Jasim
Department of Pediatrics (Division of Neonatology), King Saud University, King Khalid University Hospital and College of Medicine, Department of Pediatrics (39), P.O. Box 2925, Riyadh, Saudi Arabia, 11461.
Cochrane Database Syst Rev. 2014 Apr 10(4):CD005496. doi: 10.1002/14651858.CD005496.pub4.
Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity.
To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants.
For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013).
Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome.
Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis.
Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective.
AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized.
坏死性小肠结肠炎（NEC）和医院感染性败血症与早产儿发病率和死亡率的增加相关。预防性肠内益生菌（活微生物补充剂）可通过防止细菌穿过黏膜迁移、竞争性排除病原菌以及增强宿主免疫反应，在降低NEC及其相关发病率方面发挥作用。
比较预防性肠内给予益生菌与安慰剂或不治疗在预防早产儿严重NEC或败血症或两者方面的疗效和安全性。
本次更新检索了MEDLINE（1966年至2013年10月）、EMBASE（1980年至2013年10月）、Cochrane图书馆中Cochrane对照试验中心注册库（CENTRAL）（2013年第10期）以及儿科学会年会摘要（1995年至2013年）。
仅纳入孕周小于37周或出生体重小于2500g或两者均满足的早产儿的随机或半随机对照试验。若试验涉及任何活微生物补充剂（益生菌）的肠内给药并测量至少一项预先指定的临床结局，则纳入该试验。
采用Cochrane协作网及其新生儿组的标准方法评估试验的方法学质量并进行数据收集与分析。
纳入了24项符合条件的试验。纳入试验在纳入标准（即出生体重和孕周）、对照组NEC的基线风险、时间、剂量、益生菌制剂以及喂养方案方面差异很大。在对试验数据的荟萃分析中，肠内补充益生菌显著降低了严重NEC（II期及以上）的发生率（典型相对危险度（RR）0.43，95%置信区间（CI）0.33至0.56；20项研究，5529例婴儿）和死亡率（典型RR 0.65，95%CI 0.52至0.81；17项研究，5112例婴儿）。没有证据表明医院感染性败血症显著降低（典型RR 0.91，95%CI 0.80至1.03；19项研究，5338例婴儿）。纳入试验未报告补充益生菌菌株导致的全身感染。发现单独含有乳酸杆菌或与双歧杆菌联合的益生菌制剂有效。
肠内补充益生菌可预防早产儿严重NEC和全因死亡率。我们对现有证据的更新综述有力支持了实践中的改变。需要进行直接比较研究以评估最有效的制剂、治疗时间和疗程。
