益生菌预防早产儿坏死性小肠结肠炎的系统评价和Meta分析

摘要

Objective To systematically evaluate the efficacy and safety of prophylactic probiotic supplementation for preventing necrotizing enterocolitis( NEC ) in preterm neonates. Methods Databases including PubMed,Ovid-EMbase,The Cochrane Library,CNKI,WanFang Data and VIP were searched to collect RCTs about probiotics for preventing necrotizing enterocolitis in preterm neonates up to March 2016. Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies. Meta-analysis was conducted by RevMan 5. 3 software. Results A total of 33 RCTs,involving 8 248 patients were included. The results of meta-analysis showed that,for low birth weight infants( LBWI ),probiotics could significantly reduce the incidence of NEC( stage Ⅱ or more),the incidence of severe NEC( stageⅢ),time to full enteral feeds [the incidence of NEC:OR=0. 26(95%CI:0. 10 to 0. 66),P=0. 004;the incidence of severe NEC:OR=0. 29(95%CI:0. 11 to 0. 78),P=0. 01;time to full enteral feeds:WMD= -3. 57(95%CI:-5. 79 to -1. 34),P=0. 002],but did not decrease overall mortality and the risk for sepsis[overall mortality:OR=0. 80(95%CI:0. 50 to 1. 28),P=0. 35;the risk for sepsis:OR=0. 50 (95%CI:0.13 to 1. 99),P =0. 33];for very low birth weight infants(VLBWI),probiotic supplement was associated with a significantly decreased incidence of NEC and severe NEC,overall mortality,NEC related mortality,the risk for sepsis[ the incidence of NEC:OR=0. 34(95%CI:0. 26 to 0. 44),P﹤0. 000 01;the incidence of severe NEC:OR=0. 39(95%CI:0. 20 to 0. 76),P=0. 006;overall mortality:OR=0. 55(95%CI:0. 44 to 0. 69),P﹤0. 000 01;NEC related mortality:OR=0. 38(95%CI:0. 21 to 0. 69),P=0. 001;the risk for sepsis:OR=0. 77(95%CI:0. 62 to 0. 95),P=0. 02]. There was no evidence of significant reduction of time to full enteral feeds[WMD= -1. 28(95%CI:-2. 62 to 0. 06),P=0. 06];for extreme low birth weight infants ( ELBWI),probiotics administration didnˊt decrease the incidence of NEC and severe NEC,overall mortality,NEC related mortality,the risk for sepsis[the incidence of NEC:OR=0. 67(95%CI:0. 25 to 1. 79),P=0. 43;the incidence of severe NEC:OR=1. 02(95%CI:0. 14 to 7. 54),P =0. 98;overall mortality:OR =0. 96(95%CI:0. 34 to1. 43),P =0. 32;NEC related mortality:OR=0. 73(95%CI:0. 12 to 4. 48),P=0. 74;the risk for sepsis:OR=0. 50(95%CI:0. 20 to 1. 23),P=0. 13],but could significantly shorten time to full enteral feeds [ WMD = - 1. 70( 95% CI:- 2. 85 to - 0. 55 ),P = 0. 004 ]. Conclusion Probiotic supplement could reduce risk of NEC and time to full enteral feeds in LBWI and VLBW,and showed a decreasing trend of mortality and the risk for sepsis. The above conclusions need more high quality studies to be verified.%目的：评价益生菌预防早产儿坏死性小肠结肠炎（ NEC）的有效性和安全性。方法计算机检索PubMed、Ovid-Embase、The Cochrane Library、中国知网、维普、中国生物医学文献和万方数据库，收集益生菌预防早产儿NEC的RCT，检索时间均从建库至2016年3月。2名评价员独立筛选文献、提取资料和评价偏倚风险，采用 RevMan5.3软件进行Meta分析。结果最终纳入33个RCT（n=8248）。Meta分析结果显示：①低出生体重儿（LBWI）：益生菌降低NEC 2级以上（包括2级和3级）发生率[OR=0.26（95%CI：0.10~0.66）]、3级发生率[OR=0.29（95%CI：0.11~0.78）]、缩短达全肠道喂养时间[WMD=-3.57（95%CI：-5.79~-1.34）]，差异有统计学意义，益生菌组和对照组总病死率[OR=0.80（95%CI：0.50~1.28）]和脓毒症发生率[OR=0.50（95%CI：0.13~1.99）]差异无统计学意义；②极低出生体重儿（VLBWI）：益生菌降低NEC 2级以上发生率[OR=0.34（95%CI：0.26~0.44）]、3级发生率[OR=0.39（95%CI：0.20~0.76）]、总病死率[OR=0.55（95%CI：0.44~0.69）]、NEC相关病死率[OR =0.38（95%CI：0.21~0.69）]和脓毒症发生率[OR =0.77（95%CI：0.62~0.95）]，差异均有统计学意义，益生菌组和对照组达全肠道喂养时间[ WMD=-1.28（95%CI：-2.62~0.06）]差异无统计学意义；③超低出生体重儿（ELBWI）：益生菌缩短达全肠道喂养时间[WMD=-1.70（95%CI：-2.85~-0.55）]，差异有统计学意义，益生菌组和对照组的NEC 2级以上和3级发病率、总病死率、NEC相关病死率和脓毒症发生率差异无统计学意义。结论预防性使用益生菌可减少LBWI和VLBWI的NEC 2级以上以及3级发生率，缩短达全肠道喂养时间，并降低VLBW的总病死率、NEC相关病死率和脓毒症发生率，但纳入研究在研究设计、方法学等方面仍存在局限性，仍需开展更多高质量研究予以验证。