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

王小玲; 李雄; 康兰; 王胜会; 董文斌

doi:10.7499/j.issn.1008-8830.2015.08.018

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中国当代儿科杂志 ›› 2015, Vol. 17 ›› Issue (8) : 852-858. DOI: 10.7499/j.issn.1008-8830.2015.08.018

论著·临床研究

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

王小玲, 李雄, 康兰, 王胜会, 董文斌

作者信息 +

Prophylactic probiotics for preventing necrotizing enterocolitis and reducing mortality in very low birth weight infants: a Meta analysis

WANG Xiao-Ling, LI Xiong, KANG Lan, WANG Sheng-Hui, DONG Wen-Bin

Author information +

文章历史 +

摘要

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);P< 0.01]和总病死率[RR=0.63;95%CI(0.51~0.78),P< 0.01];而益生菌使用组和对照组间败血症的发生率[RR=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。

Abstract

Objective To systematically evaluate the efficacy and safety of probiotic supplementation for preventing necrotizing enterocolitis (NEC) and reducing mortality in preterm very low birth weight (VLBW) infants. Methods The randomized controlled trials (RCTs) about probiotics for preventing NEC in preterm neonates were searched in PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), the ISI Web of Knowledge databases, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Weipu and Wanfang Data from their establishment to March 2014. The Cochrane Collaboration's RevMan 5.1 Software was used for a Meta analysis. Results A total of 21 RCTs involving 4 607 preterm VLBW infants were eligible for inclusion in the Meta analysis. The Meta analysis showed that probiotic supplement was associated with a significantly decreased risk of NEC in preterm VLBW infants (RR=0.47; 95%CI: 0.35-0.62; P< 0.001). Risk of mortality was also significantly reduced in the probiotic group (RR=0.63; 95%CI: 0.51-0.78; P< 0.01). Probiotic supplement did not decrease the risk for sepsis (RR=0.87; 95%CI: 0.72-1.06; P=0.17) and NEC related mortality (RR=0.68; 95%CI: 0.31-1.48, P=0.33). Conclusions The results confirm that probiotic supplement can reduce risk of NEC and mortality in preterm VLBW infants. However, the long-term effects and safety of probiotics need to be assessed in large trials.

导出引用

王小玲, 李雄, 康兰, 王胜会, 董文斌. 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[J]. 中国当代儿科杂志. 2015, 17(8): 852-858 https://doi.org/10.7499/j.issn.1008-8830.2015.08.018

WANG Xiao-Ling, LI Xiong, KANG Lan, WANG Sheng-Hui, DONG Wen-Bin. Prophylactic probiotics for preventing necrotizing enterocolitis and reducing mortality in very low birth weight infants: a Meta analysis[J]. Chinese Journal of Contemporary Pediatrics. 2015, 17(8): 852-858 https://doi.org/10.7499/j.issn.1008-8830.2015.08.018

参考文献

[1] Obladen M. Necrotizing enterocolitis-150 years of fruitless search for the cause[J]. Neonatology, 2009, 96(4): 203-210.
[2] Neu J, Walker WA. Necrotizing enterocolitis[J]. N Engl J Med, 2011, 364(3): 255-264.
[3] Hsueh W, Caplan MS, Qu XW, et al. Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts[J]. Pediatr Dev Pathol, 2003, 6(1): 6-23.
[4] Lin PW, Stoll BJ. Necrotising enterocolitis[J]. Lancet, 2006, 368(9543): 1271-1283.
[5] Caplan MS. Probiotic and prebiotic supplementation for the prevention of neonatal necrotizing enterocolitis[J]. J Perinatol, 2009, 29(Suppl 2): S2-S6.
[6] Deshpande G, Rao S, Patole S, et al. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates[J]. Pediatrics, 2010, 125(5): 921-930.
[7] Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials blinding necessary?[J]. Controlled Clin Trials, 1996, 17(1): 1-12.
[8] Bin-Nun A, Bromiker R, Wilschanski M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates[J]. J Pediatr, 2005, 147(2): 192-196.
[9] Braga TD, da Silva GA, de Lira PI, et al. Efficacy of Bifido- bacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight preterm infants: a double-blind, randomized, controlled trial[J]. Am J Clin Nutr, 2011, 93(1): 81-86.
[10] Costalos C, Skouteri V, Gounaris A, et al. Enteral feeding of premature infants with Saccharomyces boulardii[J]. Early Hum Dev, 2003, 74(2): 89-96.
[11] Dani C, Biadaioli R, Bertini G, et al. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study[J]. Biol Neonate, 2002, 82(2): 103-108.
[12] Demirel G, Erdeve O, Celik IH, et al. Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm infants: A randomized, controlled study[J]. Acta Paediatr, 2013, 102(12): e560-e565.
[13] Fernández-Carrocera LA, Solis-Herrera A, Cabanillas-Ayón M, et al. Double blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1 500 g in the prevention of necrotising enterocolitis[J]. Arch Dis Child Fetal Neonatal Ed, 2013, 98(1): F5-F9.
[14] Kitajima H, Sumida Y, Tanaka R, et al. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial[J]. Arch Dis Child Fetal Neonatal Ed, 1997, 76(2): F101-F107.
[15] Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants[J]. Pediatrics, 2005, 115(1): 1-4.
[16] Lin HC, Hsu CH, Chen HL, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial[J]. Pediatrics, 2008, 122(4): 693-700.
[17] Manzoni P, Mostert M, Leonessa ML, et al. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study[J]. Clin Infect Dis, 2006, 42(12): 1735-1742.
[18] Manzoni P, Rinaldi M, Cattani S, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low birth weight neonates: a randomized trial[J]. JAMA, 2009, 302(13): 1421-1428.
[19] Mihatsch WA, Vossbeck S, Eikmanns B, et al. Effect of Bifidobacterium lactis on the incidence of nosocomial infections in very low birth weight infants: a randomized controlled trial[J]. Neonatology, 2010, 98(2): 156-163.
[20] Mohan R, Koebnick C, Schildt J, et al. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study[J]. J Clin Microbiol, 2006, 44(11): 4025-4031.
[21] Oncel MY, Sari FN, Arayici S, et al. Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birth weight infants: a randomised controlled trial[J]. Arch Dis Child Fetal Neonatal Ed, 2014, 99(2): F110-F115.
[22] Rojas MA, Lozano JM, Rojas MX, et al. Prophylactic probiotics to prevent death and nosocomial infection in preterm infants[J]. Pediatrics, 2012,130(5): e1113-e1120.
[23] Rougé C, Piloquet H, Butel MJ, et al. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized,double-blind, placebo-controlled trial[J]. Am J Clin Nutr, 2009, 89(6): 1828-1835.
[24] Samanta M, Sarkar M, Ghosh P, et al. Prophylactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns[J]. J Trop Pediatr, 2009, 55(2): 128-131.
[25] Sari FN, Dizdar EA, Oguz S, et al. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial[J]. Eur J Clin Nutr, 2011, 65(4): 434-439.
[26] Serce O, Benzer D, Gursoy T, et al. Efficacy of saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial[J]. Early Hum Dev, 2013, 89(12): 1033-1036.
[27] Stratiki Z, Costalos C, Sevastiadou S, et al. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants[J]. Early Hum Dev, 2007, 83(9): 575-579.
[28] Underwood MA, Salzman NH, Bennett SH, et al. A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids[J]. J Pediatr Gastroenterol Nutr, 2009, 48(2): 216-225.
[29] Deshpande G, Rao S, Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials[J]. Lancet, 2007, 369(9573): 1614-1620.
[30] Agarwal R, Sharma N, Chaudhry R, et al. Effects of oral Lactobacillus GG on enteric microflora in low-birth-weight neonates[J]. J Pediatr Gastroenterol Nutr, 2003, 36(3): 397-402.
[31] Li Y, Shimizu T, Hosaka A, et al. Effects of Bifidobacterium breve supplementation on intestinal flora of low birth weight infants[J]. Pediatr Int, 2004, 46(5): 509-515.