PDF(Pubmed)
Abstract：
Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants.
To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials.
MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023.
Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants.
A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach.
All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization.
A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively).
In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.
To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials.
MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023.
Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants.
A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach.
All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization.
A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively).
In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.
摘要：
■通过施用益生菌调节肠道微生物组，益生元,或者两者都可以预防早产儿的发病率和死亡率。
■通过随机临床试验的网络荟萃分析（NMA）评估替代预防策略的比较有效性。
■MEDLINE,EMBASE,科学引文索引扩展，CINAHL,Scopus,科克伦中部,和谷歌学者从成立到2023年5月10日。
■合格试验测试了益生菌，益生元,乳铁蛋白,以及预防早产儿发病或死亡的组合产品。
■NMA使用了频率随机效应模型，使用等级方法评估了有关相对有效性的证据和推论的确定性。
■全因死亡率，严重坏死性小肠结肠炎,培养证实的败血症，喂养不耐受，达到完全肠内喂养的时间，和住院时间。
■共纳入106项试验，涉及25840名早产儿。与安慰剂相比，只有多菌株益生菌与全因死亡率降低相关(风险比[RR]，0.69；95%CI，0.56至0.86；风险差异[RD]，-1.7%；95%CI，-2.4%至-0.8%）。单用多菌株益生菌（与安慰剂相比：RR，0.38；95%CI，0.30至0.50；RD，-3.7％；95％CI，-4.1％至-2.9％）或与寡糖联合使用（与安慰剂相比：RR，0.13；95%CI，0.05至0.37；RD，-5.1％；95％CI，-5.6％至-3.7％）是减少严重坏死性小肠结肠炎的最有效干预措施之一。单菌株益生菌与乳铁蛋白的组合(与安慰剂RR相比，0.33；95%CI，0.14至0.78；RD，-10.7％；95％CI，-13.7％至-3.5％）是减少脓毒症的最有效干预措施。单用多菌株益生菌(RR，0.61；95%CI，0.46至0.80；RD，-10.0％；95％CI，-13.9％至-5.1％）或与寡糖组合（RR，0.45；95%CI，0.29至0.67；RD，-14.1%；95%CI，-18.3%至-8.5%）和单菌株益生菌（RR，0.61；95%CI，0.51至0.72；RD，-10.0％；95％CI，-12.6％至-7.2％）与安慰剂相比，在减少喂养不耐受方面具有最佳效果。单菌株益生菌（MD，-1.94天；95%CI，-2.96至-0.92）和多菌株益生菌（MD，-2.03天；95％CI，-3.04至-1.02）被证明与安慰剂相比，在减少达到完全肠内喂养的时间方面最有效。与安慰剂相比，只有单菌株和多菌株益生菌在减少住院时间方面具有更大的有效性（MD，-3.31天；95%CI，-5.05至-1.58；和MD，-2.20天；95%CI，分别为-4.08至-0.31）。
■在本系统综述和NMA中，中度至高度确定性的证据表明,多菌株益生菌与降低全因死亡率之间存在关联;这些干预措施还与其他关键结局的最佳效果相关.组合产品,包括与益生元或乳铁蛋白结合的单株和多株益生菌，与发病率和死亡率的最大降低相关。
■通过随机临床试验的网络荟萃分析（NMA）评估替代预防策略的比较有效性。
■MEDLINE,EMBASE,科学引文索引扩展，CINAHL,Scopus,科克伦中部,和谷歌学者从成立到2023年5月10日。
■合格试验测试了益生菌，益生元,乳铁蛋白,以及预防早产儿发病或死亡的组合产品。
■NMA使用了频率随机效应模型，使用等级方法评估了有关相对有效性的证据和推论的确定性。
■全因死亡率，严重坏死性小肠结肠炎,培养证实的败血症，喂养不耐受，达到完全肠内喂养的时间，和住院时间。
■共纳入106项试验，涉及25840名早产儿。与安慰剂相比，只有多菌株益生菌与全因死亡率降低相关(风险比[RR]，0.69；95%CI，0.56至0.86；风险差异[RD]，-1.7%；95%CI，-2.4%至-0.8%）。单用多菌株益生菌（与安慰剂相比：RR，0.38；95%CI，0.30至0.50；RD，-3.7％；95％CI，-4.1％至-2.9％）或与寡糖联合使用（与安慰剂相比：RR，0.13；95%CI，0.05至0.37；RD，-5.1％；95％CI，-5.6％至-3.7％）是减少严重坏死性小肠结肠炎的最有效干预措施之一。单菌株益生菌与乳铁蛋白的组合(与安慰剂RR相比，0.33；95%CI，0.14至0.78；RD，-10.7％；95％CI，-13.7％至-3.5％）是减少脓毒症的最有效干预措施。单用多菌株益生菌(RR，0.61；95%CI，0.46至0.80；RD，-10.0％；95％CI，-13.9％至-5.1％）或与寡糖组合（RR，0.45；95%CI，0.29至0.67；RD，-14.1%；95%CI，-18.3%至-8.5%）和单菌株益生菌（RR，0.61；95%CI，0.51至0.72；RD，-10.0％；95％CI，-12.6％至-7.2％）与安慰剂相比，在减少喂养不耐受方面具有最佳效果。单菌株益生菌（MD，-1.94天；95%CI，-2.96至-0.92）和多菌株益生菌（MD，-2.03天；95％CI，-3.04至-1.02）被证明与安慰剂相比，在减少达到完全肠内喂养的时间方面最有效。与安慰剂相比，只有单菌株和多菌株益生菌在减少住院时间方面具有更大的有效性（MD，-3.31天；95%CI，-5.05至-1.58；和MD，-2.20天；95%CI，分别为-4.08至-0.31）。
■在本系统综述和NMA中，中度至高度确定性的证据表明,多菌株益生菌与降低全因死亡率之间存在关联;这些干预措施还与其他关键结局的最佳效果相关.组合产品,包括与益生元或乳铁蛋白结合的单株和多株益生菌，与发病率和死亡率的最大降低相关。
