Data_Sheet_1_Probiotics for the prevention of mortality and sepsis in preterm very low birth weight neonates from low- and middle-income countries: a Bayesian network meta-analysis.zip

BackgroundProbiotics have been shown to reduce the risk of mortality and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) neonates. The probiotic species with the maximal benefits in neonates from low- and middle-income countries are unknown.
ObjectiveTo identify the strain of probiotics with the maximum benefit in preventing neonatal mortality, sepsis, and NEC using the Bayesian network meta-analysis.
Search methodsWe searched Medline via PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We also hand-searched reference lists of previous systematic reviews to identify eligible studies.
Selection criteriaRandomized controlled trials (RCTs) from LMICs comparing enteral supplementation of one or more probiotics with another probiotic species or placebo were included.
Data collection and analysisTwo authors screened the studies, extracted the data, and examined the risk of bias using the Cochrane risk of bias 2 (RoB 2) tools. Bayesian network meta-analysis was performed using the “BUGSnet” package in R and RStudio (version 1.4.1103). The confidence in the findings was assessed using the Confidence in Network Meta-analysis (CINeMA) web application.
ResultsTwenty-nine RCTs enrolling 4,906 neonates and evaluating 24 probiotics were included. Only 11 (38%) studies had a low risk of bias. All the studies compared the probiotics with a placebo; none had a head-to-head comparison of different probiotic species. Also, only one study each had evaluated most probiotic regimens. When compared to placebo, the combination of B longum, B bifidum, B infantis, and L acidophilus may reduce the risk of mortality (relative risk [RR] 0.26; 95% credible interval [CrI] 0.07 to 0.72), sepsis (RR 0.47; 95% CrI 0.25 to 0.83), and NEC (RR 0.31; 95% CrI 0.10 to 0.78) but the evidence is very uncertain. There is low certainty evidence that the single probiotic species, B lactis, could reduce the risk of mortality (RR 0.21; 0.05 to 0.66) and NEC (RR 0.09; 0.01 to 0.32).
ConclusionGiven the low to very low certainty of evidence for the efficacy of the two probiotics found to reduce mortality and necrotizing enterocolitis, no firm conclusions can be made on the optimal probiotics for use in preterm neonates in low- and middle-income countries.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353242, identifier: CRD42022353242.

研究背景：益生菌已被证实可降低极低出生体重（VLBW）新生儿的死亡及坏死性小肠结肠炎（NEC）发生风险。但目前尚不明确，在中低收入国家的新生儿中，哪种益生菌菌株可带来最大获益。
研究目的：采用贝叶斯网络meta分析，明确在中低收入国家新生儿中，预防新生儿死亡、败血症及坏死性小肠结肠炎（NEC）获益最优的益生菌菌株。
检索方法：通过PubMed检索Medline数据库、Embase数据库以及Cochrane对照试验中心注册库（CENTRAL）；同时手工检索既往系统评价的参考文献列表，以筛选符合纳入标准的研究。
纳入标准：纳入中低收入国家（LMICs）开展的随机对照试验（RCTs），对比一种或多种益生菌肠内补充与另一种益生菌菌株或安慰剂的研究。
数据收集与分析：由2名研究者独立筛选研究、提取数据，并采用Cochrane偏倚风险2（RoB 2）工具评估偏倚风险。采用R及RStudio（版本1.4.1103）中的"BUGSnet"包开展贝叶斯网络meta分析；使用网络meta分析置信度（CINeMA）网页应用评估研究结果的置信度。
研究结果：共纳入29项随机对照试验（RCTs），涉及4906名新生儿，评估了24种益生菌方案。其中仅11项研究（占比38%）的偏倚风险较低。所有研究均为益生菌与安慰剂的对比，未开展不同益生菌菌株间的头对头比较；且多数益生菌方案仅由1项研究评估。与安慰剂相比，长双歧杆菌（B longum）、双歧双歧杆菌（B bifidum）、婴儿双歧杆菌（B infantis）及嗜酸乳杆菌（L acidophilus）联合方案可降低新生儿死亡（相对危险度[RR] 0.26；95%可信区间[CrI] 0.07~0.72）、败血症（RR 0.47；95% CrI 0.25~0.83）及坏死性小肠结肠炎（NEC，RR 0.31；95% CrI 0.10~0.78）的发生风险，但该证据的不确定性极高。现有低置信度证据显示，单一益生菌菌株乳酸双歧杆菌（B lactis）可降低新生儿死亡（RR 0.21；95% CrI 0.05~0.66）及坏死性小肠结肠炎（NEC，RR 0.09；95% CrI 0.01~0.32）的发生风险。
研究结论：鉴于现有针对两种可降低新生儿死亡及坏死性小肠结肠炎风险的益生菌的证据置信度为低至极低，目前无法明确中低收入国家早产儿使用的最优益生菌方案。
系统评价注册信息：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353242，注册标识符：CRD42022353242。