Supplementary Material for: Enteral Feeding Strategies in Preterm Neonates ≤32 weeks Gestational Age: A Systematic Review and Network Meta-Analysis

<b><i>Introduction:</i></b> Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered. <b><i>Methods:</i></b> Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (&lt;72 h), moderately early (72 h–7 days), and late (&gt;7 days); advancement day: early (&lt;72 h), moderately early (72 h–7 days), and late (&gt;7 days); increment volume: small volume (SV) (&lt;20 mL/kg/day), moderate volume (MoV) (20–&lt; 30 mL/kg/day), and large volume (≥30 mL/kg/day); and full enteral feeding from the first day. Sixteen regimens were evaluated. Combined outcome of necrotizing enterocolitis (NEC) stage ≥ II or mortality before discharge was the primary outcome. <b><i>Results:</i></b> A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE–very low). <b><i>Conclusions:</i></b> Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted.<b><i>引言：</i></b> 早产儿（preterm neonates）肠内喂养启动时机、喂养进展速度及喂养增量体积的关键临床问题，目前仍未得到充分解答。<b><i>方法：</i></b> 本研究检索了Medline、Embase、CENTRAL及CINAHL数据库，检索时限从建库至2020年9月25日。采用贝叶斯方法（Bayesian approach）开展网络meta分析（network meta-analysis）。纳入评估胎龄≤32周早产儿的随机对照试验（Randomized Controlled Trial, RCT）。根据以下类别对喂养方案进行分类：喂养启动时机分为早期（＜72小时）、中度早期（72小时~7天）及晚期（＞7天）；喂养进展时机分为早期（＜72小时）、中度早期（72小时~7天）及晚期（＞7天）；喂养增量体积分为小容量组（SV，＜20mL/kg/天）、中容量组（MoV，20~＜30mL/kg/天）及大容量组（≥30mL/kg/天）；以及首日达成全肠内喂养方案。共计评估16种喂养方案。主要结局指标为坏死性小肠结肠炎（Necrotizing Enterocolitis, NEC）≥Ⅱ期或出院前死亡的复合结局。<b><i>结果：</i></b> 共计39项研究，纳入约6982名早产儿。与早期启动喂养（Early initiation, EI）且采用小容量增量、早期推进喂养的方案相比，采用中容量增量（Moderate volume, MoV）并早期启动喂养、中度早期或晚期推进喂养的肠内喂养方案，在降低NEC≥Ⅱ期或死亡风险方面效果最优（风险比[95%可信区间]：0.39[0.12, 0.95]；0.34[0.10, 0.86]）（GRADE分级证据质量极低）。<b><i>结论：</i></b> 早期启动喂养、采用中容量增量并中度早期或晚期推进喂养的方案，或是降低NEC≥Ⅱ期或死亡风险的最优方案。鉴于当前证据质量极低，需开展效力充足的随机对照试验（Randomized Controlled Trial, RCT）对这两类方案进行评估。