Supplementary Material for: Meconium Evacuation for Facilitating Feed Tolerance in Preterm Neonates: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> A delayed passage of meconium is considered as a risk factor for feed intolerance in preterm neonates. <b><i>Objectives:</i></b> The aim of this study was to review the effects of different therapeutic agents for meconium evacuation on feed tolerance in preterm neonates. <b><i>Methods:</i></b> A systematic review of randomised controlled trials (RCTs) of different therapeutic agents for meconium evacuation in preterm neonates (gestation &lt;32 weeks and/or birth weight &lt;1,500 g) using the Cochrane systematic review methodology was undertaken. Databases including Google Scholar were searched in January 2016. The primary outcome was the time to reach full feeds (TFF; ≥120 ml/kg feeds with stoppage of parenteral nutrition &gt;24 h). Secondary outcomes included necrotising enterocolitis (NEC), weight at discharge and adverse effects. The results were summarised as per the GRADE guidelines. <b><i>Results:</i></b> Six RCTs (2 each of glycerine suppository and enema, 1 normal saline enema and 1 oral osmotic contrast agent; n = 442) with a low or unclear risk of bias were included. The pooled estimate (random effects model) showed no reduction in TFF [mean difference (MD) -0.03, 95% CI -2.47, 2.41, p = 0.98; level of evidence: low]. No differences in NEC [risk ratio (RR) 1.71, 95% CI 0.63, 4.65, p = 0.30; level of evidence: low] and weight at discharge (MD -0.08, 95% CI -0.30, 0.15, p = 0.50; level of evidence: low) were found. The trial assessing oral osmotic contrast agents reported a trend towards a higher incidence of NEC ≥ stage II. There were no other adverse effects. <b><i>Conclusion:</i></b> Limited low-quality evidence indicates that prophylactic glycerine suppository, small volume glycerine/normal saline enema or oral osmotic contrast agents to evacuate meconium did not reduce TFF in preterm neonates. Large, well-designed trials are essential to study this clinically significant issue.

背景：胎粪排出延迟被认为是早产儿喂养不耐受的危险因素。
目的：本研究旨在系统评价不同促胎粪排出治疗药物对早产儿喂养耐受性的影响。
方法：采用Cochrane系统评价方法，针对胎龄<32周且/或出生体重<1500g的早产儿开展不同促胎粪排出治疗药物的随机对照试验（randomised controlled trials, RCTs）系统综述。于2016年1月检索包括Google Scholar在内的多个数据库。主要结局指标为达到全肠内喂养的时间（time to reach full feeds, TFF；即肠内喂养量≥120ml/kg且停止肠外营养≥24小时）。次要结局指标包括坏死性小肠结肠炎（necrotising enterocolitis, NEC）、出院时体重及不良反应。研究结果依据GRADE指南进行总结。
结果：最终纳入6项随机对照试验（甘油栓剂、灌肠方案各2项，生理盐水灌肠剂1项，口服渗透性造影剂1项；共442例受试者），偏倚风险均为低或不明确。合并分析（随机效应模型）显示，两组间达到全肠内喂养的时间无显著缩短[均差（mean difference, MD）=-0.03，95%置信区间（confidence interval, CI）：-2.47~2.41，p=0.98；证据等级：低级别]。在坏死性小肠结肠炎发生率[风险比（risk ratio, RR）=1.71，95%CI：0.63~4.65，p=0.30；证据等级：低级别]及出院时体重[MD=-0.08，95%CI：-0.30~0.15，p=0.50；证据等级：低级别]方面，两组亦无显著差异。评估口服渗透性造影剂的试验提示，Ⅱ期及以上坏死性小肠结肠炎的发生率存在升高趋势。未观察到其他不良反应。
结论：现有有限的低质量证据表明，预防性使用甘油栓剂、小剂量甘油/生理盐水灌肠剂或口服渗透性造影剂以促进胎粪排出，并未缩短早产儿达到全肠内喂养的时间。未来需开展大规模、设计严谨的临床试验，以深入探究这一具有临床意义的课题。