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 <32 weeks and/or birth weight <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 >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.