Preventing necrotizing enterocolitis by food additives in neonates A network meta-analysis revealing the efficacy and safety

Background: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics+fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Methods: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. Results: A total of 27 eligible studies with 4649 preterm infants were included in this network meta- analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR=0.50, 95% CrIs: 0.32-0.73; OR=0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR=0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR=0.13, 95% CrIs: 0.03-0.61) or probiotic (OR=0.18, 95% CrIs: 0.03-0.83). Conclusion: Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.