Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Preterm Infants with Probiotics: A Systematic Review and Meta-analysis

Document Type: Meta-Analysis


Faculty of Medicine Kristen Krida Wacana University, Jakarta, Indonesia


Introduction:Previous studies have shown that probiotics reduce the incidence of Necrotizing enterocolitis (NEC) and sepsis; while other studies have not shown a significant difference of NEC and sepsis incidence.  To this date there is still no protocols or guidelines in regards to the use of routine probiotics in very low birth weight preterm infants.
Method: The present study was a meta-analysis research. Up to date RCTs were reviewed to see the effectiveness of probiotics in order to prevent necrotizing enterocolitis. Studies were searched through PubMed, ProQuest, and Cochrane Library searching engines from 2009 to 2019.
This meta-analysis was assessed according to PRISMA guidelines.
The inclusion criteria were randomized controlled trials of probiotics for very low birth weight preterm babies; full text English articles; and having been published from 2009 to 2019.
Results: The findings of this study reveal that the incidence of NEC in the probiotic group was significantly low (p= <0.00001, R=0.48). In the subgroup analysis, the incidence of NEC was lower in the multiple strain group and Lactobacillus group with a P value of p= 0.0004 and 0.006 respectively. The incidence of sepsis was lower in the probiotic group with a P value of p= 0.02. Also, the incidence of all-cause mortality was lower in the probiotic group with a P value of p= 0.02.
Conclusion: According to the results of the present study, it can be stated that it is beneficial to use multiple strain probiotics and Lactobacillus strain probiotics to prevent necrotizing enterocolitis in very low birth weight preterm babies. 


1. Serce O, Benzer D, Gursoy T, Karatekin G, Ovali F. Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Early human development. 2013;89(12):1033-6. doi:10.1016/j.erlhumdev.2013.08.013
2. Damirel G, Erdeve O, Celik IH, Dilmen U. Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm infants: a randomized, controlled study. Acta Paediatrica. 2013; 102:e560-565. doi:10.1111/apa.12416
3. Braga TD, da Silva GA, de Lira PI, de Carvalho Lima M. Efficacy of Bifidobacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight preterm infants: a double-blind, randomized, controlled trial. The American journal of clinical nutrition. 2010;93(1):81-6. doi: 10.3945/ajcn.2010.29799.
4. Fernández-Carrocera LA, Solis-Herrera A, Cabanillas-Ayón M, Gallardo-Sarmiento RB, García-Pérez CS, Montaño-Rodríguez R, et al. Double-blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1500 g in the prevention of necrotising enterocolitis. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2013;98(1):F5-9. doi:10.1136/archdischild-2011-300435.
5. Oncel MY, Sari FN, Arayici S, Guzoglu N, Erdeve O, Uras N, et al. Lactobacillus reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2014 Mar 1;99(2):F110-5. doi:10.1136/archdischild-2013-304745.
6. Sari FN, Dizdar EA, Oguz S, Erdeve O, Uras N, Dilmen U. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial. European Journal of Clinical Nutrition. 2011;65(4):434. doi:10.1038/ejcn.2010.278
7. Manzoni P, Meyer M, Stolfi I, Rinaldi M, Cattani S, Pugni L, et al. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early human development. 2014 Mar 1;90:S60-5. doi: 10.1016/S0378-3782(14)70020-9.
8. Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi SN, Pirotta M, Morley CJ, Garland SM. Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics. 2013;132(6):1055-62. doi:10.1542/peds.2013-1339
9. Varal IG, Koksal N. Ozkan H, Bagci O, Dogan P. The effect of early administration of combined multi-strain and multi-species probiotics on gastrointestinal morbidities and mortality in preterm infants: A randomized controlled trial in a tertiary car unit. The Turkish Journal of Pediatrics. 2017; 59:13-19. doi: 10.24953/turkjped.2017.01.003
10. Underwood MA. Impact of probiotics on necrotizing enterocolitis. InSeminars in perinatology 2017;41(1):41-51. WB Saunders. doi:10.1053/j.semperi.2016.09.017
11. Lau CS, Chamberlain RS. Probiotic administration can prevent necrotizing enterocolitis in preterm infants: a meta-analysis. Journal of pediatric surgery. 2015;50(8):1405-12. doi:10.1016/j.jpedsurg.2015.05.008
12. Sawh SC, Deshpande S, Jansen S, Reynaert CJ, Jones PM. Prevention of necrotizing enterocolitis with probiotics: a systematic review and meta-analysis. PeerJ. 2016;4:e2429. doi:10.7717/peerj.2429
13. Chang HY, Chen JH, Chang JH, Lin HC, Lin CY, Peng CC. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis. PLoS One. 2017;12(2):e0171579. doi:10.1371/journal.pone.0171579
14. Dermyshi E, Wang Y, Yan C, Hong W, Qiu G, Gong X, et al. The “golden age” of probiotics: a systematic review and meta-analysis of randomized and observational studies in preterm infants. Neonatology. 2017;112(1):9-23. doi:10.1159/000454668