Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Synbiotics use for preventing sepsis and necrotizing enterocolitis in very low birth weight neonates: a randomized controlled trial

  • Pehlevan, Ozge Serce (Neonatology Unit, Zeynep Kamil Maternity and Children's Training and Research Hospital, University of Health Sciences) ;
  • Benzer, Derya (Neonatology Unit, Zeynep Kamil Maternity and Children's Training and Research Hospital, University of Health Sciences) ;
  • Gursoy, Tugba (Neonatology Unit, Koc University School of Medicine) ;
  • Karatekin, Guner (Neonatology Unit, Zeynep Kamil Maternity and Children's Training and Research Hospital, University of Health Sciences) ;
  • Ovali, Fahri (Neonatology Unit, Zeynep Kamil Maternity and Children's Training and Research Hospital, University of Health Sciences)
  • Received : 2019.04.26
  • Accepted : 2019.12.24
  • Published : 2020.06.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Probiotics and prebiotics have strain-specific effects on the host. Synbiotics, a mixture of probiotics and prebiotics, are proposed to have more beneficial effects on the host than either agent has alone. Purpose: We performed a randomized controlled trial to investigate the effect of Lactobacillus and Bifidobacterium together with oligosaccharides and lactoferrin on the development of necrotizing enterocolitis (NEC) or sepsis in very low birth weight neonates. Methods: Neonates with a gestational age ≤32 weeks and birth weight ≤1,500 g were enrolled. The study group received a combination of synbiotics and lactoferrin, whereas the control group received 1 mL of distilled water as placebo starting with the first feed until discharge. The outcome measures were the incidence of NEC stage ≥2 or late-onset cultureproven sepsis and NEC stage ≥2 or death. Results: Mean birth weight and gestational age of the study (n=104) and the control (n=104) groups were 1,197±235 g vs. 1,151±269 g and 29±1.9 vs. 28±2.2 weeks, respectively (P>0.05). Neither the incidence of NEC stage ≥2 or death, nor the incidence of NEC stage ≥2 or late-onset culture-proven sepsis differed between the study and control groups (5.8% vs. 5.9%, P=1; 26% vs. 21.2%, P=0.51). The only significant difference was the incidence of all stages of NEC (1.9% vs. 10.6%, P=0.019). Conclusion: The combination of synbiotics and lactoferrin did not reduce NEC severity, sepsis, or mortality.

Keywords

References

  1. Johnson-Henry KC, Abrahamsson TR, Wu RY, Sherman PM. Probiotics, prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Adv Nutr 2016;7:928-37. https://doi.org/10.3945/an.116.012237
  2. Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2020; CD007137.
  3. 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 Hum Dev 2013;89:1033-6. https://doi.org/10.1016/j.earlhumdev.2013.08.013
  4. Deshpande GC, Rao SC, Keil AD, Patole SK. Evidence-based guidelines for use of probiotics in preterm neonates. BMC Med 2011;9:92. https://doi.org/10.1186/1741-7015-9-92
  5. Dilli D, Aydin B, Fettah ND, Ozyazici E, Beken S, Zenciroglu A, et al. The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. J Pediatr 2015;166:545-51.e1. https://doi.org/10.1016/j.jpeds.2014.12.004
  6. Nandhini LP, Biswal N, Adhisivam B, Mandal J, Bhat B V, Mathai B. Synbiotics for decreasing incidence of necrotizing enterocolitis among preterm neonates: a randomized controlled trial. J Matern Fetal Neonatal Med 2016;29:821-5. https://doi.org/10.3109/14767058.2015.1019854
  7. Robinson J. Cochrane in context: probiotics for prevention of necrotizing enterocolitis in preterm infants. Evid Based Child Health 2014;9:672-4. https://doi.org/10.1002/ebch.1977
  8. Hartel C, Pagel J, Rupp J, Bendiks M, Guthmann F, Rieger-Fackeldey E, et al. Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants. J Pediatr 2014;165:285-9.e1. https://doi.org/10.1016/j.jpeds.2014.04.029
  9. Duffield SD, Clarke P. Current use of probiotics to prevent necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed 2019;104:F228. https://doi.org/10.1136/archdischild-2018-316199
  10. Ovali F. Intrauterine growth curves for Turkish infants born between 25 and 42 weeks of gestation. J Trop Pediatr 2003;49:381-3. https://doi.org/10.1093/tropej/49.6.381
  11. Walsh MC, Kliegman RM, Fanaroff AA. Necrotizing enterocolitis: a practitioner's perspective. Pediatr Rev 1988;9:219-26. https://doi.org/10.1542/pir.9-7-219
  12. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529-34. https://doi.org/10.1016/S0022-3476(78)80282-0
  13. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9. https://doi.org/10.1164/ajrccm.163.7.2011060
  14. van den Akker CH, van Goudoever JB, Szajewska H, Embleton ND, Hojsak I, Reid D, et al. Probiotics for preterm infants: a strain-specific systematic review and network meta-analysis. J Pediatr Gastroenterol Nutr 2018;67:103-22. https://doi.org/10.1097/MPG.0000000000001897
  15. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2014; CD005496.
  16. Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010;125:921-30. https://doi.org/10.1542/peds.2009-1301
  17. Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very low-birth-weight infants: an updated meta-analysis of 20 randomized, controlled trials. J Pediatr Surg 2012;47:241-8. https://doi.org/10.1016/j.jpedsurg.2011.09.064
  18. Ofek Shlomai N, Deshpande G, Rao S, Patole S. Probiotics for preterm neonates: what will it take to change clinical practice? Neonatology 2014;105:64-70. https://doi.org/10.1159/000354891
  19. Mihatsch WA, Braegger CP, Decsi T, Kolacek S, Lanzinger H, Mayer B, et al. Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants. Clin Nutr 2012;31:6-15. https://doi.org/10.1016/j.clnu.2011.09.004
  20. Baucells BJ, Mercadal Hally M, Alvarez Sanchez AT, Figueras Aloy J. Probiotic associations in the prevention of necrotising enterocolitis and the reduction of late-onset sepsis and neonatal mortality in preterm infants under 1,500g: a systematic review. An Pediatr (Barc) 2016;85:247-55. https://doi.org/10.1016/j.anpedi.2015.07.038
  21. Costeloe K, Hardy P, Juszczak E, Wilks M, Millar MR; Probiotics in Preterm Infants Study Collaborative Group. Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial. Lancet 2016;387:649-60. https://doi.org/10.1016/S0140-6736(15)01027-2
  22. 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:e0171579. https://doi.org/10.1371/journal.pone.0171579
  23. Ortega-Gonzalez M, Ocon B, Romero-Calvo I, Anzola A, Guadix E, Zarzuelo A, et al. Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of $TLR4-NF{\kappa}B$. Mol Nutr Food Res 2014;58:384-93. https://doi.org/10.1002/mnfr.201300296
  24. Srinivasjois R, Rao S, Patole S. Prebiotic supplementation in preterm neonates: updated systematic review and meta-analysis of randomised controlled trials. Clin Nutr 2013;32:958-65. https://doi.org/10.1016/j.clnu.2013.05.009
  25. Jantscher-Krenn E, Zherebtsov M, Nissan C, Goth K, Guner YS, Naidu N, et al. The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut 2012;61:1417-25. https://doi.org/10.1136/gutjnl-2011-301404
  26. Sreenivasa B, Sunil Kumar P, Suresh Babu MT, Ragavendra K. Role of synbiotics in the prevention of necrotizing enterocolitis in preterm neonates: a randomized controlled trial. Int J Contemp Pediatr 2015;2:127-30. https://doi.org/10.5455/2349-3291.ijcp20150512
  27. D'Souza A, Cai CL, Kumar D, Cai F, Fordjour L, Ahmad A, et al. Cytokines and toll-like receptor signaling pathways in the terminal ileum of hypoxic/hyperoxic neonatal rats: benefits of probiotics supplementation. Am J Transl Res 2012;4:187-97.
  28. D'Souza A, Fordjour L, Ahmad A, Cai C, Kumar D, Valencia G, et al. Effects of probiotics, prebiotics, and synbiotics on messenger RNA expression of caveolin-1, NOS, and genes regulating oxidative stress in the terminal ileum of formula-fed neonatal rats. Pediatr Res 2010;67:526-31. https://doi.org/10.1203/PDR.0b013e3181d4ff2b
  29. Kadlec R, Jakubec M. The effect of prebiotics on adherence of probiotics. J Dairy Sci 2014;97:1983-90. https://doi.org/10.3168/jds.2013-7448
  30. Manzoni P, Dall'Agnola A, Tome D, Kaufman DA, Tavella E, Pieretto M, et al. Role of lactoferrin in neonates and infants: an update. Am J Perinatol 2018;35:561-5. https://doi.org/10.1055/s-0038-1639359
  31. Whelan K, Myers CE. Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials. Am J Clin Nutr 2010;91:687-703. https://doi.org/10.3945/ajcn.2009.28759
  32. Meyer MP, Alexander T. Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. J Neonatal Perinatal Med 2017;10:249-55. https://doi.org/10.3233/NPM-16130
  33. Topcuoglu S, Gursoy T, Ovali F, Serce O, Karatekin G. A new risk factor for neonatal vancomycin-resistant Enterococcus colonisation: bacterial probiotics. J Matern Fetal Neonatal Med 2015;28:1491-4. https://doi.org/10.3109/14767058.2014.958462

Cited by

  1. Current and Future Perspectives on the Role of Probiotics, Prebiotics, and Synbiotics in Controlling Pathogenic Cronobacter Spp. in Infants vol.12, 2020, https://doi.org/10.3389/fmicb.2021.755083
  2. Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies vol.13, pp.5, 2020, https://doi.org/10.3390/nu13051726
  3. Probiotics for the Management of Sepsis: Advances in Animal Models and Intensive Care Unit Environments vol.12, pp.3, 2020, https://doi.org/10.3390/microbiolres12030039