Iranian Journal of Neonatology

Iranian Journal of Neonatology

The Effect of Probiotics on Milk Tolerance and Prevention of Necrotizing Enterocolitis in Premature Infants Admitted to the Neonatal Intensive Care Unit of Bentolhoda Hospital in Bojnurd, Iran, in 2021-2022

Document Type : Original Article

Authors
Ghasem Bayani
Hojatollah Ehteshammanesh
Shahin Mafinejad
Fateme kamali
Mona Akbarian Sanavi
North Khorasan University of Medical Sciences, Bojnurd, Iran
10.22038/ijn.2026.86291.2663
Abstract
Background: Necrotizing enterocolitis is the most common gastrointestinal emergency in infants. If not treated promptly, it can progress to necrosis, rupture, peritonitis, sepsis, and death. Therefore, the use of probiotics can have health benefits.
Methods: This double-blind clinical trial was conducted on 86 premature infants admitted to the neonatal intensive care unit of Bentolhoda Hospital in Bojnurd, Iran, in 2021-2022. In this study, premature infants were randomly assigned to control and intervention groups. In the intervention group, after the infant's feeding volume reached 5 cc per kilogram of body weight per day, oral probiotics at a dose of one drop per kilogram of body weight, diluted with normal saline to a volume of 0.5 cc, were administered every 12 hours for 3 weeks.
Results: There was no statistically significant difference between the two groups in terms of variables such as weight at admission, weight at discharge, length at discharge, and head circumference at discharge. However, a statistically significant difference was observed in terms of the difference in weight between admission and discharge, as well as the duration of hospital stay. The average difference in weight between admission and discharge in the intervention group was approximately 90 grams greater than that in the control group. Also, the average duration of hospital stay in the intervention group was approximately 8 days less than that in the control group.
Conclusion: The use of probiotics in premature infants prevents necrotizing enterocolitis and shortens the time to reach full enteral feeding and the duration of hospital stay.
 
Keywords
Enterocolitis
Infant
Milk tolerance
Necrotizing
Premature
Probiotics
  1. Berken JA, Chang J. Neurologic Consequences of Neonatal Necrotizing Enterocolitis. Dev Neurosci. 2022;44(4-5):295-308.
  2. Klerk DH, van Varsseveld OC, Offringa M, Modi N, Lacher M, Zani A, et al. Development of an international core outcome set for treatment trials in necrotizing enterocolitis-a study protocol. Trials. 2023;24(1):367.
  3. Robertson C, Savva GM, Clapuci R, Jones J, Maimouni H, Brown E, et al. Incidence of necrotising enterocolitis before and after introducing routine prophylactic Lactobacillus and Bifidobacterium Arch Dis Child Fetal Neonatal Ed. 2020;105(4):380-386.
  4. Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr. 2017;17(1):105.
  5. Underwood MA. Probiotics and the prevention of necrotizing enterocolitis. J Pediatr Surg. 2019;54(3):405-412.
  6. Patel RM, Underwood MA. Probiotics and necrotizing enterocolitis. Semin Pediatr Surg. 2018;27(1):39-46.
  7. Murphy K, Ross RP, Ryan CA, Dempsey EM, Stanton C. Probiotics, prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Front Nutr. 2021;8:667188.
  8. Rolnitsky A, Ng E, Asztalos E, Shama Y, Karol D, Findlater C, et al. A quality improvement intervention to reduce necrotizing enterocolitis in premature infants with probiotic supplementation. Pediatr Qual Saf. 2019;4(5):e201.
  9. Javadi F, Shah Farhat A, Saeidi R, Mohammadzadeh A, Bakhtiari E, Kordkatouli M. Effectiveness of probiotics in treating jaundice in low birth weight infants at Imam Reza Hospital. Zahedan J Res Med Sci. 2025;27(4):e165554.
  10. Stewart CJ, Cummings SP. Gut bacteria and necrotizing enterocolitis: cause or effect? Trends Microbiol. 2015;23(6):332-333.
  11. Kaplina A, Kononova S, Zaikova E, Pervunina T, Petrova N, Sitkin S. Necrotizing enterocolitis: The role of hypoxia, gut microbiome, and microbial metabolites. Int J Mol Sci. 2023;24(3):2471.
  12. Uberos J, Aguilera-Rodríguez E, Jerez-Calero A, Molina-Oya M, Molina-Carballo A, Narbona-López E. Probiotics to prevent necrotising enterocolitis and nosocomial infection in very low birth weight preterm infants. The British journal of nutrition. 2017;117(7):994-1000.
  13. Bayani G, Mafinezhad S, Ehteshammanesh H, Sharifian E, Esmati M, Akbarian Sanavi M, et al. Effect of probiotics on enteral milk tolerance and prevention of necrotizing enterocolitis in preterm neonates. Iran J Neonatol. 2021;12(2):89-94.
  14. Bi LW, Yan BL, Yang QY, Li MM, Cui HL. Which is the best probiotic treatment strategy to prevent the necrotizing enterocolitis in premature infants: A network meta-analysis revealing the efficacy and safety. Medicine. 2019;98(41):
  15. Qasemi A, Lagzian M, Rahimi F, Majd FK, Bayat Z. The power of probiotics to combat urinary tract infections: A comprehensive review. Res Biotechnol Environ Sci. 2023;2(1):1-11.
  16. Gray KD, Messina JA, Cortina C, Owens T, Fowler M, Foster M, et al. Probiotic Use and Safety in the Neonatal Intensive Care Unit: A Matched Cohort Study. J Pediatr. 2020;222:59-64.e1.
  17. Dehghan K, Karimi S, Alilu L. The Effect of Probiotics on Late-Onset Sepsis in Very Preterm Infants: A Randomized Clinical Trial. Int J Pediatr. 2018;6(10):8371-83
  18. 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.
  19. Li D, Rosito G, Slagle T. Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year retrospective cohort study. J Clin Pharm Ther. 2013;38(6):445-44
  20. Garg BD, Balasubramanian H, Kabra NS, Bansal A. Effect of oropharyngeal colostrum therapy in the prevention of necrotising enterocolitis among very low birthweight neonates: A meta-analysis of randomised controlled trials. J Hum Nutr Diet. 2018;31(5):612-624.
  21. Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2020;10(10):CD005496.
  22. Bonsante F, Iacobelli S, Gouyon JB. Routine probiotic use in very preterm infants: retrospective comparison of two cohorts. Am J Perinatol. 2013;30(1):41-46.
  23. Norishadkam M, Naghibifard F, Mostaghasi M. The Effect of oral probiotics in prevention of necrotizing enterocolitis in premature neonates. J Shahid Sadoughi Univ Med Sc. 2015;23(3):2032-2039(persian).
  24. Granger CL, Embleton ND, Palmer JM, Lamb CA, Berrington JE, Stewart CJ. Maternal breastmilk, infant gut microbiome and the impact on preterm infant health. Acta paediatrica (Oslo, Norway : 1992). 2021;110(2):450-45
  25. Aceti A, Gori D, Barone G, Callegari ML, Di Mauro A, Fantini MP, et al. Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis. Ital J Pediatr. 2015;41:89.
  26. Koohsari H, Farifteh M, Sadegh Shesh Poli M, Kordkatouli M. Evaluation of the probiotic potential of Lactobacillus brevis and Lactococcus lactis isolated from yellow curd native to southeast Iran. Microbes Infect Dis. 2025;6(3):2095-3004..
  27. Samara J, Moossavi S, Alshaikh B, Ortega VA, Pettersen VK, Ferdous T, et al. Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants. Cell Host Microbe. 2022;30(5):696-711.e5.
  28. Dai Y, Yu Q, Zhang F, Ma K, Yan X, Chen W, et al. Effect of probiotics on necrotizing enterocolitis in preterm infants: A network meta-analysis of randomized controlled trials. BMC Pediatr. 2025;25(1):237.
  29. Jin YT, Duan Y, Deng XK, Lin J. Prevention of necrotizing enterocolitis in premature infants - an updated review. World J Clin Pediatr. 2019;8(2):23-32.
  30. Samanta M, Sarkar M, Ghosh P, Ghosh J, Sinha M, Chatterjee S. Prophylactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns. J Trop Pediatr. 2009;55(2):128-1
  31. 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. Am J Clin Nutr. 2011;93(1):81-86.
  32. Bernardo WM, Aires FT, Carneiro RM, Sá FPd, Rullo VEV, Burns DA. Effectiveness of probiotics in the prophylaxis of necrotizing enterocolitis in preterm neonates: A systematic review and meta-analysis. J Pediatr (Rio J). 2013;89(1):18-24.

 

 

 

Iranian Journal of Neonatology
Volume 17, Issue 2
Spring 2026
Pages 3-12