The effectiveness of Lactobacillus reuteri on serum bilirubin levels in neonatal hyperbilirubinemia with phototherapy

  • Deska Andina Rezki USK
  • Isra Firmansyah Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital
  • Dora Darussalam Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital
  • Sulaiman Yusuf Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital
  • Nora Sovira
  • Bakhtiar Bakhtiar
Keywords: probiotics; L. reuteri; hyperbilirubinemia; full-term neonates; phototherapy


Background Hyperbilirubinemia occurs in 60% of full term and 80% of premature infants. Phototherapy is the main treatment, but it has side effects, sometimes requires hospitalization, and causes the baby to be separated from the mother. Underdeveloped gut microflora and increased enterohepatic circulation in newborns contribute to increased serum bilirubin levels in early life.

Objective To assess the efficacy of adding probiotic L. reuteri on phototherapy in full-term neonates with hyperbilirubinemia.

Methods In this double-blind, randomized clinical trial, full term infants with hyperbilirubinemia at Dr. Zainoel Abidin Hospital, Banda Aceh, Aceh, Indonesia, were randomly assigned to either an intervention or control group. All subjects received phototherapy. The intervention group was also given five drops of L. reuteri once a day orally before phototherapy started, while the control group received a placebo. Bilirubin levels after 24-hour phototherapy were evaluated in both groups.

Results A total of 42 term neonates met the inclusion criteria. The intervention group had a significantly greater decrease in total serum bilirubin (TSB) level (6,517 mg/dL) than did the control group (4,434 mg/dL) (P<0.001), as well in indirect bilirubin levels in the intervention group had decrease 6.40 mg/dL while in the control group 4.43 mg/dL after 24 hours of phototherapy (P<0.001).

Conclusion In full-term neonates with hyperbilirubinemia who underwent 24-hour phototherapy, adding probiotic L. reuteri leads to a significantly greater reduction in total and indirect bilirubin levels compared to the control group.


1. Gomella TL, Cunningham MD, Eyal FG. Hyperbilirubinemia. Neonatology: Management, procedures, on-call problems, diseases, and drugs. 5th ed. New York: Lange Medical Book/McGraw-Hill; 2013. p. 293-301.
2. Sukadi A. Hiperbilirubinemia. In: Kosim MS, Yunanto A, Dewi R, Sarosa GI, Usman A, editors. Buku ajar neonatologi. 1st ed. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia; 2008. p. 147-69.
3. Young Infants Clinical Signs Study Group. Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet. 2008;371:135–42. DOI:
4. Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM. Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, 1988-2005. Pediatrics. 2009;123:524–32. DOI:
5. Marcdante KJ, Kliegman R. Hyperbilirubinemia. In: Clarence W, Gowen J, editors. Nelson essentials of pediatrics. 8th ed. Philadelphia: Saunders; 2019. p. 672-9.
6. Hansen TW, Wong RJ, Stevenson DK. Molecular physiology and pathophysiology of bilirubin handling by the blood, liver, intestine, and brain in the newborn. Physiol Rev. 2020;100:1291-346. DOI:
7. Wrong RJGH, Sibley DG. Therapy of unconjugated hyperbilirubinemia. 8th ed. Philadelphia: Mosby; 2006. p. 1440–5.
8. Zahed Pasha Y, Ahmadpour-Kacho M, Ahmadi Jazi A, Gholinia H. Effect of probiotics on serum bilirubin level in term neonates with jaundice: a randomized clinical trial. Int J Pediatr. 2017;5:5925-30. DOI:
9. Tomashek KM, Crouse CJ, Iyasu S, Johnson CH, Flowers LM. A comparison of morbidity rates attributable to conditions originating in the perinatal period among newborns discharged from United States hospitals, 1989–90 and 1999–2000. Paediatr Perinat Epidemiol. 2006;20:24–34. DOI:
10. Chen K, Yuan T. The role of microbiota in neonatal hyperbilirubinemia. Am J Transl Res. 2020;12:7459–74. PMID: 33312382.
11. Dennery PA. Pharmacological interventions for the treatment of neonatal jaundice. In: Seminars in Neonatology. United States: WB Saunders. 2002;7:111-9. DOI:
12. Serce O, Gursoy T, Ovali F, Karatekin G. Effects of Saccharomyces boulardii on neonatal hyperbilirubinemia: a randomized controlled trial. Am J Perinatol. 2015;30:137-42. DOI:
13. Deshmukh J, Deshmukh M, Patole S. Probiotics for the management of neonatal hyperbilirubinemia: a systematic review of randomized controlled trials. J Matern Fetal Neonatal Med. 2019;32:154-63. DOI:
14. Armanian AM, Barekatain B, Hoseinzadeh M, Salehimehr N. Prebiotics for the management of hyperbilirubinemia in preterm neonates. J Matern Fetal Neonatal Med. 2016;29:3009–13. DOI:
15. Yang N, Yang RX, Wang AH, Zhang YQ. The effect of intestinal flora on the neural development of severe hyperbilirubinemia neonates. Eur Rev Med Pharmacol Sci. 2019;23:1291-5. DOI:
16. Vanderhoof JA, Young RJ. Pediatric applications of probiotics. Gastroenteral Clin North Am. 2005;34:451-63. DOI:
17. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297-316. DOI:
18. Torkaman M, Mottaghizadeh F, Khosravi MH, Najafian B, Amirsalari S, Afsharpaiman S. The effect of probiotics on reducing hospitalization duration in infants with hyperbilirubinemia. Iran J Pediatr. 2017;27:5096. DOI:
19. Ambalavanan N, Carlo WA. Jaundice and hyperbilirubinemia in the newborn. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, editors. Nelson textbook of pediatrics. 20th ed. Philadelphia: Saunders;2016. p. 871-80.
20. Drew JH, Marriage K, Bayle VV, Bajraszewski E, McNammara JM. Phototherapy. Short and long-term complications. Arch Dis Child. 1976;51:454–8. DOI:
21. LaRusso J, Wilson J, Ceilley R. Phototherapy-induced purpuric eruption in a neonate. J Clin Aesthet Dermatol. 2015;8:46–8. PMID: 25852815
22. Tan KL. Phototherapy for neonatal jaundice. Clin Perinatol. 1991;18:423–39. DOI:
23. Hansen TWR, Maisels MJ, Ebbesen F, Vreman HJ, Stevenson DK, Wong RJ, et al. Sixty years of phototherapy for neonatal jaundice–from serendipitous observation to standardized treatment and rescue for millions. J Perinatol. 2020;40:180–93. DOI:
24. Britton RA. Lactobacillus reuteri. The microbiota in gastrointestinal pathophysiology. Academic Press. 2017;1:89-97. DOI:
25. Srinivasan R, Kesavelu D, Veligandla KC, Muni SK, Mehta SC. Lactobacillus reuteri DSM 17938: review of evidence in functional gastrointestinal disorders. Pediatr Ther. 2018;8:2161-5. DOI:
26. Coccorullo P, Strisciuglio C, Martinelli M, Miele E, Greco L, Staiano A. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. J Pediatr. 2010;157:598-602. DOI:
27. Halloran K, Underwood MA. Probiotic mechanisms of action. Early Hum Dev. 2019;135:58-65. DOI:
28. Demirel G, Celik I, Erdeve O, Dilmen U. Impact of probiotics on the course of indirect hyperbilirubinemia and phototherapy duration in very low birth weight infants. J Matern Fetal Neonatal Med. 2013;26:215-8. DOI:
29. Mutlu M, Irmak E, Aslan Y, Kader S. Effects of Lactobacillus rhamnosus GG as a probiotic on neonatal hyperbilirubinemia. Turk J Pediatr. 2018;60:482-7. DOI: 10.24953/turkjped.2018.05.003.
30. Liu W, Liu H, Tang X. Therapeutic effects of probiotics on neonatal jaundice. Pak J Med Sci. 2015;31:1172-8. DOI:
31. Chen Z, Zhang L, Zeng L, Yang X, Jiang L, Gui G, et al. Probiotics supplementation therapy for pathological neonatal jaundice: a systematic review and meta-analysis. Front Pharmacol. 2017;8:432-6. DOI:
32. Goodarzi, Saadat S, Arshadzadeh M, Hengami NK, Darban B, Haghshenaz H. Efficacy and safety of probiotics in neonatal hyperbilirubinemia: randomized controlled trial. J Neonatal Nurs. 2021;6:432-8. DOI:
How to Cite
Rezki D, Firmansyah I, Darussalam D, Yusuf S, Sovira N, Bakhtiar B. The effectiveness of Lactobacillus reuteri on serum bilirubin levels in neonatal hyperbilirubinemia with phototherapy. PI [Internet]. 31Jul.2023 [cited 3Oct.2023];63(4):219-5. Available from:
Received 2022-04-12
Accepted 2023-07-31
Published 2023-07-31