The Impact of Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Infants Treated with Photo-therapy: A Single-Blind Randomized Clinical Trial

Document Type : Original Article

Authors

1 Neonatal and Children’s Health Research Center, Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran

2 Neonatal and Children’s Health Research Center , Golestan University of Medical Sciences, Gorgan, Iran

3 Neonatal and Children and rsquo, Health Research Center, Clinical Research Development Unit (CRDU), Sayad Shirazi Hospital Golestan University of Medical Sciences, Gorgan, Iran Golestan University of Medical Sciences, Gorgan, Iran

10.22038/ijn.2024.76943.2490

Abstract

Background: Infantile jaundice affects up to 84% of term infants and is a primary cause of re-hospitalization. Phototherapy, the primary therapeutic intervention, may be associated with several complications. Therefore, employing additional compensatory therapies could reduce the duration of phototherapy and its adverse effects.
Methods: A single-blind randomized clinical trial was conducted on newborns with indirect hyperbilirubinemia (IHB) undergoing phototherapy. Patients were randomly assigned to two groups: the intervention group received phototherapy and 10mg/kg of Ursodeoxycholic acid, taken twice a day with water as the solvent, while the control group received phototherapy and a placebo (water). Total bilirubin levels were measured every 12 hours, and the groups were compared regarding the reduction duration of bilirubin <10 mg/dl and the duration of phototherapy. Data analysis used SPSS-V22 software, with statistical tests done at a significance level of <0.05.
Results: In total, 128 neonates, comprising 56 (43.8%) males and 72 (56.2%) females, with a mean gestational age of 39.02±0.86 weeks and a mean age of 2.77±1.45 days, were subjected to analysis. After 96 hours, the mean bilirubin level was 9.23±2.81 mg/dl overall, 7.27±2.12 mg/dl in the case group, and 10.91±2.17 mg/dl in the control group (p<0.001). The mean time to reach a bilirubin level below 10 mg/dl was 51.66±17.27 hours overall, 58.38±10.05 hours for the case group, and 62.61±14.39 hours for the control group (p<0.001).
Conclusion: Ursodeoxycholic acid (UDCA) effectively reduces elevated bilirubin levels and the duration of phototherapy when employed as an adjunct treatment to phototherapy in cases of infantile indirect hyperbilirubinemia.
 

Keywords

References

  1. Muchowski KE. Evaluation and Treatment of Neonatal Hyperbilirubinemia. Am Fam Physician. 2014;89(11):873-878.
  2. Faulhaber FRS, Procianoy RS, Silveira RC. Side Effects of Phototherapy on Neonates. Am J Perinatol. 2019;36(3):252-257.
  3. Drew JH, Marriage K, Bayle VV, Bajraszewski E, McNammara JM. Phototherapy. Short and Long-term Complications. Arch Dis Child. 1976; 51(6):454-458.
  4. Kemper AR, Newman TB, Slaughter JL, Maisels MJ, Watchko JF, Downs SM, et al. Clinical Practice Guideline Revision: Management of Hyper-bilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2022;150(3):
  5. Krenitsky A, Ghamrawi RI, Feldman SR. Phototherapy: A Review and Update of Treatment Options in Dermatology. Curr Dermatol Rep. 2020;9:10-21.
  6. Ahmadpour-kacho M, Zahed Pasha Y, Ranjbar B, Pouramir M, Hajian K, Pounasrollah M. The Effect of Oral Zinc Sulfate on Serum Bilirubine Level in Term Neonates with Jaundice. Int J Pediatr. 2017; 5(6):5053-50
  7. 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(1):5
  8. Cifuentes-Silva E, Cabello-Verrugio C. Bile Acids as Signaling Molecules: Role of Ursodeoxycholic Acid in Cholestatic Liver Disease. Curr Protein Pept Sci. 2024;25(3):206-214.
  9. Reardon J, Hussaini T, Alsahafi M, Azalgara VM, Erb SR, Partovi N, et al. Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review. J Clin Transl Hepatol. 2016;4(3):192-205.
  10. Steinacher D, Claudel T, Trauner M. Therapeutic Mechanisms of Bile Acids and Nor-Ursodeoxycholic Acid in Non-Alcoholic Fatty Liver Disease. Dig Dis. 2017;35(3):282-287.
  11. Kriegermeier A, Green R. Pediatric Cholestatic Liver Disease: Review of Bile Acid Metabolism and Discussion of Current and Emerging Therapies. Front Med (Lausanne). 2020;7:149.
  12. Wang JY, Wu SD. Ursodeoxycholic acid for the treatment of liver diseases. InLiver Pathophysiology 2017;767-779. Academic Press.
  13. Honar N, Ghashghaei Saadi E, Saki F, Pishva N, Shakibazad N, Hosseini Teshnizi S. Effect of Ursodeoxycholic Acid on Indirect Hyperbili-rubinemia in Neonates Treated With Phototherapy. J Pediatr Gastroenterol Nutr. 2016;62(1):97-100.
  14. Mirzarahimi M, Barak M, Moghaddam SS, Moghaddam EE. Effect of Ursodeoxycholic Acid (USDA) on Indirect Hyperbilirubinemia in Neonates Treated with Phototherapy. Progress Asp Pediatr Neonatol. 2019;2(3):138-1
  15. Shahramian I, Tabrizian K, Ostadrahimi P, Afshari M, Soleymanifar M, Bazi A. Therapeutic Effects of Ursodeoxycholic Acid in Neonatal Indirect Hyperbilirubinemia: A Randomized Double-blind Clinical Trial. Arch Anesthesiol Crit Care. 2019;5(3):99-103.
  16. Akefi R, Hashemi SM, Alinejad S, Almasi-Hashiani A. The Effect of Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Neonates Treated with Phototherapy: A Randomized Clinical Trial. J Matern Fetal Neonatal Med. 2022;35(21):4075-4080.
  17. Jafari S, Khan KA, Bhatnagar S, Srivastava G, Nanda C, Chandra A. Role of Ursodeoxycholic Acid in Neonates with Indirect Hyperbilirubinemia-an Open Labelled Randomised Control Trial. Int J Contemp Pediatr. 2018;5(2):432-43
  18. Watchko JF, Tiribelli C. Bilirubin-Induced Neurologic Damage--Mechanisms and Management Approaches. N Engl J Med. 2013;369(21):2021-2030.
  19. Kafory A, El-Sayed E, El-Gendy FM, Bahbah WA. Effect of Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Neonates Treated with Phototherapy. Menoufia Med 2019;32(3):1059-1063.
  20. Hassan AM, Abdulrahman A, Husain RH. Effect of Ursodeoxycholic Acid in Lowering Neonatal Indirect Hyperbilirubinemia: A Randomized Controlled Trial. Merit Res J Med Med Sci. 2015;3(9):402-40
  21. Ughasoro MD, Adimorah GN, Chukwudi NK, Nnakenyi ID, Iloh KK, Udemba CE. Reductive Effect of Ursodeoxycholic Acid on Bilirubin Levels in Neonates on Phototherapy. Clin Exp Gastroenterol. 2019;12:349-354.
  22. Kuitunen I, Kiviranta P, Sankilampi U, Renko M. Ursodeoxycholic Acid as Adjuvant Treatment to Phototherapy for Neonatal Hyperbilirubinemia: A Systematic Review and Meta-analysis. World J Pediatr. 2022;18(9):589-597.
  23. Lazarus G, Francie J, Roeslani RD, Saldi SRF, Oswari H. Role of Ursodeoxycholic Acid in Neonatal Indirect Hyperbilirubinemia: A Systematic Review and Meta-analysis of randomized Controlled Trials. Ital J Pediatr. 2022;48(1):179.
  24. Zadkarami M, Rahimpour F, Hardani AK, Javaherizadeh H. Ursodeoxycholic acid and phototherapy versus phototherapy and placebo on neonatal indirect hyperbilirubinemia. Immunopathol 2023.
  25. Bhatia V, Bavdekar A, Matthai J, Waikar Y, Sibal A. Management of Neonatal Cholestasis: Consensus Statement of the Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics. Indian Pediatr. 2014;51(3):203-210.
  26. Zarkesh M, Mahdipour S, Aghili S, Jafari A, Nouri SAH, Hassanzadeh Rad A, et al. Evaluation of Therapeutic Effect of Oral Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Term Neonates Undergoing Phototherapy: A Randomized Controlled Clinical Trial. PLoS One. 2023;18(12):e0273516. 

 

Iranian Journal of Neonatology
Volume 15, Issue 4
October 2024
Pages 17-23

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