Therapeutic Effects of Ursodeoxycholic Acid in Neonatal Indirect Hyperbilirubinemia: A Randomized Double-blind Clinical Trial

  • Iraj Shahramian
  • Kaveh Tabrizian
  • Pouya Ostadrahimi
  • Mahdi Afshari
  • Mahdieh Soleymanifar
  • Ali Bazi
Keywords: Unconjugated hyperbilirubinemia, Ursodeoxycholic acid, Phototherapy


Background: Ursodeoxycholic acid (UDCA) is a safe drug used in the treatment of cholestatic liver disorders in children. The aim of this study was to investigate the synergistic effect of UDCA in combination with phototherapy in treating indirect neonatal hyperbilirubinemia. Methods: Present double-blinded, randomized clinical trial was conducted among neonates with jaundice who were under treatment with phototherapy in the neonatal ward affiliated with the Zabol University of Medical Sciences in 2017. The patients (200 neonates) were randomly divided into intervention (phototherapy+ UDCA) and control (phototherapy alone) groups. The intervention group received 15 mg/kg UDCA daily. Results: Total bilirubin levels at birth, 24, 48, and 72 hours after therapy were 16.89± 2.49, 14.28± 2.05, 11.62± 2.46, and 10.26± 1.92 mg/dl in controls and 15.79± 2.18, 12.77± 1.86, 10.08± 1.66, and 8.94± 1.38 mg/dl in intervention group respectively (P< 0.001). The ratio of neonates with total bilirubin< 10 mg/dl were 28% and 55% after 48 hours, and 64% and 90% after 72 hours of therapy initiation in phototherapy alone and phototherapy+ UDCA groups respectively (P< 0.001). The mean reduction of direct bilirubin was not significantly different between the groups. Conclusion: UDCA was effective in accelerating reduction of total bilirubin level in neonates with unconjugated hyperbilirubinemia under phototherapy but had no effect on direct bilirubin levels.


1. Chen J, Sadakata M, Ishida M, Sekizuka N, Sayama M. Baby massage ameliorates neonatal jaundice in full-term newborn infants. Tohoku J Exp Med. 2011; 223(2):97-102.
2. Ho NK. Neonatal jaundice in Asia. Baillieres Clin Haematol. 1992;5(1):131-42.
3. Maisels MJ. Neonatal jaundice. Pediatrics in Review. 2006; 27(12):443.
4. Jackson JC. Adverse events associated with exchange transfusion in healthy and ill newborns. Pediatrics. 1997;99(5):e7-e.
5. Ramy N, Ghany E, Alsharany W, Nada A, Darwish R, Rabie W, et al. Jaundice, phototherapy and DNA damage in full-term neonates. J Perinatol. 2016; 36(2):132-6.
6. Xiong T, Qu Y, Cambier S, Mu D. The side effects of phototherapy for neonatal jaundice: what do we know? What should we do? Eur J Pediatr. 2011; 170(10):1247-55.
7. Eghbalian F, Monsef A. Phototherapy-induced hypocalcemia in icteric newborns. Iranian Journal of Medical Sciences. 2015;27(4):169-71.
8. Hansen T. Treatment of neonatal jaundice. Tidsskrift for den Norske laegeforening: tidsskrift for praktisk medicin, ny raekke. Europe PMC. 2005;125(5):594-8.
9. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002; 36(3):525-31.
10. Rodrigues CM, Ma X, Linehan-Stieers C, Fan G, Kren BT, Steer CJ. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ. 1999; 6(9):842-54.
11. Mizoguchi Y, Kioka K, Seki S, Kobayashi K, Morisawa S. Effects of ursodeoxycholic acid on intrahepatic cholestasis. Osaka city medical journal. 1989;35(2):71-82.
12. Honar N, Saadi EG, Saki F, Pishva N, Shakibazad N, Teshnizi SH. Effect of ursodeoxycholic acid on indirect hyperbilirubinemia in neonates treated with phototherapy. J Pediatr Gastroenterol Nutr. 2016; 62(1):97-100.
13. 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):402-5.
14. Perez E, Cooper T, Moise A, Ferry G, Weisman L. Treatment of obstructive jaundice in erythroblastosis fetalis with ursodeoxycholic acid (UDCA): a case report. J Perinatol. 1998; 18(4):317-9.
15. George R, Stevens A, Berkenbosch JW, Turpin J, Tobias J. Ursodeoxycholic acid in the treatment of cholestasis and hyperbilirubinemia in pediatric intensive care unit patients. South Med J. 2002; 95(11):1276-9.
16. Dubreuil M, Ruiz-Gaspa S, Guanabens N, Peris P, Alvarez L, Monegal A, et al. Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells. Liver Int. 2013; 33(7):1029-38.
17. Najib KS, Saki F, Hemmati F, Inaloo S. Incidence, risk factors and causes of severe neonatal hyperbilirubinemia in the South of iran (fars province). Iran Red Crescent Med J. 2013; 15(3):260.
18. Cuperus FJ, Hafkamp AM, Havinga R, Vitek L, Zelenka J, Tiribelli C, et al. Effective treatment of unconjugated hyperbilirubinemia with oral bile salts in Gunn rats. Gastroenterology. 2009; 136(2):673-82. e1.
19. Méndez–Sánchez N, Brink MA, Paigen B, Carey MC. Ursodeoxycholic acid and cholesterol induce enterohepatic cycling of bilirubin in rodents. Gastroenterology. 1998; 115(3):722-32.
How to Cite
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 Anesth & Crit Care. 5(3):99-03.
Research Article(s)