Evaluation of the Effect of Oral Clofibrate Intake on Neonatal Total Serum Bilirubin: a Randomized Clinical Trial

Document Type: Original Article

Authors

1 Associate Professor, Mother and Newborn Health Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences , Yazd, Iran

2 Pediatrician, Ayatolla Khatam Hospital, Yazd, Iran

3 PhD, Assistant Professor of Nursing, Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: Clofibrate is a pharmacological agent, which affects the lipid metabolism. This compound could be involved in bilirubin accumulation and excretion process. Therefore, this study aimed to evaluate the effect of oral clofibrate intake on total serum bilirubin (TSB) of neonates hospitalized at Khatam Hospital.
Methods: This clinical trial was conducted on 73 neonates with hyperbilirubinemia. Samples were divided into clofibrate (n=41) and control (n=32) groups. In the Clofibrate group, samples were given a single oral dose of 100 mg/kg clofibrate, whereas the control group received distilled water in an equal amount and color as placebo. Birth weight, type of delivery, gender, age and primary TSB level were recorded prior to the intervention and TSB was measured 24, 48 and 72 hours after the intervention.
Results: In this study,no significant difference was observed between the groups on the first and third day of intervention in terms of mean TSB in neonates. However, a significant reduction was found on the second day in mean TSB of neonates, who received clofibrate (P=0.04).
Conclusion: According to the results of this study, application of clofibrate was associated with faster alleviation of mean TSB and shorter duration of hospital stay without major side effects. Therefore, it is recommended that clofibrate be only used for clinical management of neonatal hyperbilirubinemia.

Keywords


References

  1. Ahadi A, Mirzarahimi M, Ahmadabadi F, Tavasoli A, Parvaneh N. Comparison of the efficacy of Clofibrate with Phenobarbital in decreasing neonatal hyperbilirubinemia. Iran J Neonatol. 2013; 4(3):13-9.
  2. Olusanya BO, Ogunlesi TA, Kumar P, Boo NY, Iskander IF, de Almeida MF, et al. Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings. BMC Pediatr. 2015; 15(1):39.
  3. Petrova A, Mehta R, Birchwood G, Ostfeld B, Hegyi T. Management of neonatal hyperbilirubinemia: pediatricians' practices and educational needs. BMC Pediatr. 2006; 6:6.
  4. Stoddard JJ, Cull WL, Jewett EA, Brotherton SE, Mulvey HJ, Alden ER. Providing pediatric subspecialty care: a workforce analysis. AAP Committee on Pediatric Workforce Subcommittee on Subspecialty Workforce. Pediatrics. 2000; 106(6):1325-33.
  5. Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res. 2004; 56(5):682-9.
  6. Hamidi M, Mesripour A, Zamanzad B. Comparing the effect of clofibrate and phenobarbital on the newborns with hyperbilirubinemia. EXLI J. 2013; 12:75-8.
  7. Bulbul A, Cayonu N, Sanli ME, Uslu S. Evaluation of risk factors for development of severe hyperbilirubinemia in term and near term infants in Turkey. Pak J Med Sci. 2014; 30(5):1113-8.
  8. Lin KW, Humphrey ME. Putting prevention into practice. Screening of infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Am Fam Physician. 2010; 82(4):411-2.
  9. Newman J. Re: Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks' gestation)- Summary. Paediatr Child Health 2007;12(5):401-7. Paediatr Child Health. 2007; 12(7):613.
10. Dennery PA. Pharmacological interventions for the treatment of neonatal jaundice. Semin Neonatol. 2002; 7(2):111-9.

11. Ah YM, Kim YM, Kim MJ, Choi YH, Park KH, Son IJ, et al. Drug-induced hyperbilirubinemia and the clinical influencing factors. Drug Metab Rev. 2008; 40(4):511-37.

12. Litherland NB, Bionaz M, Wallace RL, Loor JJ, Drackley JK. Effects of the peroxisome proliferator-activated receptor-alpha agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves. J Dairy Sci. 2010; 93(6):2404-18.

13. Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010; 30(5):894-9.

14. Eghbalian F, Monsef F, Alam Ghomi N, Monsef A. Effect of low versus moderate dose of clofibrate on serum bilirubin in healthy term neonates with indirect hyperbilirubinemia. Iran J Med Sci. 2013; 38(4):349-50.

15. Kutz K, Kandler H, Gugler R, Fevery J. Effect of clofibrate on the metabolism of bilirubin, bromosulphophthalein and indocyanine green and on the biliary lipid composition in Gilbert's syndrome. Clin Sci (Lond). 1984; 66(4):389-97.

16. Lindenbaum A, Hernandorena X, Vial M, Benattar C, Janaud JC, Dehan M, et al. Clofibrate for the treatment of hyperbilirubinemia in neonates born at term: a double blind controlled study (author's transl). Arch Fr Pediatr. 1981; 38(Suppl 1):867-73.

17. Bucheli Jiménez ER, Quiróz Maldonado M, Flores Colín I. Chlorifibrate effect associated with phototherapy on bilirubin concentration in newly-born babies. Rev Mex Pediatr. 2001; 68:176-80.

18. Zahedpasha Y, Ahmadpour-Kacho M, Hajiahmadi M, Naderi S. Effect of clofibrate in jaundiced full-term infants: a randomized clinical trial. Arch Iran Med. 2007; 10(3):349-53.

19. Mohammadzadeh A, Farhat AS, Iranpour R. Effect of clofibrate in jaundiced term newborns. Indian J Pediatr. 2005; 72(2):123-6.

20. Bourget P, Broise I, Quinquis-Desmaris V, Gabilan JC. Pharmacokinetics of clofibrate in jaundiced newborn infants at term. Arch Pediatr. 1995; 2(8):722-8.

21. Brun S, Carmona MC, Mampel T, Vinas O, Giralt M, Iglesias R, et al. Activators of peroxisome proliferator-activated receptor-alpha induce the expression of the uncoupling protein-3 gene in skeletal muscle: a potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth. Diabetes. 1999; 48(6):1217-22.

22. Steiner A, Weisser B, Vetter W. A comparative review of the adverse effects of treatments for hyperlipidaemia. Drug Saf. 1991; 6(2):118-30.

23. Gabilan JC. Pharmacologic treatment of neonatal jaundice. A new approach. Arch Pediatr. 1998; 5(11):1274-8