Clofibrate as an Adjunct to Phototherapy for Unconjugated Hyperbilirubinemia in Term Neonates

Original Article
  • 55 Downloads

Abstract

Objective

To evaluate the efficacy of oral clofibrate as an adjunct to phototherapy for unconjugated hyperbilirubinemia in term neonates.

Methods

This randomized controlled trial was done in the level III neonatal intensive care unit (NICU) of a tertiary care hospital. Ninety term neonates with unconjugated hyperbilirubinemia with serum bilirubin 15–25 mg/dl were randomized to either intervention group (single dose of clofibrate in a dose of 50 mg/kg prior to starting phototherapy) or standard care group (only phototherapy). Primary outcome was absolute fall in bilirubin by 48 h. Secondary outcomes were duration of phototherapy, absolute fall in bilirubin levels at 12, 24, 36, 48 h, need for exchange transfusion and incidence of side-effects.

Results

After 48 h of intervention, significantly lower bilirubin levels were noted in the intervention group compared to standard care group with a mean difference of 7 mg/dl (95% CI 6.7 mg/dl to 7.2 mg/dl). Duration of phototherapy required was less in the intervention group compared to standard care group with mean difference of 23.82 h (95% CI 30.46 h to 17.18 h). Exchange transfusion was needed for 4 neonates in the standard care group and none in the intervention group. No side-effects were noted with clofibrate.

Conclusions

Single dose clofibrate prior to starting phototherapy in term neonates with uncomplicated unconjugated hyperbilirubinemia reduces the duration of phototherapy significantly.

Keywords

Newborn Hyperbilirubinemia Clofibrate Phototherapy 

References

  1. 1.
    Bhutani VK, Stark AR, Lazzeroni LC, et al; Initial Clinical Testing Evaluation and Risk Assessment for Universal Screening for Hyperbilirubinemia Study Group. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr. 2013;162:477–82. e1Google Scholar
  2. 2.
    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;170:1247–55.CrossRefPubMedGoogle Scholar
  3. 3.
    Gholitabar M, McGuire H, Rennie J, Manning D, Lai R. Clofibrate in combination with phototherapy for unconjugated neonatal hyperbilirubinaemia. Cochrane Database Syst Rev. 2012;12:CD009017.PubMedGoogle Scholar
  4. 4.
    Xiong T, Chen D, Duan Z, Qu Y, Mu D. Clofibrate for unconjugated hyperbilirubinemia in neonates: a systematic review. Indian Pediatr. 2012;49:35–41.CrossRefPubMedGoogle Scholar
  5. 5.
    Sharafi R, Mortazavi Z, Sharafi S, Parashkouh RM. The effect of clofibrate on decreasing serum bilirubin in healthy term neonates under home phototherapy. Iran J Pediatr. 2010;20:48–52.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Fallah R, Islami Z, Lotfi SR. Single dose of 50 mg/kg clofibrate in jaundice of healthy term neonates: randomized clinical trial of efficacy and safety. Indian J Pediatr. 2012;79:194–7.CrossRefPubMedGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 8.
    Evidence based clinical practice guidelines -National Neonatology forum. Available at: http://www.nnfi.org/images/pdf/nnf_cpg_consolidated_file-january102011.pdf. Accessed on 22 March 2016.
  9. 9.
    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’ssyndrome. Clin Sci (Lond). 1984;66:389–97.CrossRefGoogle Scholar
  10. 10.
    Bourget P, Broise I, Quinquis-Desmaris V, Gabilan JC. Pharmacokinetics of clofibrate in jaundiced newborn infants at term. Arch Pediatr. 1995;2:722–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Gabilan JC. Pharmacologic treatment of neonatal jaundice. A new approach. Arch Pediatr. 1998;5:1274–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Badeli HR, Sahrafi R, Sajedi SA. The effect of clofibrate on neonatal hyperbilirubinemia in uncomplicated jaundice. Iran J Ped. 2008;18:20–4.Google Scholar
  13. 13.
    Zahedpasha Y, Ahmadpour M, Hajiahmadi M, Naderi S. Effect of clofibrate in jaundiced full term infants: a randomized clinical trial. Arch Iran Med. 2007;10:349–53.PubMedGoogle Scholar
  14. 14.
    Zahedpasha Y, Ahmadpour M, Hajiahmadi M, Naderi S, Kamali AA. Efficacy of clofibrate on severe neonatal jaundice associated with glucose 6 phosphate dehydrogenase deficiency. Southeast Asian J Trop Med Public Health. 2008;39:557–61.PubMedGoogle Scholar
  15. 15.
    Torabi Z, Eskandarzadeh A, Ahmadiafshar A. The effect of clofibrate with phototherapy on full-term newborns with non-hemolytic jaundice. Iran Red Crescent Med J. 2013;15:285–6.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Lindenbaum A, Hernandorena X, Vial M, et al. Clofibrate for the treatment of hyperbilirubinemia in neonates born at term: a double blind controlled study (author’s transl). [Article in French]. Arch Fr Pediatr. 1981;38:867–7.Google Scholar
  17. 17.
    Flores Nava G, Vargas Perez C, Lopez Padilla M, Escobedo Chavez E. Clofibrate in the prevention of neonatal hyperbilirubinemia. Pract Pediatr. 1996;5:40–6.Google Scholar
  18. 18.
    Penna F, Bonelli G, Baccino FM, Costelli P. Cytotoxic properties of clofibrate and other peroxisome proliferators: relevance to cancer progression. Curr Med Chem. 2010;17:309–20.CrossRefPubMedGoogle Scholar
  19. 19.
    Fidaleo M. Human health risk assessment for peroxisome proliferators: more than 30 years of research. Exp Toxicol Pathol. 2009;61:215–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Sakha SH, Gharehbaghi MM, Rahbani ME. The effect of clofibrate with phototherapy in late pre-term newborns with non-hemolytic jaundice. Indian J Med Sci. 2009;63:174–9.CrossRefPubMedGoogle Scholar
  21. 21.
    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;38:349–50.PubMedPubMedCentralGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2017

Authors and Affiliations

  1. 1.Department of NeonatologyJawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)PondicherryIndia

Personalised recommendations