The Effects of Clofibrate on Neonatal Jaundice: A Systematic Review

Fathemeh Eghbalian, Ali Hasanpour‑Dehkordi, Roya Raeisi


Background: Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy isobutyric acid derivate can be effectively applied for the treatment of neonatal jaundice. Thus, this review was carried out to investigate the effects and mechanism of action of clofibrate on neonatal jaundice.

Methods: The keywords such as “Clofibrate” in combination with “Neonatal jaundice” or “Neonatal hyperbilirubinemia” or “Newborn Jaundice” were used to search for relevant publications indexed in the Institute for Scientific Information (ISI), Scopus, PubMed, and Google Scholar databases. Finally, after reviewing the studies, 24 papers were included in this study.

Results: Results showed that the processes of albumin‑bound bilirubin transfer to the hepatocytes, hepatic uptake, and storage via ligandin, hepatic conjugation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), conjugation into the bile via MRP2 represent the main action mechanism of clofibrate that turns it into the bilirubin conjugates and expels it from the bile. Besides, clofibrate has been shown to reduce the level of Total Serum Bilirubin (TSB) in infants even at a dosage of 25 mg/kg without leaving side effects.

Conclusions: The results of this review revealed that clofibrate effectively reduces TSB in short‑term usage and can even have a promising effect at the dosage of 25 mg/kg in full‑term infants. Most studies have shown this property over a short period in term infants, and there is no evidence about long‑term usage in this regard.


Clofibrate; hyperbilirubinemia; neonatal jaundice; newborn jaundice

Full Text:



Ullah S, Rahman K, Hedayati M. Hyperbilirubinemia in

neonates: Types, causes, clinical examinations, preventive

measures and treatments: A narrative review article. Iran J Public

Health 2016;45:558‑68.

Rennie J, Burman‑Roy S, Murphy MS. Neonatal jaundice:

Summary of NICE guidance. BMJ 2010;340:c2409.

Porter ML, Dennis BL. Hyperbilirubinemia in the term newborn.

Am Fam Phys 2002;65:599‑606.

Babaei H, Parham S. Risk factors of severe hyperbilirubinemia

in neonates undergoing exchange transfusion in Imam Reza

Hospital Kermanshah‑Iran, during 2012 to 2016. Int J Pediatr


Davutoglu M, Garipardic M, Guler E, Karabiber H, Erhan D. The

etiology of severe neonatal hyperbilirubinemia and complications

of exchange transfusion. Turk J Pediatr 2010;52:163‑6.

Das S, van Landeghem FKH. Clinicopathological spectrum

of bilirubin encephalopathy/kernicterus. Diagnostics (Basel)


Waite WM, Taylor JA. Phototherapy for the treatment of neonatal

jaundice and breastfeeding duration and exclusivity. Breastfee

Med 2016;11:180‑5.

Romero HM, Ringer C, Leu MG, Beardsley E, Kelly K,

Fesinmeyer MD, et al. Neonatal jaundice: Improved quality

and cost savings after implementation of a standard pathway.

Pediatrics 2018;141:e20161472.

Mitra S, Rennie J. Neonatal jaundice: Aetiology, diagnosis and

treatment. Br J Hosp Med (Lond) 2017;78:699‑704.

Rasul CH, Hasan MA, Yasmin F. Outcome of neonatal

hyperbilirubinemia in a tertiary care hospital in Bangladesh.

Malays J Med Sci 2010;17:40‑4.

Slusher TM, Zamora TG, Appiah D, Stanke JU, Strand MA,

Lee BW, et al. Burden of severe neonatal jaundice:

A systematic review and meta‑analysis. BMJ Paediatr Open


Wan A, Mat Daud S, Teh SH, Choo YM, Kutty FM. Management of

neonatal jaundice in primary care. Malays Fam Phys 2016;11:16‑9.

Drew JH, Marriage K, Bayle VV, Bajraszewski E,

McNammara JM. Phototherapy. Short and long‑term

complications. Arch Dis Child 1976;51:454‑8.

Eghbalian F, Pourhossein A, Zandevakili H. Effect of clofibrate

in non‑hemolytic indirect hyperbiliru‑binemia in full term

neonates. Indian J Pediatr 2007;74:1003‑6.

Peinado‑Acevedo JS, Chacon‑Valenzuela E,

Rodriguez‑Moncada LL. [Bronze baby syndrome, an

unpredictable complication of phototherapy: A case report].

Biomedica 2018;38:15‑8.

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.

Woodgate P, Jardine LA. Neonatal jaundice: Phototherapy. BMJ

Clin Evid 2015;2015:0319.

Monsef A, Eghbalian F, Rahimi N. Comparison of purgative

manna drop and phototherapy with phototherapy treatment of

neonatal jaundice: A randomized double‑blind clinical trial.

Osong Public Health Res Perspect 2019;10:152.

Raeisi R, Heidari‑Soureshjani S, Asadi‑Samani M, Luther T.

A systematic review of phytotherapies for newborn jaundice in

iran. Int J Pharm Sci Res 2017;8:1953‑8.

Gharehbaghi MM, Sani AM, Refeey M. Evaluating the effects

of different doses of ursodeoxycholic acid on neonatal jaundice.

Turk J Pediatr 2020;62:424‑30.

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;62:97‑100.

Habibi M, Mahyar A, Ayazi P, Ahmadabadi F, Javadi A. The

effect of clofibrate on hyperbilirubinemia of term neonates. Acta

Med Iran 2012;50:21‑5.

Mohammadzadeh A, Farhat A, Iranpour R. Effect of clofibrate in

jaundiced term newborns. Indian J Pediatr 2005;72:123‑6.

Zahedpasha Y, Naderi S, Ahmadpour M. Effect of clofibrate

plus phototherapy on bilirubin concentration of. Hormozgan

Medical Journal.2006:10:207-12.

Moslehi M, Pishva N. Determination of effect of low dose vs

moderate dose clofibrate on decreasing serum bilirubin in healthy

term neonates. Iran J Pediatr 2007;17:108‑12.

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;10:349‑53.

Badeli HR, Sharafi R, Sajedi SA. The effect of clofibrate on

neonatal hyperbilirubinemia in uncomplicated jaundice. Iran J

Pediatr 2008;18:20‑4.

Mohammadzadeh A, Sh FA, Jafarzadeh M, Mirzarahimi M,

Esmaeli H, Amiri R. Prophylactic effect of clofibrate in low birth

weight neonates hyperbilirubinemia. J Chin Clin Med 2008;3.

Zahedpasha Y, Ahmadpour‑Kacho M, Hajiahmadi M, Naderi S,

Kamali AA. Efficacy of clofibrate on severe neonatal jaundice

associated with glucose‑6‑phosphate dehydrogenase deficiency

(a randomized clinical trial). Southeast Asian J Trop Med Public

Health 2008;39:557‑61.

Ghotbi F, Tghiloo M, Gashb A. The effect of clofibrate on

neonatal jaundice. Pejouhesh dar Pezeshki (Research in Medicine). 2009;33:31‑4.

Mohammadzadeh A, Farhat AS, Amiri R, Esmaely H,

Bagheri S. Treatment effect of clofibrate in jaundiced low birth

weight neonates. International Journal of Hematology and

Oncology. 2009;30:100-5.

Sakha SH, Gharehbaghi M, Rahbani M. The effect of clofibrate

with phototherapy in late pre‑term newborns with non‑hemolytic

jaundice. Indian J Med Sci 2009;63:174‑9.

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.

Alipour AA, Babaee H, Barghaei A, Hashemian AH, Azizi M.

The effect of clofibrate and phototherapy on physiological

jaundice in term newborns. Behbood 2011;15:233‑7.

Eghbalian F, Ghomi Tabataei N. Aalam, and A.R. Monsef.

"Effect Of Different Doses Of Clofibrate On Neonatal Jaundice."

Annals of Military and Health Sciences Research 2011:9:192-8.

Fallah R, Islami Z, Lotfi SR. Single dose of 50 mg/kg clofibrate

in jaundice of healthy term neonates: Randomised clinical trial

of efficacy and safety. Indian J Pediatr 2012;79:194‑7.

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;4:13‑9.

Hamidi M, Zamanzad B, Mesripour A. Comparing the

effect of clofibrate and phenobarbital on the newborns with

hyperbilirubinemia. Excli J 2013;12:75‑8.

Poursakha SH, Gharehbaghi MM, Rahbani ME. The effect of

clofibrate in near term newborns with non hemolytic jaundice.

Int J Med Med Sci 2013;5:251‑4.

Zahed Pasha Y, Mahdipour S, Ahmadpour‑Kacho M,

Bijani A, Taheri M. Preventive effect of clofibrate on neonatal

hyperbilirubinemia. Caspian J Pediatr 2015;1:5‑8.

Nourishadkam M, Mohammadi MJ, Nasiriani K. Evaluation

of the effect of oral clofibrate intake on neonatal total

serum bilirubin: A randomized clinical trial. Iranian Journal of

Neonatology IJN.. 2016;7:5‑8.

Alosy BDM. Benefit of Clofibrate on indirect hyperbilirubinemia

in newborn. Al‑Mustansiriyah J Pharm Sci 2017;17:134‑9.

Kumar P, Adhisivam B, Bhat BV. Clofibrate as an adjunct

to phototherapy for unconjugated hyperbilirubinemia in term

neonates. Indian J Pediatr 2017;84:763‑7.

Bhutani VK. Editorial: Building evidence to manage newborn

jaundice worldwide. Indian J Pediatr 2012;79:253‑5.

Mancuso C. Bilirubin and brain: A pharmacological approach.

Neuropharmacology 2017;118:113‑23.

Sticova E, Jirsa M. New insights in bilirubin metabolism and their

clinical implications. World J Gastroenterol 2013;19:6398‑407.

Cuperus FJ, Hafkamp AM, Hulzebos CV, Verkade HJ.

Pharmacological therapies for unconjugated hyperbilirubinemia.

Curr Pharm Des 2009;15:2927‑38.

Gholitabar M, McGuire H, Rennie J, Manning D, Lai R.

Clofibrate in combination with phototherapy for unconjugated

neonatal hyperbilirubinaemia. Cochrane Database Syst Rev


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;48:1217‑22.

Steiner A, Weisser B, Vetter W. A comparative review of the

adverse effects of treatments for hyperlipidaemia. Drug Saf


Erkul I, Yavuz H, Ozel A. Clofibrate treatment of neonatal

jaundice. Pediatrics 1991;88:1292‑4.

Pokroy N, Ress S, Gregory MC. Clofibrate‑induced complications

in renal disease: A case report. S Afr Med J 1977;52:806‑8.

Pierides AM, Alvarez‑Ude F, Kerr DN. Clofibrate‑induced

muscle damage in patients with chronic renal failure. Lancet


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


Torkaman M, Saburi A. What is important about the effect

of clofibrate on neonatal hyperbilirubinemia? Acta Med Iran


Martinez N, White V, Kurtz M, Higa R, Capobianco E,

Jawerbaum A. Activation of the nuclear receptor PPARalpha

regulates lipid metabolism in foetal liver from diabetic rats:

Implications in diabetes‑induced foetal overgrowth. Diabetes

Metab Res Rev 2011;27:35‑46.

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.