Etiologies of Prolonged Unconjugated Hyperbilirubinemia in Neonates Admitted to Neonatal Wards

Document Type : Original Article


1 Department of Pediatrics, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran

2 General Practitioner, Hamadan University of Medical Sciences, Hamadan, Iran


Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran.
Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia.
Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants.
Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.


  1. Mackinlay GA. Jaundice persisting beyond 14 days after birth. BMJ. 1993; 306(6890):1426-7.
  2. Hannam S, McDonnell M, Rennie JM. Investigation of prolonged neonatal jaundice. Acta Paediatr. 2000; 89(6):694-7.
  3. Schneider AP. Breast milk jaundice in the newborn: A real entity. JAMA. 1986; 255(23):3270–4.
  4. Hargreaves T. Breast-milk jaundice. BMJ. 1970; 3(5723):647.
  5. Alonso EM, Whitington PF, Whitington SH, Rivard WA, Given G. Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk. J Pediatr. 1991; 118(3):425-30.
  6. Garcia FJ, Nager AL. Jaundice as an early diagnostic sign of urinary tract infection in infancy. Pediatrics. 2002; 109(5):846-51.
  7. Jafarzadeh M, Mohammadzadeh A. Should urine culture be considered in the hyperbilirubinemia workup of neonate. J Chinese Clin Med. 2009; 4(3):136-8.
  8. Najati N, Gharehbaghi MM, Mortazavi F. Underlying etiologies of prolonged icterus in neonates. Pak J Biol Sci. 2010; 13(14):711-4.
  9. Pashapour N, Nikibakhsh AA, Golmohammadlou S. Urinary tract infection in term neonates with prolonged jaundice. Urol J. 2007; 4(2):91-4.
  10. Kurtoğlu S, Çoban D, Akın MA, Akın L, Yıkılmaz A. Neonatal sludge: A finding of congenital hypothyroidism. J Clin Res Pediatr Endocrinol. 2009; 1(4):197–200.
  11. Araz NC. Frequency of congenital hypothyroidism in the newborns with prolonged jaundice. Gaziantep tip Dergisi. 2009; 15(1):28-30. (Turkish)
  12. Honarpisheh A. Frequency of congenital hypothyroidism among neonates with prolonged jaundice in Kashan. Teb Va Tazkieh. 2004; (51):33-6.
  13. Unal S, Aktas A, Ergenekon E, Koc E, Atalay Y. Prolonged jaundice in newborns: What is it actually due to? Gazi Med J. 2003; 14(4):147-51.
  14. Bilgen H, Ozek E, Unver T, Biyikli N, Alpay H, Cebeci D. Urinary tract infection and hyperbilirubinemia. Turk J Pediatr. 2006; 48(1): 51-5. (Turkish)
  15. Ghaemi S, Fesharaki RJ, Kelishadi R. Late onset jaundice and urinary tract infection in neonates. Indian J Pediatr. 2007; 74(2):139-41.
  16. Khalesi N, Sharaki T, Haghighe M. Prevalence of urinary tract infection in neonates with prolonged jaundice. J Qazvin Univ Med Sci. 2007; 11(3):14-8.
  17. Chen HT, Jeng MJ, Soong WJ, Yang CF, Tsao PC, Lee YS, et al. Hyperbilirubinemia with urinary tract infection in infants younger than eight weeks old. J Chin Med Assoc. 2010; 74(4):159-63.
  18. Scott R, Aladangady N, Maalouf E. Neonatal hypopituitarism presenting with poor feeding, hypoglycemia and prolonged unconjugated hyperbilirubinemia. J Matern Fetal Neonatal Med. 2004; 16(2):131-3.
  19. Abdel Fattah M, Abdel Ghany E, Adel A, Mosallam D, Kamal S. Glucose-6-phosphate dehydrogenase and red cell pyruvate kinase deficiency in neonatal jaundice cases in Egypt. Pediatr Hematol Oncol. 2010; 27(4):262-71.
  20. Abolghasemi H, Mehrani H, Amid A. An update on the prevalence of glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Tehran neonates. Clin Biochem. 2004; 37(3):241-4.
  21. Ahmadi AH, Ghazizadeh Z. Evaluation of glucose-6-phosphate dehydrogenase deficiency without hemolysis in icteric newborns at Mazandaran province, Iran. Pak J Biol Sci. 2008; 11(10):1394-7.
  22. Kamal S, Sayedda K, Shahir Ahmed Q. Breast non feeding: Main cause of neonatal hyperbilirubinemia in areas adjoining Shri Ram Murti smarak institute of medical sciences, a tertiary care teaching hospital, Bareilly. Natl J Physiol Pharm Pharmacol. 2012; 2(2):108-12.