Effects of Hyperbilirubinemia on Auditory Brainstem Response of Neonates Treated with Phototherapy

Document Type: Original


Department of Audiology, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.


One of the most common pathologies in neonates is hyperbilirubinemia, which is a good marker for damage to the central nervous system. The sensitivity of the auditory system to bilirubin has been previously documented, with much discrepancy in its effects on Auditory Brainstem Response results. Thus the objective of this study was to evaluate the effects of hyperbilirubinemia on Auditory Brainstem Response of neonates treated with phototherapy.
Materials and Methods:
Forty-two term neonates with hyperbilirubinemia, who underwent phototherapy participated in this cross sectional study. The recording of Auditory Brainstem Response was made shortly after confirming that the total serum bilirubin level was greater than 15 µg/dl. Latency of waves I, III, V and inter-peak latencies of the waves were measured. To test the hypothesis about the difference of means between the two groups, continuous variables were compared using either the t-test (normal distribution) or the Mann-Whitney test (non-normal distribution).
There was a significant increase in the absolute latencies of waves III and V, and I-III and I-V inter-peak latencies of the sample group compared to the control group in both ears (P<0.05). However, wave I absolute latency and III-V inter-peak interval did not show a significant difference between the two study groups (P>0.05).
The results of this study underline the importance of the Auditory Brainstem Response Test as an efficient tool for monitoring the auditory brainstem pathway in neonates who are at risk of neurotoxicity and for diagnosing the earliest stages of auditory damage caused by high levels of bilirubin.


Main Subjects

1. de Steuben C. Breast-feeding and jaundice: a review. Journal of nurse-midwifery 1992; 37(2):

2. Gubernick JA, Rosenberg HK, Ilaslan H, Kessler A. US Approach to Jaundice in Infants and Children 1. Radiographics 2000; 20(1):173-95.

3. Fay DL, Schellhase KG, Suresh GK. Bilirubin screening for normal newborns: a critique of the hour-specific bilirubin nomogram. Pediatrics  2009; 124(4): 1203-5.

4. Protocol A. ABM Clinical Protocol# 22: Guidelines for Management of Jaundice in the Breastfeeding Infant Equal to or Greater Than 35 Weeks’ Gestation. Breastfeeding Medicine 2010; 5(2): 87-93.

5. Bhutani VK, Maisels MJ, Stark AR, Buonocore G. Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants≥ 35 weeks gestation. Neonatology 2008;94(1):63-7.

6. Johnson L, Bhutani VK, editors. The clinical syndrome of bilirubin-induced neurologic dysfunction.  Seminars in perinatology. 2011; 35(3): 101-13.

7. Bhutani VK, Stevenson DK, editors. The need for technologies to prevent bilirubin-induced neurologic dysfunction syndrome. Seminars in perinatology; 2011: Elsevier.

8. Boo N, Oakes M, Lye M, Said H. Risk factors associated with hearing loss in term neonates with hyperbilirubinaemia. 1994.

9. Oh W, Tyson JE, Fanaroff AA, Vohr BR, Perritt R, Stoll BJ, et al. Association between peak serum bilirubin and neurodevelopmental outcomes in extremely low birth weight infants. Pediatrics. 2003;112(4):773-9.

10. Graziani LJ, Mitchell DG, Kornhauser M, Pidcock FS, Merton DA, Stanley C, et al. Neurodevelopment of preterm infants: neonatal neurosonographic and serum bilirubin studies. Pediatrics. 1992;89(2):229-34.

11. Okhravi T, Eslami ST, Ahmadi AH, Nassirian H, Najibpour R. Evaluation of Auditory Brain Stems Evoked Response in Newborns With Pathologic Hyperbilirubinemia in Mashhad, Iran. Iranian Red Crescent Medical Journal. 2015;17(2).

12. Zhang S, Wickesberg RE, Oertel D. Jaundiced Gunn rats have increased synaptic delays in the ventral cochlear nucleus. Brain research. 1989;501(1):194-7.

13. Shaia WT, Shapiro SM, Spencer RF. The jaundiced Gunn rat model of auditory neuropathy/dyssynchrony. The Laryngoscope. 2005;115(12):2167-73.

14. Nakamura H, Takada S, Shimabuku R, Matsuo M, Matsuo T, Negishi H. Auditory nerve and brainstem responses in newborn infants with hyperbilirubinemia. Pediatrics. 1985;75(4):703-8.

15. Deorari A, Singh M, Ahuja G, Bisht M, Verma A, Paul V, et al. One year outcome of babies with severe neonatal hyperbilirubinemia and reversible abnormality in brainstem auditory evoked responses. Indian pediatrics. 1994;31(8):915-21.

16. Agrawal V, Shukla R, Misra P, Kapoor R, Malik G. Brainstem auditory evoked response in newborns with hyperbilirubinemia. Indian pediatrics. 1998;35:513-8.

17. Moeller MP. Early intervention and language development in children who are deaf and hard of hearing. Pediatrics. 2000;106(3):e43-e.

18. Hall JW. New handbook of auditory evoked responses: ASHA; 2007.

19. Wilkinson AR, Jiang ZD, editors. Brainstem auditory evoked response in neonatal neurology. Seminars in Fetal and Neonatal Medicine; 2006: Elsevier.

20. Amin SB, Ahlfors C, Orlando MS, Dalzell LE, Merle KS, Guillet R. Bilirubin and serial auditory brainstem responses in premature infants. Pediatrics. 2001;107(4):664-70.

21. Smith CM, Barnes GP, Jacobson CA, Oelberg DG. Auditory brainstem response detects early bilirubin neurotoxicity at low indirect bilirubin values. Journal of perinatology. 2004;24(11):730-2.

22. Soares I, Collet L, Delorme C, Salle B, Morgon A. Are click-evoked BAEPs useful in case of neonate hyperbilirubinemia? International journal of pediatric otorhinolaryngology. 1989;17(3):231-7.

23. Streletz L, Graziani L, Branca P, Desai H, Travis S, Mikaelian D. Brainstem auditory evoked potentials in fullterm and preterm newborns with hyperbili- rubinemia and hypoxemia. Neuropediatrics. 1986; 17(2):66-71.

24. Wong V, Chen W-X, Wong K-Y. Short-and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia. Journal of child neurology. 2006;21(4):309-15.

25. Watchko JF. Neonatal Hyperbilirubinemia-What Are the Risks? New England Journal of Medicine. 2006;354(18):1947-9.

26. Shapiro SM. Bilirubin toxicity in the developing nervous system. Pediatric neurology. 2003; 29(5): 410-21.

27. Fakhim SA, Naderpoor M, Shahidi N, Basharhashemi F, Nejati N, Sakha SH, et al. Study of prevalence and causes of hearing loss in high risk neonates admitted to neonatal ward and neonatal intensive care unit. Int Adv Otol. 2010;6:365-70.

28. Smitherman H, Stark AR, Bhutan VK, editors. Early recognition of neonatal hyperbilirubinemia and its emergent management. Seminars in Fetal and Neonatal Medicine; 2006: Elsevier.

29. Hansen TWR, editor Kernicterus: an international perspective. Seminars in neonatology; 2002: Elsevier.

30. Shapiro SM, Popelka GR, editors. Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction. Seminars in perinatology; 2011: Elsevier.

31. Sharma R, Grover N, Sankhyan N, Sharma M. Auditory brainstem responses in neonatal hyperbilirubinemia and effect of therapy. Indian Journal of Otolaryngology and Head and Neck Surgery. 2006; 58(4):340-2.

32. Rattay F, Danner SM. Peak I of the human auditory brainstem response results from the somatic

regions of type I spiral ganglion cells: Evidence from computer modeling. Hearing research. 2014;315:    67-79.

33. Jiang ZD, Chen C, Liu TT, Wilkinson AR.
Changes in brainstem auditory evoked response latencies in term neonates with hyperbilirubinemia. Pediatric neurology. 2007;37(1):35-41.

34. Jiang ZD, Wilkinson AR. Impaired function of the auditory brainstem in term neonates with hyperbilirubinemia. Brain and Development. 2014; 36(3):212-8.

35. Ahlfors CE, Parker AE. Unbound bilirubin concentration is associated with abnormal automated auditory brainstem response for jaundiced newborns. Pediatrics. 2008;121(5):976-8.

36. Perlman M, Fainmesser P, Sohmer H, Tamari H, Wax Y, Pevsmer B. Auditory nerve-brainstem evoked responses in hyperbilirubinemic neonates. Pediatrics. 1983;72(5):658-64.

37. Shapiro SM. Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatric research. 1988; 23(3):306-10.

38. Shapiro SM. Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatric research. 1993; 34(5): 629-33.

39. Mohammadi M, Ashrafi M, Shabanian R. Auditory brainstem responses (ABR) in hyperbilirubinemic newborns. Medical Journal of The Islamic Republic of Iran (MJIRI). 2002; 16(2): 63-6.

40. Sharma P, Chhangani N, Meena KR, Jora R, Sharma N, Gupta B. Brainstem evoked response audiometry (BAER) in neonates with hyperbili rubinemia. The Indian Journal of Pediatrics. 2006; 73(5):413-6.