European Journal of Pediatrics

, Volume 168, Issue 10, pp 1243–1250 | Cite as

Changes in BAER wave amplitudes in relation to total serum bilirubin level in term neonates

  • Ze Dong Jiang
  • Dorothea Mary Brosi
  • Andrew Robert Wilkinson
Original Paper



Whether the severity of bilirubin neurotoxicity is closely related to the level of total serum bilirubin (TSB) remains to be determined.

Materials and methods

We studied the amplitudes of brainstem auditory evoked response (BAER) components in 83 term neonates with TSB >10 mg/dL to detect any differences in bilirubin ototoxic effect on the amplitudes between different levels of TSB.

Results and discussion

Compared to age-matched normal controls, the amplitudes of BAER waves III and V were reduced significantly (P<0.01 and 0.001). The V/I and V/III amplitude ratios were also decreased significantly (P<0.001 and 0.01). Although all amplitudes tended to be lower at higher TSB levels than at lower levels, none of the amplitudes correlated significantly with the level of TSB. Neither the V/I amplitude ratio nor the V/III amplitude ratio correlated with the TSB. No significant differences were found in any BAER wave amplitudes among the TSB levels 11–15, 16–20 and >20 mg/dL. In the comparison of amplitude data between any two of the three TSB levels, only wave V amplitude showed significant difference between TSB levels 11–15 and >20 mg/dL (P < 0.05).


BAER wave amplitudes were significantly reduced in neonates with hyperbilirubinemia. However, there was no close correlation between the degree of amplitude reduction and the level of TSB. These results indicate that bilirubin toxicity to the neonatal brain is not closely related to the level of TSB.


Brainstem auditory evoked potential Hyperbilirubinemia Neonatal hearing impairment Neonates Ototoxity 



brainstem auditory evoked response


normal hearing level


total serum bilirubin



This research was supported by Deafness Research and WellChild, UK. Dr Rong Yin participated in collecting and analysing part of the data.

Conflict of interest

We have no financial relationships relevant to this article to disclose.


  1. 1.
    Amin SB, Ahlfors C, Orlando MS et al (2001) Bilirubin and serial auditory brainstem responses in premature infants. Pediatrics 107:664–670. doi:10.1542/peds.107.4.664 PubMedCrossRefGoogle Scholar
  2. 2.
    Boo NY, Oakes M, Lye MS et al (1994) Risk factors associated with hearing loss in term neonates with hyperbilirubinaemia. J Trop Pediatr 40:194–197PubMedGoogle Scholar
  3. 3.
    Chiappa KH (1990) Brainstem auditory evoked potentials: Methodology. In: Chiappa KH (ed) Evoked potentials in clinical medicine. Raven, New York, pp 173–221Google Scholar
  4. 4.
    Dennery PA, Seidman DS, Stevenson DK (2001) Neonatal hyperbilirubinaemia. N Engl J Med 344:581–590. doi:10.1056/NEJM200102223440807 PubMedCrossRefGoogle Scholar
  5. 5.
    Funato M, Tamai H, Shimada S et al (1994) Vigintiphobia, unbound bilirubin, and auditory brainstem responses. Pediatrics 93:50–53PubMedGoogle Scholar
  6. 6.
    Funato M, Teraoka S, Tamai H et al (1996) Follow-up study of auditory brainstem responses in hyperbilirubinemic newborns treated with exchange transfusion. Acta Paediatr Jpn 38:17–21PubMedGoogle Scholar
  7. 7.
    Gupta AK, Mann SB (1998) Is auditory brainstem response a bilirubin neurotoxicity marker? Am J Otolaryngol 19:232–236. doi:10.1016/S0196-0709(98)90123-5 PubMedCrossRefGoogle Scholar
  8. 8.
    Gustafson PA, Boyle DW (1995) Bilirubin index: a new standard for intervention? Med Hypotheses 45:409–416. doi:10.1016/0306-9877(95)90213-9 PubMedCrossRefGoogle Scholar
  9. 9.
    Hansen TWR, Paulsen O, Gjerstad L et al (1988) Short-term exposure to bilirubin reduces synaptic activation in rat transverse hippocampal slices. Pediatr Res 23:453–456. doi:10.1203/00006450-198802000-00018 PubMedCrossRefGoogle Scholar
  10. 10.
    Hansen TWR, Bratlid D, Walaas SI (1988) Bilirubin decreases phosphorylation of synapsin I, a synaptic vesicle-associated neuronal phosphoprotein, in intact synaptosomes from rat cerebral cortex. Pediatr Res 23:219–223. doi:10.1203/00006450-198802000-00018 PubMedCrossRefGoogle Scholar
  11. 11.
    Hung KL (1989) Auditory brainstem responses in patients with neonatal hyperbilirubinaemia and bilirubin encephalopathy. Brain Dev 11:297–301PubMedGoogle Scholar
  12. 12.
    Jiang ZD, Brosi DM, Wilkinson AR (2002) Auditory neural responses to click stimuli of different rates in the brainstem of very preterm babies at term. Pediatr Res 51:454–459. doi:10.1203/00006450-200204000-00009 PubMedCrossRefGoogle Scholar
  13. 13.
    Jiang ZD, Shao XM, Wilkinson AR (2006) Changes in BAER amplitudes after perinatal asphyxia during the neonatal period in term infants. Brain Dev 28:554–559. doi:10.1016/j.braindev.2006.03.004 PubMedCrossRefGoogle Scholar
  14. 14.
    Jiang ZD, Chen C, Liu TT et al (2007) Changes in BAER wave latencies in term neonates with hyperbilirubinaemia. Pediatr Neurol 37:35–41. doi:10.1016/j.pediatrneurol.2007.03.006 PubMedCrossRefGoogle Scholar
  15. 15.
    Kountakis SE, Skoulas I, Phillips D et al (2002) Risk factors for hearing loss in neonates: a prospective study. Am J Otolaryngol 23:133–137. doi:10.1053/ajot.2002.123453 PubMedCrossRefGoogle Scholar
  16. 16.
    Newman TB, Liljestrand P, Jeremy RJ et al (2006) Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more. N Engl J Med 354:1889–1900. doi:10.1056/NEJMoa054244 PubMedCrossRefGoogle Scholar
  17. 17.
    Newton V (2001) Adverse perinatal conditions and the inner ear. Semin Neonatol 6:543–551. doi:10.1053/siny.2001.0076 PubMedCrossRefGoogle Scholar
  18. 18.
    Sano M, Kaga K, Kitazumi E et al (2005) Sensorineural hearing loss in patients with cerebral palsy after asphyxia and hyperbilirubinemia. Int J Pediatr Otorhinolaryngol 69:1211–1217. doi:10.1016/j.ijporl.2005.03.014 PubMedCrossRefGoogle Scholar
  19. 19.
    Shapiro SM (2003) Bilirubin toxicity in the developing nervous system. Pediatr Neurol 29:410–421. doi:10.1016/j.pediatrneurol.2003.09.011 PubMedCrossRefGoogle Scholar
  20. 20.
    Shi HB, Kakazu Y, Shibata S et al (2006) Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive neurons of the rat. Neurosci Res 55:161–170. doi:10.1016/j.neures.2006.02.015 PubMedCrossRefGoogle Scholar
  21. 21.
    Smith CM, Barnes GP, Jacobson CA et al (2004) Auditory brainstem response detects early bilirubin neurotoxicity at low indirect bilirubin values. J Perinatol 24:730–732. doi:10.1038/ PubMedCrossRefGoogle Scholar
  22. 22.
    Soares I, Collet L, Delorme C et al (1989) Are click-evoked BAEPs useful in case of neonate hyperbilirubinaemia? Int J Pediatr Otorhinolaryngol 117:231–237. doi:10.1016/0165-5876(89)90050-5 CrossRefGoogle Scholar
  23. 23.
    Streletz LJ, Graziani LJ, Branca PA et al (1986) Brainstem auditory evoked potentials in fullterm and preterm newborns with hyperbilirubinemia and hypoxemia. Neuropediatrics 17:66–71. doi:10.1055/s-2008-1052503 PubMedCrossRefGoogle Scholar
  24. 24.
    Wilkinson AR, Jiang ZD (2006) Brainstem auditory evoked response in neonatal neurology. Semin Fetal Neonatal Med 11:444–451. doi:10.1016/j.siny.2006.07.005 PubMedCrossRefGoogle Scholar
  25. 25.
    Wong V, Chen WX, Wong KY (2006) Short- and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia. J Child Neurol 21:309–315. doi:10.1177/08830738060210040301 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ze Dong Jiang
    • 1
    • 2
  • Dorothea Mary Brosi
    • 2
  • Andrew Robert Wilkinson
    • 2
  1. 1.Department of Paediatrics, Children’s HospitalFudan UniversityShanghaiChina
  2. 2.Neonatal Unit, Department of Paediatrics, John Radcliffe HospitalUniversity of OxfordOxfordUK

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