Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Frequency-following response among neonates with progressive moderate hyperbilirubinemia

Journal of Perinatology volume 40, pages 203–211 (2020)Cite this article

Subjects

Abstract

Objective

To evaluate the feasibility of auditory monitoring of neurophysiological status using frequency-following response (FFR) in neonates with progressive moderate hyperbilirubinemia, measured by transcutaneous (TcB) levels.

Study design

ABR and FFR measures were compared and correlated with TcB levels across three groups. Group I was a healthy cohort (n = 13). Group II (n = 28) consisted of neonates with progressive, moderate hyperbilirubinemia and Group III consisted of the same neonates, post physician-ordered phototherapy.

Result

FFR amplitudes in Group I controls (TcB = 83.1 ± 32.5µmol/L; 4.9 ± 1.9 mg/dL) were greater than Group II (TcB = 209.3 ± 48.0µmol/L; 12.1 ± 2.8 mg/dL). After TcB was lowered by phototherapy, FFR amplitudes in Group III were similar to controls. Lower TcB levels correlated with larger FFR amplitudes (r = −0.291, p = 0.015), but not with ABR wave amplitude or latencies.

Conclusion

The FFR is a promising measure of the dynamic neurophysiological status in neonates, and may be useful in tracking neurotoxicity in infants with hyperbilirubinemia.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Downs MP. Universal newborn hearing screening–the Colorado story. Int J Pedia Otorhinolaryngol. 1995;32:257–9.

    Article  CAS  Google Scholar 

  2. Jacobson GP. Universal newborn hearing loss: screening, identification, intervention. Am J Audio. 2001;10:52.

    Article  CAS  Google Scholar 

  3. Boo NY, Oakes M, Lye MS, Said H. Risk factors associated with hearing loss in term neonates with hyperbilirubinaemia. J Trop Pedia. 1994;40:194–7.

    Article  CAS  Google Scholar 

  4. Ortiz-Mantilla S, Choudhury N, Leevers H, Benasich AA. Understanding language and cognitive deficits in very low birth weight children. Dev Psychobiol. 2008;50:107–26.

    Article  PubMed  Google Scholar 

  5. Jiang ZD, Wilkinson AR. Impaired function of the auditory brainstem in term neonates with hyperbilirubinemia. Brain Dev. 2014;36:212–8.

    Article  PubMed  Google Scholar 

  6. Fenwick JD. Neonatal jaundice as a cause of deafness. J Laryngol Otol. 1975;89:925–32.

    Article  CAS  PubMed  Google Scholar 

  7. Shapiro SM, Popelka GR. Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction. Semin Perinatol. 2011;35:162–70.

    Article  PubMed  Google Scholar 

  8. Johnson L, Bhutani VK. The clinical syndrome of bilirubin-induced neurologic dysfunction. Semin Perinatol. 2011;35:101–13.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  10. Agrawal VK, Shukla R, Misra PK, Kapoor RK, Malik GK. Brainstem auditory evoked response in newborns with hyperbilirubinemia. Indian Pedia. 1998;35:513–8.

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Berlin CI, Hood LJ, Morlet T, Wilensky D, Li L, Mattingly KR, et al. Multi-site diagnosis and management of 260 patients with auditory neuropathy/dys-synchrony (auditory neuropathy spectrum disorder). Int J Audio. 2010;49:30–43. https://doi.org/10.3109/14992020903160892

    Article  Google Scholar 

  13. Smith JC, Marsh JT, Brown WS. Far-field recorded frequency-following responses: evidence for the locus of brainstem sources. Electro Neurophysiol. 1975;39:465–72.

    Article  CAS  Google Scholar 

  14. Gardi J, Merzenich M, McKean C. Origins of the scalp recorded frequency-following response in the cat. Audiology. 1979;18:358–81.

    CAS  PubMed  Google Scholar 

  15. Sohmer H, Pratt H, Kinarti R. Sources of frequency following responses (FFR) in man. Electroencephalogr Clin Neurophysiol. 1977;42:656–64.

    Article  CAS  PubMed  Google Scholar 

  16. Hoormann J, Falkenstein M, Hohnsbein J, Blanke L. The human frequency-following response (FFR): normal variability and relation to the click-evoked brainstem response. HearRes. 1992;59:179–88.

    CAS  Google Scholar 

  17. Anderson S, Parbery-Clark A, White-Schwoch T, Kraus N. Development of subcortical speech representation in human infants. J Acoust Soc Am. 2015;137:3346–55.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Musacchia G, Ortiz-Mantilla S, Roesler CP, Rajendran S, Morgan-Byrne J, Benasich AA. Effects of noise and age on the infant brainstem response to speech. Clin Neurophysiol. 2018;129:2623–34.

    Article  PubMed  Google Scholar 

  19. Krishnan A, Xu Y, Gandour J, Cariani P. Encoding of pitch in the human brainstem is sensitive to language experience. Cogn Brain Res. 2005;25:161–8.

    Article  Google Scholar 

  20. Cunningham J, Nicol T, King C, Zecker SG, Kraus N. Effects of noise and cue enhancement on neural responses to speech in auditory midbrain, thalamus and cortex. Hear Res. 2002;169:97–111.

    Article  PubMed  Google Scholar 

  21. Russo N, Nicol T, Musacchia G, Kraus N. Brainstem responses to speech syllables. Clin Neurophysiol. 2004;115:2021–30.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Musacchia G, Sams M, Skoe E, Kraus N. Musicians have enhanced subcortical auditory and audiovisual processing of speech and music. Proc Natl Acad Sci USA. 2007;104:15894–8.

    Article  CAS  PubMed  Google Scholar 

  23. Musacchia G, Strait D, Kraus N. Relationships between behavior, brainstem and cortical encoding of seen and heard speech in musicians and non-musicians. Hear Res. 2008;241:34–42.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kraus N, Lindley T, Colegrove D, Krizman J, Otto-Meyer S, Thompson EC, et al. The neural legacy of a single concussion. Neurosci Lett. 2017;646:21–23.

    Article  CAS  PubMed  Google Scholar 

  25. Cunningham J, Nicol T, Zecker SG, Bradlow A, Kraus N. Neurobiologic responses to speech in noise in children with learning problems: deficits and strategies for improvement. Clin Neurophysiol. 2001;112:758–67.

    Article  CAS  PubMed  Google Scholar 

  26. King C, Warrier CM, Hayes E, Kraus N. Deficits in auditory brainstem pathway encoding of speech sounds in children with learning problems. Neurosci Lett. 2002;319:111–5.

    Article  CAS  PubMed  Google Scholar 

  27. Wible B, Nicol T, Kraus N. Atypical brainstem representation of onset and formant structure of speech sounds in children with language-based learning problems. Biol Psychol. 2004;67:299–317.

    Article  PubMed  Google Scholar 

  28. Du L-z. Neonatal hyperbilirubinemia diagnosis and treatment expert consensus. Chin J Pedia. 2014;52:745–8.

    Google Scholar 

  29. Hall JW 3rd. Anatomy and Physiology Principles of Auditory Evoked Responses. New Handbook of Auditory Evoked Responses. Needham Heights, MA: Allyn and Bacon; 2007. p. 41–47.

    Google Scholar 

  30. Hall JW 3rd, Rupp KA. Auditory brainstem response: recent developments in recording and analysis. Adv Otorhinolaryngol. 1997;53:21–45.

    PubMed  Google Scholar 

  31. Issa A, Ross HF. An improved procedure for assessing ABR latency in young subjects based on a new normative data set. Int J Pedia Otorhinolaryngol. 1995;32:35–47.

    Article  CAS  Google Scholar 

  32. Musacchia G, Sams M, Nicol T, Kraus N. Seeing speech affects acoustic information processing in the human brainstem. Exp Brain Res. 2006;168:1–10.

    Article  PubMed  Google Scholar 

  33. Klatt DH. Software for a cascade/parallel formant synthesizer. J Acoust Soc Am. 1980;67:971–95.

    Article  Google Scholar 

  34. Skoe E, Krizman J, Anderson S, Kraus N. Stability and plasticity of auditory brainstem function across the lifespan. Cereb Cortex. 2015;25:1415–26.

    Article  PubMed  Google Scholar 

  35. Jeng FC, Schnabel EA, Dickman BM, Hu J, Li X, Lin CD, et al. Early maturation of frequency-following responses to voice pitch in infants with normal hearing. Percept Mot Skills. 2010;111:765–84.

    Article  PubMed  Google Scholar 

  36. Worden FG, Marsh JT. Frequency-following (microphonic-like) neural responses evoked by sound. Electro Neurophysiol Suppl. 1968;25:42–62.

    Article  CAS  Google Scholar 

  37. Song JH, Nicol T, Kraus N. Test-retest reliability of the speech-evoked auditory brainstem response. Clin Neurophysiol. 2011;122:346–55.

    Article  PubMed  Google Scholar 

  38. Bhagat S The Freqency Following Response. In: Atcherson SS,TM (ed). Auditory Eletrophysiology Thieme: NY, NY, 2012, pp 86–102.

  39. Bidelman GM. Subcortical sources dominate the neuroelectric auditory frequency-following response to speech. Neuroimage. 2018;175:56–69.

    Article  PubMed  Google Scholar 

  40. Chandrasekaran B, Kraus N. The scalp-recorded brainstem response to speech: neural origins and plasticity. Psychophysiology. 2010;47:236–46.

    Article  PubMed  Google Scholar 

  41. Coultrap SJ, Bayer KU. CaMKII regulation in information processing and storage. Trends Neurosci. 2012;35:607–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shapiro SM, Nakamura H. Bilirubin and the auditory system. J Perinatol. 2001;21(Suppl 1): S52–55. discussion S59-62

    Article  PubMed  Google Scholar 

  43. Churn SB, DeLorenzo RJ, Shapiro SM. Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro. Pediatr Res. 1995;38:949–54.

    Article  CAS  PubMed  Google Scholar 

  44. Uboha NV, Flajolet M, Nairn AC, Picciotto MR. A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth. J Neurosci. 2007;27:4413–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Eggermont JJ. Physiology of the Developing Auditory System. In: Trehub SES,B (ed). Auditory Development in Infancy Springer: Switzerland, 1985, pp 21–45.

    Chapter  Google Scholar 

  46. Eilers RE. Infant Speech Perception. Auditory Development in Infancy. Switzerland: Springer; 1985. p. 197–213.

    Chapter  Google Scholar 

  47. Campbell DM, Danayan KC, McGovern V, Cheema S, Stade B, Sgro M. Transcutaneous bilirubin measurement at the time of hospital discharge in a multiethnic newborn population. Paediatr Child Health. 2011;16:141–5.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Banai K, Nicol T, Zecker SG, Kraus N. Brainstem timing: implications for cortical processing and literacy. JNeurosci. 2005;25:9850–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ms. Yaofang Hu and Drs. Anna Zhdamirova, Esther Pugh, and Hayley Shillington for their assistance in data collection.

Funding

This work was supported in part by the Department of Audiology at University of the Pacific and the Department of Pediatrics at the Nanjing Maternal and Child Health Hospital Associated to Nanjing Medical University.

Author information

Authors and Affiliations

  1. Department of Audiology, University of the Pacific, San Francisco, CA, 94103, USA

    Gabriella Musacchia & Jiong Hu

  2. Department of Otolaryngology - Head and Neck Surgery, Stanford University, Stanford, CA, 94305, USA

    Gabriella Musacchia, Nikolas H. Blevins & Matthew B. Fitzgerald

  3. Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Stanford, CA, 94305, USA

    Vinod K. Bhutani & Ronald J. Wong

  4. Department of Pediatrics, Nanjing Maternal and Child health Hospital of Nanjing Medical University, Nanjing, China

    Mei-Ling Tong & Shuping Han

Authors
  1. Gabriella Musacchia
    View author publications

    Search author on:PubMed Google Scholar

  2. Jiong Hu
    View author publications

    Search author on:PubMed Google Scholar

  3. Vinod K. Bhutani
    View author publications

    Search author on:PubMed Google Scholar

  4. Ronald J. Wong
    View author publications

    Search author on:PubMed Google Scholar

  5. Mei-Ling Tong
    View author publications

    Search author on:PubMed Google Scholar

  6. Shuping Han
    View author publications

    Search author on:PubMed Google Scholar

  7. Nikolas H. Blevins
    View author publications

    Search author on:PubMed Google Scholar

  8. Matthew B. Fitzgerald
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Gabriella Musacchia.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Musacchia, G., Hu, J., Bhutani, V.K. et al. Frequency-following response among neonates with progressive moderate hyperbilirubinemia. J Perinatol 40, 203–211 (2020). https://doi.org/10.1038/s41372-019-0421-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41372-019-0421-y

This article is cited by

Search

Advanced search

Quick links