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Brainstem auditory pathway maturation in term neonates with congenital cytomegalovirus infection: a cohort study

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Abstract

Congenital cytomegalovirus infection (cCMVi) is a leading cause of sensorineural hearing loss (SNHL) and developmental delay. Brainstem auditory evoked potentials (BAEPs) recording allows assessment of central auditory pathway maturation in neonates. We aimed to characterize the effect of cCMVi on the maturation of the brainstem auditory pathway in term neonates. We retrospectively reviewed medical records of neonates born with cCMVi in 2010–2018 and characterized their auditory pathway maturation using brainstem auditory-evoked potentials (BAEPs). We compared inter-peak latency differences (IPLDs) of the main BAEP components (I–V, I–III, and III–V) in terms of cCMVi patients and healthy controls and described their changes in cCMVi patients throughout the first year of life. Of 101 cCMVi patients, 57 (56.4%) were considered symptomatic, 6 (5.9%) were small for gestational age, 6 (5.9%) had microcephaly, 4 (4%) had thrombocytopenia, 5 (6.6%) had hepatitis, 2 (2.1%) had retinitis, 47 (49.5%) had typical abnormalities on head ultrasound, 9 (8.9%) developed SNHL, and 34 (59.6%) received antiviral therapy. No significant difference was found between IPLDs of full-term cCMVi patients compared to controls throughout the entire auditory pathway (I–III, III–V, and I–V IPLDs), for both ears (p > 0.05). On serial BAEP examinations, cCMVi patients presented decreased IPLDs throughout the first year of life (p < 0.05 of compared 1st, 2nd, and 3rd BAEPs in both ears).

   Conclusions: Intrauterine cytomegalovirus infection does not affect the auditory brainstem maturation process in term neonates. Our findings support previous studies noting the normal neurodevelopmental outcome of asymptomatic cCMVi patients, suggesting antiviral treatment is not warranted in these cases.

What is Known:

• cCMVi is a leading cause of developmental delay and hearing loss. Treatment is recommended for patients with symptomatic diseases who are at significant risk of long-term sequelae.

• It is unknown whether cCMVi affects the central nervous system maturation process.

What is New:

• We performed a neurophysiological evaluation of brainstem conduction by recording the BAEPs. We found that cCMVi has no significant impact on central conduction times along the auditory pathways in the brainstem at birth nor changes the neuronal maturation process during the first year of life.

• Our findings suggest that cCMVi does not universally affect central nervous system maturation, supporting a highly selective approach when considering the benefits of antiviral therapy.

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Data availability

All data and materials are available to the authors and will be provided upon specific requests.

Abbreviations

BAEP:

Brainstem auditory evoked potentials

CCMVi:

Congenital cytomegalovirus infection

CI:

Confidence interval

CNS:

Central nervous system

dB:

Decibels

HUS:

Head ultrasound

IPLD:

Inter-peak latency differences

LSV:

Lenticulostriate vasculopathy

MRI:

Magnetic resonance imaging

SGA:

Small for gestational age

SNHL:

Sensorineural hearing loss

References

  1. Kimberlin DW, Jester PM, Sanchez PJ et al (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372(10):933–943

    Article  CAS  Google Scholar 

  2. Luck SE, Wieringa JW, Blázquez-Gamero D et al (2017) Congenital cytomegalovirus: a European expert consensus statement on diagnosis and management. Pediatr Infect Dis J 36(12):1205–1213

    Article  Google Scholar 

  3. Boppana SB, Ross SA, Fowler KB (2013) Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis an Off Publ Infect Dis Soc Am 57 Suppl 4(Suppl 4):S178–81

  4. Ross SA, Kimberlin D (2021) Clinical outcome and the role of antivirals in congenital cytomegalovirus infection. Antiviral Res 191:105083

    Article  CAS  Google Scholar 

  5. Lopez AS, Lanzieri TM, Claussen AH et al (2017) Intelligence and academic achievement with asymptomatic congenital cytomegalovirus infection. Pediatrics 140(5):e20171517

    Article  Google Scholar 

  6. Rawlinson WD, Boppana SB, Fowler KB et al (2017) Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 17(6):e177–e188

    Article  Google Scholar 

  7. Wilkinson AR, Jiang ZD (2006) Brainstem auditory evoked response in neonatal neurology. Semin Fetal Neonatal Med 11(6):444–451

    Article  Google Scholar 

  8. Eggermont JJ (2019) Auditory brainstem response. Handb Clin Neurol 160:451–464

    Article  Google Scholar 

  9. Hafner H, Pratt H, Joachims Z, Feinsod M, Blazer S (1991) Development of auditory brainstem evoked potentials in newborn infants: a three-channel Lissajous’ trajectory study. Hear Res 51(1):33–47

    Article  CAS  Google Scholar 

  10. Raposo D, Orfão J, Menezes M, Trindade-Soares M, Guimarães A, Freire F (2021) Auditory brainstem response in preterm infants in the neonatal intensive care unit. Otolaryngol neck Surg Off J Am Acad Otolaryngol Neck Surg 164(4):884–888

    Article  Google Scholar 

  11. Coenraad S, Hoeve LJ, Goedegebure A (2011) Incidence and clinical value of prolonged I-V interval in NICU infants after failing neonatal hearing screening. Eur Arch oto-rhino-laryngology Off J Eur Fed Oto-Rhino-Laryngological Soc Affil with Ger Soc Oto-Rhino-Laryngology - Head Neck Surg 268(4):501–505

    CAS  Google Scholar 

  12. Antinmaa J, Lapinleimu H, Salonen J, Stolt S, Kaljonen A, Jääskeläinen S (2020) Neonatal brainstem auditory function associates with early receptive language development in preterm children. Acta Paediatr 109(7):1387–1393

    Article  Google Scholar 

  13. Talge NM, Adkins M, Kileny PR, Frownfelter I (2022) Click-evoked auditory brainstem responses and autism spectrum disorder: a meta-analytic investigation of disorder specificity. Pediatr Res 92(1):40–46

    Article  Google Scholar 

  14. Matin F, Haumann S, Roßberg W, Mitovska D, Lenarz T, Lesinski-Schiedat A (2021) Monitoring of the auditory pathway maturation after early intervention during the first year of life in infants with sensorineural hearing loss. Eur Arch oto-rhino-laryngology Off J Eur Fed Oto-Rhino-Laryngological Soc Affil with Ger Soc Oto-Rhino-Laryngology - Head Neck Surg 278(11):4187–4197

    CAS  Google Scholar 

  15. Giannattasio A, Bruzzese D, Di Costanzo P et al (2018) Neuroimaging profiles and neurodevelopmental outcome in infants with congenital cytomegalovirus infection. Pediatr Infect Dis J 37(10):1028–1033

    Article  Google Scholar 

  16. Giannattasio A, Di Costanzo P, Milite P et al (2017) Is lenticulostriated vasculopathy an unfavorable prognostic finding in infants with congenital cytomegalovirus infection? J Clin Virol Off Publ Pan Am Soc Clin Virol 91:31–35

    Article  Google Scholar 

  17. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon E-S (2005) Birth weight standards in the live-born population in Israel. Isr Med Assoc J 7(5):311–314

    Google Scholar 

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Authors and Affiliations

  1. Pediatric Infectious Disease Unit, Rambam Health Care Campus, Haifa, Israel

    Imad Kassis, Danielle Bero & Michal Meir

  2. The Neurophysiological Laboratory, Rambam Heath Care Campus, Haifa, Israel

    Hava Hafner & Andrei Chistyakov

Authors
  1. Imad Kassis
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  2. Danielle Bero
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  3. Hava Hafner
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  4. Andrei Chistyakov
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  5. Michal Meir
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Danielle Bero, Hava Hafner, Andrei Chistyakov, and Michal Meir. The first draft of the manuscript was written by Michal Meir, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Michal Meir.

Ethics declarations

Ethics approval and consent to participate

This is an observational study. The Rambam Medical Center Research Institutional Ethics Committee has approved the study in accordance with the Declaration of Helsinki.

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This was a retrospective observational study with de-identified data; therefore, no informed consent was needed to obtain or publish the data.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Tobias Tenenbaum

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Kassis, I., Bero, D., Hafner, H. et al. Brainstem auditory pathway maturation in term neonates with congenital cytomegalovirus infection: a cohort study. Eur J Pediatr 182, 95–100 (2023). https://doi.org/10.1007/s00431-022-04644-z

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  • DOI: https://doi.org/10.1007/s00431-022-04644-z

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