Skip to main content

Advertisement

SpringerLink
Log in

Treatment of congenital cytomegalovirus beyond the neonatal period: an observational study

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Recently, valganciclovir treatment of symptomatic congenital cytomegalovirus (cCMV) disease, commenced during the neonatal period (≤ 4 weeks), was found to improve hearing and developmental outcome. However, many children (symptomatic or asymptomatic at birth) present only after 4 weeks of age. The purpose of this observational retrospective study was to describe the outcome and safety of valganciclovir therapy in infants with cCMV who started treatment > 4 weeks of life. Of the 91children who started antiviral treatment > 4 weeks of age, 66/298 (22.2%) were symptomatic at birth; 25/217 (11.5%) were asymptomatic at birth. Treatment was initiated on average at 14 weeks of age (range 5–77 weeks) and at 53.3 weeks (range 12–156 weeks), respectively. Of the 45 affected ears in the symptomatic group, 30 (66.7%) improved and only 2 (4.4%) deteriorated, with most of the improved ears (27/30, 90%) returning to normal. In the asymptomatic group, late-onset treatment was initiated and out of the 42 deteriorated ears, 38 (90.5%) improved after at least 1 year of follow-up. Hematological adverse events, i.e., neutropenia, were noted in a minority of cases (4.4%).

Conclusion: Our study demonstrates the benefits and safety aspects of treating symptomatic and asymptomatic children with cCMV even beyond the recommended neonatal period.

What is Known:

• Valganciclovir treatment of symptomatic congenital cytomegalovirus (cCMV) disease, commenced during the neonatal period, is beneficial in improving hearing and developmental outcome.

• However, data of treatment started beyond the neonatal period is lacking.

What is New:

• Our study demonstrates the benefits of treating symptomatic children with cCMV as well as asymptomatic children that develop late-onset hearing loss even beyond the recommended neonatal period.

• This was true for symptomatic children who presented > 4 weeks as well as to those were asymptomatic at birth but experienced late hearing deterioration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abbreviations

BERA:

Brainstem evoked response audiometry

cCMV:

Congenital cytomegalovirus

CMV:

Cytomegalovirus

CNS:

Central nervous system

SNHL:

Sensorineural hearing loss

US:

Ultrasound

References

  1. Bilavsky E, Pardo J, Attias J, Levy I, Magny FJ, Ville Y, Leruez-Ville M, Amir J (2016) Clinical implications for children born with congenital cytomegalovirus infection following a negative amniocentesis. Clin Infect Dis 63(1):33–38. https://doi.org/10.1093/cid/ciw237

    Article  PubMed  Google Scholar 

  2. Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG, Ashouri N, Englund JA, Estrada B, Jacobs RF, Romero JR, Sood SK, Whitworth MS, Abzug MJ, Caserta MT, Fowler S, Lujan-Zilbermann J, Storch GA, DeBiasi RL, Han JY, Palmer A, Weiner LB, Bocchini JA, Dennehy PH, Finn A, Griffiths PD, Luck S, Gutierrez K, Halasa N, Homans J, Shane AL, Sharland M, Simonsen K, Vanchiere JA, Woods CR, Sabo DL, Aban I, Kuo H, James SH, Prichard MN, Griffin J, Giles D, Acosta EP, Whitley RJ, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372(10):933–943. https://doi.org/10.1056/NEJMoa1404599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bilavsky E, Shahar-Nissan K, Pardo J, Attias J, Amir J (2016) Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. Arch Dis Child 101(5):433–438. https://doi.org/10.1136/archdischild-2015-309154

    Article  PubMed  Google Scholar 

  4. Lombardi G, Garofoli F, Stronati M (2016) Congenital cytomegalovirus infection: treatment, sequelae and follow-up. J Matern Fetal Neonatal Med 23:45–48. https://doi.org/10.3109/14767058.2010.506753

  5. Goderis J, Keymeulen A, Smets K, Van Hoecke H, De Leenheer E, Boudewyns A, Desloovere C, Kuhweide R, Muylle M, Royackers L, Schatteman I, Dhooge I (2016) Hearing in children with congenital cytomegalovirus infection: results of a longitudinal study. J Pediatr 172:110–115. https://doi.org/10.1016/j.jpeds.2016.01.024

  6. Amir J, Attias J, Pardo J (2014) Treatment of late-onset hearing loss in infants with congenital congenital cytomegalovirus infection. Clin Pediatr 53:444–448. https://doi.org/10.1177/0009922813510204

    Article  Google Scholar 

  7. del Rosal T, Baquero-Artigao F, Blázquez D, Noguera-Julian A, Moreno-Perez D, Reyes A, Vilas J (2012) Treatment of symptomatic congenital cytomegalovirus infection beyond the neonatal period. J Clin Virol 55:72–74. https://doi.org/10.1016/j.jcv.2012.06.001

    Article  PubMed  Google Scholar 

  8. Imamura T, Suzutani T, Ogawa H, Asano K, Nomoto M, Matsui T, Momoi N, Ikuta K, Inoue N, Hosoya M (2011) Oral valganciclovir treatment for congenital cytomegalovirus infection. Pediatr Int 53:249–252. https://doi.org/10.1111/j.1442-200X.2010.03217.x

    Article  CAS  PubMed  Google Scholar 

  9. https://clinicaltrials.gov/ct2/show/NCT01649869?term=NCT01649869&rank=1. Accessed October 3, 2018

  10. Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, Daly K, Doutré S, Gibson L, Giles ML, Greenlee J, Hamilton ST, Harrison GJ, Hui L, Jones CA, Palasanthiran P, Schleiss MR, Shand AW, van Zuylen WJ (2017) Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 17:e177–e188. https://doi.org/10.1016/S1473-3099(17)30143-3

    Article  PubMed  Google Scholar 

  11. Luck SE, Wieringa JW, Blázquez-Gamero D, Henneke P, Schuster K, Butler K, Capretti MG, Cilleruelo MJ, Curtis N, Garofoli F, Heath P, Iosifidis E, Klein N, Lombardi G, Lyall H, Nieminen T, Pajkrt D, Papaevangelou V, Posfay-Barbe K, Puhakka L, Roilides E, Rojo P, Saavedra-Lozano J, Shah T, Sharland M, Saxen H Vossen ACTM; ESPID Congenital CMV Group Meeting, Leipzig 2015 (2017) Congenital cytomegalovirus: a European expert consensus statement on diagnosis and management. Pediatr Infect Dis J 36:1205–1213. https://doi.org/10.1097/INF.0000000000001763

  12. Faure-Bardon V, Magny JF, Parodi M, Couderc S, Garcia P, Maillotte AM, Benard M, Pinquier D, Astruc D, Patural H, Pladys Ppladys P, Parat S, Guillois B, Garenne A, Bussières L, Guilleminot T, Stirnemann J, Ghout I, Ville Y, Leruez-Ville M (2018) Sequelae of congenital cytomegalovirus (cCMV) following maternal primary infection are limited to those acquired in the first trimester of pregnancy. Clin Infect Dis doi: https://doi.org/10.1093/cid/ciy1128

  13. Kimberlin DW, Lin CY, Sánchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong SJ, Whitley RJ, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (2003) Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 143:16–25

    Article  CAS  Google Scholar 

  14. Dahle AJ, Fowler KB, Wright JD, Boppana SB, Wj B, Pass RF (2000) Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol 11:283–290

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Mrs. Phyllis Curchack Kornspan for her editorial services.

Author information

Authors and Affiliations

  1. Department of Pediatrics C, Schneider Children’s Medical Center, Petah Tiqva, Israel

    Lev Dorfman, Jacob Amir & Efraim Bilavsky

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Lev Dorfman, Jacob Amir & Efraim Bilavsky

  3. Institute of Audiology and Clinical Neurophysiology, Schneider Children’s Medical Center, Petah Tiqva, Israel

    Joseph Attias

  4. Department of Communication Sciences & Disorders, University of Haifa, Haifa, Israel

    Joseph Attias

Authors
  1. Lev Dorfman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacob Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph Attias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Efraim Bilavsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Dorfman collected tha data and wrote the manuscript. Dr. Amir and Dr. Attias helped in writing of the manuscript. Dr. Bilavsky was responsible for protocol development, data collection and writing of the manuscript.

Corresponding author

Correspondence to Efraim Bilavsky.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with animals performed by any of the authors. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Communicated by Nicole Ritz

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

Dorfman, L., Amir, J., Attias, J. et al. Treatment of congenital cytomegalovirus beyond the neonatal period: an observational study. Eur J Pediatr 179, 807–812 (2020). https://doi.org/10.1007/s00431-019-03558-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-019-03558-7

Keywords

Search

Navigation