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

  • Lev Dorfman
  • Jacob Amir
  • Joseph Attias
  • Efraim BilavskyEmail author
Original Article

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.

Keywords

Cytomegalovirus Congenital cytomegalovirus cCMV Congenital infection Late treatment Late hearing loss Hearing loss Valganciclovir Ganciclovir 

Abbreviations

BERA

Brainstem evoked response audiometry

cCMV

Congenital cytomegalovirus

CMV

Cytomegalovirus

CNS

Central nervous system

SNHL

Sensorineural hearing loss

US

Ultrasound

Notes

Acknowledgements

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

Authors’ 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.

Compliance with ethical standards

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.

References

  1. 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 CrossRefPubMedGoogle Scholar
  2. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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 CrossRefPubMedGoogle Scholar
  4. 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 CrossRefGoogle Scholar
  5. 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 CrossRefGoogle Scholar
  6. 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 CrossRefGoogle Scholar
  7. 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 CrossRefPubMedGoogle Scholar
  8. 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 CrossRefPubMedGoogle Scholar
  9. 9.
  10. 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 CrossRefPubMedGoogle Scholar
  11. 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 CrossRefGoogle Scholar
  12. 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 CrossRefGoogle Scholar
  13. 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 143:16–25CrossRefGoogle Scholar
  14. 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 11:283–290PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Pediatrics CSchneider Children’s Medical CenterPetah TiqvaIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Institute of Audiology and Clinical NeurophysiologySchneider Children’s Medical CenterPetah TiqvaIsrael
  4. 4.Department of Communication Sciences & DisordersUniversity of HaifaHaifaIsrael

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