Targeted screening for congenital cytomegalovirus infection in infants who fail universal newborn hearing screen.
Abstract Introduction: Given the importance of early antiviral treatment in infants with sensorineural hearing loss secondary to congenital cytomegalovirus infection (cCMV), we submit a protocol for early diagnosis of cCMV according to the outcome of universal newborn hearing screening using automated auditory brainstem responses (AABR) (targeted CMV screening). Material and methods: Based on current knowledge provides by literature, we elaborate an action algorithm agreed between the coordinators of the Early Hearing Detection and Intervention program in Castilla y León (Spain). Results: If the first AABR test is a refer result for one or both ears, we request the identification of the viral genome by PCR in a urine sample within 15 days. The confirmation of uni or bilateral sensorineural hearing loss, allows the beginning of the antiviral treatment, before the first month of life. Discussion: Universal screening of cCMV enables monitoring of all infected infants, identifying cases of late-onset/progressive hearing loss sooner; but in the presence of an unknown cause- sensorineural hearing loss from the first two weeks of life, efforts must be made to rule out cCMV infection, although it is more complicated under these conditions. Conclusion: The inclusion of cCMV diagnosis into neonatal hearing screening program, will allow early detection of congenital infection in some infants, improving their quality of life.
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American Academy of Pediatrics, Joint Committee on Infant Hearing. Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs, Pediatrics 120 (2007) 898–921.
Alarcón Allen A, Baquero-Artigao F. Grupo de estudio de la infección por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Revisión y recomendaciones sobre la prevención, diagnóstico y tratamiento de la infección posnatal por citomegalovirus. An Pediatr (Barc). 2011;74(1):52.e1-52.e13. doi: 10.1016/j.anpedi.2010.05.024.
Baquero-Artigao F y Grupo de estudio de la infección congénita por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Documento de consenso de la Sociedad Española de Infectología Pediátrica sobre el diagnóstico y el tratamiento de la infección congénita por citomegalovirus. An Pediatr (Barc). 2009;71(6):535-47. doi: 10.1016/j.anpedi.2009.07.029.
Barbi M, Binda S, Caroppo S, Ambrosetti U, Corbetta C, Sergi P. A wider role for congenital cytomegalovirus infection in sensorineural hearing loss. Pediatr Infect Dis J. 2003;22(1):39-42.
Barkai G, Ari-Even Roth D, Barzilai A, Tepperberg-Oikawa M, Mendelson E, Hildesheimer M, et al. Universal neonatal cytomegalovirus screening using saliva - report of clinical experience. J Clin Virol. 2014;60(4):361-6. doi: 10.1016/j.jcv.2014.04.024.
Bartlett AW, Hall BM, Palasanthiran P, McMullan B, Shand AW, Rawlinson WD. Recognition, treatment, and sequelae of congenital cytomegalovirus in Australia: An observational study. J Clin Virol. 2018;108:121-5. doi: 10.1016/j.jcv.2018.09.017.
Bergevin A, Zick CD, McVicar SB, Park AH. Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection. Int J Pediatr Otorhinolaryngol. 2015;79(12):2090-3. doi: 10.1016/j.ijporl.2015.09.019.
Cannon MJ. Congenital cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol. 2009;46 Suppl 4:S6-10. doi: 10.1016/j.jcv.2009.09.002.
Cannon MJ, Griffiths PD, Aston V, Rawlinson WD. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?. Rev Med Virol. 2014;24(5):291-307. doi: 10.1002/rmv.1790.
Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202-13. doi: 10.1002/rmv.655.
Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007;17(5):355-63.
Dahle AJ, Fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol. 2000;11(5):283-90.
Engman ML, Malm G, Engstrom L, Petersson K, Karltorp E, Tear Fahnehjelm K, et al. Congenital CMV infection: prevalence in newborns and the impact on hearing deficit. Scand J Infect Dis. 2008;40(11-12):935-42. doi: 10.1080/00365540802308431.
Foulon I, Naessens A, Faron G, Foulon W, Jansen AC, Gordts F. Hearing thresholds in children with a congenital CMV infection: a prospective study. Int J Pediatr Otorhinolaryngol. 2012 May;76(5):712-7. doi: 10.1016/j.ijporl.2012.02.026.
Fowler KB, Dahle AJ, Boppana SB, Pass RF. Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?. J Pediatr. 1999;135(1):60-4.
Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr. 1997;130(4):624-30.
Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014;134(5):972-82. doi: 10.1542/peds.2014-1173.
Grosse SD, Ross DS, Dollard SC. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol. 2008;41(2):57-62.
Ibáñez-Muñoz C, Calle-Cabanillas MI, Pérez-Sáez J, Navazo-Eguía AI, Clemente-García A, García-Vicario F, et al. Evolución de la audición en niños con infección congénita por citomegalovirus. Rev Soc Otorrinolaringol Castilla Leon Cantab La Rioja. 2013;4(21):159-64.
Junta de Castilla y León. Consejería de Sanidad. Programa de detección precoz y atención integral de la hipoacusia infantil. 2004. 78 pp.
Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011;87(11):723-8. doi: 10.1016/j.earlhumdev.2011.08.021.
Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007;17(4):253-76.
Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933-43. doi: 10.1056/NEJMoa1404599.
Korver AM, de Vries JJ, Konings S, de Jong JW, Dekker FW, Vossen AC, et al. DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands. J Clin Virol. 2009;46 Suppl 4:S27-31. doi: 10.1016/j.jcv.2009.09.007.
Luck SE, Wieringa JW, Blázquez-Gamero D, Henneke P, Schuster K, Butler K, et al. Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management. Pediatr Infect Dis J. 2017 Dec;36(12):1205-13. doi: 10.1097/INF.0000000000001763.
Moteki H, Isaka Y, Inaba Y, Motobayashi M, Nishio SY, Ohira S, et al. A rational approach to identifying newborns with hearing loss caused by congenital cytomegalovirus infection by dried blood spot screening. Acta Otolaryngol. 2018;138(8):708-12. doi: 10.1080/00016489.2018.1441545.
Núñez-Batalla F, Trinidad-Ramos G, Sequí-Canet JM, Alzina De Aguilar V, Jáudenes-Casaubón C. Risk factors for sensorineural hearing loss in children. Acta Otorrinolaringol Esp. 2012;63(5):382-90. doi: 10.1016/j.otorri.2011.02.007.
Ory F de, Ramírez R, García Comas L, León P, Sagües MJ, Sanz JC. Is there a change in cytomegalovirus seroepidemiology in Spain?. Eur J Epidemiol. 2004;19(1):85-9.
Pass RF. Congenital cytomegalovirus infection and hearing loss. Herpes. 2005;12(2):50-5. Review.
Pass RF, Fowler KB, Boppana SB, Britt WJ, Stagno S. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol. 2006;35(2):216-20.
Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017;17(6):e177-e188. doi: 10.1016/S1473-3099(17)30143-3. Epub 2017 Mar 11.
Rawlinson WD, Palasanthiran P, Hall B, Al Yazidi L, Cannon MJ, Cottier C, et al. Neonates with congenital Cytomegalovirus and hearing loss identified via the universal newborn hearing screening program. J Clin Virol. 2018;102:110-5. doi: 10.1016/j.jcv.2018.03.006.
Riga M, Korres G, Chouridis P, Naxakis S, Danielides V. Congenital cytomegalovirus infection inducing non-congenital sensorineural hearing loss during childhood; a systematic review. Int J Pediatr Otorhinolaryngol. 2018;115:156-64. doi: 10.1016/j.ijporl.2018.10.005.
Reina J, Weber I, Riera E, Busquets M, Morales C. Utilidad de una técnica de Reacción en Cadena de la Polimerasa (PCR) cuantitativa en tiempo real en el diagnóstico de infección congénita y posnatal por citomegalovirus. An Pediatr (Barc). 2014;80(5):299-303. doi: 10.1016/j.anpedi.2013.06.036.
Royackers L, Rector E, Verhaert N, Desloovere C. Long-term audiological follow-up of children with congenital cytomegalovirus. B-ENT. 2013;Suppl 21:57-64.
Stehel EK, Shoup AG, Owen KE, Jackson GL, Sendelbach DM, Boney LF, et al. Newborn hearing screening and detection of congenital cytomegalovirus infection. Pediatrics. 2008;121(5):970-5. doi: 10.1542/peds.2006-3441.
Toumpas CJ, Clark J, Harris A, Beswick R, Nourse CB. Congenital cytomegalovirus infection is a significant cause of moderate to profound sensorineural hearing loss in Queensland children. J Paediatr Child Health. 2015;51(5):541-4. doi: 10.1111/jpc.12776.
Williams EJ, Gray J, Luck S, Atkinson C, Embleton ND, Kadambari S, et al. First estimates of the potential cost and cost saving of protecting childhood hearing from damage caused by congenital CMV infection. Arch Dis Child Fetal Neonatal Ed. 2015;100(6):F501-6. doi: 10.1136/archdischild-2014-306756.
Williamson WD, Demmler GJ, Percy AK, Catlin FI. Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection. Pediatrics. 1992;90(6):862-6.
Yamamoto AY, Mussi-Pinhata MM, Marin LJ, Brito RM, Oliveira PF, Coelho TB. Is saliva as reliable as urine for detection of cytomegalovirus DNA for neonatal screening of congenital CMV infection? J Clin Virol. 2006 Jul;36(3):228-30.
Alarcón Allen A, Baquero-Artigao F. Grupo de estudio de la infección por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Revisión y recomendaciones sobre la prevención, diagnóstico y tratamiento de la infección posnatal por citomegalovirus. An Pediatr (Barc). 2011;74(1):52.e1-52.e13. doi: 10.1016/j.anpedi.2010.05.024.
Baquero-Artigao F y Grupo de estudio de la infección congénita por citomegalovirus de la Sociedad Española de Infectología Pediátrica. Documento de consenso de la Sociedad Española de Infectología Pediátrica sobre el diagnóstico y el tratamiento de la infección congénita por citomegalovirus. An Pediatr (Barc). 2009;71(6):535-47. doi: 10.1016/j.anpedi.2009.07.029.
Barbi M, Binda S, Caroppo S, Ambrosetti U, Corbetta C, Sergi P. A wider role for congenital cytomegalovirus infection in sensorineural hearing loss. Pediatr Infect Dis J. 2003;22(1):39-42.
Barkai G, Ari-Even Roth D, Barzilai A, Tepperberg-Oikawa M, Mendelson E, Hildesheimer M, et al. Universal neonatal cytomegalovirus screening using saliva - report of clinical experience. J Clin Virol. 2014;60(4):361-6. doi: 10.1016/j.jcv.2014.04.024.
Bartlett AW, Hall BM, Palasanthiran P, McMullan B, Shand AW, Rawlinson WD. Recognition, treatment, and sequelae of congenital cytomegalovirus in Australia: An observational study. J Clin Virol. 2018;108:121-5. doi: 10.1016/j.jcv.2018.09.017.
Bergevin A, Zick CD, McVicar SB, Park AH. Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection. Int J Pediatr Otorhinolaryngol. 2015;79(12):2090-3. doi: 10.1016/j.ijporl.2015.09.019.
Cannon MJ. Congenital cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol. 2009;46 Suppl 4:S6-10. doi: 10.1016/j.jcv.2009.09.002.
Cannon MJ, Griffiths PD, Aston V, Rawlinson WD. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?. Rev Med Virol. 2014;24(5):291-307. doi: 10.1002/rmv.1790.
Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202-13. doi: 10.1002/rmv.655.
Dollard SC, Grosse SD, Ross DS. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007;17(5):355-63.
Dahle AJ, Fowler KB, Wright JD, Boppana SB, Britt WJ, Pass RF. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol. 2000;11(5):283-90.
Engman ML, Malm G, Engstrom L, Petersson K, Karltorp E, Tear Fahnehjelm K, et al. Congenital CMV infection: prevalence in newborns and the impact on hearing deficit. Scand J Infect Dis. 2008;40(11-12):935-42. doi: 10.1080/00365540802308431.
Foulon I, Naessens A, Faron G, Foulon W, Jansen AC, Gordts F. Hearing thresholds in children with a congenital CMV infection: a prospective study. Int J Pediatr Otorhinolaryngol. 2012 May;76(5):712-7. doi: 10.1016/j.ijporl.2012.02.026.
Fowler KB, Dahle AJ, Boppana SB, Pass RF. Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?. J Pediatr. 1999;135(1):60-4.
Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr. 1997;130(4):624-30.
Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014;134(5):972-82. doi: 10.1542/peds.2014-1173.
Grosse SD, Ross DS, Dollard SC. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol. 2008;41(2):57-62.
Ibáñez-Muñoz C, Calle-Cabanillas MI, Pérez-Sáez J, Navazo-Eguía AI, Clemente-García A, García-Vicario F, et al. Evolución de la audición en niños con infección congénita por citomegalovirus. Rev Soc Otorrinolaringol Castilla Leon Cantab La Rioja. 2013;4(21):159-64.
Junta de Castilla y León. Consejería de Sanidad. Programa de detección precoz y atención integral de la hipoacusia infantil. 2004. 78 pp.
Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011;87(11):723-8. doi: 10.1016/j.earlhumdev.2011.08.021.
Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007;17(4):253-76.
Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933-43. doi: 10.1056/NEJMoa1404599.
Korver AM, de Vries JJ, Konings S, de Jong JW, Dekker FW, Vossen AC, et al. DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands. J Clin Virol. 2009;46 Suppl 4:S27-31. doi: 10.1016/j.jcv.2009.09.007.
Luck SE, Wieringa JW, Blázquez-Gamero D, Henneke P, Schuster K, Butler K, et al. Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management. Pediatr Infect Dis J. 2017 Dec;36(12):1205-13. doi: 10.1097/INF.0000000000001763.
Moteki H, Isaka Y, Inaba Y, Motobayashi M, Nishio SY, Ohira S, et al. A rational approach to identifying newborns with hearing loss caused by congenital cytomegalovirus infection by dried blood spot screening. Acta Otolaryngol. 2018;138(8):708-12. doi: 10.1080/00016489.2018.1441545.
Núñez-Batalla F, Trinidad-Ramos G, Sequí-Canet JM, Alzina De Aguilar V, Jáudenes-Casaubón C. Risk factors for sensorineural hearing loss in children. Acta Otorrinolaringol Esp. 2012;63(5):382-90. doi: 10.1016/j.otorri.2011.02.007.
Ory F de, Ramírez R, García Comas L, León P, Sagües MJ, Sanz JC. Is there a change in cytomegalovirus seroepidemiology in Spain?. Eur J Epidemiol. 2004;19(1):85-9.
Pass RF. Congenital cytomegalovirus infection and hearing loss. Herpes. 2005;12(2):50-5. Review.
Pass RF, Fowler KB, Boppana SB, Britt WJ, Stagno S. Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome. J Clin Virol. 2006;35(2):216-20.
Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017;17(6):e177-e188. doi: 10.1016/S1473-3099(17)30143-3. Epub 2017 Mar 11.
Rawlinson WD, Palasanthiran P, Hall B, Al Yazidi L, Cannon MJ, Cottier C, et al. Neonates with congenital Cytomegalovirus and hearing loss identified via the universal newborn hearing screening program. J Clin Virol. 2018;102:110-5. doi: 10.1016/j.jcv.2018.03.006.
Riga M, Korres G, Chouridis P, Naxakis S, Danielides V. Congenital cytomegalovirus infection inducing non-congenital sensorineural hearing loss during childhood; a systematic review. Int J Pediatr Otorhinolaryngol. 2018;115:156-64. doi: 10.1016/j.ijporl.2018.10.005.
Reina J, Weber I, Riera E, Busquets M, Morales C. Utilidad de una técnica de Reacción en Cadena de la Polimerasa (PCR) cuantitativa en tiempo real en el diagnóstico de infección congénita y posnatal por citomegalovirus. An Pediatr (Barc). 2014;80(5):299-303. doi: 10.1016/j.anpedi.2013.06.036.
Royackers L, Rector E, Verhaert N, Desloovere C. Long-term audiological follow-up of children with congenital cytomegalovirus. B-ENT. 2013;Suppl 21:57-64.
Stehel EK, Shoup AG, Owen KE, Jackson GL, Sendelbach DM, Boney LF, et al. Newborn hearing screening and detection of congenital cytomegalovirus infection. Pediatrics. 2008;121(5):970-5. doi: 10.1542/peds.2006-3441.
Toumpas CJ, Clark J, Harris A, Beswick R, Nourse CB. Congenital cytomegalovirus infection is a significant cause of moderate to profound sensorineural hearing loss in Queensland children. J Paediatr Child Health. 2015;51(5):541-4. doi: 10.1111/jpc.12776.
Williams EJ, Gray J, Luck S, Atkinson C, Embleton ND, Kadambari S, et al. First estimates of the potential cost and cost saving of protecting childhood hearing from damage caused by congenital CMV infection. Arch Dis Child Fetal Neonatal Ed. 2015;100(6):F501-6. doi: 10.1136/archdischild-2014-306756.
Williamson WD, Demmler GJ, Percy AK, Catlin FI. Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection. Pediatrics. 1992;90(6):862-6.
Yamamoto AY, Mussi-Pinhata MM, Marin LJ, Brito RM, Oliveira PF, Coelho TB. Is saliva as reliable as urine for detection of cytomegalovirus DNA for neonatal screening of congenital CMV infection? J Clin Virol. 2006 Jul;36(3):228-30.
Benito-Orejas, J. I., Benito-González, F., García-Vicario, F., Martín-Sigüenza, G., Rey-Marcos, M., Serrano-Madrid, M. L., Gil-Carcedo-Sañudo, E., San-Román-Carbajo, J., Curieses-Becerril, L., & Marugán-Isabel, V. M. (2019). Targeted screening for congenital cytomegalovirus infection in infants who fail universal newborn hearing screen. Revista ORL, 10(4), 253–261. https://doi.org/10.14201/orl.21117
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