Newborn

Register      Login

VOLUME 2 , ISSUE 4 ( October-December, 2023 ) > List of Articles

REVIEW ARTICLE

CMV-induced Hearing Loss

Suresh Boppana

Keywords : ABR thresholds, Auditory brainstem response and otoacoustic emissions, Aural preference syndrome, Behavioral audiometry, Betaherpesvirus, Blood-labyrinth barrier, Cerebellar hypoplasia, Cerebral atrophy, CMV PCR, CMV-specific hyperimmune globulin, Cochlear blood–labyrinth barrier, Cochlear implant, Cytomegalic inclusion disease, Cytomegalovirus (CMV), Dried blood spot (DBS), Endocochlear potential, Fluctuating hearing loss, Ganciclovir, Herpesviridae, Human Herpes Virus 5, Icosahedral capsid, Impedance audiometry, Intracranial calcifications, Lenticulostriate vasculopathy, MF59-adjuvanted CMV glycoprotein B subunit vaccine, Migrational abnormalities, Natural killer, Neurotrophins, Newborn hearing screening, Nlrp3, Non-primary maternal infection, Organ of corti, Periventricular echo density, Play audiometry, Pure tone audiometry, Sensorineural hearing loss (SNHL), Seroimmune, Speech audiometry, Spiral ganglion cells, Spiral ganglion neurons, Strain-specific epitopes, Stria vascularis, Tegument layer, Tympano

Citation Information : Boppana S. CMV-induced Hearing Loss. 2023; 2 (4):249-262.

DOI: 10.5005/jp-journals-11002-0081

License: CC BY-NC 4.0

Published Online: 05-01-2024

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Congenital cytomegalovirus (cCMV) infection is the most common fetal viral infection and contributes to about 25% of childhood hearing loss by the age of 4 years. It is the leading nongenetic cause of sensorineural hearing loss (SNHL). Infants born to seroimmune mothers are not completely protected from SNHL, although the severity of their hearing loss may be milder than that seen in those whose mothers had a primary infection. Both direct cytopathic effects and localized inflammatory responses contribute to the pathogenesis of cytomegalovirus (CMV)-induced hearing loss. Hearing loss may be delayed onset, progressive or fluctuating in nature, and therefore, a significant proportion will be missed by universal newborn hearing screening (NHS) and warrants close monitoring of hearing function at least until 5–6 years of age. A multidisciplinary approach is required for the management of hearing loss. These children may need assistive hearing devices or cochlear implantation depending on the severity of their hearing loss. In addition, early intervention services such as speech or occupational therapy could help better communication, language, and social skill outcomes. Preventive measures to decrease intrauterine CMV transmission that have been evaluated include personal protective measures, passive immunoprophylaxis and valacyclovir treatment during pregnancy in mothers with primary CMV infection. Several vaccine candidates are currently in testing and one candidate vaccine in phase 3 trials. Until a CMV vaccine becomes available, behavioral and educational interventions may be the most effective strategy to prevent maternal CMV infection.


HTML PDF Share
  1. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007;17(4):253–276. DOI: 10.1002/RMV.535.
  2. Foulon I, Naessens A, Foulon W, et al. Hearing loss in children with congenital cytomegalovirus infection in relation to the maternal trimester in which the maternal primary infection occurred. Pediatrics 2008;122(6):e1123–e1127. DOI: 10.1542/PEDS.2008-0770.
  3. Schleiss MR. Cytomegalovirus. Maternal Immunization 2020:253–288. DOI: 10.1016/B978-0-12-814582-1.00013-9.
  4. Wilkinson GWG, Davison AJ, Tomasec P, et al. Human cytomegalovirus: Taking the strain. Med Microbiol Immunol 2015;204(3):273–284. DOI: 10.1007/S00430-015-0411-4/TABLES/1.
  5. Martí-Carreras J, Maes P. Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: Revision and future challenges. Virus Genes 2019;55(2):138–164. DOI: 10.1007/S11262-018-1627-3/TABLES/2.
  6. Morton CC, Nance WE. Newborn hearing screening–A silent revolution. N Engl J Med 2006;354(20):2151–2164. DOI: 10.1056/NEJMRA050700.
  7. Elek SD, Stern H. Development of a vaccine against mental retardation caused by cytomegalovirus infection in utero. Lancet 1974;1(7845): 1–5. DOI: 10.1016/S0140-6736(74)92997-3.
  8. Mocarski ES, Bonyhadi M, Salimi S, et al. Human cytomegalovirus in a SCID-hu mouse: Thymic epithelial cells are prominent targets of viral replication. Proc Natl Acad Sci USA 1993;90(1):104–108. DOI: 10.1073/PNAS.90.1.104.
  9. Ma Y, Wang N, Li M, et al. Human CMV transcripts: An overview. Future Microbiol 2012;7(5):577–593. DOI: 10.2217/FMB.12.32.
  10. Gatherer D, Seirafian S, Cunningham C, et al. High-resolution human cytomegalovirus transcriptome. Proc Natl Acad Sci USA 2011;108(49):19755–19760. DOI: 10.1073/PNAS.1115861108/SUPPL_FILE/SD01.XLS.
  11. Schottstedt DrV, Blümel DrJ, Burger ProfDrR, et al. Human cytomegalovirus (HCMV) – Revised. Transfusion medicine and hemotherapy 2010;37(6):365. DOI: 10.1159/000322141.
  12. Britt WJ, Mach M. Human cytomegalovirus glycoproteins. Intervirology 1996;39(5–6):401–412. DOI: 10.1159/000150510.
  13. Kschonsak M, Rougé L, Arthur CP, et al. Structures of HCMV trimer reveal the basis for receptor recognition and cell entry. Cell 2021;184(5):1232–1244.e16. DOI: 10.1016/J.CELL.2021.01.036.
  14. Stein KR, Gardner TJ, Hernandez RE, et al. CD46 facilitates entry and dissemination of human cytomegalovirus. Nature Commun 2019;10(1):1–13. DOI: 10.1038/s41467-019-10587-1.
  15. Gardner TJ, Stein KR, Duty JA, et al. Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein. Nature Commun 2016;7(1):1–15. DOI: 10.1038/ncomms13627.
  16. Lee MK, Hyeon S, Ahn JH. The human cytomegalovirus transmembrane protein pUL50 induces loss of VCP/p97 and is regulated by a small isoform of pUL50. J Virol 2020;94(13). DOI: 10.1128/JVI.00110-20.
  17. Van Bergen J, Koning F. The tortoise and the hare: Slowly evolving T-cell responses take hastily evolving KIR. Immunology 2010;131(3):301. DOI: 10.1111/J.1365-2567.2010.03337.X.
  18. Burke HG, Heldwein EE. Crystal Structure of the human cytomegalovirus glycoprotein B. PLoS Pathog 2015;11(10). DOI: 10.1371/JOURNAL.PPAT.1005227.
  19. Yu X, Jih J, Jiang J, et al. Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150. Science 2017;356(6345). DOI: 10.1126/SCIENCE.AAM6892.
  20. Bauer DW, Huffman JB, Homa FL, et al. Herpes virus genome, the pressure is on. J Am Chem Soc 2013;135(30):11216–11221. DOI: 10.1021/JA404008R.
  21. Baxter MK, Gibson W. Cytomegalovirus basic phosphoprotein (pUL32) binds to capsids in vitro through its amino one-third. J Virol 2001;75(15):6865–6873. DOI: 10.1128/JVI.75.15.6865-6873.2001.
  22. Yu X, Shah S, Lee M, et al. Biochemical and structural characterization of the capsid-bound tegument proteins of human cytomegalovirus. J Struct Biol 2011;174(3):451–460. DOI: 10.1016/J.JSB.2011.03.006.
  23. Dai X, Yu X, Gong H, et al. The smallest capsid protein mediates binding of the essential tegument protein pp150 to stabilize DNA-containing capsids in human cytomegalovirus. PLoS Pathog 2013;9(8). DOI: 10.1371/JOURNAL.PPAT.1003525.
  24. Terhune SS, Schröer J, Shenk T. RNAs are packaged into human cytomegalovirus virions in proportion to their intracellular concentration. J Virol 2004;78(19):10390. DOI: 10.1128/JVI.78.19.10390-10398.2004.
  25. Li Z, Pang J, Dong L, et al. Structural basis for genome packaging, retention, and ejection in human cytomegalovirus. Nature Commun 2021;12(1):1–14. DOI: 10.1038/s41467-021-24820-3.
  26. Borst EM, Harmening S, Sanders S, et al. A Unique role of the human cytomegalovirus small capsid protein in capsid assembly. mBio 2022;13(5). DOI: 10.1128/MBIO.01007-22/SUPPL_FILE/MBIO.01007-22-S0006.DOCX.
  27. Mancebo FJ, Parras-Moltó M, García-Ríos E, et al. Deciphering the potential coding of human cytomegalovirus: New predicted transmembrane proteome. Int J Mol Sci 2022;23(5). DOI: 10.3390/IJMS23052768/S1.
  28. Brignole EJ, Gibson W. Enzymatic Activities of Human Cytomegalovirus Maturational Protease Assemblin and Its Precursor (pPR, pUL80a): Maximal Activity of pPR Requires Self-Interaction through Its Scaffolding Domain. J Virol 2007;81(8):4091. DOI: 10.1128/JVI.02821-06.
  29. Zalckvar E, Paulus C, Tillo D, et al. Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in chromatin organization linked to a major IE protein. Proc Natl Acad Sci USA 2013;110(32):13126–13131. DOI: 10.1073/PNAS.1305548110/-/DCSUPPLEMENTAL.
  30. Hage E, Wilkie GS, Linnenweber-Held S, et al. Characterization of Human Cytomegalovirus Genome Diversity in Immunocompromised Hosts by Whole-Genome Sequencing Directly From Clinical Specimens. J Infect Dis 2017;215(11):1673–1683. DOI: 10.1093/INFDIS/JIX157.
  31. Bankier AT, Beck S, Bohni R, et al. The DNA sequence of the human cytomegalovirus genome. DNA Seq 1991;2(1):1–11. DOI: 10.3109/10425179109008433.
  32. Jones TR, Sun L, Bebernitz GA, et al. Proteolytic activity of human cytomegalovirus UL80 protease cleavage site mutants. J Virol 1994;68(6):3742. DOI: 10.1128/JVI.68.6.3742-3752.1994.
  33. Wahren B, Eriksson B. Cytomegalovirus DNA polymerase inhibition and kinetics. Adv Enzyme Regul 1985;23(C):263–274. DOI: 10.1016/0065-2571(85)90051-2.
  34. Fillet AM, Auray L, Alain S, et al. Natural polymorphism of cytomegalovirus dna polymerase lies in two nonconserved regions located between domains Delta-C and II and between Domains III and I. Antimicrob Agents Chemother 2004;48(5):1865. DOI: 10.1128/AAC.48.5.1865-1868.2004.
  35. Kostopoulou ON, Wilhelmi V, Raiss S, et al. Human cytomegalovirus and herpes simplex type I virus can engage RNA polymerase I for transcription of immediate early genes. Oncotarget 2017;8(57):96536. DOI: 10.18632/ONCOTARGET.22106.
  36. Diener ML, Zick CD, McVicar SB, et al. Outcomes From a Hearing-Targeted Cytomegalovirus Screening Program. Pediatrics 2017;139(2). DOI: 10.1542/PEDS.2016-0789.
  37. Stehel EK, Shoup AG, Owen KE, et al. Newborn hearing screening and detection of congenital cytomegalovirus infection. Pediatrics 2008;121(5):970–975. DOI: 10.1542/PEDS.2006-3441.
  38. 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. DOI: 10.1016/J.JCV.2007.09.004.
  39. Barbi M, Binda S, Caroppo S, et al. A wider role for congenital cytomegalovirus infection in sensorineural hearing loss. Pediatr Infect Dis J 2003;22(1):39–42. DOI: 10.1097/00006454-200301000-00012.
  40. Park AH, Duval M, McVicar S, et al. A diagnostic paradigm including cytomegalovirus testing for idiopathic pediatric sensorineural hearing loss. Laryngoscope 2014;124(11):2624–2629. DOI: 10.1002/LARY.24752.
  41. Dahle AJ, Fowler KB, Wright JD, et al. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus. J Am Acad Audiol 2000;11(5):283–290. PMID: 10821506.
  42. Hanshaw JB. Cytomegaloviruses. Infectious Diseases in Obstetrics and Gynecology, Sixth Edition. Published online January 1, 2008:48–56. DOI: 10.1007/978-3-662-39771-8_1/COVER.
  43. Goderis J, De Leenheer E, Smets K, et al. Hearing loss and congenital cmv infection: a systematic review. Pediatrics 2014;134(5):972–982. DOI: 10.1542/PEDS.2014-1173.
  44. Gaytant MA, Steegers EAP, Semmekrot BA, et al. Congenital cytomegalovirus infection: Review of the epidemiology and outcome. Obstet Gynecol Surv 2002;57(4):245–256. DOI: 10.1097/00006254-200204000-00024.
  45. Cannon MJ, Hyde TB, Schmid DS. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol 2011;21(4):240–255. DOI: 10.1002/RMV.695.
  46. Rosenthal LS, Fowler KB, Boppana SB, et al. Cytomegalovirus shedding and delayed sensorineural hearing loss: Results from longitudinal follow-up of children with congenital infection. Pediatr Infect Dis J 2009;28(6):515. DOI: 10.1097/INF.0B013E318198C724.
  47. Faure-Bardon V, Magny JF, Parodi M, et al. Sequelae of congenital cytomegalovirus following maternal primary infections are limited to those acquired in the first trimester of pregnancy. Clin Infect Dis 2019;69(9):1526–1532. DOI: 10.1093/CID/CIY1128.
  48. Stagno S, Pass RF, Cloud G, et al. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 1986;256(14):1904–1908.
  49. Liesnard C, Donner C, Brancart F, et al. Prenatal diagnosis of congenital cytomegalovirus infection: Prospective study of 237 pregnancies at risk. Obstetrics and Gynecology 2000;95(6):881–888. DOI: 10.1016/S0029-7844(99)00657-2.
  50. Fowler KB, Boppana SB. Congenital cytomegalovirus (CMV) infection and hearing deficit. J Clin Virol 2006;35(2):226–231. DOI: 10.1016/J.JCV.2005.09.016.
  51. Iwasaki S, Yamashita M, Maeda M, et al. Audiological outcome of infants with congenital cytomegalovirus infection in a prospective study. Audiol Neurootol 2007;12(1):31–36. DOI: 10.1159/000096156.
  52. Koyano S, Morioka I, Oka A, et al. Congenital cytomegalovirus in Japan: More than 2 year follow up of infected newborns. Pediatrics International 2018;60(1):57–62. DOI: 10.1111/PED.13433.
  53. 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): 355–363. DOI: 10.1002/RMV.544.
  54. Lanzieri TM, Dollard SC, Bialek SR, et al. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis 2014;22:44. DOI: 10.1016/J.IJID.2013.12.010.
  55. Ludwig A, Hengel H. Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. Euro Surveill 2009;14(9):26–32. PMID: 19317969.
  56. Townsend CL, Forsgren M, Ahlfors K, et al. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis 2013;56(9):1232–1239. DOI: 10.1093/CID/CIT018.
  57. Stagno S, Pass RF, Reynolds DW, et al. Comparative study of diagnostic procedures for congenital cytomegalovirus infection. Pediatrics 1980;65(2):251–257. DOI: 10.1542/PEDS.65.2.251.
  58. Ross SA, Ahmed A, Palmer AL, et al. Newborn dried blood spot polymerase chain reaction to identify infants with congenital cytomegalovirus-associated sensorineural hearing loss. J Pediatr 2017;184:57–61.e1. DOI: 10.1016/J.JPEDS.2017.01.047.
  59. Ross SA, Novak Z, Fowler KB, et al. Cytomegalovirus blood viral load and hearing loss in young children with congenital infection. Pediatr Infect Dis J 2009;28(7):588–592. DOI: 10.1097/INF.0B013E3181979A27.
  60. Noyola DE, Demmler GJ, Williamson WD, et al. Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group. Pediatr Infect Dis J 2000;19(6):505–510. DOI: 10.1097/00006454-200006000-00003.
  61. Saigal S, Lunyk O, Larke RP, et al. The outcome in children with congenital cytomegalovirus infection. A longitudinal follow–up study. Am J Dis Child 1982;136(10):896–901. DOI: 10.1001/archpedi.1982.03970460026006.
  62. Foulon I, Naessens A, Foulon W, et al. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. J Pediatr 2008;153(1):84–88. DOI: 10.1016/J.JPEDS.2007.12.049.
  63. Williamson WD, Desmond MM, LaFevers N, et al. Symptomatic congenital cytomegalovirus. Disorders of language, learning, and hearing. Am J Dis Child 1982;136(10):902–905. DOI: 10.1001/archpedi.1982.03970460032007.
  64. Pass RF, Stagno S, Myers GJ, et al. Outcome of symptomatic congenital cytomegalovirus infection: Results of long-term longitudinal follow-up. Pediatrics 1980;66(5):758–762.
  65. Yamamoto AY, Mussi-Pinhata MM, Isaac MDL, et al. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediat Infect Dis J 2011;30(12):1043–1046. DOI: 10.1097/INF.0B013E31822D9640.
  66. Hagay ZJ, Biran G, Ornoy A, et al. Congenital cytomegalovirus infection: a long-standing problem still seeking a solution. Am J Obstet Gynecol 1996;174(1 Pt 1):241–245. DOI: 10.1016/S0002-9378(96)70401-5.
  67. Kimberlin DW, Lin CY, Sánchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: A randomized, controlled trial. J Pediatr 2003;143(1):16–25. DOI: 10.1016/S0022-3476(03)00192-6.
  68. Kimberlin DW, Jester PM, Sánchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015;372(10):933–943. DOI: 10.1056/NEJMOA1404599.
  69. Li X, Shi X, Qiao Y, et al. Observation of permeability of blood–labyrinth barrier during cytomegalovirus-induced hearing loss. Int J Pediatr Otorhinolaryngol 2014;78(7):995–999. DOI: 10.1016/J.IJPORL.2014.03.013.
  70. Dollard SC, Schleiss MR, Grosse SD. Public health and laboratory considerations regarding newborn screening for congenital cytomegalovirus. J Inherit Metab Dis 2010;33(Suppl 2). DOI: 10.1007/S10545-010-9125-3.
  71. Ahlfors K, Ivarsson SA, Harris S, et al. Congenital cytomegalovirus infection and disease in Sweden and the relative importance of primary and secondary maternal infections. Preliminary findings from a prospective study. Scand J Infect Dis 1984;16(2):129–137. DOI: 10.3109/00365548409087131.
  72. Singh G, Gaidhane A. A review of sensorineural hearing loss in congenital cytomegalovirus infection. Cureus 2022;14(10). DOI: 10.7759/CUREUS.30703.
  73. Duval M, Park AH. Congenital cytomegalovirus: What the otolaryngologist should know. Curr Opin Otolaryngol Head Neck Surg 2014;22(6):495–500. DOI: 10.1097/MOO.0000000000000104.
  74. Hamprecht K, Maschmann J, Vochem M, et al. Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Lancet 2001;357(9255):513–518. DOI: 10.1016/S0140-6736(00)04043-5.
  75. Stagno S, Reynolds DW, Pass RF, et al. Breast milk and the risk of cytomegalovirus infection. N Engl J Med 1980;302(19):1073–1076. DOI: 10.1056/NEJM198005083021908.
  76. Brandt CT, Cayé-Thomasen P, Lund SP, et al. Hearing loss and cochlear damage in experimental pneumococcal meningitis, with special reference to the role of neutrophil granulocytes. Neurobiol Dis 2006;23(2):300–311. DOI: 10.1016/J.NBD.2006.03.006.
  77. Schachtele SJ, Mutnal MB, Schleiss MR, et al. Cytomegalovirus induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice. J Neurovirol 2011;17(3):201. DOI: 10.1007/S13365-011-0024-7.
  78. Bradford RD, Yoo YG, Golemac M, et al. Murine CMV-induced hearing loss is associated with inner ear inflammation and loss of spiral ganglia neurons. PLoS Pathog 2015;11(4):e1004774. DOI: 10.1371/JOURNAL.PPAT.1004774.
  79. Almishaal AA, Mathur PD, Hillas E, et al. Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice. PLoS Pathog 2017;13(8):e1006599. DOI: 10.1371/JOURNAL.PPAT.1006599.
  80. Harris JA, Rubel EW. Afferent regulation of neuron number in the cochlear nucleus: cellular and molecular analyses of a critical period. Hear Res 2006;216–217(1–2):127–137. DOI: 10.1016/J.HEARES.2006.03.016.
  81. Rubel EW, Fritzsch B. Auditory system development: Primary auditory neurons and their targets. Annu Rev Neurosci 2002;25:51–101. DOI: 10.1146/ANNUREV.NEURO.25.112701.142849.
  82. Tierney TS, Russell FA, Moore DR. Susceptibility of developing cochlear nucleus neurons to deafferentation-induced death abruptly ends just before the onset of hearing. J Comp Neurol 1997;378(2):295–306. DOI: 10.1002/(sici)1096-9861(19970210)378:2<295::aid-cne11>3.0.co;2-r.
  83. Harris JA, Iguchi F, Seidl AH, et al. Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus. J Neurosci 2008;28(43):10990–11002. DOI: 10.1523/JNEUROSCI.2697-08.2008.
  84. Leake PA, Hradek GT, Hetherington AM, et al. Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats. J Comp Neurol 2011;519(8):1526–1545. DOI: 10.1002/CNE.22582.
  85. Firbas W, Gruber H, Wicke W. The blood vessels of the limbus spiralis. Arch Otorhinolaryngol 1981;232(2):131–137. DOI: 10.1007/BF00505032/METRICS.
  86. Miller JM, Le Prell CG, Prieskorn DM, et al. Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factor. J Neurosci Res 2007;85(9):1959–1969. DOI: 10.1002/JNR.21320.
  87. Zhai SQ, Guo W, Hu YY, et al. Protective effects of brain-derived neurotrophic factor on the noise-damaged cochlear spiral ganglion. J Laryngol Otol 2011;125(5):449–454. DOI: 10.1017/S0022215110002112.
  88. Zhuang W, Wang C, Shi X, et al. MCMV triggers ROS/NLRP3-associated inflammasome activation in the inner ear of mice and cultured spiral ganglion neurons, contributing to sensorineural hearing loss. Int J Mol Med 2018;41(6):3448–3456. DOI: 10.3892/IJMM.2018.3539/HTML.
  89. Shi X, Qiu S, Zhuang W, et al. NLRP3-inflammasomes are triggered by age-related hearing loss in the inner ear of mice. Am J Transl Res 2017;9(12):5611–5618.
  90. Teissier N, Delezoide AL, Mas AE, et al. Inner ear lesions in congenital cytomegalovirus infection of human fetuses. Acta Neuropathol 2011;122(6):763–774. DOI: 10.1007/S00401-011-0895-Y.
  91. Klein M, Koedel U, Pfister HW, et al. Morphological correlates of acute and permanent hearing loss during experimental pneumococcal meningitis. Brain Pathol 2003;13(2):123–132. DOI: 10.1111/J.1750-3639.2003.TB00012.X.
  92. Nadol JB, Hsu W. Histopathologic correlation of spiral ganglion cell count and new bone formation in the cochlea following meningogenic labyrinthitis and deafness. Ann Otol Rhinol Laryngol 1991;100(9 Pt 1):712–716. DOI: 10.1177/000348949110000904.
  93. Ramekers D, Versnel H, Grolman W, et al. Neurotrophins and their role in the cochlea. Hear Res 2012;288(1–2):19–33. DOI: 10.1016/J.HEARES.2012.03.002.
  94. Mostafapour SP, Del Puerto NM, Rubel EW. bcl-2 Overexpression eliminates deprivation-induced cell death of brainstem auditory neurons. J Neurosci 2002;22(11):4670–4674. DOI: 10.1523/JNEUROSCI.22-11-04670.2002.
  95. Lombardi G, Garofoli F, Stronati M. Congenital cytomegalovirus infection: Treatment, sequelae and follow-up. J Matern Fetal Neonatal Med 2010;23 Suppl 3(SUPPL. 3):45–48. DOI: 10.3109/14767058.2010.506753.
  96. Hammer Q, Rückert T, Romagnani C. Natural killer cell specificity for viral infections. Nature Immunology 2018;19(8):800–808. DOI: 10.1038/s41590-018-0163-6.
  97. Nickel R, Forge A. Gap junctions and connexins in the inner ear: Their roles in homeostasis and deafness. Curr Opin Otolaryngol Head Neck Surg 2008;16(5):452–457. DOI: 10.1097/MOO.0B013E32830E20B0.
  98. Ciuman RR. Stria vascularis and vestibular dark cells: Characterisation of main structures responsible for inner-ear homeostasis, and their pathophysiological relations. J Laryngol Otol 2009;123(2):151–162. DOI: 10.1017/S0022215108002624.
  99. Cohen-Salmon M, Regnault B, Cayet N, et al. Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis. Proc Natl Acad Sci USA 2007;104(15):6229–6234. DOI: 10.1073/PNAS.0605108104.
  100. Mittal R, Aranke M, Debs LH, et al. Indispensable role of ion channels and transporters in the auditory system. J Cell Physiol 2017;232(4):743–758. DOI: 10.1002/JCP.25631.
  101. Teissier N, Bernard S, Quesnel S, et al. Audiovestibular consequences of congenital cytomegalovirus infection. Eur Ann Otorhinolaryngol Head Neck Dis 2016;133(6):413–418. DOI: 10.1016/J.ANORL.2016.03.004.
  102. Wu J, Han W, Chen X, et al. Matrix metalloproteinase-2 and -9 contribute to functional integrity and noise-induced damage to the blood-labyrinth-barrier. Mol Med Rep 2017;16(2):1731–1738. DOI: 10.3892/MMR.2017.6784/HTML.
  103. Juhn SK, Rybak LP. Labyrinthine Barriers and Cochlear Homeostasis. Acta Otolaryngol 2009;91(1–6):529–534. DOI: 10.3109/00016488109138538.
  104. Kimura RS, Nye CL, Southard RE. Normal and pathologic features of the limbus spiralis and its functional significance. Am J Otolaryngol 1990;11(2):99–111. DOI: 10.1016/0196-0709(90)90006-H.
  105. Bailey EM, Green SH. Postnatal expression of neurotrophic factors accessible to spiral ganglion neurons in the auditory system of adult hearing and deafened rats. J Neurosci 2014;34(39):13110–13126. DOI: 10.1523/JNEUROSCI.1014-14.2014.
  106. Li X, Shi X, Wang C, et al. Cochlear spiral ganglion neuron apoptosis in neonatal mice with murine cytomegalovirus-induced sensorineural hearing loss. J Am Acad Audiol 2016;27(4):345–353. DOI: 10.3766/JAAA.15061/BIB.
  107. Schmutzhard J, Glueckert R, Pritz C, et al. Sepsis otopathy: Experimental sepsis leads to significant hearing impairment due to apoptosis and glutamate excitotoxicity in murine cochlea. Dis Model Mech 2013;6(3):745–754. DOI: 10.1242/DMM.011205.
  108. Manicklal S, Emery VC, Lazzarotto T, et al. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 2013;26(1):86–102. DOI: 10.1128/CMR.00062-12.
  109. Boppana SB, Ross SA, Fowler KB. Congenital cytomegalovirus infection: Clinical outcome. Clin Infect Dis 2013;57 Suppl 4(Suppl 4): S178–S181. DOI: 10.1093/CID/CIT629.
  110. Hicks T, Fowler K, Richardson M, et al. Congenital cytomegalovirus infection and neonatal auditory screening. J Pediatr 1993;123(5):779–782. DOI: 10.1016/S0022-3476(05)80859-5.
  111. Fowler KB, McCollister FP, Dahle AJ, et al. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr 1997;130(4):624–630. DOI: 10.1016/S0022-3476(97)70248-8.
  112. Williamson WD, Demmler GJ, Percy AK, et al. Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection. Pediatrics 1992;90(6):862–866.
  113. Yow MD, Williamson DW, Leeds LJ, et al. Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants. Am J Obstet Gynecol 1988;158(5):1189–1195. DOI: 10.1016/0002-9378(88)90252-9.
  114. Puhakka L, Lappalainen M, Lönnqvist T, et al. Hearing outcome in congenitally CMV infected children in Finland – results from follow-up after three years age. Int J Pediatr Otorhinolaryngol 2022;156. DOI: 10.1016/J.IJPORL.2022.111099.
  115. Ahlfors K, Ivarsson SA, Harris S. Report on a long-term study of maternal and congenital cytomegalovirus infection in Sweden. Review of prospective studies available in the literature. Scand J Infect Dis 1999;31(5):443–457. DOI: 10.1080/00365549950163969.
  116. Lanzieri TM, Chung W, Flores M, et al. Hearing loss in children with asymptomatic congenital cytomegalovirus infection. Pediatrics 2017;139(3). DOI: 10.1542/PEDS.2016-2610/53745.
  117. Fowler KB. Congenital Cytomegalovirus Infection: Audiologic Outcome. Clin Infect Dis 2013;57(Suppl 4): S182–S184. DOI: 10.1093/CID/CIT609.
  118. Fowler KB, Dable AJ, Boppana SB, et al. Newborn hearing screening: Will children with hearing loss caused by congenital cytomegalovirus infection be missed? J Pediatr 1999;135(1):60–64. DOI: 10.1016/S0022-3476(99)70328-8.
  119. Understanding Hearing Loss. Parent's Guide to Hearing Loss. CDC. Accessed August 16, 2023. https://www.cdc.gov/ncbddd/hearingloss/parentsguide/understanding/understandinghearingloss.html.
  120. Konrad-Martin D, James KE, Gordon JS, et al. Evaluation of audiometric threshold shift criteria for ototoxicity monitoring. J Am Acad Audiol 2010;21(5):301–304. DOI: 10.3766/JAAA.21.5.3.
  121. Demmler-Harrison GJ, Miller JA. Group O behalf of the HCCLS. Maternal cytomegalovirus immune status and hearing loss outcomes in congenital cytomegalovirus-infected offspring. PLoS One 2020;15(10). DOI: 10.1371/JOURNAL.PONE.0240172.
  122. Congenital cytomegalovirus infection: Clinical features and diagnosis - UpToDate. Accessed August 16, 2023.
  123. Prince HE, Lapé-Nixon M. Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy. Clin Vaccine Immunol 2014;21(10):1377–1384. DOI: 10.1128/CVI.00487-14.
  124. Davis NL, King CC, Kourtis AP. Cytomegalovirus infection in pregnancy. Birth Defects Res 2017;109(5):336–346. DOI: 10.1002/BDRA.23601.
  125. Navti OB, Al-Belushi M, Konje JC. Cytomegalovirus infection in pregnancy – an update. Eur J Obstet Gynecol Reprod Biol 2021;258:216–222. DOI: 10.1016/J.EJOGRB.2020.12.006.
  126. Jückstock J, Rothenburger M, Friese K, et al. Passive immunization against congenital cytomegalovirus infection: Current state of knowledge. Pharmacology 2015;95(5–6):209–217. DOI: 10.1159/000381626.
  127. Lipitz S, Hoffmann C, Feldman B, et al. Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection. Ultrasound Obstet Gynecol 2010;36(6):709–717. DOI: 10.1002/UOG.7657.
  128. Mestas E. Congenital cytomegalovirus. Adv Neonatal Care 2016;16(1):60–65. DOI: 10.1097/ANC.0000000000000242.
  129. Chiopris G, Veronese P, Cusenza F, et al. Congenital cytomegalovirus infection: update on diagnosis and treatment. Microorganisms 2020;8(10):1–17. DOI: 10.3390/MICROORGANISMS8101516.
  130. Revello MG, Lilleri D, Zavattoni M, et al. Prenatal diagnosis of congenital human cytomegalovirus infection in amniotic fluid by nucleic acid sequence-based amplification assay. J Clin Microbiol 2003;41(4):1772–1774. DOI: 10.1128/JCM.41.4.1772-1774.2003.
  131. Bodéus M, Hubinont C, Bernard P, et al. Prenatal diagnosis of human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to congenital infection. Prenat Diagn 1999;19(4):314–317. DOI: 10.1002/(sici)1097-0223(199904)19:4<314:: aid-pd542>3.0.co;2-h.
  132. Boppana SB, Ross SA, Shimamura M, et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 2011;364(22):2111. DOI: 10.1056/NEJMOA1006561.
  133. Ross SA, Michaels MG, Ahmed A, et al. Contribution of breastfeeding to false-positive saliva polymerase chain reaction for newborn congenital cytomegalovirus screening. J Infect Dis 2018;217(10): 1612–1615. DOI: 10.1093/INFDIS/JIY057.
  134. Boppana SB, Ross SA, Novak Z, et al. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 2010;303(14):1375–1382. DOI: 10.1001/JAMA.2010.423.
  135. Pinninti SG, Ross SA, Shimamura M, et al. Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection. Pediatr Infect Dis J 2015;34(5):536–537. DOI: 10.1097/INF.0000000000000609.
  136. Kadambari S, Williams EJ, Luck S, et al. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev 2011;87(11):723–728. DOI: 10.1016/J.EARLHUMDEV.2011.08.021.
  137. Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: New prospects for prevention and therapy. Pediatr Clin North Am 2013;60(2):335–349. DOI: 10.1016/J.PCL.2012.12.008.
  138. Sahiner F, Cekmez F, Cetinkaya M, et al. Congenital cytomegalovirus infections and glycoprotein B genotypes in live-born infants: A prevalence study in Turkey. Infect Dis (Lond) 2015;47(7):465–471. DOI: 10.3109/23744235.2015.1018316.
  139. Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol 2018;42(3):149–154. DOI: 10.1053/J.SEMPERI.2018.02.002.
  140. Foulon I, De Brucker Y, Buyl R, et al. Hearing loss with congenital cytomegalovirus infection. Pediatrics 2019;144(2). DOI: 10.1542/PEDS.2018-3095.
  141. Cannon MJ, Griffiths PD, Aston V, et al. Universal newborn screening for congenital CMV infection: What is the evidence of potential benefit? Rev Med Virol 2014;24(5):291. DOI: 10.1002/RMV.1790.
  142. Reynolds DW, Stagno S, Hosty TS, et al. Maternal cytomegalovirus excretion and perinatal infection. N Engl J Med 1973;289(1):1–5. DOI: 10.1056/NEJM197307052890101.
  143. Lim Y, Lyall H. Congenital cytomegalovirus – who, when, what-with and why to treat? J Infect 2017;74 Suppl 1:S89–S94. DOI: 10.1016/S0163-4453(17)30197-4.
  144. Nicloux M, Peterman L, Parodi M, et al. Outcome and management of newborns with congenital cytomegalovirus infection. Arch Pediatr 2020;27(3):160–165. DOI: 10.1016/J.ARCPED.2020.01.006.
  145. Yoshinaga-Itano C, Sedey AL, Coulter DK, et al. Language of early- and later-identified children with hearing loss. Pediatrics 1998;102(5):1161–1171. DOI: 10.1542/PEDS.102.5.1161.
  146. Kuk FK, Kollofski C, Brown S, et al. Use of a digital hearing aid with directional microphones in school-aged children. J Am Acad Audiol 1999;10(10):535–548.
  147. Bamford J, McCracken W, Peers I, et al. Trial of a two-channel hearing aid (low-frequency compression-high-frequency linear amplification) with school age children. Ear Hear 1999;20(4):290–298. DOI: 10.1097/00003446-199908000-00002.
  148. Federspil PA, Tretbar SH, Böhlen FH, et al. Measurement of skull bone thickness for bone-anchored hearing aids: An experimental study comparing both a novel ultrasound system (SonoPointer) and computed tomographic scanning to mechanical measurements. Otol Neurotol 2010;31(3):440–446. DOI: 10.1097/MAO.0B013E3181D2775F.
  149. Thomas JP, Neumann K, Dazert S, et al. Cochlear implantation in children with congenital single-sided deafness. Otol Neurotol 2017;38(4):496–503. DOI: 10.1097/MAO.0000000000001343.
  150. Colletti L, Mandalà M, Colletti V. Cochlear implants in children younger than 6 months. Otolaryngol Head Neck Surg 2012;147(1):139–146. DOI: 10.1177/0194599812441572.
  151. Goderis J, Keymeulen A, Smets K, et al. Hearing in children with congenital cytomegalovirus infection: Results of a longitudinal study. J Pediatr 2016;172:110–115.e2. DOI: 10.1016/J.JPEDS.2016.01.024.
  152. van Wieringen A, Boudewyns A, Sangen A, et al. Unilateral congenital hearing loss in children: Challenges and potentials. Hear Res 2019;372:29–41. DOI: 10.1016/J.HEARES.2018.01.010.
  153. Fitzpatrick EM, Gaboury I, Durieux-Smith A, et al. Auditory and language outcomes in children with unilateral hearing loss. Hear Res 2019;372:42–51. DOI: 10.1016/J.HEARES.2018.03.015.
  154. Gordon K, Henkin Y, Kral A. Asymmetric hearing during development: The aural preference syndrome and treatment options. Pediatrics 2015;136(1):141–153. DOI: 10.1542/PEDS.2014-3520.
  155. Kawada J ichi, Torii Y, Kawano Y, et al. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening. J Clin Virol 2015;65:41–45. DOI: 10.1016/J.JCV.2015. 01.015.
  156. Revello MG, Lazzarotto T, Guerra B, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 2014;370(14):1316–1326. DOI: 10.1056/NEJMOA1310214.
  157. Hughes BL, Clifton RG, Rouse DJ, et al. A Trial of hyperimmune globulin to prevent congenital cytomegalovirus infection. N Engl J Med 2021;385(5):436–444. DOI: 10.1056/NEJMOA1913569.
  158. Stratton KR, Durch JS, Lawrence RS. Vaccines for the 21st Century: A Tool for Decisionmaking. DOI: 10.17226/5501.
  159. Boppana SB, van Boven M, Britt WJ, et al. Vaccine value profile for cytomegalovirus. Vaccine 2023;41(Suppl 2):S53–S75. DOI: 10.1016/J.VACCINE.2023.06.020.
  160. Pass RF, Zhang C, Evans A, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 2009;360(12):1191–1199. DOI: 10.1056/NEJMOA0804749.
  161. Dekker CL, Arvin AM. One step closer to a CMV vaccine. N Engl J Med 2009;360(12):1250–1252. DOI: 10.1056/NEJME0900230.
  162. Bernstein DI, Munoz FM, Callahan ST, et al. Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial. Vaccine 2016;34(3):313–319. DOI: 10.1016/J.VACCINE.2015.11.056.
  163. Fowler KB, M
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.