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Narrative Review

Vol. 20 No. 2 (2022): New Horizons: Innovation in Medicine

Congenital Cytomegalovirus Infection: Transmission, Diagnosis and Treatment.

DOI
https://doi.org/10.26443/mjm.v20i2.876
Submitted
April 6, 2021
Published
2022-04-19

Abstract

Introduction: Cytomegalovirus (CMV) is a linear, dsDNA virus that is regarded as the prototype of the Betaherpesvirinae subfamily of viruses. It has an established endemic status in certain locations around the globe, and is also reported to be the most prevalently occurring congenital infection in humans. Furthermore, Cytomegalovirus is notorious for being a persistent lifelong pathogen that poses a threat of reactivation as well.

Discussion: Congenital cytomegalovirus infection causes numerous ophthalmologic, and neurologic sequelae, and is also known for being the principal reason behind sensorineural hearing loss of non-genetic etiology in neonates. These symptoms, if present, may give rise to a premonition of congenital Cytomegalovirus disease, and so, a diagnosis can be established  through serology, radiology, and  PCR of salivary, urinary, or dried blood spot samples. Timely administration of ganciclovir or valganciclovir has proven to be effective in managing symptomatic cases of congenital CMV.

Conclusion: A well-timed delivery of pharmacological and non-pharmacological interventions is necessary to achieve healthy developmental outcomes for the neonate. Moreover, there is still  a need to study the role of antiviral therapy in silent cases since asymptomatic patients are at a risk of developing long-term clinical sequelae as well.

Relevance: An estimated 60-90% of women of child-bearing age get infected with Cytomegalovirus, and Congenital CMV disease is reported in 0.2-2.4% of all live births. Therefore, in order to develop effective screening and management protocols, it is vital to educate healthcare professionals regarding the various aspects of this congenital infection.

References

  1. Sijmons S, Van Ranst M, Maes P. Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing. Viruses. 2014;6(3):1049-72. https://dx.doi.org/10.3390%2Fv6031049
  2. Syggelou A, Iacovidou N, Kloudas S, Christoni Z, Papaevangelou V. Congenital cytomegalovirus infection. Ann N Y Acad Sci. 2010;1205:144-7. https://doi.org/10.1111/j.1749-6632.2010.05649.x
  3. Dupont L, Reeves MB. Cytomegalovirus latency and reactivation: recent insights into an age old problem. Rev Med Virol. 2016;26(2):75-89. https://doi.org/10.1002/rmv.1862
  4. Hizel S, Parker S, Onde U. Seroprevalence of cytomegalovirus infection among children and females in Ankara, Turkey, 1995. Pediatr Int. 1999;41(5):506-9. https://doi.org/10.1046/j.1442-200x.1999.01118.x
  5. Forbes BA. Acquisition of cytomegalovirus infection: an update. Clin Microbiol Rev. 1989;2(2):204-16. https://dx.doi.org/10.1128%2Fcmr.2.2.204
  6. Roback JD. CMV and blood transfusions. Rev Med Virol. 2002;12(4):211-9. https://doi.org/10.1002/rmv.353
  7. Pass RF, Anderson B. Mother-to-Child Transmission of Cytomegalovirus and Prevention of Congenital Infection. Journal of the Pediatric Infectious Diseases Society. 2014;3 Suppl 1(Suppl 1):S2-6. https://doi.org/10.1093/jpids/piu069
  8. Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang ML, et al. Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med. 2009;360(12):1191-9. 10.1056/NEJMoa0804749.
  9. Liesnard C, Donner C, Brancart F, Gosselin F, Delforge ML, Rodesch F. Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk. Obstet Gynecol. 2000;95(6 Pt 1):881-8. https://doi.org/10.1016/s0029-7844(99)00657-2
  10. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med. 2001;344(18):1366-71. https://doi.org/10.1056/nejm200105033441804
  11. Gaytant MA, Rours GI, Steegers EA, Galama JM, Semmekrot BA. Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature. Eur J Pediatr. 2003;162(4):248-53. https://doi.org/10.1007/s00431-002-1115-5
  12. Hamprecht K, Goelz R. Postnatal Cytomegalovirus Infection Through Human Milk in Preterm Infants: Transmission, Clinical Presentation, and Prevention. Clin Perinatol. 2017;44(1):121-30. https://doi.org/10.1016/j.clp.2016.11.012
  13. Vochem M, Hamprecht K, Jahn G, Speer CP. Transmission of cytomegalovirus to preterm infants through breast milk. Pediatr Infect Dis J. 1998;17(1):53-8. https://doi.org/10.1097/00006454-199801000-00012
  14. Stagno S, Brasfield DM, Brown MB, Cassell GH, Pifer LL, Whitley RJ, et al. Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: a prospective study. Pediatrics. 1981;68(3):322-9.
  15. Kadambari S, Whittaker E, Lyall H. Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage? Archives of Disease in Childhood - Fetal and Neonatal Edition. 2020;105(3):334. https://doi.org/10.1136/archdischild-2019-317650
  16. Goldblum RM, Dill CW, Albrecht TB, Alford ES, Garza C, Goldman AS. Rapid high-temperature treatment of human milk. J Pediatr. 1984;104(3):380-5. https://doi.org/10.1016/s0022-3476(84)81099-9
  17. Bryant P, Morley C, Garland S, Curtis N. Cytomegalovirus transmission from breast milk in premature babies: does it matter? Arch Dis Child Fetal Neonatal Ed. 2002;87(2):F75-7. https://doi.org/10.1136/fn.87.2.f75
  18. Ronchi A, Zeray F, Lee LE, Owen KE, Shoup AG, Garcia F, et al. Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection. J Perinatol. 2020;40(1):89-96. https://doi.org/10.1038/s41372-019-0501-z
  19. Kashden J, Frison S, Fowler K, Pass RF, Boll TJ. Intellectual assessment of children with asymptomatic congenital cytomegalovirus infection. J Dev Behav Pediatr. 1998;19(4):254-9. https://doi.org/10.1097/00004703-199808000-00003
  20. Fowler KB, Boppana SB. Congenital cytomegalovirus (CMV) infection and hearing deficit. J Clin Virol. 2006;35(2):226-31. https://doi.org/10.1016/j.jcv.2005.09.016
  21. Zhang XW, Li F, Yu XW, Shi XW, Shi J, Zhang JP. Physical and intellectual development in children with asymptomatic congenital cytomegalovirus infection: a longitudinal cohort study in Qinba mountain area, China. J Clin Virol. 2007;40(3):180-5. https://doi.org/10.1016/j.jcv.2007.08.018
  22. Kylat RI, Kelly EN, Ford-Jones EL. Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection. Eur J Pediatr. 2006;165(11):773-8. https://doi.org/10.1007/s00431-006-0172-6
  23. La Torre R, Nigro G, Mazzocco M, Best AM, Adler SP. Placental enlargement in women with primary maternal cytomegalovirus infection is associated with fetal and neonatal disease. Clin Infect Dis. 2006;43(8):994-1000. https://doi.org/10.1086/507634
  24. Boppana SB, Pass RF, Britt WJ, Stagno S, Alford CA. Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr Infect Dis J. 1992;11(2):93-9. https://doi.org/10.1097/00006454-199202000-00007
  25. Bale JF. Chapter 15 - Congenital cytomegalovirus infection. In: Tselis AC, Booss J, editors. Handb Clin Neurol. 123: Elsevier; 2014. p. 319-26.
  26. Ouellette C, Ronchi A, Mejias A, Chavez-Bueno S, Salamon D, Pugni L, et al. 998: Detection of Cytomegalovirus (CMV) in Cerebrospinal Fluid of Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture?: Open Forum Infect Dis. 2014 Dec;1(Suppl 1):S292. doi: 10.1093/ofid/ofu052.706. Epub 2014 Dec.
  27. Schleiss MR, Choo DI. Mechanisms of congenital cytomegalovirus-induced deafness. Drug Discov Today Dis Mech. 2006;3(1):105-13. https://doi.org/10.1016/j.ddmec.2006.02.009
  28. Davis GL, Spector GJ, Strauss M, Middlekamp JN. Cytomegalovirus endolabyrinthitis. Arch Pathol Lab Med. 1977;101(3):118-21.
  29. Fowler KB. Congenital cytomegalovirus infection: audiologic outcome. Clin Infect Dis. 2013;57 Suppl 4(Suppl 4):S182-4. https://doi.org/10.1093/cid/cit609
  30. Lanzieri TM, Chung W, Flores M, Blum P, Caviness AC, Bialek SR, et al. Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics. 2017;139(3). https://doi.org/10.1542/peds.2016-2610
  31. Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. 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):e1123-7. https://doi.org/10.1542/peds.2008-0770
  32. Yoshinaga-Itano C. Early intervention after universal neonatal hearing screening: impact on outcomes. Mental retardation and developmental disabilities research reviews. 2003;9(4):252-66. https://doi.org/10.1002/mrdd.10088
  33. Patel H, Feldman M. Universal newborn hearing screening. Paediatr Child Health. 2011;16(5):301-10. https://dx.doi.org/10.1093%2Fpch%2F16.5.301
  34. Jin HD, Demmler-Harrison GJ, Coats DK, Paysse EA, Bhatt A, Edmond JC, et al. Long-term Visual and Ocular Sequelae in Patients With Congenital Cytomegalovirus Infection. Pediatr Infect Dis J. 2017;36(9):877-82. https://doi.org/10.1097/inf.0000000000001599
  35. Coats DK, Demmler GJ, Paysse EA, Du LT, Libby C. Ophthalmologic findings in children with congenital cytomegalovirus infection. J AAPOS. 2000;4(2):110-6. https://doi.org/10.1067/mpa.2000.103870
  36. Noyola DE, Demmler GJ, Nelson CT, Griesser C, Williamson WD, Atkins JT, et al. Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection. J Pediatr. 2001;138(3):325-31. https://doi.org/10.1067/mpd.2001.112061
  37. Fink KR, Thapa MM, Ishak GE, Pruthi S. Neuroimaging of Pediatric Central Nervous System Cytomegalovirus Infection. 2010;30(7):1779-96. https://doi.org/10.1148/rg.307105043
  38. Kawasaki H, Kosugi I, Meguro S, Iwashita T. Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection. Pathol Int. 2017;67(2):72-82. https://doi.org/10.1111/pin.12502
  39. Ancora G, Lanari M, Lazzarotto T, Venturi V, Tridapalli E, Sandri F, et al. Cranial Ultrasound Scanning and Prediction of Outcome in Newborns with Congenital Cytomegalovirus Infection. The Journal of Pediatrics. 2007;150(2):157-61. https://doi.org/10.1016/j.jpeds.2006.11.032
  40. Practice bulletin no. 151: Cytomegalovirus, parvovirus B19, varicella zoster, and toxoplasmosis in pregnancy. Obstet Gynecol. 2015;125(6):1510-25. https://doi.org/10.1097/01.aog.0000466430.19823.53
  41. Beswick R, McHugh L, Clark JE. Integrating congenital cytomegalovirus screening within a newborn hearing screening program: Is it worthwhile? Int J Pediatr Otorhinolaryngol. 2021;142:110594. https://doi.org/10.1016/j.ijporl.2020.110594
  42. Williams EJ, Kadambari S, Berrington JE, Luck S, Atkinson C, Walter S, et al. Feasibility and acceptability of targeted screening for congenital CMV-related hearing loss. Arch Dis Child Fetal Neonatal Ed. 2014;99(3):F230-6. https://doi.org/10.1136/archdischild-2013-305276
  43. Courtmans I, Mancilla V, Ligny C, Le Bon SD, Naessens A, Foulon I. Incidence of congenital CMV in children at a hearing rehabilitation center. B-ent. 2015;11(4):303-8.
  44. 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. https://doi.org/10.1002/rmv.1790
  45. Beswick R, David M, Higashi H, Thomas D, Nourse C, Koh G, et al. Integration of congenital cytomegalovirus screening within a newborn hearing screening programme. J Paediatr Child Health. 2019;55(11):1381-8. https://doi.org/10.1111/jpc.14428
  46. Hughes BL, Gyamfi-Bannerman C. Diagnosis and antenatal management of congenital cytomegalovirus infection. Am J Obstet Gynecol. 2016;214(6):B5-b11. https://doi.org/10.1016/j.ajog.2016.02.042
  47. Gantt S, Bitnun A, Renaud C, Kakkar F, Vaudry W. Diagnosis and management of infants with congenital cytomegalovirus infection. Paediatr Child Health. 2017;22(2):72-4. https://doi.org/10.1093/pch/pxx002
  48. Lazzarotto T, Blázquez-Gamero D, Delforge ML, Foulon I, Luck S, Modrow S, et al. Congenital Cytomegalovirus Infection: A Narrative Review of the Issues in Screening and Management From a Panel of European Experts. Frontiers in pediatrics. 2020;8:13. https://doi.org/10.3389/fped.2020.00013
  49. Bilavsky E, Watad S, Levy I, Linder N, Pardo J, Ben-Zvi H, et al. Positive IgM in Congenital CMV Infection. Clin Pediatr (Phila). 2017;56(4):371-5. https://doi.org/10.1177/0009922816684596
  50. Guerra B, Lazzarotto T, Quarta S, Lanari M, Bovicelli L, Nicolosi A, et al. Prenatal diagnosis of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol. 2000;183(2):476-82. https://doi.org/10.1067/mob.2000.106347
  51. Kimberlin DW, Lin CY, Sánchez PJ, Demmler GJ, Dankner W, Shelton M, 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. https://doi.org/10.1016/s0022-3476(03)00192-6
  52. Oliver SE, Cloud GA, Sánchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. J Clin Virol. 2009;46 Suppl 4(Suppl 4):S22-6. https://doi.org/10.1016/j.jcv.2009.08.012
  53. Kimberlin DW, Acosta EP, Sánchez PJ, Sood S, Agrawal V, Homans J, et al. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008;197(6):836-45. https://doi.org/10.1086/528376
  54. 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. https://doi.org/10.1056/nejmoa1404599
  55. Mareri A, Lasorella S, Iapadre G, Maresca M, Tambucci R, Nigro G. Anti-viral therapy for congenital cytomegalovirus infection: pharmacokinetics, efficacy and side effects. J Matern Fetal Neonatal Med. 2016;29(10):1657-64. https://doi.org/10.3109/14767058.2015.1058774
  56. Pasternak Y, Ziv L, Attias J, Amir J, Bilavsky E. Valganciclovir Is Beneficial in Children with Congenital Cytomegalovirus and Isolated Hearing Loss. The Journal of Pediatrics. 2018;199:166-70. https://doi.org/10.1016/j.jpeds.2018.02.028
  57. Shahar-Nissan K, Pardo J, Peled O, Krause I, Bilavsky E, Bilavsky E, et al. LB20. Valacyclovir to Prevent Vertical Transmission of Cytomegalovirus After Maternal Primary Infection During Pregnancy. Open Forum Infect Dis. 2019;6(Suppl 2):S1002-S. https://dx.doi.org/10.1093%2Fofid%2Fofz415.2503

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