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CC BY-NC-ND 4.0 · J Pediatr Infect Dis 2024; 19(06): 317-326
DOI: 10.1055/s-0044-1790288
Original Article

Outcome of Children with Congenital Cytomegalovirus Infection: A Retrospective Observational Study

Chiara Mardegan 
1   Division of Pediatric Intensive Care and Neonatology, Department of Women, Children and Adolescents, University Hospitals of Geneva, Geneva, Switzerland
,
Helene Cao Van
2   Division of Otorhinolaryngology, Department of Clinical Neurosciences, University Hospitals of Geneva, Geneva, Switzerland
,
Sylviane Hanquinet
3   Pediatric Radiology Unit, Diagnostic Department, University Hospitals of Geneva, Geneva, Switzerland
,
Cristina Borradori Tolsa
4   Division of Development and Growth, Department of Women, Children and Adolescents, University Hospital of Geneva, Geneva, Switzerland
,
Laure F. Pittet
5   Division of General Pediatrics, Department of Women, Children and Adolescents, University Hospitals of Geneva, Geneva, Switzerland
,
Klara M. Posfay-Barbe
5   Division of General Pediatrics, Department of Women, Children and Adolescents, University Hospitals of Geneva, Geneva, Switzerland
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Abstract

Objective Congenital cytomegalovirus (CMV) infection is a common intrauterine infection and the leading cause of nonhereditary sensorineural hearing loss. This study aims to assess the long-term outcome of the infection and to identify infants at risk of developing long-term sequelae.

Methods This retrospective single-center observational study includes infants born between 2003 and 2019 with confirmed congenital CMV (based on current criteria). Brain imaging (ultrasound and magnetic resonance imaging [MRI]), clinical monitoring of neurosensory development, and auditory brainstem evoked responses were performed, as well as long-term neurodevelopmental follow-up to assess sequelae.

Results A total of 66 infants with congenital CMV were included in the study. Median gestational age at birth was 38.6 weeks (interquartile range: 36.9–40.1). Clinical findings included intrauterine growth restriction (39%), microcephaly (29%), thrombocytopenia (17%), and jaundice (11%). Brain abnormalities were observed on ultrasound (30%) and MRI (42%). Neurodevelopmental scores were abnormal in 21 subjects (43%) and associate with the vacuolization of anterior temporal lobe and ventricular septations on MRI (both p = 0.05). Fourteen patients (21%) had sensorineural hearing loss, which was more common in patients with abnormal cerebral images at birth, determined by ultrasound (p = 0.06). Microcephaly (p = 0.05) and abnormal MRI (p = 0.03) at birth were associated with poor long-term outcomes.

Conclusion Early detection of congenital CMV infection is important to prevent long-term complications in affected infants. Understanding the predictors of poor outcomes may help improving management and treatment strategies for this condition.

Keywords

congenital infection - cytomegalovirus - long-term sequelae


Publication History

Received: 25 October 2023

Accepted: 19 August 2024

Article published online:
04 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Demmler GJ. Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease. Rev Infect Dis 1991; 13 (02) 315-329
    CrossrefPubMedSearch in Google Scholar
  • 2 Lanzieri TM, Dollard SC, Bialek SR, Grosse SD. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis 2014; 22: 44-48
    CrossrefPubMedSearch in Google Scholar
  • 3 Boppana SB, Ross SA, Fowler KB. Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis 2013; 57 (Suppl 4, Suppl 4): S178-S181
    CrossrefPubMedSearch in Google Scholar
  • 4 Walker SP, Palma-Dias R, Wood EM, Shekleton P, Giles ML. Cytomegalovirus in pregnancy: to screen or not to screen. BMC Pregnancy Childbirth 2013; 13 (01) 96
    CrossrefPubMedSearch in Google Scholar
  • 5 Stein O, Sheinberg B, Schiff E, Mashiach S, Seidman DS. Prevalence of antibodies to cytomegalovirus in a parturient population in Israel. Isr J Med Sci 1997; 33 (01) 53-58
    PubMedSearch in Google Scholar
  • 6 Chiopris G, Veronese P, Cusenza F. et al. Congenital cytomegalovirus infection: update on diagnosis and treatment. Microorganisms 2020; 8 (10) 1516
    CrossrefPubMedSearch in Google Scholar
  • 7 Adler SP. Screening for cytomegalovirus during pregnancy. Infect Dis Obstet Gynecol 2011; 2011: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 8 Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17 (04) 253-276
    CrossrefPubMedSearch in Google Scholar
  • 9 Ornoy A, Diav-Citrin O. Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reprod Toxicol 2006; 21 (04) 399-409
    CrossrefPubMedSearch in Google Scholar
  • 10 Fowler KB, Stagno S, Pass RF. Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 2003; 289 (08) 1008-1011
    CrossrefPubMedSearch in Google Scholar
  • 11 Nigro G, Adler SP, La Torre R, Best AM. Congenital Cytomegalovirus Collaborating Group. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 2005; 353 (13) 1350-1362
    CrossrefPubMedSearch in Google Scholar
  • 12 Giorgione V, Krajden Haratz K, Gull I. et al. Myocardial function in fetuses with congenital cytomegalovirus infection. Fetal Diagn Ther 2023; 50 (06) 430-437
    CrossrefPubMedSearch in Google Scholar
  • 13 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
    CrossrefPubMedSearch in Google Scholar
  • 14 Boppana SB, Pass RF, Britt WJ, Stagno S, Alford CA. Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr Infect Dis J 1992; 11 (02) 93-99
    CrossrefPubMedSearch in Google Scholar
  • 15 Williamson WD, Demmler GJ, Percy AK, Catlin FI. Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection. Pediatrics 1992; 90 (06) 862-866
    CrossrefPubMedSearch in Google Scholar
  • 16 Harris S, Ahlfors K, Ivarsson S, Lernmark B, Svanberg L. Congenital cytomegalovirus infection and sensorineural hearing loss. Ear Hear 1984; 5 (06) 352-355
    CrossrefPubMedSearch in Google Scholar
  • 17 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 (05) 283-290
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 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 (01) 39-42
    CrossrefPubMedSearch in Google Scholar
  • 19 Willame A, Blanchard-Rohner G, Combescure C, Irion O, Posfay-Barbe K, Martinez de Tejada B. Awareness of cytomegalovirus infection among pregnant women in Geneva, Switzerland: a cross-sectional study. Int J Environ Res Public Health 2015; 12 (12) 15285-15297
    CrossrefPubMedSearch in Google Scholar
  • 20 de Vries JJC, van der Eijk AA, Wolthers KC. et al. Real-time PCR versus viral culture on urine as a gold standard in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 2012; 53 (02) 167-170
    CrossrefPubMedSearch in Google Scholar
  • 21 Luck SE, Wieringa JW, Blázquez-Gamero D. et al; ESPID Congenital CMV Group Meeting, Leipzig 2015. Congenital cytomegalovirus: a European expert consensus statement on diagnosis and management. Pediatr Infect Dis J 2017; 36 (12) 1205-1213
    CrossrefPubMedSearch in Google Scholar
  • 22 Kimberlin DW, Jester PM, Sánchez PJ. et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015; 372 (10) 933-943
    CrossrefPubMedSearch in Google Scholar
  • 23 Bain SK, Gray R. Test reviews: Kaufman, A. S., & Kaufman, N. L. (2004). Kaufman Assessment Battery for Children, Second edition. Circle Pines, MN: AGS. J Psychoeduc Assess 2008; 26 (01) 92-101
    CrossrefPubMedSearch in Google Scholar
  • 24 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 (05) 972-982
    CrossrefPubMedSearch in Google Scholar
  • 25 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 (05) 355-363
    CrossrefPubMedSearch in Google Scholar
  • 26 Townsend CL, Forsgren M, Ahlfors K, Ivarsson SA, Tookey PA, Peckham CS. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis 2013; 56 (09) 1232-1239
    CrossrefPubMedSearch in Google Scholar
  • 27 Dreher AM, Arora N, Fowler KB. et al. Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection. J Pediatr 2014; 164 (04) 855-859
    CrossrefPubMedSearch in Google Scholar
  • 28 Pass RF. Cytomegalovirus infection. Pediatr Rev 2002; 23 (05) 163-170
    CrossrefPubMedSearch in Google Scholar
  • 29 Fink KR, Thapa MM, Ishak GE, Pruthi S. Neuroimaging of pediatric central nervous system cytomegalovirus infection. Radiographics 2010; 30 (07) 1779-1796
    CrossrefPubMedSearch in Google Scholar
  • 30 Noyola DE, Demmler GJ, Nelson CT. et al; Houston Congenital CMV Longitudinal Study Group. Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection. J Pediatr 2001; 138 (03) 325-331
    CrossrefPubMedSearch in Google Scholar
  • 31 Capretti MG, Lanari M, Tani G. et al. Role of cerebral ultrasound and magnetic resonance imaging in newborns with congenital cytomegalovirus infection. Brain Dev 2014; 36 (03) 203-211
    CrossrefPubMedSearch in Google Scholar
  • 32 Malinger G, Lev D, Lerman-Sagie T. Imaging of fetal cytomegalovirus infection. Fetal Diagn Ther 2011; 29 (02) 117-126
    CrossrefPubMedSearch in Google Scholar
  • 33 Lucignani G, Rossi Espagnet MC, Napolitano A. et al. A new MRI severity score to predict long-term adverse neurologic outcomes in children with congenital cytomegalovirus infection. J Matern Fetal Neonatal Med 2021; 34 (06) 859-866
    CrossrefPubMedSearch in Google Scholar
  • 34 Inaba Y, Motobayashi M, Nishioka M. et al. Correlation between white matter lesions and intelligence quotient in patients with congenital cytomegalovirus infection. Pediatr Neurol 2016; 55: 52-57
    CrossrefPubMedSearch in Google Scholar
  • 35 Diogo MC, Glatter S, Binder J, Kiss H, Prayer D. The MRI spectrum of congenital cytomegalovirus infection. Prenat Diagn 2020; 40 (01) 110-124
    CrossrefPubMedSearch in Google Scholar
  • 36 Alarcón A, De Vries LS, Parodi A. et al. Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities. Arch Dis Child Fetal Neonatal Ed 2024; 109 (02) 151-158
    CrossrefPubMedSearch in Google Scholar
  • 37 de Vries LS, Gunardi H, Barth PG, Bok LA, Verboon-Maciolek MA, Groenendaal F. The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection. Neuropediatrics 2004; 35 (02) 113-119
    Thieme ConnectPubMedSearch in Google Scholar
  • 38 Doneda C, Parazzini C, Righini A. et al. Early cerebral lesions in cytomegalovirus infection: prenatal MR imaging. Radiology 2010; 255 (02) 613-621
    CrossrefPubMedSearch in Google Scholar
  • 39 Duval M, Park AH. Congenital cytomegalovirus: what the otolaryngologist should know. Curr Opin Otolaryngol Head Neck Surg 2014; 22 (06) 495-500
    CrossrefPubMedSearch in Google Scholar
  • 40 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 (01) 60-64
    CrossrefPubMedSearch in Google Scholar
  • 41 Pinninti S, Christy J, Almutairi A, Cochrane G, Fowler KB, Boppana S. Vestibular, gaze, and balance disorders in asymptomatic congenital cytomegalovirus infection. Pediatrics 2021; 147 (02) e20193945
    CrossrefPubMedSearch in Google Scholar
  • 42 Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. J Pediatr 2008; 153 (01) 84-88
    CrossrefPubMedSearch in Google Scholar
  • 43 Courtois C, Blanchard M, Rouillon I. et al. Outcome for bilateral cochlear implantation in patients with congenital cytomegalovirus infection. Eur Ann Otorhinolaryngol Head Neck Dis 2021; 138 (05) 337-341
    CrossrefPubMedSearch in Google Scholar
  • 44 Teissier N, Delezoide AL, Mas AE. et al. Inner ear lesions in congenital cytomegalovirus infection of human fetuses. Acta Neuropathol 2011; 122 (06) 763-774
    CrossrefPubMedSearch in Google Scholar
  • 45 Dhondt C, Maes L, Rombaut L. et al. Vestibular function in children with a congenital cytomegalovirus infection: 3 years of follow-up. Ear Hear 2021; 42 (01) 76-86
    CrossrefPubMedSearch in Google Scholar
  • 46 Novelli M, Natale F, Di Norcia A. et al. Early neurodevelopmental outcomes in children with asymptomatic congenital CMV infection. Ital J Pediatr 2022; 48 (01) 203
    CrossrefPubMedSearch in Google Scholar
  • 47 Shahar-Nissan K, Pardo J, Peled O. et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial. Lancet 2020; 396 (10253): 779-785
    CrossrefPubMedSearch in Google Scholar