Skip to main content

Advertisement

Springer Nature Link
Log in

Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Introduction

Congenital cytomegalovirus (CCMV) infection is a common neonatal infection affecting 1% of all live births, 10% of which are symptomatic. Many of these infants have long-term sequelae. The objective is to document the clinical presentation of SCCMV infection in neonates, the frequency of sequelae and severity of adverse neurologic outcomes and risk factors.

Methods

A review and analysis of all symptomatic infants diagnosed with SCCMV infection are given. SCCMV was defined as a diagnosis of CCMV infection in the first three weeks of life in the presence of any clinical manifestations. Outcome data from 2 years of age and later are analyzed.

Results

There were 104 patients identified as having SCCMV infection and of these 42 cases had definite infection. The common findings at presentation were hepatosplenomegaly 19/42 (45%), thrombocytopenia 21/42 (50%), elevated transaminases 21/42(50%), abnormal cranial US scan 24/41(56%), abnormal head CT scan 29/41(71%) and abnormal brain MRI 17/19(89%). The risk factors for an adverse outcome including death or deafness or blindness or moderate to severe neurological deficits included an abnormal cranial US scan (OR 8.5), abnormal head CT scan (OR 21) and abnormal brainstem auditory evoked responses (BAER) (OR 8.7).

Conclusions

There was only three (7%) patients without any deficits and severely affected infants have been identified with a diverse clinical presentation, reinforcing the importance of CMV as a major public health problem.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CMV:

Cytomegalovirus

CCMV:

congenital CMV

HCMV:

Human CMV

ACCMV:

asymptomatic CCMV

CT:

computed tomography

MRI:

magnetic resonance imaging

SCCMV:

symptomatic congenital cytomegalovirus

SD:

standard deviation

db:

decibel

BAER:

brainstem auditory evoked responses

CI:

confidence intervals

OR:

odds ratio

US:

ultrasound

HC:

head circumference

IUGR:

intrauterine growth retardation

SNHL:

sensorineural hearing loss

SGA:

small for gestational age

HUSS:

cranial ultrasound scan

HCT:

head computed tomography

EEG:

electroencephalogram

AST:

Aspartate aminotransferase

SSEP:

somatosensory evoked potentials

ALT:

Alanine aminotransferase

References

  1. Ahlfors K, Ivarsson SA, Bjerre I (1986) Microcephaly and congenital cytomegalovirus infection: a combined prospective and retrospective study of a Swedish infant population. Pediatrics 78(6):1058–1063

    PubMed  CAS  Google Scholar 

  2. Ahlfors K, Ivarsson SA, Harris S (1999) Report of a long-term study of maternal and congenital cytomegalovirus infection in Sweden. Review of prospective studies available in the literature. Scand J Infect Dis 31(5):443–457

    Article  PubMed  CAS  Google Scholar 

  3. American Academy of Pediatrics (2003) Cytomegalovirus. In: Pickering LK (ed) Red book: report of the committee on infectious diseases, 26th edn. American Academy of Pediatrics, Elk Grove Village, Illinois, pp 59

    Google Scholar 

  4. Bale JF, Blackman JA, Sato Y (1990) Outcome in children with symptomatic congenital cytomegalovirus infection. J Child Neurol 5(2):131–136

    PubMed  Google Scholar 

  5. Barbi M, Binda S, Primache V, Clerici D (1998) Congenital cytomegalovirus infection in a northern Italian region. NEOCMV Group. Eur J Epidemiol 14(8):791–796

    Article  PubMed  CAS  Google Scholar 

  6. Boppana SB, Pass RF, Britt WJ, Stagno S, Alford CA (1992) Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr Infect Dis J 11(2):93–99

    Article  PubMed  CAS  Google Scholar 

  7. Burny W, Liesnard C, Donner C, Marchant A (2004) Epidemiology, pathogenesis and prevention of congenital cytomegalovirus infection. Expert Rev Anti Infect Ther 2(6):881–894

    Article  PubMed  Google Scholar 

  8. Conboy TJ, Pass RF, Stagno S, Alford CA, Myers GJ, Britt WJ, McCollister FP, Summers MN, McFarland CE, Boll TJ (1987) Early clinical manifestations and intellectual outcome in children with symptomatic congenital cytomegalovirus infection. J Pediatr 111(3):343–348

    Article  PubMed  CAS  Google Scholar 

  9. Demmler GJ (1994) Congenital cytomegalovirus infection. Semin Pediatr Neurol 1(1):36–42

    PubMed  CAS  Google Scholar 

  10. Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF (1997) Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr 130(4):624–630

    Article  PubMed  CAS  Google Scholar 

  11. Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA (1992) The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med 326(10):663–667

    Article  PubMed  CAS  Google Scholar 

  12. Griffiths PD (2002) Strategies to prevent CMV infection in the neonate. Semin Neonatol 7(4):293–299

    PubMed  Google Scholar 

  13. Ivarsson SA, Jonssson K, Jonsson B (2003) Birth characteristics and growth pattern in children with congenital cytomegalovirus infection. J Ped Endocrin 16(9):1233–1238

    Google Scholar 

  14. Kimberlin DW, Lin CY, Sanchez 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(1):16–25

    Article  PubMed  CAS  Google Scholar 

  15. Michaels MG, Greenberg DP, Sabo DL, Wald ER (2003) Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J 22(6):504–509

    Article  PubMed  Google Scholar 

  16. Morita M, Morishima T, Yamazaki T, Chiba S, Kawana T (1998) Clinical survey of congenital cytomegalovirus in Japan. Acta Paediatr Jpn 40(5):432–436

    PubMed  CAS  Google Scholar 

  17. Pass RF (2001) Cytomegalovirus infection. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed) Field’s virology, 4th edn. Lippincott-Williams & Wilkins, Philadelphia, PA, pp 2675–2705

    Google Scholar 

  18. Pass RF, Burke RL (2002) Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection. Semin Pediatr Infect Dis 13(3):196–204

    Article  PubMed  Google Scholar 

  19. Pass RF, Stagno S, Myers GJ, Alford CA (1980) Outcome of symptomatic congenital cytomegalovirus infection: results of long-term longitudinal follow-up. Pediatrics 66(5):758–762

    PubMed  CAS  Google Scholar 

  20. Plotkin SA (2004) Congenital cytomegalovirus infection and its prevention. Clin Infect Dis 38(7):1038–1039

    Article  PubMed  Google Scholar 

  21. Ramsey MEB, Miller E, Peckhan CS (1991) Outcome of confirmed symptomatic congenital cytomegalovirus infection. Arch Dis Child 66(9):1068–1069

    Article  Google Scholar 

  22. Revello MG, Gerna G (2002) Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev 15(4):680–715

    Article  PubMed  Google Scholar 

  23. Rivera LB, Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF (2002) Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection. Pediatrics 110(4):762–767

    Article  PubMed  Google Scholar 

  24. Ross SA, Boppana SB (2005) Congenital cytomegalovirus infection: outcome and diagnosis. Semin Pediatr Infect Dis 16(1):44–49

    Article  PubMed  Google Scholar 

  25. Schleiss MR (2005) Antiviral therapy of congenital cytomegalovirus infection. Semin Pediatr Infect Dis 16(1):50–59

    Article  PubMed  Google Scholar 

  26. Stagno S (2001) Cytomegalovirus. In: Remington JS, Klein JO (ed) Infectious diseases of the fetus and newborn infant, 5th edn. Saunders Philadelphia, PA, pp 389–424

    Google Scholar 

  27. Whitley RJ (2004) Congenital cytomegalovirus infection: epidemiology and treatment. Adv Exp Med Biol 549:155–160

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neonatology, Pediatrics Department, University of Tennessee, Le Bonheur Children’s Hospital, 50 N Dunlap St, Memphis, TN, 38103, USA

    Ranjit I. Kylat

  2. Pediatrics Department, University of Toronto, Toronto, Canada

    Ranjit I. Kylat, Edmond N. Kelly & Elizabeth Lee Ford-Jones

Authors
  1. Ranjit I. Kylat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edmond N. Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elizabeth Lee Ford-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ranjit I. Kylat.

Appendix

Appendix

Definitions

Sensorineural Hearing Loss: unequivocal failed or >30 db hearing loss on two or more age-appropriate audiologic tests (soundfield or pure tone audiometry) and middle ear disease ruled out or use of hearing aids in one or both ears

Visual impairment: blindness in one or both eyes or the need for corrective lenses

Blindness: visual acuity in both eyes of less than 6/60

Abnormal ophthalmologic exam: chorioretinitis, retinal scars, cataracts and other anomalies, like high myopia, strabismus, glaucoma, corneal opacities

Neuro-developmental delay: delay of more than 2SD below the mean for age (<70) when assessed by the Bayley Scales of Infant Development or equivalent scale

Abnormal CT scan of brain: cortical atrophy, cortical dysgenesis/dysplasia, moderate to severe ventriculomegaly/ hydrocephalus, cerebellar hypoplasia/asymmetry, migration abnormalities, intracranial calcifications (any one). Isolated abnormalities like subependymal, choroidal cysts, cephalhematoma were not included as an abnormal scan

Abnormal head ultrasound scan of brain: moderate to severe ventriculomegaly/hydrocephalus intracranial calcifications (any one). Presence of subependymal and choroidal cysts were also noted but not included as abnormal scan

Abnormal MRI scan of brain: the presence of any of the following: cortical atrophy, cortical dysgenesis, moderate to severe ventriculomegaly/ hydrocephalus, cerebellar hypoplasia/asymmetry, migration abnormalities, intracranial calcifications, pachygyria, lissencephaly (any one)

Abnormal EEG: abnormal background activity, assymmetric background activity, burst suppression or focal abnormality or if electrographical seizures, rolandic sharp waves (any one)

Cerebral Palsy: nonprogressive central nervous system disorder characterised by abnormal motor tone in at least one extremity and a decreased range or abnormal control of movement or posture, accompanied by neurologic signs

Microcephaly: HC<2SD below mean for age

SGA: birth weight<2SD below mean for gestational age

SCCMV infection: CMV detected in urine, saliva, secretions or tissue obtained within the first three weeks of life in a newborn with any clinical manifestations of an intrauterine infection including one or more of the following: petechiae or purpura, splenomegaly, hepatomegaly, jaundice at birth, microcephaly (<2SD), chorioretinitis, unexplained neurologic abnormalities, seizures, small for gestational age (SGA) or intrauterine growth retardation (<2SD), intracranial calcifications, hearing impairment, thrombocytopenia<100,000 mm3, alanine aminotransferase (ALT)>100 IU/dl, aspartate aminotransferase (AST)>100  IU/dl, conjugated hyperbilirubinemia>3 mg/dl

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kylat, R.I., Kelly, E.N. & Ford-Jones, E.L. Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection. Eur J Pediatr 165, 773–778 (2006). https://doi.org/10.1007/s00431-006-0172-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-006-0172-6

Keywords

Search

Navigation