CMV-Induced Neonatal Thrombocytopenia: A Case Report and Review of the Literature

ABSTRACT

Cytomegalovirus (CMV) is a member of the Herpesviridae family of DNA viruses. It is unique in its ability to cause latent infection with secondary reactivation. Neonatal infection results from congenital and/or perinatal transmission. We present the case of a full-term infant with petechiae and splenomegaly at birth with no significant antenatal history. She was noted to have thrombocytopenia, but maternal platelet count was normal. Routine workup was normal, which prompted evaluation for toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex (TORCH infection); she was noted to have a positive urine CMV. She received multiple platelet transfusions and after consultation with an infectious disease specialist, she was started on intravenous (IV) ganciclovir. She continued to have persistent thrombocytopenia and received three doses of CMV immunoglobulin with gradual resolution. IV ganciclovir was changed to oral valganciclovir for a total treatment duration of 6 weeks. She failed her hearing screen, but eye examination was normal. She was discharged home after clinical stabilization with a close follow-up.

KEYWORDS

Cytomegalovirus - thrombocytopenia - TORCH - hearing loss - intracranial calcifications - ganciclovir - CMV immunoglobulin

REFERENCES

• 1 Demmler G J. Cytomegalovirus. In: Feigin RD, Cherry JD, Demmler GJ, Kaplan SL Textbook of Pediatric Infectious Diseases. 5th ed. Philadelphia; Saunders 2004: 1912
• 2 Mocarski E S. Cytomegaloviruses and their replication. In: Fields B, Knipe D, Howley P Virology. Vol. 2. 3rd ed. Philadelphia; Lippincott-Raven 1996: 2447
• 3 Walker A, Petheram S J, Ballard L et al.. Characterization of human cytomegalovirus strains by analysis of short tandem repeat polymorphisms.  J Clin Microbiol. 2001;  39 2219-2226
• 4 Demmler G J. Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease.  Rev Infect Dis. 1991;  13 315-329
• 5 Hamprecht K, Maschmann J, Vochem M et al.. Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding.  Lancet. 2001;  357 513-518
• 6 Maschmann J, Hamprecht K, Dietz K et al.. Cytomegalovirus infection of extremely low-birth weight infants via breast milk.  Clin Infect Dis. 2001;  33 1998-2003
• 7 Neuberger P, Hamprecht K, Vochem M et al.. Case-control study of symptoms and neonatal outcome of human milk-transmitted cytomegalovirus infection in premature infants.  J Pediatr. 2006;  148 326-331
• 8 Malm G, Engman M L. Congenital cytomegalovirus infections.  Semin Fetal Neonatal Med. 2007;  12 154-159
• 9 Fowler K B, Stagno S, Pass R F. Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990.  J Infect Dis. 1993;  168 552-556
• 10 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. 2006;  165 773-778
• 11 Noyola D E, Demmler G J, Nelson C T et al.. Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.  J Pediatr. 2001;  138 325-331
• 12 Boppana S B, Fowler K B, Vaid Y et al.. Neuroradiographic findings in the newborn period and long-term outcome in children with symptomatic congenital cytomegalovirus infection.  Pediatrics. 1997;  99 409-414
• 13 Coats D K, Demmler G J, Paysse E A et al.. Ophthalmologic findings in children with congenital cytomegalovirus infection.  J AAPOS. 2000;  4 110-116
• 14 Istas A S, Demmler G J, Dobbins J G et al.. Surveillance for congenital cytomegalovirus disease: a report from the National Congenital Cytomegalovirus Disease Registry.  Clin Infect Dis. 1995;  20 665-670
• 15 Hicks T, Fowler K, Richardson M et al.. Congenital cytomegalovirus infection and neonatal auditory screening.  J Pediatr. 1993;  123 779-782
• 16 Williamson W D, Demmler G J, Percy A K, Catlin F I. Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection.  Pediatrics. 1992;  90 862-866
• 17 Fowler K B, McCollister F P, Dahle A J et al.. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection.  J Pediatr. 1997;  130 624-630
• 18 Boppana S B, Fowler K B, Pass R F et al.. Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss.  J Pediatr. 2005;  146 817-823
• 19 Ross S A, Fowler K B, Ashrith G et al.. Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity.  J Pediatr. 2006;  148 332-336
• 20 Jones R N, Neale M L, Beattie B et al.. Development and application of a PCR-based method including an internal control for diagnosis of congenital cytomegalovirus infection.  J Clin Microbiol. 2000;  38 1-6
• 21 Grazia Revello M, Zavattoni M, Sarasini A et al.. Prenatal diagnostic and prognostic value of human cytomegalovirus load and IgM antibody response in blood of congenitally infected fetuses.  J Infect Dis. 1999;  180 1320-1323
• 22 Nelson C T, Istas A S, Wilkerson M K, Demmler G J. PCR detection of cytomegalovirus DNA in serum as a diagnostic test for congenital cytomegalovirus infection.  J Clin Microbiol. 1995;  33 3317-3318
• 23 Demmler G J, Buffone G J, Schimbor C M, May R A. Detection of cytomegalovirus in urine from newborns by using polymerase chain reaction DNA amplification.  J Infect Dis. 1988;  158 1177-1184
• 24 Whitley R J, Cloud G, Gruber W et al.. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study.  J Infect Dis. 1997;  175 1080-1086
• 25 Kimberlin D W, Lin C Y, Sanchez P J 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 16-25
• 26 Crumpacker C S. Ganciclovir.  N Engl J Med. 1996;  335 721-729
• 27 Vallejo J G, Englund J A, Garcia-Prats J A, Demmler G J. Ganciclovir treatment of steroid-associated cytomegalovirus disease in a congenitally infected neonate.  Pediatr Infect Dis J. 1994;  13 239-241
• 28 Nigro G, Scholz H, Bartmann U. Ganciclovir therapy for symptomatic congenital cytomegalovirus infection in infants: a two-regimen experience.  J Pediatr. 1994;  124 318-322
• 29 Xu H R, Li X N, Chen W L, Liu G Y. Chu NN, Yu C. A sensitive assay for simultaneous determination of plasma concentrations of valganciclovir and its active metabolite ganciclovir by LC/MS/MS.  J Chromatogr B Analyt Technol Biomed Life Sci. 2007;  848 329-334
• 30 Adler S P, Nigro G, Pereira L. Recent advances in the prevention and treatment of congenital cytomegalovirus infections.  Semin Perinatol. 2007;  31 10-18
• 31 Plotkin S A. Vaccination against cytomegalovirus, the changeling demon.  Pediatr Infect Dis J. 1999;  18 313-325
• 32 Pass R F, Duliege A M, Boppana S et al.. A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant.  J Infect Dis. 1999;  180 970-975
• 33 American College of Obstetricians and Gynecologists (ACOG) .Perinatal viral and parasitic infections. Washington, DC; American College of Obstetricians and Gynecologists 2000 13. ACOG practice bulletin, no. 20