Trends in Congenital Cytomegalovirus: A Review of Current Screening Methods and Prevention Strategies

ABSTRACT

Cytomegalovirus (CMV) is one of the leading causes of congenital sensorineural hearing loss. Currently, ∼40,000 infants in the United States are infected annually with CMV, and of these 40,000 infants, upward of 6000 infants will develop sensorineural hearing loss. Most of these infants will go undetected for congenital hearing loss by a newborn screening program, due to having late-onset or progressive hearing loss. An efficient CMV screening program of newborns will help to identify those infected and at risk for developing sensorineural hearing loss. Also, it will allow close monitoring of these infants for maximum speech and language development. Reliable methods are needed for an effective CMV screening program. Because the dried blood spot (DBS) sample is routinely collected at birth for metabolic screenings, there is growing interest to adapt this as the universal screening method. However, sensitivity of the DBS in detecting CMV has varied, and recent evidence has shown it less reliable than urine or saliva analysis. Further research is needed to develop the most efficient, reliable, and cost-effective programs. Models such as the Quebec metabolic screening program may ensure earlier identification of CMV. We are closer to a means of prophylactic prevention with a CMV vaccine; however, increased patient education of CMV prevention by health care professionals, including audiologists, is the current best practice for reducing the incidence of CMV infection.

KEYWORDS

Cytomegalovirus - dried blood spot - prevention - congenital sensorineural hearing loss

REFERENCES

• 1 Moeller M P. Early intervention and language development in children who are deaf and hard of hearing.  Pediatrics. 2000;  106 E43 Available at: http://www.pediatrics.org/cgi/content/full/106/3/e43 Accessed June 26, 2010; 
• 2 Joint Committee on Infant Hearing .Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs. Available at: http://www.asha.org/docs/html/PS2007-00281.html Accessed October 31, 2007
• 3 ACMG . Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss. Genetic evaluation of congenital hearing loss expert panel. ACMG statement.  Genet Med. 2002;  4 162-171
• 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 Demmler G J, Greisser C. Unique perspectives on children affected by congenital cytomegalovirus (CMV). February 10, 2009 CDC EHDI Special Topics Teleconference.  Accessed June 26, 2010; 
• 6 Barbi M, Binda S, Caroppo S. Diagnosis of congenital CMV infection via dried blood spots.  Rev Med Virol. 2006;  16 385-392
• 7 New York State Department of Health .Cytomegalovirus (CMV). Available at: http://www.health.state.ny.us/diseases/communicable/cytomegalovirus/fact_sheet.htm Updated November 2006. Accessed June 26, 2010
• 8 Barbi M B, Binda S, Primache V, Luraschi C, Corbetta C. Diagnosis of congenital cytomegalovirus infection by detection of viral DNA in dried blood spots.  Clin Diagn Virol. 1996;  6 27-32
• 9 Pass R F. Congenital cytomegalovirus infection and hearing loss.  Herpes. 2005;  12 50-55
• 10 Fowler K B, Boppana S B. Congenital cytomegalovirus (CMV) infection and hearing deficit.  J Clin Virol. 2006;  35 226-231
• 11 Barbi M, Binda S, Caroppo S, Primache V. Neonatal screening for congenital cytomegalovirus infection and hearing loss.  J Clin Virol. 2006;  35 206-209
• 12 McCollister F P, Simpson L C, Dahle A J et al.. Hearing loss and congenital symptomatic cytomegalovirus infection: a case report of multidisciplinary longitudinal assessment and intervention.  J Am Acad Audiol. 1996;  7 57-62
• 13 Dahle A J, Fowler K B, Wright J D, Boppana S B, Britt W J, Pass R F. Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus.  J Am Acad Audiol. 2000;  11 283-290
• 14 Fowler K B. Congenital cytomegalovirus (CMV) infection and hearing loss. Available at: http://www.idph.state.ia.us/iaehdi/common/pdf/cmv.pdf Accessed September 23, 2010
• 15 Grosse S D, Ross D S, Dollard S C. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment.  J Clin Virol. 2008;  41 57-62
• 16 CDC .Summary of 2007 national CDC EDHI data. Available at: http://www.cdc.gov/ncbddd/hearingloss/2007-data/2007_EHDI_HSFS_Summary_Ver2.pdf Accessed September 23, 2010
• 17 Rosenthal L S, Fowler K B, Boppana S B et al.. Cytomegalovirus shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with congenital infection.  Pediatr Infect Dis J. 2009;  28 515-520
• 18 Larke R P, Wheatley E, Saigal S, Chernesky M A. Congenital cytomegalovirus infection in an urban Canadian community.  J Infect Dis. 1980;  142 647-653
• 19 Peckham C S, Chin K S, Coleman J C, Henderson K, Hurley R, Preece P M. Cytomegalovirus infection in pregnancy: preliminary findings from a prospective study.  Lancet. 1983;  1 1352-1355
• 20 Ahlfors K, Ivarsson S A, 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;  16 129-137
• 21 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
• 22 Gerday E, Grose C. Demographic differences in congenital cytomegalovirus infection in the United States.  J Pediatr. 2004;  145 435-436
• 23 Fowler K B, Stagno S, Pass R F. Maternal immunity and prevention of congenital cytomegalovirus infection.  JAMA. 2003;  289 1008-1011
• 24 Dowd J B, Aiello A E. Socioeconomic differentials in immune response.  Epidemiology. 2009;  20 902-908
• 25 Dollard S C, Grosse S D, Ross D S. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection.  Rev Med Virol. 2007;  17 355-363
• 26 Fowler K B, Dahle A J, Boppana S B, Pass R F. Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?.  J Pediatr. 1999;  135 60-64
• 27 Rivera L B, Boppana S B, Fowler K B, Britt W J, Stagno S, Pass R F. Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection.  Pediatrics. 2002;  110 762-767
• 28 Foulon I, Naessens A, Foulon W, Casteels A, Gordts F A. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection.  J Pediatr. 2008;  153 84-88
• 29 Yamamoto A Y, Mussi-Pinhata M M, Marin L J, Brito R M, Oliveira P F, Coelho T B. Is saliva as reliable as urine for detection of cytomegalovirus DNA for neonatal screening of congenital CMV infection?.  J Clin Virol. 2006;  36 228-230
• 30 Grosse S D, Dollard S C, Ross D S, Cannon M J. Newborn screening for congenital cytomegalovirus: options for hospital-based and public health programs.  J Clin Virol. 2009;  46 (Suppl 4) S32-S36
• 31 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
• 32 Warren W P, Balcarek K, Smith R, Pass R F. Comparison of rapid methods of detection of cytomegalovirus in saliva with virus isolation in tissue culture.  J Clin Microbiol. 1992;  30 786-789
• 33 Carroll A E, Downs S M. Comprehensive cost-utility analysis of newborn screening strategies.  Pediatrics. 2006;  117 (5 Pt 2) S287-S295
• 34 Johansson P J, Jönsson M, Ahlfors K, Ivarsson S A, Svanberg L, Guthenberg C. Retrospective diagnostics of congenital cytomegalovirus infection performed by polymerase chain reaction in blood stored on filter paper.  Scand J Infect Dis. 1997;  29 465-468
• 35 Barbi M, Binda S, Primache V et al.. Cytomegalovirus DNA detection in Guthrie cards: a powerful tool for diagnosing congenital infection.  J Clin Virol. 2000;  17 159-165
• 36 Yamamoto A Y, Mussi-Pinhata M M, Pinto P C, Figueiredo L T, Jorge S M. Usefulness of blood and urine samples collected on filter paper in detecting cytomegalovirus by the polymerase chain reaction technique.  J Virol Methods. 2001;  97 (1–2) 159-164
• 37 Boppana S B, Ross S A, Novak Z National Institute on Deafness and Other Communication Disorders CMV and Hearing Multicenter Screening (CHIMES) Study et al. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection.  JAMA. 2010;  303 1375-1382
• 38 Auray-Blais C, Giguère R, Lemieux B. Newborn urine screening programme in the province of Quebec: an update of 30 years' experience.  J Inherit Metab Dis. 2003;  26 393-402
• 39 Jeon J, Victor M, Adler S P et al.. Knowledge and awareness of congenital cytomegalovirus among women.  Infect Dis Obstet Gynecol. 2006;  2006 80383
• 40 Ross D S, Victor M, Sumartojo E, Cannon M J. Women's knowledge of congenital cytomegalovirus: results from the 2005 HealthStyles survey.  J Womens Health (Larchmt). 2008;  17 849-858
• 41 Demmler-Harrison G J. Congenital cytomegalovirus: public health action towards awareness, prevention, and treatment.  J Clin Virol. 2009;  46 (Suppl 4) S1-S5
• 42 Pass R F, Zhang C, Evans A et al.. Vaccine prevention of maternal cytomegalovirus infection.  N Engl J Med. 2009;  360 1191-1199
• 43 Cannon M J. Congenital cytomegalovirus (CMV) epidemiology and awareness.  J Clin Virol. 2009;  46 (Suppl 4) S6-S10
• 44 Vauloup-Fellous C, Picone O, Cordier A G et al.. Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital.  J Clin Virol. 2009;  46 (Suppl 4) S49-S53
• 45 NC Program on Health Literacy .The problem of health literacy. Available at: http://nchealthliteracy.org/about.html Accessed April 1, 2010
• 46 DeWalt D, Pignone M. Health literacy 101. Defining the problem and what we can do about it. Available at: http://www.nchealthliteracy.org/presentations/Health%20Literacy%20101.ppt Accessed April 1, 2010

APPENDIX A: CMV PREVENTION AND AWARENESS WEBSITES

• Brendan B. McGinnis Congenital CMV Foundation: www.cmvfoundation.org

• Centers for Disease Control and Prevention (CDC) CMV Homepage: http://www.cdc.gov/cmv/index.html

• CDC podcast on congenital CMV: http://www2.cdc.gov/podcasts/player.asp?f=7925

• CDC: 10 tips for preventing infections during pregnancy: http://www.cdc.gov/ncbddd/pregnancy_gateway/infection.htm

• American College of Obstetricians and Gynecologists: http://www.acog.org/

• National Congenital CMV Disease Registry: http://www.bcm.edu/pedi/infect/cmv

• Stop CMV: http://www.stopcmv.com/

• Lisa Saunders: What you need to know about CMV: http://www.authorlisasaunders.com/mycustompage0042.htm

• CMV support: http://www.cmvsupport.org/modules/news/

• CMV Kids: http://cmvkids.com/