Cytomegalovirus: Should We Screen Pregnant Women for Primary Infection?

Abstract

Congenital cytomegalovirus (CMV) is a leading cause of neonatal morbidity, affecting ∼0.5 to 1% of infants born each year. Primary maternal infection during early pregnancy is the greatest risk factor for severe neonatal morbidity/mortality. The current recommendation from national organizations advises against routine screening of pregnant women for primary infection. Recent advancements in diagnosis and treatment raise the issue of implementation of a national screening program. Prior to development of a major screening program for a highly prevalent and costly disease, the screening test must be safe, reliable, and valid with an effective and feasible intervention. This article reviews recent literature regarding available screening tests and potential interventions and whether criteria for a screening program are met in the current state of science. Although screening women using CMV immunoglobulin (Ig) G, IgM, and IgG avidity testing is reliable, effective intervention with hygiene modification or treatment with CMV-specific hyperimmune globulin is not as well established. More evidence from randomized controlled trials is needed prior to moving forward with a screening program for congenital CMV.

Keywords

congenital cytomegalovirus - primary CMV infection - CMV hyperimmune globulin - screening program

• References

• 1 Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007; 17: 253-276
• 2 Grosse SD, Ross DS, Dollard SC. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol 2008; 41: 57-62
• 3 Centers for Disease Control and Prevention. Congenital CMV trends and statistics. Available at: http://www.cdc.gov/cmv/trends-stats.html . Accessed December 21, 2012
• 4 Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R. National Vaccine Advisory Committee. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 2004; 39: 233-239
• 5 Cannon MJ, Davis KF. Washing our hands of the congenital cytomegalovirus disease epidemic. BMC Public Health 2005; 5: 70
• 6 Cahill AG, Odibo AO, Stamilio DM, Macones GA. Screening and treating for primary cytomegalovirus infection in pregnancy: where do we stand? A decision-analytic and economic analysis. Am J Obstet Gynecol 2009; 201: e1-e7
• 7 Adler SP. Screening for cytomegalovirus during pregnancy. Infect Dis Obstet Gynecol 2011; 2011: 1-9
• 8 Gaytant MA, Steegers EAP, Semmekrot BA, Merkus HM, Galama JM. Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv 2002; 57: 245-256
• 9 Staras SAS, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin Infect Dis 2006; 43: 1143-1151
• 10 Stagno S, Pass RF, Dworsky ME, Alford Jr CA. Maternal cytomegalovirus infection and perinatal transmission. Clin Obstet Gynecol 1982; 25: 563-576
• 11 Ludwig A, Hengel H. Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. Euro Surveill 2009; 14: 26-32
• 12 Colugnati FAF, Staras SAS, Dollard SC, Cannon MJ. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infect Dis 2007; 7: 71
• 13 Fowler KB, Stagno S, Pass RF. Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 2003; 289: 1008-1011
• 14 Stagno S, Pass RF, Cloud G , et al. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA 1986; 256: 1904-1908
• 15 Enders G, Daiminger A, Bäder U, Exler S, Enders M. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 2011; 52: 244-246
• 16 Cannon MJ, Westbrook K, Levis D, Schleiss MR, Thackeray R, Pass RF. Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prev Med 2012; 54: 351-357
• 17 Centers for Disease Control and Prevention. Cytomegalovirus (CMV) and congenital CMV infection. At-risk patients. Available at: http://www.cdc.gov/cmv/risk/infants-children.html . Accessed December 21, 2012
• 18 ACOG. ACOG Practice Bulletin #20. Perinatal viral and parasitic infections. ACOG 2011;
• 19 Revello MG, Gerna G. Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. Clin Microbiol Rev 2002; 15: 680-715
• 20 Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 2008; 41: 192-197
• 21 Maidji E, McDonagh S, Genbacev O, Tabata T, Pereira L. Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta by neonatal Fc receptor-mediated transcytosis. Am J Pathol 2006; 168: 1210-1226
• 22 Dollard SC, Staras SAS, Amin MM, Schmid DS, Cannon MJ. National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM antibody titer and low IgG avidity. Clin Vaccine Immunol 2011; 18: 1895-1899
• 23 Centers for Disease Control and Prevention. Cytomegalovirus (CMV) and congenital CMV infection. Testing and diagnosis of CMV infection. Available at: http://www.cdc.gov/cmv/testing-diagnosis.html . Accessed December 21, 2012
• 24 Centers for Disease Control and Prevention. Cytomegalovirus (CMV) and congenital CMV infection. Preventing congenital CMV infection. Available at: http://www.cdc.gov/cmv/prevention.html . Accessed December 21, 2012
• 25 Maine GT, Stricker R, Schuler M , et al. Development and clinical evaluation of a recombinant-antigen-based cytomegalovirus immunoglobulin M automated immunoassay using the Abbott AxSYM analyzer. J Clin Microbiol 2000; 38: 1476-1481
• 26 Lazzarotto T, Galli C, Pulvirenti R , et al. Evaluation of the Abbott AxSYM cytomegalovirus (CMV) immunoglobulin M (IgM) assay in conjunction with other CMV IgM tests and a CMV IgG avidity assay. Clin Diagn Lab Immunol 2001; 8: 196-198
• 27 Revello MG, Genini E, Gorini G, Klersy C, Piralla A, Gerna G. Comparative evaluation of eight commercial human cytomegalovirus IgG avidity assays. J Clin Virol 2010; 48: 255-259
• 28 Adler SP, Finney JW, Manganello AM, Best AM. Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: a randomized controlled trial. Pediatr Infect Dis J 1996; 15: 240-246
• 29 Adler SP, Finney JW, Manganello AM, Best AM. Prevention of child-to-mother transmission of cytomegalovirus among pregnant women. J Pediatr 2004; 145: 485-491
• 30 Picone O, Vauloup-Fellous C, Cordier AG , et al. A 2-year study on cytomegalovirus infection during pregnancy in a French hospital. BJOG 2009; 116: 818-823
• 31 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: 1350-1362
• 32 Adler SP. Editorial commentary: primary maternal cytomegalovirus infection during pregnancy: do we have a treatment option?. Clin Infect Dis 2012; 55: 504-506