Summary
Congenital cytomegalovirus is the most frequent, yet under-recognised, infectious
cause of newborn malformation in developed countries. Despite its clinical and public
health importance, questions remain regarding the best diagnostic methods for identifying
maternal and neonatal infection, and regarding optimal prevention and therapeutic
strategies for infected mothers and neonates. The absence of guidelines impairs global
efforts to decrease the effect of congenital cytomegalovirus. Data in the literature
suggest that congenital cytomegalovirus infection remains a research priority, but
data are yet to be translated into clinical practice. An informal International Congenital
Cytomegalovirus Recommendations Group was convened in 2015 to address these questions
and to provide recommendations for prevention, diagnosis, and treatment. On the basis
of consensus discussions and a review of the literature, we do not support universal
screening of mothers and the routine use of cytomegalovirus immunoglobulin for prophylaxis
or treatment of infected mothers. However, treatment guidelines for infected neonates
were recommended. Consideration must be given to universal neonatal screening for
cytomegalovirus to facilitate early detection and intervention for sensorineural hearing
loss and developmental delay, where appropriate. The group agreed that education and
prevention strategies for mothers were beneficial, and that recommendations will need
continual updating as further data become available.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D; use, select 'Corporate R&D; Professionals'
Access any 5 articles from the Lancet Family of journals
Subscribe:
Subscribe to The Lancet Infectious DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 1.Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population.Clin Infect Dis. 2009; 49: 522-528
- 2.Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection.Rev Med Virol. 2007; 17: 253-276
- 3.The “silent” global burden of congenital cytomegalovirus.Clin Microbiol Rev. 2013; 26: 86-102
- 4.Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review.Rev Med Virol. 2014; 24: 420-433
- 5.Newborn hearing screening vs later hearing screening and developmental outcomes in children with permanent childhood hearing impairment.JAMA. 2010; 304: 1701-1708
- 6.Valganciclovir for symptomatic congenital cytomegalovirus disease.N Engl J Med. 2015; 372: 933-943
- 7.Congenital cytomegalovirus: Public health action towards awareness, prevention, and treatment.J Clin Virol. 2009; 46: S1-S5
- 8.Hawaii House Bill 782.https://legiscan.com/HI/text/HB782/2015(accessed Feb 10, 2017).Date: 2015
- 9.Cytomegalovirus (CMV) public health initiative.(accessed Feb 10, 2017).
- 10.Texas Senate Bill 791.https://legiscan.com/TX/bill/SB791/2015(accessed Feb 10, 2017).Date: 2015
- 11.International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.Transplantation. 2010; 89: 779-795
- 12.Towards early inclusion of children in tuberculosis drugs trials: a consensus statement.Lancet Infect Dis. 2015; 15: 711-720
- 13.Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5).Lancet Infect Dis. 2016; 16: 606-617
- 14.The Oxford Levels of Evidence.(accessed Feb 10, 2017).
- 15.Prevention of congenital and perinatal infections.Euro Surveill. 2009; 14: 2-4
- 16.Congenital cytomegalovirus infection—a question of screening.Isr Med Assoc J. 2007; 9: 392-394
- 17.Reducing congenital cytomegalovirus infection through policy and legislation in the United States.Microbiology Australia. 2015; (November): 162-164
- 18.Cytomegalovirus in pregnancy: to screen or not to screen.BMC Pregnancy Childbirth. 2013; 13: 96
- 19.Congenital cytomegalovirus infection following first trimester maternal infection: symptoms at birth and outcome.J Clin Virol. 2006; 35: 216-220
- 20.Prevention of child-to-mother transmission of cytomegalovirus by changing behaviors: a randomized controlled trial.Pediatr Infect Dis J. 1996; 15: 240-246
- 21.Prevention of primary cytomegalovirus infection in pregnancy.EBioMedicine. 2015; 2: 1205-1210
- 22.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: S49-S53
- 23.Prevention of child-to-mother transmission of cytomegalovirus among pregnant women.J Pediatr. 2004; 145: 485-491
- 24.Cytomegalovirus and child day care: risk factors for maternal infection.Pediatr Infect Dis J. 1991; 10: 590-594
- 25.Factors predictive of cytomegalovirus immune status in pregnant women.J Infect Dis. 1988; 157: 172-177
- 26.Acquisition of cytomegaloviral infections in families with young children: a serological study.J Infect Dis. 1985; 151: 948-952
- 27.Factors associated with primary cytomegalovirus infection during pregnancy.J Med Virol. 1984; 13: 347-353
- 28.Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection.N Engl J Med. 1982; 306: 945-949
- 29.Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection.Clin Infect Dis. 2011; 52: e11-e13
- 30.Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom.Clin Infect Dis. 2013; 56: 1232-1239
- 31.Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity.N Engl J Med. 2001; 344: 1366-1371
- 32.Cytomegalovirus reinfections in healthy seroimmune women.J Infect Dis. 2010; 201: 386-389
- 33.Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population.Am J Obstet Gynecol. 2010; 202 (297 e8): 297 e1
- 34.Fetal effects of primary and secondary cytomegalovirus infection in pregnancy.Reprod Toxicol. 2006; 21: 399-409
- 35.Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population.Pediatr Infect Dis J. 2011; 30: 1043-1046
- 36.Report on a long-term study of maternal and congenital cytomegalovirus infection in Sweden. Review of prospective studies available in the literature.Scand J Infect Dis. 1999; 31: 443-457
- 37.Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature.Eur J Pediatr. 2003; 162: 248-253
- 38.Secondary cytomegalovirus infection can cause severe fetal sequelae despite maternal preconceptional immunity.Ultrasound Obstet Gynecol. 2008; 31: 417-420
- 39.Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus.Pediatrics. 1999; 104: 55-60
- 40.Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity.J Pediatr. 2006; 148: 332-336
- 41.Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection.BJOG. 2003; 110: 572-577
- 42.Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant.Clin Microbiol Rev. 2002; 15: 680-715
- 43.Diagnosis of and screening for cytomegalovirus infection in pregnant women.J Clin Microbiol. 2005; 43: 4713-4718
- 44.Maternal IgG avidity and IgM detected by blot as diagnostic tools to identify pregnant women at risk of transmitting cytomegalovirus.Viral Immunol. 2000; 13: 137-141
- 45.A serological testing algorithm for the diagnosis of primary CMV infection in pregnant women.Prenat Diagn. 2004; 24: 861-863
- 46.Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy.Clin Microbiol Infect. 2011; 17: 1285-1293
- 47.Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy.Clin Vaccine Immunol. 2014; 21: 1377-1384
- 48.Improving diagnosis of primary cytomegalovirus infection in pregnant women using immunoblots.J Med Virol. 2013; 85: 315-319
- 49.The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy.J Clin Virol. 2013; 56: 102-107
- 50.MRI and ultrasound fusion imaging for prenatal diagnosis.Am J Obstet Gynecol. 2013; 209 (148 e9): 148 e1
- 51.Risk of fetal loss associated with invasive testing following combined first-trimester screening for Down syndrome: a national cohort of 147,987 singleton pregnancies.Ultrasound Obstet Gynecol. 2016; 47: 38-44
- 52.Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk.Obstet Gynecol. 2000; 95: 881-888
- 53.Accuracy of amniotic fluid testing before 21 weeks’ gestation in prenatal diagnosis of congenital cytomegalovirus infection.Prenat Diagn. 1994; 14: 1055-1059
- 54.Pathogenesis and prenatal diagnosis of human cytomegalovirus infection.J Clin Virol. 2004; 29: 71-83
- 55.Prenatal diagnosis of congenital cytomegalovirus infection.Obstet Gynecol. 2001; 97: 443-448
- 56.Prenatal indicators of congenital cytomegalovirus infection.J Pediatr. 2000; 137: 90-95
- 57.Prenatal diagnosis of symptomatic congenital cytomegalovirus infection.Am J Obstet Gynecol. 2000; 183: 476-482
- 58.Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.Am J Obstet Gynecol. 2016; 215 (342 e9): 342 e1
- 59.Does normal fetal brain ultrasound predict normal neurodevelopmental outcome in congenital cytomegalovirus infection?.Prenat Diagn. 2011; 31: 360-366
- 60.Ultrasound prediction of symptomatic congenital cytomegalovirus infection.Am J Obstet Gynecol. 2008; 198 (380 e7): 380 e1
- 61.The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus.BJOG. 2008; 115: 823-829
- 62.A prognostic neonatal neuroimaging scale for symptomatic congenital cytomegalovirus infection.Neonatology. 2016; 110: 277-285
- 63.Comparison between ultrasound and magnetic resonance imaging in assessment of fetal cytomegalovirus infection.Prenat Diagn. 2008; 28: 753-758
- 64.Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection.Ultrasound Obstet Gynecol. 2010; 36: 709-717
- 65.Quantification of human cytomegalovirus DNA in amniotic fluid of mothers of congenitally infected fetuses.J Clin Microbiol. 1999; 37: 3350-3352
- 66.Clinical predictive value of real-time PCR quantification of human cytomegalovirus DNA in amniotic fluid samples.J Clin Microbiol. 2009; 47: 660-665
- 67.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
- 68.Prognostic markers of symptomatic congenital cytomegalovirus infection.Braz J Infect Dis. 2008; 12: 38-43
- 69.Identification of symptomatic fetuses infected with cytomegalovirus using amniotic fluid peptide biomarkers.PLoS Pathog. 2016; 12: e1005395
- 70.Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood.BJOG. 2011; 118: 448-456
- 71.Prenatal diagnosis of congenital cytomegalovirus infection by detection of immunoglobulin M antibodies to the 70-kd heat shock protein in fetal serum.Am J Obstet Gynecol. 2002; 187: 955-959
- 72.Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome.Prenat Diagn. 2001; 21: 362-377
- 73.Vaccine prevention of maternal cytomegalovirus infection.N Engl J Med. 2009; 360: 1191-1199
- 74.Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: a randomized clinical trial.Vaccine. 2016; 34: 313-319
- 75.Human cytomegalovirus quantification in toddlers saliva from day care centers and emergency unit: a feasibility study.J Clin Virol. 2014; 61: 371-377
- 76.Cytomegalovirus survival on common environmental surfaces: opportunities for viral transmission.J Infect Dis. 2012; 205: 211-214
- 77.Cytomegalovirus survival and transferability and the effectiveness of common hand-washing agents against cytomegalovirus on live human hands.Appl Environ Microbiol. 2014; 80: 455-461
- 78.Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children.BMC Infect Dis. 2014; 14: 569
- 79.Hygiene interventions for prevention of cytomegalovirus infection among childbearing women: systematic review.J Adv Nurs. 2008; 63: 440-450
- 80.Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore.Int J Gynaecol Obstet. 2012; 117: 268-272
- 81.Knowledge and awareness of congenital cytomegalovirus among women.Infect Dis Obstet Gynecol. 2006; 2006: 80383
- 82.Observational study to assess pregnant women's knowledge and behaviour to prevent toxoplasmosis, listeriosis and cytomegalovirus.BMC Pregnancy Childbirth. 2013; 13: 98
- 83.Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus.Prev Med. 2012; 54: 351-357
- 84.Awareness of and knowledge about mother-to-child infections in Japanese pregnant women.Congenit Anom (Kyoto). 2014; 54: 35-40
- 85.Awareness of cytomegalovirus infection among pregnant women in Geneva, Switzerland: a cross-sectional study.Int J Environ Res Public Health. 2015; 12: 15285-15297
- 86.Awareness of cytomegalovirus and risk factors for susceptibility among pregnant women, in Montreal, Canada.BMC Pregnancy Childbirth. 2016; 16: 54
- 87.Survey of congenital cytomegalovirus (cCMV) knowledge among medical students.J Clin Virol. 2014; 60: 222-242
- 88.Awareness of congenital cytomegalovirus among doctors in the Netherlands.J Clin Virol. 2009; 46: S11-S15
- 89.Awareness and knowledge of congenital cytomegalovirus infection among health care providers in France.J Clin Virol. 2012; 55: 158-163
- 90.An email survey of midwives knowledge about CytoMegaloVirus (CMV) in Hannover and a skeletal framework for a proposed teaching program.Nurse Educ Pract. 2013; 13: 481-486
- 91.The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model.Rev Med Virol. 2013; 23: 241-249
- 92.Passive immunization during pregnancy for congenital cytomegalovirus infection.N Engl J Med. 2005; 353: 1350-1362
- 93.A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.N Engl J Med. 2014; 370: 1316-1326
- 94.Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis.J Perinat Med. 2012; 40: 439-446
- 95.Primary maternal cytomegalovirus infections during pregnancy: association of CMV hyperimmune globulin with gestational age at birth and birth weight.J Matern Fetal Neonatal Med. 2015; 28: 1-4
- 96.Hyperimmune globulin to prevent congenital CMV infection.N Engl J Med. 2014; 370: 2543
- 97.Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection.BJOG. 2007; 114: 1113-1121
- 98.Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy—a case-control study of the outcome in children.J Infect Dis. 2012; 205: 215-227
- 99.Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age.Clin Infect Dis. 2012; 55: 497-503
- 100.A trial of immunoglobulin fetal therapy for symptomatic congenital cytomegalovirus infection.J Reprod Immunol. 2012; 95: 73-79
- 101.Fetal hyperechogenic bowel may indicate congenital cytomegalovirus disease responsive to immunoglobulin therapy.J Matern Fetal Neonatal Med. 2012; 25: 2202-2205
- 102.Foscarnet treatment of genital infection due to acyclovir-resistant herpes simplex virus type 2 in a pregnant patient with AIDS: case report.Clin Infect Dis. 1999; 29: 937-938
- 103.Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.Transpl Infect Dis. 2005; 7: 71-74
- 104.Placental transfer of ganciclovir in a woman with acquired immunodeficiency syndrome and cytomegalovirus disease.Pediatr Infect Dis J. 2002; 21: 796-797
- 105.Renal transplantation one week after conception.Transplantation. 1995; 60: 1353-1354
- 106.Absence of teratogenicity of oral ganciclovir used during early pregnancy in a liver transplant recipient.Transplantation. 1999; 67: 758-759
- 107.Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group.N Engl J Med. 1999; 340: 1462-1470
- 108.Adverse pregnancy outcome in women exposed to acyclovir during pregnancy: a population-based observational study.Scand J Infect Dis. 2003; 35: 255-259
- 109.The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England.Br J Obstet Gyncaecol. 1998; 105: 882-889
- 110.Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999.Birth Defects Res A Clin Mol Teratol. 2004; 70: 201-207
- 111.Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects.JAMA. 2010; 304: 859-866
- 112.In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study.Am J Obstet Gynecol. 2016; 215: 462 e1-462462
- 113.Hearing loss and congenital CMV infection: a systematic review.Pediatrics. 2014; 134: 972-982
- 114.Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit?.Rev Med Virol. 2014; 24: 291-307
- 115.Language ability after early detection of permanent childhood hearing impairment.N Engl J Med. 2006; 354: 2131-2141
- 116.First estimates of the potential cost and cost saving of protecting childhood hearing from damage caused by congenital CMV infection.Arch Dis Child Fetal Neonatal Ed. 2015; 100: F501-F506
- 117.Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.Brain Dev. 2016; 38: 209-216
- 118.Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection.Int J Pediatr Otorhinolaryngol. 2015; 79: 2090-2093
- 119.Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection.JAMA Pediatr. 2016; 170: 1173-1180
- 120.Universal neonatal cytomegalovirus screening using saliva–report of clinical experience.J Clin Virol. 2014; 60: 361-366
- 121.Evaluating the feasibility of integrating salivary testing for congenital CMV into the newborn hearing screening programme in the UK.Eur J Pediatr. 2015; 174: 1117-1121
- 122.Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study.BMJ Open. 2011; 1: e000118
- 123.Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection.JAMA. 2010; 303: 1375-1382
- 124.Evaluation of DNA extraction methods for the detection of Cytomegalovirus in dried blood spots.J Clin Virol. 2015; 66: 95-99
- 125.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
- 126.Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns.N Engl J Med. 2011; 364: 2111-2118
- 127.Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding.Lancet. 2001; 357: 513-518
- 128.Cytomegalovirus infection of breast milk and transmission in infancy.Pediatrics. 1983; 72: 295-299
- 129.Newborn screening of congenital cytomegalovirus infection using saliva can be influenced by breast feeding.Arch Dis Child Fetal Neonatal Ed. 2013; 98: F182
- 130.Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.J Infect Dis. 1997; 175: 1080-1086
- 131.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
- 132.Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system.J Clin Virol. 2009; 46: S22-S26
- 133.Treatment of children with congenital cytomegalovirus infection with ganciclovir.Pediatr Infect Dis J. 2003; 22: 504-509
- 134.Ganciclovir therapy for congenital cytomegalovirus infection in six infants.Pediatr Infect Dis J. 2005; 24: 782-785
- 135.Ganciclovir therapy for symptomatic congenital cytomegalovirus infection in infants: a two-regimen experience.J Pediatr. 1994; 124: 318-322
- 136.Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up.J Laryngol Otol. 2009; 123: 391-396
- 137.Oral valganciclovir treatment in newborns with symptomatic congenital cytomegalovirus infection.Eur J Clin Microbiol Infect Dis. 2009; 28: 1465-1470
- 138.Treatment of symptomatic congenital cytomegalovirus infection beyond the neonatal period.J Clin Virol. 2012; 55: 72-74
- 139.Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease.J Infect Dis. 2008; 197: 836-845
Article info
Publication history
Published: March 10, 2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.