Review and meta‐analysis of the epidemiology of congenital cytomegalovirus (CMV) infection

We reviewed studies that reported results of systematic cytomegalovirus (CMV) screening on fetuses and/or live‐born infants. The overall birth prevalence of congenital CMV infection was 0.64%, but varied considerably among different study populations. About 11% of live‐born infants with congenital CMV infection were symptomatic, but the inter‐study differences in definitions of symptomatic cases limit the interpretation of these data. Non‐white race, low socioeconomic status (SES), premature birth, and neonatal intensive care unit admittance were risk factors for congenital CMV infection. Birth prevalence increased with maternal CMV seroprevalence. Maternal seroprevalence accounted for 29% of the variance in birth prevalence between study populations. Maternal seroprevalence and birth prevalence were both higher in study populations that were ascertained at birth rather than in the prenatal period. Thus, timing of ascertainment should be considered when interpreting birth prevalence estimates. Birth prevalence was inversely correlated with mean maternal age, but this relationship was not significant when controlling for maternal seroprevalence. The rate of transmission to infants born to mothers who had a primary infection or a recurrent infection during pregnancy was 32% and 1.4%, respectively. Possible maternal primary infections (i.e. seropositive mother with CMV IgM) resulted in congenital infections about 20% of the time, but are likely to represent a mixture of primary and recurrent infections. In summary, CMV is a common congenital infection worldwide that can lead to permanent disabilities. There is an urgent need for interventions that can reduce the substantial burden of this often overlooked disease. Copyright © 2007 John Wiley & Sons, Ltd.

[1]  S. Yagel,et al.  Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies , 2006, BJOG : an international journal of obstetrics and gynaecology.

[2]  F. Mosca,et al.  Multicity Italian Study of Congenital Cytomegalovirus Infection , 2006, The Pediatric infectious disease journal.

[3]  M. Furione,et al.  Lymphoproliferative response in primary human cytomegalovirus (HCMV) infection is delayed in HCMV transmitter mothers. , 2006, The Journal of infectious diseases.

[4]  A. Best,et al.  Passive immunization during pregnancy for congenital cytomegalovirus infection. , 2005, The New England journal of medicine.

[5]  W. Rawlinson,et al.  Symptomatic infant characteristics of congenital cytomegalovirus disease in Australia , 2005, Journal of paediatrics and child health.

[6]  U. Bäder,et al.  Pre- and periconceptional primary cytomegalovirus infection: risk of vertical transmission and congenital disease. , 2005, BJOG : an international journal of obstetrics and gynaecology.

[7]  M. Cannon,et al.  Permissive nicotine regulation as a complement to traditional tobacco control , 2005, BMC public health.

[8]  J. Galama,et al.  The incidence of congenital cytomegalovirus infections in The Netherlands , 2005, Journal of medical virology.

[9]  A. Eidelman,et al.  Congenital cytomegalovirus infection in Israel: screening in different subpopulations. , 2005, The Israel Medical Association journal : IMAJ.

[10]  W. Foulon,et al.  A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection. , 2005, The Journal of pediatrics.

[11]  E. Endreffy,et al.  Incidence and outcome of congenital cytomegalovirus infection in selected groups of preterm and full-term neonates under intensive care. , 2004, In vivo.

[12]  M. Mussi-Pinhata,et al.  Perinatal or early-postnatal cytomegalovirus infection in preterm infants under 34 weeks gestation born to CMV-seropositive mothers within a high-seroprevalence population. , 2004, The Journal of pediatrics.

[13]  R. Rabinovich,et al.  Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  T. Fujikawa,et al.  Chronological changes of incidence and prognosis of children with asymptomatic congenital cytomegalovirus infection in Sapporo, Japan , 2004, BMC infectious diseases.

[15]  A. Distéfano,et al.  Human Cytomegalovirus: detection of congenital and perinatal infection in Argentina , 2004, BMC pediatrics.

[16]  E. C. Neto,et al.  Newborn Screening for Congenital Infectious Diseases , 2004, Emerging infectious diseases.

[17]  M. Sassi,et al.  Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection. , 2004, Human immunology.

[18]  M. Barbi,et al.  Congenital cytomegalovirus infection in a northern Italian region , 1998, European Journal of Epidemiology.

[19]  A. Shaamash,et al.  Preconceptional immunity to cytomegalovirus and the risk of symptomatic congenital infection , 2003, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[20]  A. Eidelman,et al.  Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection , 2003, Archives of disease in childhood. Fetal and neonatal edition.

[21]  S. Soong,et al.  Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. , 2003, The Journal of pediatrics.

[22]  D. Noyola,et al.  Congenital cytomegalovirus infection in San Luis Potosi, Mexico. , 2003, The Pediatric infectious disease journal.

[23]  G. Gerna,et al.  Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant , 2002, Clinical Microbiology Reviews.

[24]  J. Galama,et al.  Congenital Cytomegalovirus Infection: Review of the Epidemiology and Outcome , 2002, Obstetrical & gynecological survey.

[25]  S. Tantivanich,et al.  Prevalence of congenital cytomegalovirus and Toxoplasma antibodies in Thailand. , 2001, The Southeast Asian journal of tropical medicine and public health.

[26]  T. Lazzarotto,et al.  New developments in the diagnosis of maternal and congenital CMV infection , 2001, Expert review of molecular diagnostics.

[27]  U. Bäder,et al.  Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome , 2001, Prenatal diagnosis.

[28]  L. T. Moraes Figueiredo,et al.  Congenital cytomegalovirus infection in preterm and full-term newborn infants from a population with a high seroprevalence rate. , 2001, The Pediatric infectious disease journal.

[29]  M. Barbi,et al.  Cytomegalovirus DNA detection in Guthrie cards: a powerful tool for diagnosing congenital infection. , 2000, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[30]  T. Lazzarotto,et al.  Prenatal diagnosis of symptomatic congenital cytomegalovirus infection. , 2000, American journal of obstetrics and gynecology.

[31]  C. Donner,et al.  Prenatal Diagnosis of Congenital Cytomegalovirus Infection: Prospective Study of 237 Pregnancies at Risk , 2000, Obstetrics and gynecology.

[32]  A. Cotta,et al.  Congenital cytomegalovirus infection in a neonatal intensive care unit in brazil evaluated by PCR and association with perinatal aspects. , 2000, Revista do Instituto de Medicina Tropical de Sao Paulo.

[33]  B. Fölsch,et al.  Screening and diagnosis of congenital cytomegalovirus infection: a 5-y study. , 2000, Scandinavian journal of infectious diseases.

[34]  G Nigro,et al.  Prenatal diagnosis of fetal cytomegalovirus infection after primary or recurrent maternal infection. , 1999, Obstetrics and gynecology.

[35]  S. A. Yasseen,et al.  Follow-up of pregnant women with active cytomegalovirus infection. , 1999, Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit.

[36]  Allen Hy,et al.  Follow-up of pregnant women with active cytomegalovirus infection. , 1999 .

[37]  M. Schluchter,et al.  CYTOMEGALOVIRUS INFECTION AND HIV-1 DISEASE PROGRESSION IN INFANTS BORN TO HIV-1–INFECTED WOMEN , 1999 .

[38]  W. Britt,et al.  Symptomatic Congenital Cytomegalovirus Infection in Infants Born to Mothers With Preexisting Immunity to Cytomegalovirus , 1999, Pediatrics.

[39]  S. Ivarsson,et al.  Report on a long-term study of maternal and congenital cytomegalovirus infection in Sweden. Review of prospective studies available in the literature. , 1999, Scandinavian journal of infectious diseases.

[40]  M. Schluchter,et al.  Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group. , 1999, The New England journal of medicine.

[41]  S B Boppana,et al.  Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed? , 1999, The Journal of pediatrics.

[42]  L. de Catte,et al.  Neonatal screening for congenital cytomegalovirus infections , 1999, Journal of perinatal medicine.

[43]  F. Audibert,et al.  Should We Routinely Screen for Cytomegalovirus Antibody during Pregnancy? , 1999, Intervirology.

[44]  T. Lazzarotto,et al.  Prenatal Diagnosis of Congenital Cytomegalovirus Infection , 1998, Journal of Clinical Microbiology.

[45]  J. Bale,et al.  Epidemiology of congenital cytomegalovirus infection: maternal risk factors and molecular analysis of cytomegalovirus strains. , 1998, American journal of epidemiology.

[46]  E. Shalev,et al.  Prenatal diagnosis of fetal primary cytomegalovirus infection , 1997, Obstetrics and gynecology.

[47]  C. Chezzi,et al.  Cytomegalovirus infection in an Italian population: antibody prevalence, virus excretion and maternal transmission. , 1997, The new microbiologica.

[48]  P. Lebon,et al.  Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women. , 1997, The Journal of infectious diseases.

[49]  I. R. Rivera-Matos,et al.  Congenital cytomegalovirus infection in infants infected with human immunodeficiency virus type 1. , 1996, The Pediatric infectious disease journal.

[50]  F. Tsai,et al.  Catabolic effect in premature infants with early dexamethasone treatment , 1996, Acta paediatrica.

[51]  F. Tsai,et al.  Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction , 1996, Acta paediatrica.

[52]  A. Soliman,et al.  Maternal and neonatal prevalence of toxoplasma and cytomegalovirus (CMV) antibodies and hepatitis-B antigens in an Egyptian rural area. , 1996, Journal of tropical pediatrics.

[53]  G. Redzwan,et al.  The role of cytomegalovirus (CMV) infection in congenital diseases in Malaysia. , 1994, The Medical journal of Malaysia.

[54]  K. Heinonen,et al.  Screening for congenital cytomegalovirus infection among preterm infants born before the 34th gestational week in Finland. , 1994, Scandinavian journal of infectious diseases.

[55]  Joshua M. Pearce,et al.  Lymphocyte responses and virus excretion as risk factors for intrauterine infection with cytomegalovirus , 1993, Journal of medical virology.

[56]  K. Fowler,et al.  Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980-1990. , 1993, The Journal of infectious diseases.

[57]  N. Blackburn,et al.  Is antenatal screening for rubella and cytomegalovirus justified? , 1993, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[58]  C. Lee,et al.  Congenital cytomegalovirus infection in Korean population with very high prevalence of maternal immunity. , 1992, Journal of Korean medical science.

[59]  W. Britt,et al.  Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. , 1992, The Pediatric infectious disease journal.

[60]  J. Gadisseux,et al.  Prenatal diagnosis of fetal cytomegalovirus infection. , 1992, American journal of obstetrics and gynecology.

[61]  H. Whittle,et al.  Cytomegalovirus infection in Gambian mothers and their babies. , 1991, Journal of clinical pathology.

[62]  C. Baboonian,et al.  Congenital and maternal cytomegalovirus infections in a London population , 1991, British journal of obstetrics and gynaecology.

[63]  P. Griffiths,et al.  Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants. , 1988, American journal of obstetrics and gynecology.

[64]  W. Britt,et al.  Primary Cytomegalovirus Infection in Pregnancy: Incidence, Transmission to Fetus, and Clinical Outcome , 1987 .

[65]  L. Hatherley The Incidence of Cytomegalic Inclusion Disease (CID) in an Obstetric Teaching Hospital, 1975–1984 , 1985, The Australian & New Zealand journal of obstetrics & gynaecology.

[66]  M. Strauss A clinical pathologic study of hearing loss in congenital cytomegalovirus infection , 1985, The Laryngoscope.

[67]  G. Cloud,et al.  Immunoglobulin M antibodies detected by enzyme-linked immunosorbent assay and radioimmunoassay in the diagnosis of cytomegalovirus infections in pregnant women and newborn infants , 1985, Journal of clinical microbiology.

[68]  C. Ernhart,et al.  Primary cytomegalovirus infection in adolescent pregnancy. , 1984, Pediatrics.

[69]  C. Baboonian,et al.  A prospective study of primary cytomegalovirus infection during pregnancy: final report , 1984, British journal of obstetrics and gynaecology.

[70]  P. Griffiths,et al.  Intra-uterine transmission of cytomegalovirus in women known to be immune before conception , 1984, Journal of Hygiene.

[71]  C. Peckham,et al.  CYTOMEGALOVIRUS INFECTION IN PREGNANCY: PRELIMINARY FINDINGS FROM A PROSPECTIVE STUDY , 1983, The Lancet.

[72]  S. Chiba,et al.  A prospective study of congenital cytomegalovirus infection in Japan. , 1983, Scandinavian journal of infectious diseases.

[73]  S. Stagno,et al.  Prevalence and importance of congenital cytomegalovirus infection in three different populations. , 1982, The Journal of pediatrics.

[74]  C. Alford,et al.  Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection. , 1982, The New England journal of medicine.

[75]  E. Edmond,et al.  A prospective study of cytomegalovirus infection in pregnancy. I. Laboratory evidence of congenital infection following maternal primary and reactivated infection. , 1981, The Journal of infection.

[76]  R. Larke,et al.  Congenital cytomegalovirus infection in an urban Canadian community. , 1980, The Journal of infectious diseases.

[77]  S. Tantivanich,et al.  Serological studies on possible causes of intra-uterine infections in Thai infants. , 1980, The Southeast Asian journal of tropical medicine and public health.

[78]  E. Mason,et al.  Prospective Study of Congenital Cytomegalovirus Infection , 1980, Southern medical journal.

[79]  M. Moore,et al.  Comparative study of diagnostic procedures for congenital cytomegalovirus infection. , 1980, Pediatrics.

[80]  O. Østerballe,et al.  A PROSPECTIVE STUDY ON THE INCIDENCE AND SIGNIFICANCE OF CONGENITAL CYTOMEGALOVIRUS INFECTION , 1979, Acta paediatrica Scandinavica.

[81]  H. Macdonald,et al.  Congenital Cytomegalovirus Infection: a Collaborative Study on Epidemiological, Clinical and Laboratory Findings , 1978, Developmental medicine and child neurology.

[82]  E. Lauber,et al.  Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. , 1978, Archives of disease in childhood.

[83]  Richard Smith,et al.  Congenital cytomegalovirus infection. , 1977, The New England journal of medicine.

[84]  P. Leinikki,et al.  Perinatal cytomegalovirus infection in man. , 1977, Archives of disease in childhood.

[85]  Poser Cm,et al.  Letter: Transfer factor therapy in multiple sclerosis. , 1976 .

[86]  M. Melish,et al.  Congenital cytomegalovirus infection. Developmental progress of infants detected by routine screening. , 1973, American journal of diseases of children.

[87]  M. Kumar,et al.  Inapparent congenital cytomegalovirus infection. A follow-up study. , 1973, The New England journal of medicine.

[88]  H. Stern,et al.  Prospective Study of Cytomegalovirus Infection in Pregnancy , 1973, British medical journal.

[89]  J. Tobin,et al.  Cytomegalovirus Infection in the North West of England , 1970, Archives of disease in childhood.

[90]  R. Bart,et al.  Inapparent congenital cytomegalovirus infection. Clinical and epidemiologic characteristics in early infancy. , 1970, The New England journal of medicine.

[91]  M. Ismail,et al.  Bephenium Hydroxynaphthoate in Treatment of Ascariasis , 1960, British medical journal.