Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection

Lazzarotto, Tiziana; Gabrielli, Liliana; Lanari, Marcello; Guerra, Brunella; Bellucci, T.; Sassi, Monica; Landini, Maria Paola

doi:10.1016/j.humimm.2004.02.006

Cited by 81 publications

(49 citation statements)

References 16 publications

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“…Are intermediate results comparable to low-avidity results or high-avidity results? The Bologna group analyzed the proportion of mothers transmitting the infection in relation to their CMV IgG avidity result and found transmission rates of 30% in the low-avidity group, 4% in the intermediate-avidity group, and 2% in the high-avidity group (58). Very similar transmission percentages were subsequently reported by another group (15).…”

Section: How Should Intermediate CMV Igg Avidity Results Be Used?mentioning

confidence: 71%

“…Many laboratories using CMV IgG avidity to discriminate primary from nonprimary CMV infection follow a reflexive algorithm whereby only CMV IgG-positive samples that are also CMV IgM positive are tested for CMV IgG avidity (6,17,18,31,34,48,58); yet, investigators that have tested all CMV IgG-positive samples for avidity, regardless of the CMV IgM result, have consistently found that 1% to 3% of IgG-positive, IgMnegative samples exhibit low IgG avidity (16,48,57), suggesting an increased risk of intrauterine transmission. Indeed, transmission has been documented in patients who lacked CMV IgM but exhibited low IgG avidity (14,61); it is likely that these women were in the narrow time window when IgM reversion has occurred but avidity is still low (3,(28)(29)(30)(31).…”

Section: How Should Intermediate CMV Igg Avidity Results Be Used?mentioning

confidence: 99%

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Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

Prince

Lapé-Nixon

2014

Clin Vaccine Immunol

184

141

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The risk of intrauterine transmission of cytomegalovirus (CMV) during pregnancy is much greater for women who contract primary CMV infection after conception than for women with evidence of infection (circulating CMV antibodies) before conception. Thus, laboratory tests that aid in the identification of recent primary CMV infection are important tools for managing the care of pregnant women suspected of having been exposed to CMV. CMV IgM detection is a sensitive marker of primary CMV infection, but its specificity is poor because CMV IgM is also produced during viral reactivation and persists following primary infection in some individuals. Studies conducted over the last 20 years convincingly demonstrate that measurement of CMV IgG avidity is both a sensitive and a specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. IgG avidity is defined as the strength with which IgG binds to antigenic epitopes expressed by a given protein; it matures gradually during the 6 months following primary infection. Low CMV IgG avidity is an accurate indicator of primary infection within the preceding 3 to 4 months, whereas high avidity excludes primary infection within the preceding 3 months. In this minireview, we summarize published data demonstrating the clinical utility of CMV IgG avidity results for estimating time since primary infection in pregnant women, describe commercially available CMV IgG avidity assays, and discuss some of the issues and controversies surrounding CMV IgG avidity testing during pregnancy. C ongenital cytomegalovirus (CMV) infection is the most common intrauterine infection, occurring in approximately 40,000 newborns each year in the United States (1-4). The clinical manifestations include sensorineural hearing loss, visual impairment, mental retardation, and cognitive defects; 4% of infected infants do not survive (1,2,5,6).Several studies have demonstrated a strong link between primary CMV infection of the mother and in utero CMV transmission. The risk of congenital infection is approximately 40% in babies born to mothers who acquire a primary (initial) CMV infection after conception; in contrast, the risk is only about 1% in infants born to mothers who have evidence of CMV infection (i.e., circulating CMV antibodies) before conception (1,3,(6)(7)(8)(9). The few cases of CMV transmission in seropositive mothers reflect nonprimary CMV infections, defined as either viral reactivation or infection with a different strain of CMV during pregnancy (2, 3, 5). Preexisting maternal antibodies thus appear to offer substantial protection against congenital infection, most likely due to the ability of antibodies to control viremia (2, 9, 10).The established link between primary CMV infection during pregnancy and congenital infection makes identification of primary CMV infection an important goal in maternal and neonatal health care. However, Ͼ95% of pregnant women with primary CMV infection are asymptomatic and thus cannot be ...

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Section: How Should Intermediate CMV Igg Avidity Results Be Used?mentioning

confidence: 71%

Section: How Should Intermediate CMV Igg Avidity Results Be Used?mentioning

confidence: 99%

Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

Prince

Lapé-Nixon

2014

Clin Vaccine Immunol

184

141

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“…Nigro et al examined whether CMV-specific hyperimmune globulin therapy could be useful for the prevention and treatment of congenital CMV infection, yet the results of the study did not allow any conclusions to be drawn (28). Despite the drawbacks of the diagnosis and treatment of a congenital CMV infection, gynecologists do screen their patients for CMV (18). Supporters of routine prenatal screening argue that the use of precautionary hygienic measures can be suggested to CMV-seronegative pregnant women.…”

mentioning

confidence: 99%

Clinical Predictive Value of Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples

Goegebuer¹,

Meensel²,

Beuselinck³

et al. 2009

J Clin Microbiol

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The aim of this study was to evaluate the diagnostic reliability and prognostic significance of the quantification of cytomegalovirus (CMV) DNA in amniotic fluid (AF). We retrospectively reviewed the results for 282 amniotic fluid samples that had been tested for CMV by a quantitative real-time PCR. We observed three cases in which no CMV genomes were detected in the AF but in which the children were nevertheless congenitally infected. Hence, we conclude that a negative result by PCR for CMV in AF cannot rule out the possibility of congenital infection. No false-positive PCR results were observed. A correlation between the CMV viral load in AF and the fetal and neonatal outcomes could not be demonstrated in our study. Instead, a correlation was found between the CMV viral load and the gestational age at the time of amniocentesis.Human cytomegalovirus (CMV) is the leading cause of congenital viral infection in developed countries, with the reported incidence varying between 0.2 and 2.2% of all live births (15,35). The transmission rate following primary infection of the mother is about 40%. Only 10 to 15% of the CMV-infected children are symptomatic at birth, and the symptoms range from mild to life-threatening disease. The remaining 85 to 90% of the children are asymptomatic at birth, but 10% of them will develop complications later on, mainly neurodevelopmental defects and sensorineural hearing loss. Among pregnant women with recurrent infection, the rate of transmission to the infant is about 1%. Despite a preexisting immunity in the mother, epidemiological data suggest that the frequency and the severity of symptoms might be in the same range as those for a primary CMV infection (11,12).The issue of whether pregnant women should be screened for CMV during pregnancy has been debated for many years, but no consensus has been agreed upon (6). None of the current international guidelines recommend routine serologic screening of pregnant women (1,7,16,23,26). Indeed, there is no prognostic marker in the mother to predict whether the virus will be transmitted to the fetus (32). To obtain more information, invasive prenatal diagnostic techniques, such as amniocentesis or cordocentesis, have been used. Moreover, CMV infection of the fetus can lead to a great variety of clinical and biological conditions, but there is no reliable marker that can be used to predict which infected fetuses will have serious sequelae (32, 33). Finally, no vaccine or prophylactic therapy is available at present (24, 32). Nigro et al. examined whether CMV-specific hyperimmune globulin therapy could be useful for the prevention and treatment of congenital CMV infection, yet the results of the study did not allow any conclusions to be drawn (28). Despite the drawbacks of the diagnosis and treatment of a congenital CMV infection, gynecologists do screen their patients for CMV (18). Supporters of routine prenatal screening argue that the use of precautionary hygienic measures can be suggested to CMV-seronegative pregnant women. Otherwise, the k...

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“…2 In pregnant women, CMV isolation and/or detection of viral DNA by polymerase chain reaction (PCR) in amniotic fluid is useful in defining the risk for fetal infection. [3][4][5][6][7] The diagnosis of congenital CMV is best accomplished by viral culture of saliva or urine or by PCR testing of either specimen within the first 2 weeks of life. 8 Congenitally infected infants are asymptomatic at birth in ϳ85% to 90% of cases.…”

mentioning

confidence: 99%

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

Lanari¹,

Lazzarotto

Venturi³

et al. 2006

Pediatrics

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251

164

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OBJECTIVE. Human cytomegalovirus (CMV) is a ubiquitous human-specific DNA virus and is the main cause of congenital virus infection in developed countries leading to psychomotor impairment and deafness. Diagnostic techniques for CMV detection have greatly improved during recent years with the advent of sophisticated serological and virological methods. The aim of the present study was to assess the diagnostic and prognostic value of detection and quantification of virus in neonatal blood samples of symptomatic and asymptomatic newborns with CMV congenital infection.METHODS. Between January 1997 and December 2003, we studied 99 newborns who were born to women with primary, recurrent, and undefined CMV infection during pregnancy. CMV congenital infection was identified by isolation of the virus in urine within the second week of life. Fifty-eight of 99 infants were infected and were assessed clinically for disease in the newborn period and classified as having symptomatic or asymptomatic infection on the basis of physical, instrumental, and laboratory findings. The infants were followed up from birth according to a protocol of the tertiary NICU at the University of Bologna in a prospective study of long-term sequelae of congenital infection. Forty-seven blood samples were obtained from 47 infants in the neonatal period: 34 were examined for pp65 antigenemia test and 44 for qualitative and quantitative polymerase chain reaction (PCR and qPCR). Sequelae at 12 months were evaluated in a group of 50 infants.RESULTS. Antigenemia was positive in only 10 of 34 samples of infected newborns (29.4% sensitivity). PCR was performed in 44 samples of infected newborns and was positive in all (100% sensitivity). qPCR showed a finding of Ն100 copies per 10 5 of polymorphonuclear leukocytes (PMNLs) in 39 of 44 samples; in the other 5 cases, the number of copies per 10 5 PMNLs was Ͻ100. Between symptomatic and asymptomatic newborns, the mean values of viral blood load determined by qPCR turned out to be significantly higher in symptomatic newborns. Mean values of neonatal blood viral load were statistically higher in newborns who developed sequelae than in those who did not. Of 20 children with a neonatal viral blood load of Ͻ1000 copies per 10 5 PMNLs, 19 did not develop sequelae (negative predictive value: 95%), whereas 2 of 3 with a viral blood load of Ͼ10 000 copies did develop sequelae.CONCLUSIONS. Different viremia value ranges are correlated to a different risk of sequelae: ϳ70% sequelae were found in newborns with a qPCR higher than 10 000 copies per 10 5 PMNLs. Low neonatal viral blood load detected by pp65 antigenemia test and qPCR was highly predictive of absence of sequelae: DNAemia Ͻ1000 copies per 10 5 PMNLs has a negative predictive value of 95%. As an independent predictive factor of outcome, neonatal viremia is another useful element for neonatal counseling and therapeutic choices in symptomatic and asymptomatic newborns.H UMAN CYTOMEGALOVIRUS (CMV) is a ubiquitous human-specific DNA virus that belongs to t...

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Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection

Cited by 81 publications

References 16 publications

Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

Role of Cytomegalovirus (CMV) IgG Avidity Testing in Diagnosing Primary CMV Infection during Pregnancy

Clinical Predictive Value of Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples

Neonatal Cytomegalovirus Blood Load and Risk of Sequelae in Symptomatic and Asymptomatic Congenitally Infected Newborns

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