Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers

Guerra, Brunella; Simonazzi, Giuliana; Banfi, Alessandra; Lazzarotto, Tiziana; Farina, Antonio; Lanari, Marcello; Rizzo, Nicola

doi:10.1016/j.ajog.2006.08.039

Cited by 78 publications

(59 citation statements)

References 34 publications

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“…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%

“…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).…”

Section: Ongenital Cytomegalovirus (Cmv) Infection Is the Most Commmentioning

confidence: 99%

“…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).…”

Section: Ongenital Cytomegalovirus (Cmv) Infection Is the Most Commmentioning

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: 99%

Section: Ongenital Cytomegalovirus (Cmv) Infection Is the Most Commmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Relying on the experience of the two reference diagnostic centers, in Pavia and Bologna, 24,25 we defined the onset of primary infection as the reported date of the onset of symptoms or signs when those reports were in agreement with serologic results. In this study, symptoms and signs were reported by about 60% of the women.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus

Revello¹,

et al. 2014

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Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection\ud significantly reduced the rate of intrauterine transmission, from 40% to 16%. Methods: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary\ud CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth\ud or by means of amniocentesis. Results: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the\ud placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, −3 to 31; P = 0.13). There was no significant difference\ud between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell–mediated immune response, or viral DNA in the blood. The clinical\ud outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). Conclusions: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.

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“…In other countries the main rationale for universal serial screening was apparently to allow for an elective termination of pregnancy. In Israel approximately half of women who seroconvert to CMV electively terminate, although this rate is much lower in other countries [61,62]. Figure 2 shows one possible algorithm for limited maternal screening.…”

Section: Commentmentioning

confidence: 99%

Screening for cytomegalovirus during pregnancy

Adler

Nigro

Pereira

2010

American Journal of Obstetrics and Gynecology

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The epidemiology and pathogenesis of CMV infections among pregnant women have been intensely studied over the last three decades. This paper highlights recent developments that make either universal or limited serologic screening for CMV during pregnancy potentially attractive. The developments include an understanding of the pathogenesis of CMV infections, a knowledge of high-risk women, the availability of accurate methods for the serologic diagnosis of a primary CMV infection using either single or serial blood samples, accurate methods for the diagnosis of fetal infection via amniotic fluid, sensitive fetal and placental indicators for neonatal outcomes, and the availability of potentially effective interventions.

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Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers

Cited by 78 publications

References 34 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

A Randomized Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus

Screening for cytomegalovirus during pregnancy

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