Experimental primary cytomegalovirus infection in pregnancy: Timing and fetal outcome

Kumar, Mary L.; Prokay, Sandra L.

doi:10.1016/0002-9378(83)90339-3

Cited by 34 publications

(11 citation statements)

References 13 publications

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“…Clearly identifiable signs and symptoms are not observed in pregnant women as they are often asymptomatic or the infection displays signs and symptoms that are nonspecific. In this population, it is very important to differentiate primary from secondary infection, as primary infection is much more injurious for the fetus than secondary infection and the clinical sequelae more severe if transmission occurs early in pregnancy [42][43][44] .…”

Section: Cytomegalovirus Infectionmentioning

confidence: 99%

Clinical utility of avidity assays

Hazell¹

2007

Expert Opinion on Medical Diagnostics

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IgM may persist for months, presenting a risk of an erroneous diagnosis where serology is the only available tool. Indeed, IgM may be detected in secondary infection as a result of crossreactivity and/or nonspecific stimulation of the immune system. One test that can aid the serologist is IgG avidity testing, in that the avidity of IgG is low early in infection with the avidity of IgG antibodies increasing over time. Congenital toxoplasmosis can induce serious sequelae. Detectable IgM usually persists long after the acute infection. IgG avidity can be an important aid in diagnosis and assessing the risk to the fetus. Another infection that is of concern in pregnancy is cytomegalovirus (CMV). In pregnant women it is very important to differentiate primary from secondary infection, as primary infection presents the highest risk to the fetus. Serologic detection of IgM alone is not a specific marker of primary CMV infection. IgG avidity can have utility in identifying or excluding primary CMV infections during pregnancy. Outside of pregnancy, IgG avidity testing is increasingly recognized as a valuable tool. During the recent West Nile virus (WNV) epidemic in the US, it was recognized that WNV-specific IgM may persist for 6 - 12 months following exposure. Thus, a person presenting to their clinician with nonspecific symptoms may be tested and return a positive WNV IgM that may be the product of exposure during the previous period. In this environment, WNV IgG avidity testing is able to provide some assistance. IgG avidity testing should not be used alone and without an understanding of the limitations of the technique. Serology remains an important tool for the diagnosis and management of infectious disease. Classically, IgM is defined as a marker of acute infection and IgG, in the absence of clinical disease, is often considered a marker of past infection. However, the clinical reality can be quite different.

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Section: Cytomegalovirus Infectionmentioning

confidence: 99%

Clinical utility of avidity assays

Hazell¹

2007

Expert Opinion on Medical Diagnostics

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“…In utero transmission of CMV can occur during primary maternal infection, reactivation, or reinfection of seropositive mothers. Most concern centers on primary maternal infection, due to the potential for significant fetal damage when the infection is acquired and transmitted during the first trimester (30,48). Perinatal infections can result through virus transmission from many parts of the birth canal (39); however, the majority of these infections are asymptomatic (43).…”

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confidence: 99%

“…Continuing advancements in technology, however, mean reliable and inexpensive serologic tests are available, prenatal diagnostic procedures with acceptable negative predictive values (NPV) can be performed, and trials of neonatal antiviral treatments are ongoing (25,34,37,50,52). Proposed diagnostic algorithms have focused on first-trimester screening, since the time of infection can be accurately obtained in the absence of seroconversion data, and the clinical sequelae of congenital CMV is usually more severe if transmission occurs early in gestation (30,48). A high positive predictive value (PPV) and NPV for clinical disease have been determined for quantitative PCR testing of amniotic fluid (26); however, there is an increased risk of a false-negative result if fewer than 7 weeks have elapsed between the onset of maternal infection and the time of amniocentesis (5,36).…”

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confidence: 99%

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

et al. 2005

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No single diagnostic test for cytomegalovirus (CMV) infection is currently available for pregnant women at all stages of gestation. Improved accuracy in estimating the timing of primary infections can be used to identify women at higher risk of giving birth to congenitally infected infants. A diagnostic algorithm utilizing immunoglobulin G (IgG), IgM, and IgG avidity was used to prospectively screen serum from 600 pregnant women enrolled from two groups: <20 weeks gestation (n ‫؍‬ 396) or >20 weeks gestation (n ‫؍‬ 204). PCR testing of urine and/or blood was performed on all seropositive women (n ‫؍‬ 341). The majority (56.8%) of women were CMV IgG seropositive, with 5.5% being also CMV IgM positive. In the IgM-positive women, 1.2% had a low-avidity IgG, indicating a primary CMV infection and a high risk of intrauterine transmission. Two infants with asymptomatic CMV infection were born of mothers who had seroconverted in the second trimester of pregnancy. Baseline, age-stratified CMV serostatus was established from 1,018 blood donors. Baseline seropositivity from a blood donor population increased with age from 34.9% seroprevalence at less than 20 years of age to 72% seroprevalence at 50 years of age. Women at high risk of intrauterine transmission of CMV were identified at all stages of gestation. Women infected with CMV during late gestation may be more likely to transmit the virus, so failure to detect seroconversions in late gestation may result in failure to detect infected neonates.Human cytomegalovirus (CMV) is the most common cause of congenital malformation resulting from viral intrauterine infection in developed countries (12,21,48). Primary CMV infection occurs in 0.15 to 2.0% of all pregnancies and may be transmitted to the fetus in up to 40% of cases (48). Up to 15% of intrauterine CMV infections result in symptomatic congenital disease at birth, and 10 to 15% of those born with asymptomatic congenital CMV will develop significant clinical sequelae in infancy (7,10,18). In utero transmission of CMV can occur during primary maternal infection, reactivation, or reinfection of seropositive mothers. Most concern centers on primary maternal infection, due to the potential for significant fetal damage when the infection is acquired and transmitted during the first trimester (30, 48). Perinatal infections can result through virus transmission from many parts of the birth canal (39); however, the majority of these infections are asymptomatic (43).The usefulness of prenatal testing for CMV has been questioned due to the absence of clearly effective intervention (1, 27) and to evidence for severe congenital malformation resulting from viral reactivation (6,8,20). Continuing advancements in technology, however, mean reliable and inexpensive serologic tests are available, prenatal diagnostic procedures with acceptable negative predictive values (NPV) can be performed, and trials of neonatal antiviral treatments are ongoing (25,34,37,50,52). Proposed diagnostic algorithms have focused on first-trimester screeni...

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“…Burton and Watson (6) suggest that the basement membrane is an important placental barrier, since transient trophoblast damage down to the TBM followed by repair is often observed without concomitant fetal consequences (5,54). Lack of basal release from infected trophoblasts and/or the presence of a TBM acting as an effective barrier may explain why vertical transmission does not occur more frequently in the first trimester than in the third trimester (9,29) even though first-trimester trophoblasts are more readily infected (22).…”

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Polarized Release of Human Cytomegalovirus from Placental Trophoblasts

Hemmings

Guilbert

2002

J Virol

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Human cytomegalovirus (HCMV) is a ubiquitous infectious pathogen that, when transmitted to the fetus in utero, can result in numerous sequelae, including late-onset sensorineural damage. The villous trophoblast, the cellular barrier between maternal blood and fetal tissue in the human placenta, is infected by HCMV in vivo. Primary trophoblasts cultured on impermeable surfaces can be infected by HCMV, but release of progeny virus is delayed and minimal. It is not known whether these epithelial cells when fully polarized can release HCMV and, if so, if release is from the basal membrane surface toward the fetus. We therefore ask whether, and in which direction, progeny virus release occurs from HCMV-infected trophoblasts cultured on semipermeable (3.0-m-pore-size) membranes that allow functional polarization. We show that infectious HCMV readily diffuses across cell-free 3.0-m-pore-size membranes and that apical infection of confluent and multilayered trophoblasts cultured on these membranes reaches cells at the membrane surface. Using two different infection and culture protocols, we found that up to 20% of progeny virus is released but that <1% of released virus is detected in the basal culture chamber. These results suggest that very little, if any, HCMV is released from an infected villous trophoblast into the villous stroma where the virus could ultimately infect the fetus.Human cytomegalovirus (HCMV) is endemic, infecting 40 to 80% of urban populations in developed countries (10). The incidence of congenital HCMV infection is between 0.2 and 2.2% of all live-born infants. Such infections are one of the most common causes of mental retardation and nonhereditary sensorineural deafness in children (46,48). Only 40% of pregnant women with primary HCMV infections give birth to infected infants (47) suggesting an effective fetal barrier, either physical or immunological. How HCMV is transmitted to the fetus during pregnancy is unknown; however, congenital infections are associated with chronic villitis (38, 41) and infection of the placenta (1, 4, 16, 32, 36-39, 41, 44, 45), which may also act as a viral reservoir (19). Passage through the placenta (2, 3) could occur in two directions: through the cytotrophoblast (CT) columns in anchoring villi or across the villous syncytiotrophoblast (ST) in the intervillous space.Infection originating in the uterine wall could lead to infection of extravillous CT involved in either interstitial or endovascular invasion. Infection could then progress in a cell-to-cell manner through the CT columns of anchoring villi to the chorionic stroma and eventually infect the fetus (15). Although this route is possible during a reactivated uterine infection, endovascular CT comes into direct contact with maternal blood and therefore could also be exposed to a primary infection.The ST lines all chorionic villi within the intervillous space, thereby interfacing maternal blood and fetal tissues. The ST is thus positioned to either physically prevent or to actively participate in the dissemina...

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Experimental primary cytomegalovirus infection in pregnancy: Timing and fetal outcome

Cited by 34 publications

References 13 publications

Clinical utility of avidity assays

Clinical utility of avidity assays

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

Polarized Release of Human Cytomegalovirus from Placental Trophoblasts

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