Cytomegalovirus Infection In Pregnant Women Research Articles

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is considered in the context of the epidemiology of CMV infection in pregnant women and newborn infants, and the clinical manifestations of brain injury are reviewed. The prospects for intervention, including antiviral therapies and vaccines, are summarized. Priorities for future research are suggested to improve the understanding of this common and disabling illness of infancy.

Molecular epidemiology of primary human cytomegalovirus infection in pregnant women and their families

The source of human cytomegalovirus (HCMV) infection was investigated in 29 pregnant women with primary HCMV infection by comparing DNA sequences of UL146, UL144 and a portion of UL55 gene of HCMV strains circulating within each family. Thirteen families were identified in which the pregnant woman, the husband and/or a child were shedding HCMV. In three of these families, both the woman and the husband suffered from a concomitant primary HCMV infection. Phylogenetic analysis of UL146, UL144, and UL55 genes indicated that strains circulating within each family were identical, whereas strains from different families appeared to be distinct. However, identical UL146, UL144, and UL55 DNA sequences were observed sporadically among unrelated strains. A child rather than the husband was the virus source for the great majority of pregnant women. No association was observed between UL144 polymorphisms and intrauterine transmission.

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

Diagnosis of and Screening for Cytomegalovirus Infection in Pregnant Women

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: < or =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.

Prenatal diagnosis of congenital cytomegalovirus infection by detection of immunoglobulin M antibodies to the 70-kd heat shock protein in fetal serum

Objective: Antibodies to the 70-kd heat shock protein were evaluated as biomarkers for cytomegalovirus infection. Study Design: Fetal sera that was obtained by cordocentesis at 22 to 25 weeks of gestation from 53 mothers with a confirmed primary cytomegalovirus infection and 28 mothers (control group) without cytomegalovirus infection who had been screened for Rh incompatibility, were assayed by enzyme-linked immunosorbent assay for immunoglobulin M and G anti–70-kd heat shock protein antibodies. Results: Eighteen of 53 fetuses (34.0%) from cytomegalovirus-positive mothers were infected, which was determined by culture or polymerase chain reaction. Anti–70-kd heat shock protein immunoglobulin M was detected in 17 of 18 sera (94.4%) from cytomegalovirus-infected fetuses, in 3 of 35 sera (8.6%) from uninfected fetuses, and in 0 of 28 sera from the control group (P <.0001). The level of antibody reactivity was correlated positively with fetal disease. Anti–70-kd heat shock protein immunoglobulin G was detected in sera from 52 of 53 fetuses (98.1%) from cytomegalovirus-infected mothers. Conclusion: The anti–70-kd heat shock protein immunoglobulin M assay may be of value in the assessment of fetal cytomegalovirus infection in pregnant women with a primary cytomegalovirus infection. (Am J Obstet Gynecol 2002;187:955-9.)

Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus infection in pregnant women

Background: Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from non-primary infection in pregnant females. IgM tests often used for this purpose are not reliable enough. Objective: To evaluate an HCMV–IgG urea-elution assay for its ability to distinguish primary from non-primary infection. In this assay, soaking the antigen–antibody complex with an urea containing solution frees antibodies with low avidity but has no influence on those with high avidity. An avidity index (AI) was calculated: AI=(OD with urea/OD without urea)×100. Study design: HCMV–IgG avidity was measured on a single serum of 79 patients with past infection (pregnant women, graft recipients and blood donors) and of 63 patients (78 sera) with documented seroconversion (pregnant women and graft recipients). Sixty-one pregnant women positive or equivocal for HCMV–IgM but without a documented seroconversion were included in this study. Results: Most (72/79) of the patients with past infection had an AI>65% and all but one had an AI>50%. In pregnant women, in the case of a primary infection within the past 3 months, AI are usually (51/53)<50% and never>65%. Among the IgM positive pregnant women who lack a seroconversion history, 38 had AI>65% suggestive of an infection that had occured at least 3 months earlier, 11 had an AI in a grey area between 50 and 65% and 12 had an AI<50%, suggestive of a recent primary infection. Conclusions: In pregnant women, measurement of the IgG avidity may help to date a HCMV infection, an AI >65% highly suggests a past infection while an AI <50% corresponds to a recent primary infection.

Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women.

This study assessed the diagnostic value of the cytomegalovirus (CMV)-specific IgG avidity index (AI) for pregnant women without a history of CMV seroconversion. Sera were studied from 40 women with CMV seroconversion (group I), 70 with past CMV infection (group II), 10 (20 sera) with serologic reactivation (group III), and 41 with CMV-specific IgM without proven seroconversion (group IV). Sera from women in group I collected <14 weeks after seroconversion had a low AI (mean, 30% +/- 12%), whereas all sera from women in group II had an AI >60% (mean, 88% +/- 9%). Among the 41 babies born to group IV women, only 4 were infected with CMV (all born to mothers with a low [<30%] AI early in pregnancy). These results suggest that AI determination may help to date a primary CMV infection in pregnant women who lack seroconversion history.

Cytomegalovirus Infection in the Pregnant Mother, Fetus, and Newborn Infant

Cytomegalovirus (CMV) is a common virus that infects persons of all ages, races, and backgrounds. Originally described as a rare cause of "cytomegalic inclusion disease," CMV is now known to cause a broad spectrum of illness in the fetus and newborn, with most infections being asymptomatic at birth. This article discusses the epidemiology and diagnosis of CMV infection in pregnant women, the fetus, and the newborn, including recent advances in antenatal diagnosis. In addition, the challenges of treatment and prevention of congenital CMV are explored.

Dot hybridization and polymerase amplification of DNA in the prenatal diagnosis of cytomegalovirus infection

Molecular biology techniques (dot hybridization and polymerase amplification of DNA) are used to diagnose cytomegalovirus infection in pregnant women and newborns. It is concluded from the results that dot hybridization is a convenient tool in screening studies and that polymerase DNA amplification followed by verification of the reaction product using restriction enzymes and blot hybridization makes the diagnosis of this disease more reliable and may find wide application in practical laboratories.

Young children as a probable source of maternal and congenital cytomegalovirus infection.

To identify possible sources of cytomegalovirus infection in pregnant women, we studied seven families with a recent case of congenital or maternal cytomegalovirus infection and a history of maternal contact with a young child shedding the virus. We used restriction-endonuclease techniques to compare the DNA of viral isolates collected from family members. Five families contained an infant who had congenital or perinatal infection, a mother who had had evidence of primary infection during her most recent pregnancy, and a child less than three years of age who was excreting cytomegalovirus. All five of the young children attended day-care centers at least part-time. In each of these five families, strains from family members were identical, and it is most likely that the toddler-aged child was the source of the virus for both the mother and the fetus or infant. In two other families, acquisition of cytomegalovirus by children in a day-care center was followed by seroconversion in the mother along with excretion of a strain of the virus identical to that in her child, as demonstrated by restriction-endonuclease analysis. Five of the seven fathers were tested for antibody to cytomegalovirus; four were seronegative, ruling them out as a source of infection in the mothers. These results not only strengthen evidence for the transmission of cytomegalovirus from child to mother but also indicate that infections acquired by a mother from a child can be transmitted to her fetus.

A Prospective Study of Primary Cytomegalovirus Infection in Pregnant Women

Summary During a four year study, sera were obtained from 5575 women attending for antenatal care and 3188 (57.2 per cent) were shown to possess complement fixing antibodies to cytomegalovirus (CMV). A total of 1608 seronegative women were followed to term and 14 (0.87 per cent) primary CMV infections occurred in either the second or third trimester. Transplacental spread of CMV occurred in 3 out of 12 (25 per cent) of the 14 babies born to infected mothers. All 14 babies were apparently normal at birth but short term clinical follow-up has already revealed that one child has impaired hearing whilst another is microcephalic. The women were also monitored serologically throughout pregnancy for evidence of rubella infections. Only 12 infections were detected and 7 of these occurred during the large rubella epidemic of 1978. Of the 10 pregnancies which were allowed to proceed to term, transplacental spread of rubella virus occurred in 1 out of 7 (14 per cent). During this study period, CMV infections occurred as frequently as did rubella infections. We therefore conclude that, apart from those years when extensive epidemics occur, many more pregnant women are infected with CMV than with rubella virus.

A prospective study of primary cytomegalovirus infection in pregnant women.

During a four year study, sera were obtained from 5575 women attending for antenatal care and 3188 (57.2 per cent) were shown to possess complement fixing antibodies to cytomegalovirus (CMV). A total of 1608 seronegative women were followed to term and 14 (0.87 per cent) primary CMV infections occurred in either the second or third trimester. Transplacental spread of CMV occurred in 3 out of 12 (25 per cent) of the 14 babies born to infected mothers. All 14 babies were apparently normal at birth but short term clinical follow-up has already revealed that one child has impaired hearing whilst another is microcephalic. The women were also monitored serologically throughout pregnancy for evidence of rubella infections. Only 12 infections were detected and 7 of these occurred during the large rubella epidemic of 1978. Of the 10 pregnancies which were allowed to proceed to term, transplacental spread of rubella virus occurred in 1 out of 7 (14 per cent). During this study period, CMV infections occurred as frequently as did rubella infections. We therefore conclude that, apart from those years when extensive epidemics occur, many more pregnant women are infected with CMV than with rubella virus.

Maternal Immunosuppression and Cytomegalovirus Infection of the Fetus*,†

Prenatal cytomegalovirus (CMV) infection associated with severe brain damage was detected in an infant whose mother had been treated with prednisolone and azathioprine for systemic lupus erythematosus (SLE). Serology showed that maternal CMV infection had been acquired at least four months before pregnancy. Screening for CMV infection in pregnant women receiving immunosuppressive drugs is recommended.