Congenital and postnatally acquired cytomegalovirus infections: Long-term follow-up

Kumar, Mary L.; Nankervis, George A.; Jacobs, Irwin B.; Ernhart, Claire B.; Glasson, Chloe E.; McMillan, Pamella M.; Gold, E. Richard

doi:10.1016/s0022-3476(84)80942-7

Cited by 117 publications

(72 citation statements)

References 19 publications

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“…In the majority of postnatally infected children the HCMV infection remained clinically asymptomatic, however, preterm infants with very low birth weight were found to be at high risk to develop severe HCMV disease. Authors of different studies reported HCMV-associated disease in 0 to 87% of postnatally infected preterm infants (2,3,11,16,20,23,(30)(31)(32). In our recent study on the role of HCMV for development of bronchopulmonary dysplasia we observed an increased incidence of this severe lung disease in HCMVinfected in comparison to noninfected infants.…”

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confidence: 59%

Human Cytomegalovirus Reactivation during Lactation and Mother-to-Child Transmission in Preterm Infants

et al. 2005

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In a clinical trial, the incidence of cytomegalovirus reactivation in breastfeeding mothers and transmission to their preterm infants were studied. Breast milk from 73 mothers as well as urine and tracheal and pharyngeal aspirates from their 89 infants were screened weekly for human cytomegalovirus (HCMV) DNA during the first 2 months after delivery. Of the 73 mothers, 48 (66%) were positive for HCMV DNA in the lactating breast. HCMV reactivation could be confirmed for 19 of 20 (95%) immunoglobulin G-positive mothers. Of the eight immunoglobulin G-negative mothers one was positive for HCMV DNA in breast milk. In only 2 out of 13 seropositive mothers with HCMV DNA in breast milk could viral DNA be detected in the peripheral blood. HCMV mother-to-child transmission was concluded for 20 of the 48 (42%) mothers positive for DNA or 7 of 19 (37%) seropositive for HCMV and positive for HCMV DNA in breast milk and one of one mother seronegative for HCMV but positive for HCMV DNA in breast milk. One mother transmitted the virus to her twins. In addition, one infant acquired postnatal HCMV infection despite the mother's being negative for HCMV DNA in breast milk; altogether, we found 22 infants with HCMV infection. In 13 of these 22 infants, virus infection occurred definitively postnatally; two of them developed severe symptomatic HCMV infection. HCMV-infected infants demonstrated higher incidences of amniotic infection, respiratory distress syndrome, bronchopulmonary dysplasia, and retinopathia praenatalis than noninfected infants, however, the differences were not statistically significant. In summary, our study confirmed a very high incidence of HCMV reactivation in mothers during lactation and a significant risk of transmission to preterm infants with the possibility of severe disease in these babies.Human cytomegalovirus (HCMV) is the most common congenital infection. About 1 to 3% of newborns become infected during pregnancy. Around 10 to 15% of the infants born after maternal seroconversion are symptomatic, and less than 3% after reactivation (29). The main reason for prenatal HCMV transmission is primary infection of mothers during pregnancy rather than recurrent infection. Of even higher epidemiological relevance, however, is postnatal mother-to-child transmission, with breastfeeding being the main reason. In different studies, virolactia, or viral DNA in breast milk, was detected in 13 to 70% of lactating mothers (recently reviewed in references 6 and 32). Using highly sensitive methods like PCR to screen for viral DNA in breast milk or cell-free milk whey, it has been demonstrated that 40% to 96% of seropositive mothers shed the virus via their breast milk (2,11,14,20,30,32).The reason for DNA and viruses in breast milk was recurrent HCMV infections of the mothers during lactation. Interestingly, reactivation of HCMV has been mostly found restricted to the lactating breast, where the site of latency and virus production as well as the mode of reactivation are still unclear. Most of the virus in the breast milk...

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confidence: 59%

Human Cytomegalovirus Reactivation during Lactation and Mother-to-Child Transmission in Preterm Infants

et al. 2005

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“…In addition to infants with symptomatic cases, a proportion of asymptomatically infected newborns face a significant risk of late-onset sequelae (8,9,12,16,17,22,26). Since the early identification of congenitally infected newborns may lead to early intervention and antiviral treatment options (14), a simple and inexpensive assay for CMV detection is required to implement screening programs for congenital CMV infection (19).…”

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Real-Time PCR Assay Using Specimens on Filter Disks as a Template for Detection of Cytomegalovirus in Urine

et al. 2007

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Since congenital cytomegalovirus (CMV) infection causes late-onset sequelae, the identification of CMVinfected newborns is important. For this purpose, we established a simple real-time PCR assay using a filter disk. Combined with the collection of urine using filter papers placed in the diaper, this assay can make CMV screening more feasible and cost-effective.Congenital cytomegalovirus (CMV) infection occurs in 0.2 to 1% of all births. In addition to infants with symptomatic cases, a proportion of asymptomatically infected newborns face a significant risk of late-onset sequelae (8,9,12,16,17,22,26). Since the early identification of congenitally infected newborns may lead to early intervention and antiviral treatment options (14), a simple and inexpensive assay for CMV detection is required to implement screening programs for congenital CMV infection (19).In spite of the progress in PCR-based assays, the need for DNA purification from body fluid specimens as well as the labor, costs, and other problems associated with specimen collection, transportation, and storage have limited the convenience of these assays. Although a small volume of urine can be used directly for PCR, inhibitors in urine reduce PCR efficiency (6,7,13,23). Robotic systems that may simplify the DNA purification process (20) are not affordable for every facility. The use of filter papers can resolve the problems associated with collection and storage, as exemplified by the use of dried blood spots (10). Washing filter papers has reduced the amount of inhibitors, which in turn has allowed for conventional PCR on the filter disk (25). Alternatively, DNA samples have been extracted and/or purified from specimens on filters and used for PCR (3,5,18,27). Although dried blood spots can be used for CMV screening (2), the assay may not detect some cases of congenital infection, as blood specimens contain smaller amounts of CMV than urine specimens (4, 11; N. Inoue and S. Koyano, unpublished results).In this study, we developed a real-time PCR assay using urine specimens on filter disks as a template for the reaction and demonstrated the assay's technological potential for screening for congenital CMV infection.First, we selected a filter paper on which PCRs could proceed efficiently (Fig. 1). Commercially available filter papers were spiked with dilutions of purified CMV, and filter disks obtained from the filters were added directly to PCR mixtures. Since Isocode filters allowed more efficient amplification than the others, these filters were used for the following experiments. Next, we found that only instruments equipped with a photomultiplier-tube scanning system (e.g., Stratagene MX3500P) could be used for real-time PCR assays with filter disks in the reaction mixture, due to the fact that instruments using a charge-coupled device camera (e.g., ABI7700) were adversely affected by nonspecific signals from the disks. The optimized real-time PCR conditions were as follows. Fifty microliters of reaction mixture contained 1ϫ Brilliant quantitative P...

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“…Congenitally infected infants are asymptomatic at birth in about 90% of cases, and for symptomatic infants, infection ranges from mild to severe disseminated life-threatening disease resulting in up to 20% perinatal mortality (9,16,22,28,31,37). Up to 90% of the surviving symptomatic newborns will exhibit psychomotor and perceptual sequelae such as sensorineural hearing loss, mental retardation, cerebral palsy, seizures, and visual defects (2).…”

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Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples from Mothers with Primary Infection

Gault²,

et al. 2002

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A real-time PCR assay was developed to quantify human cytomegalovirus (HCMV) DNA in amniotic fluid (AF) samples collected from 30 pregnant women with primary HCMV infection as detected either from HCMV-immunoglobulin G (IgG) seroconversion or by the presence of HCMV-specific IgG and IgM associated with a low IgG avidity. Clinical information available for each case included ultrasonographic examination and fetal or newborn outcome. HCMV infection of fetuses or newborns was confirmed for the 30 studied cases. AF samples were subdivided into three groups. In group A (n ‫؍‬ 13), fetuses presented major ultrasound abnormalities, and pregnancy was terminated. In group B (n ‫؍‬ 13), fetuses had normal ultrasound findings, the pregnancy went to term, and the newborns were asymptomatic at birth. In group C (n ‫؍‬ 4), fetuses had no or minor ultrasonographic signs, and pregnancy was terminated. The HCMV DNA load values in AF samples were significantly higher in group A (median, 2.8 ؋ 10 5 genome equivalents [GE]/ml) than in group B (median, 8 ؋ 10 3 GE/ml) (P ‫؍‬ 0.014). Our findings suggest that HCMV load level in AF samples correlates with fetal clinical outcome but might also be dependent on other factors, such as the gestational age at the time of AF sampling and the time elapsed since maternal infection.Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection in developed countries, affecting 0.5 to 2% of all live births (1,32,40). Although the possibility of severe symptomatic fetal infection following recurrent maternal infection has been reported (8), fetal damage is mostly related to primary maternal infection (16,38,39). In this case, the transmission of the virus to the fetus may occur in 20 to 50% of pregnancies (18,27,38). It has been reported that HCMV transmission rates increase with gestational age and that a major risk of transmission is observed for seroconversion occurring late in pregnancy (5).Congenitally infected infants are asymptomatic at birth in about 90% of cases, and for symptomatic infants, infection ranges from mild to severe disseminated life-threatening disease resulting in up to 20% perinatal mortality (9,16,22,28,31,37). Up to 90% of the surviving symptomatic newborns will exhibit psychomotor and perceptual sequelae such as sensorineural hearing loss, mental retardation, cerebral palsy, seizures, and visual defects (2). Additionally, 10% of the infants who are asymptomatic at birth will later develop complications, mainly neurodevelopmental defects and deafness (7,15,40).The diagnosis of maternal primary HCMV infection is based mostly on serological testing, including HCMV immunoglobulin G (IgG) seroconversion and the presence of specific HCMV IgG and IgM (35). Moreover, the direct detection of viral components, including pp65 antigenemia and DNAemia, can be helpful for acute infection diagnosis. Prenatal diagnosis of HCMV congenital infection relies on virus isolation from amniotic fluid (AF) and/or viral DNA detection by PCR in AF samples (4,12,24,25,36,42)...

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Congenital and postnatally acquired cytomegalovirus infections: Long-term follow-up

Cited by 117 publications

References 19 publications

Human Cytomegalovirus Reactivation during Lactation and Mother-to-Child Transmission in Preterm Infants

Human Cytomegalovirus Reactivation during Lactation and Mother-to-Child Transmission in Preterm Infants

Real-Time PCR Assay Using Specimens on Filter Disks as a Template for Detection of Cytomegalovirus in Urine

Real-Time PCR Quantification of Human Cytomegalovirus DNA in Amniotic Fluid Samples from Mothers with Primary Infection

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