Vertically transmitted cytomegalovirus infection in newborn preterm infants

2016 ◽  
Vol 44 (5) ◽  
Author(s):  
Carla Balcells ◽  
Francesc Botet ◽  
Sònia Gayete ◽  
M Ángeles Marcos ◽  
Izaskun Dorronsoro ◽  
...  
Keyword(s):  
Breast Milk ◽  
Preterm Infants ◽  
Transmission Rate ◽  
Congenital Infection ◽  
Preterm Neonates ◽  
Cmv Infection ◽  
Fresh Milk ◽  
Vertical Transmission Rate ◽  
Congenital Cmv Infection ◽  
Preterm Newborns

AbstractTo determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV.During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols.Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05–0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk.The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.

scholarly journals Vertical Transmission and Discordance of Cytomegalovirus in Twin Pregnancies

2021 ◽  
Vol 11 ◽  
Author(s):  
Jill Hutton ◽  
Paul J. Rowan
Keyword(s):  
Vertical Transmission ◽  
Transmission Rate ◽  
Monozygotic Twin ◽  
Dizygotic Twin ◽  
Cmv Infection ◽  
Vertical Transmission Rate ◽  
Congenital Cmv Infection ◽  
Twin Pregnancies ◽  
Congenital Cmv ◽  
Singleton Pregnancies

ObjectiveThe objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and to characterize concordance within monozygotic and dizygotic twin pairs in relation to hereditability.MethodsWe first sought to estimate the vertical transmission rate of congenital CMV infection in twins by gathering cohort-based studies of congenital CMV in which vertical transmission in both singleton and twin pregnancies was reported. This also allowed us to compare singleton and twin infection rates. From the above studies and other large cohorts of congenitally infected infants, the percentage of discordantly infected twin pairs determined whether this is a rare phenomenon. Theorizing discordance is not rare, we then analyzed data from cases with twin outcomes for congenital CMV infection, according to whether the twins were monozygotic or dizygotic, and calculated their corresponding concordance rates to estimate the broad-sense heritability. Lastly, we described other factors that might affect vertical transmission.ResultsFrom five articles following at-risk pregnancies, the rate of vertical transmission in twin pregnancies is 58.7% (95% CI 43.3-72.3%) whereas in singleton pregnancies it is 31.4% (95% CI: 29.0-34.0%) p = 0.0002. Of ten studies of larger cohorts of infants with congenital CMV infection, 21 of 42 twin pairs with at least one twin infected were discordant for congenital CMV (50.0%, 95% CI: 34.4–65.6%) indicating discordance of congenital CMV infection in twin pairs is not rare. Of 28 studies covering 37 twin pairs where at least one twin had congenital CMV, and zygosity was known, eleven of thirteen monozygotic twin pairs (84.6%; 95% CI: 53.7-97.3%) were concordant for CMV infection, and nine of twenty-four dizygotic twin pairs (37.5%; 95% CI: 19.6-59.2%) were concordant for infection giving an estimated hereditability of 94.2%. Within these 37 twin pairs, factors such as primary or recurrent maternal infection, prematurity, growth discordance, and sex are described; however, in many of these cases these factors are unknown.ConclusionThe rate of vertical transmission of congenital CMV is higher for twins than singletons. Discordance of congenital CMV in twins is not rare and suggests a possible genetic susceptibility to congenital CMV.

FEATURES OF THE CONGENITAL CMV INFECTION IN THE UNBORN AND NEWBORN INFANT

2007 ◽  
Vol 18 (3) ◽  
pp. 181-199 ◽  
Author(s):  
G BENOIST ◽  
Y VILLE
Keyword(s):  
Primary Infection ◽  
Transmission Rate ◽  
Sensorineural Deafness ◽  
Recurrent Infection ◽  
Maternal Infection ◽  
Cmv Infection ◽  
Live Births ◽  
Vertical Transmission Rate ◽  
Fetal Infection ◽  
Congenital Cmv Infection

Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection,1with a prevalence of 0.5 to 1% of all live births, and the leading infectious cause of sensorineural deafness and mental retardation.1As otherHerpesviridae, CMV fetal infection can develop following both primary and recurrent maternal infection. Vertical transmission rate is around 30% following primary infection and 2 to 3% following recurrent infection.2Effects on the unborn as well as on the newborn are widely variable. It is estimated that only 5 to 10% of infected newborns have symptoms at birth, whereas around 90% of congenitally infected infants are asymptomatic although 5–15% of these infants will develop some degree of sensorineural hearing loss.3

scholarly journals Detection and gB genotyping of CMV in Mexican preterm infants in the context of maternal seropositivity

2014 ◽  
Vol 8 (06) ◽  
pp. 758-767 ◽  
Author(s):  
José Arellano-Galindo ◽  
Dina Villanueva-García ◽  
José Luis Cruz-Ramirez ◽  
Juan Pablo Yalaupari-Mejìa ◽  
Gabriel Uribe-Gutiérrez ◽  
...  
Keyword(s):  
Breast Milk ◽  
Preterm Infants ◽  
Mixed Infections ◽  
Cmv Infection ◽  
Symptomatic Infection ◽  
Blood Spots ◽  
Milk Samples ◽  
Preterm Newborns

Introduction: Congenital (CI) and perinatal cytomegalovirus (CMV) infections (PI) can be linked to maternal CMV seropositivity, with fatal consequences in preterm newborns. GB genotyping has been used to analyze genotypic similarity in mothers and infants. The frequency of CMV infection in the context of maternal seropositivity and the viral gB genotypes as well as the genotypic similarity in mothers and preterm infants were investigated. Methodology: Saliva samples and dry blood spots (DBS) were taken weekly from preterm newborns  from birth  until the first month of life, and breast milk samples were taken from their mothers weekly during the first month of lactation. CMV IgG seroprevalence of the mothers and CI or PI in the infants were established. The gB status and genotypic similarities were established retrospectively in DBS and in the breast milk samples. Results: In total, 387 neonates and 375 mothers were enrolled. The maternal CMV-positive IgG serology was 97.3% (365/375). Neonatal CMV was found in 5.1% (20/387) of newborns, and one infant presented with CMV-compatible symptoms. CI was 2.5% and PI in the first month after birth was 11.8%. GB2 was the most prevalent genotype and was also the genotype preferentially transmitted to newborns by mothers with mixed infections. Conclusions: CMV PI and CI in preterm infants from highly seropositive mothers was high, but the rate of symptomatic infection was low. The prevalent genotype was gB2, and this genotype was preferentially transmitted to newborns by mothers with mixed infections.

scholarly journals Recurrent maternal CMV infection associated with symptomatic congenital infection: results from a questionnaire study in Portugal

2019 ◽  
Vol 3 (1) ◽  
pp. e000455
Author(s):  
Paulo Paixão ◽  
Maria João Brito ◽  
Daniel Virella ◽  
Maria Teresa Neto
Keyword(s):  
Primary Infection ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
High Avidity ◽  
Maternal Infection ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Missed Diagnosis ◽  
Congenital Cmv

ObjectiveHuman cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection when compared with primary infection, the first still represents the majority of congenital infections worldwide. Based on data from active reporting, we explored the influence of maternal primary/non-primary infection both on the presentation and outcome of congenital CMV infection in early childhood.DesignInfants with positive viruria during the first 3 weeks of life were reported through the Portuguese Paediatric Surveillance Unit.PatientsInfants born between 2006 and 2011 with confirmed congenital CMV infection.MethodsMaternal infection was considered primary if CMV IgG seroconversion occurred during pregnancy or low avidity IgG was documented; it was considered non-primary if positive IgG was documented before pregnancy or high avidity CMV IgG was present early in pregnancy. Follow-up questionnaires were sent up to 6 years of age.ResultsForty confirmed cases of congenital CMV infection were reported (6.6:105 live births, 95% CI 4.81 to 8.92); 22 out of 40 were asymptomatic. The odds for non-primary maternal infection if the offspring was symptomatic at birth were 6.2 (95% CI 1.2 to 32.27).ConclusionThe reported number of confirmed cases of congenital CMV infection was much lower than expected. Under-reporting and missed diagnosis were considered possible reasons. Non-primary maternal infections were associated with symptomatic congenital CMV infection in the offspring. Maternal recurrent infections can have a significant impact on the total number of symptomatic infections in Portugal.

scholarly journals Intra-uterine transmission of cytomegalovirus in women known to be immune before conception

1984 ◽  
Vol 92 (1) ◽  
pp. 89-95 ◽  
Author(s):  
P. D. Griffiths ◽  
C. Baboonian
Keyword(s):  
Prospective Study ◽  
Pregnant Women ◽  
Congenital Infection ◽  
Infected Child ◽  
Cmv Infection ◽  
Previous Pregnancy ◽  
Congenital Cmv Infection ◽  
Retrospective Testing ◽  
A Prospective Study ◽  
Congenital Cmv

SUMMARYA prospective study identified 785 pregnant women who had been shown to possess complement fixing antibodies against cytomegalovirus (CMV) during a previous pregnancy. As these women were thus known to have been immune prior to their subsequent conception, their neonates were examined for evidence of congenital CMV infection. Specimens were obtained from 725(92%) of the neonatcs and congenital infection was found in only one (0·14%). The elder sister of the infected child was also shown, by retrospective testing of her stored cord serum for specific IgM antibodies, to have been infected in utero. Thus, one woman was identified who had delivered consecutive siblings congenitally infected with CMV. We conclude that some women have a propensity for intra-uterine transmission of CMV, despite being immune prior to conception, and speculate that such women may have acquired their infections perinatally.

scholarly journals A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

2016 ◽  
Vol 90 (17) ◽  
pp. 7902-7919 ◽  
Author(s):  
K. Yeon Choi ◽  
Matthew Root ◽  
Alistair McGregor
Keyword(s):  
Guinea Pig ◽  
Small Animal ◽  
Congenital Infection ◽  
T Cell Response ◽  
Control Group ◽  
Cmv Infection ◽  
Vaccine Strategy ◽  
Congenital Cmv Infection ◽  
Guinea Pig Cytomegalovirus ◽  
Congenital Cmv

ABSTRACTCongenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In thisdisabledinfectioussingle-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (theUL85homologGP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P= 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy.IMPORTANCECongenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. Thisdisabledinfectioussingle-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection.

Early high CMV seroprevalence in pregnant women from a population with a high rate of congenital infection

2012 ◽  
Vol 141 (10) ◽  
pp. 2187-2191 ◽  
Author(s):  
A. Y. YAMAMOTO ◽  
R. A. C. CASTELLUCCI ◽  
D. C. ARAGON ◽  
M. M. MUSSI-PINHATA
Keyword(s):  
Pregnant Women ◽  
Primary Infection ◽  
Congenital Infection ◽  
High Rate ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus ◽  
Younger Age ◽  
Congenital Cmv Infection ◽  
Stratified Sample ◽  
Congenital Cmv

SUMMARYCongenital cytomegalovirus (CMV) infection rates increase with maternal seroprevalence due to transmission from maternal non-primary infection. CMV seroprevalence estimates of pregnant women are needed for planning strategies against congenital CMV transmission. We aimed to determine the age-specific prevalence of serum antibodies for CMV in a representative age-stratified sample of unselected pregnant women from a Brazilian population. A total of 985 pregnant women, aged 12–46 years (median 24 years), were enrolled. Overall CMV seroprevalence was 97% (95% confidence interval 95·8–98·0), with age-specific (years) prevalence as follows: 12–19 (96·3%), 20–24 (97·7%), 25–29 (97·1%), and 30–46 (96·7%). CMV seroprevalence is almost universal (97%) and is found at similar levels in pregnant women of ages ranging from 12 to 46 years. Because high CMV seroprevalence is found even in women of a younger age in this population, this finding suggests that the majority of primary CMV infections occur early, in infancy or childhood. As a consequence, vaccines currently under development to prevent primary infection may not be a solution for the prevention of congenital CMV infection in this population.

scholarly journals Development and Application of a PCR-Based Method Including an Internal Control for Diagnosis of Congenital Cytomegalovirus Infection

2000 ◽  
Vol 38 (1) ◽  
pp. 1-6
Author(s):  
Rachel N. Jones ◽  
M. Lynne Neale ◽  
Brian Beattie ◽  
Diana Westmoreland ◽  
Julie D. Fox
Keyword(s):  
Amniotic Fluid ◽  
Pregnant Women ◽  
Internal Control ◽  
Congenital Infection ◽  
Diagnostic Group ◽  
Urine Samples ◽  
Diagnostic Tools ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Developed World

ABSTRACT Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world. We have designed and evaluated an assay that includes an internal control for amplification and detection of CMV DNA in amniotic fluid and neonatal urine samples. We present data on the use of this assay in the diagnosis of congenital CMV infection. A total of 145 amniotic and fetal fluid samples were examined by this assay; 83 were from healthy pregnant women and 62 were from women who were being investigated because of concerns over the pregnancy (diagnostic group). CMV DNA was detected in three amniotic fluid samples from the diagnostic group but was not detected in any samples taken from healthy pregnant women. Thirty-nine urine samples were obtained from 19 neonates with suspected congenital infection; CMV DNA was detected in urine from 6 of these patients. The assay provides useful information about CMV infection in the fetus and the neonate; when used in conjunction with other diagnostic tools it will enable mothers and obstetricians to make informed decisions about the management of pregnancies complicated by CMV infection.

Vaccination for cytomegalovirus: when, where and how

2015 ◽  
Vol 36 (4) ◽  
pp. 175
Author(s):  
Vijayendra Dasari ◽  
Rajiv Khanna
Keyword(s):  
Congenital Infection ◽  
Neurological Complications ◽  
Medical Attention ◽  
Transplacental Transmission ◽  
Cmv Infection ◽  
Seizure Disorders ◽  
Congenital Cmv Infection ◽  
Preclinical And Clinical Studies ◽  
Cmv Disease ◽  
Congenital Cmv

Although following primary human cytomegalovirus (CMV) infection in many individuals no overt symptoms are observed, CMV came to medical attention due to its significant morbidity and mortality associated with congenital infection and immunosuppressed individuals. Congenital infection occurs following transplacental transmission during pregnancy as a result of primary infection, reactivation or re-infection with a different isolate. Estimates suggest at least a million cases of congenital CMV occur annually worldwide. Congenital infection is a leading cause of neurological complications such as mental retardation, cerebral palsy, developmental delay and seizure disorders and also causes permanent disabilities, such as hearing loss and vision impairment. In addition, other common manifestation of CMV infection are stillbirth, preterm delivery and intrauterine growth restriction (IUGR) and cardiovascular disease, which are risk factors for perinatal and lifetime morbidity. Recent reports have estimated that the economic costs to public health and families due to congenital CMV infection are immense, with direct annual costs of billions of dollars. An effective CMV vaccine that could prevent transplacental transmission, reduce CMV disease and CMV-associated stillbirths has been recognised as an urgent medical need. Over the past 40 years several CMV vaccine candidates have been evaluated in a series of clinical trials and found to be effective in preclinical and clinical studies. However, in spite of extensive efforts over many decades, successful licensure of an effective CMV vaccine formulation to prevent congenital CMV infection remains elusive.

The IgG avidity value for the prediction of congenital cytomegalovirus infection in a prospective cohort study

2014 ◽  
Vol 42 (6) ◽  
Author(s):  
Yasuhiko Ebina ◽  
Toshio Minematsu ◽  
Ayako Sonoyama ◽  
Ichiro Morioka ◽  
Naoki Inoue ◽  
...  
Keyword(s):  
Cohort Study ◽  
Predictive Value ◽  
Congenital Infection ◽  
Cmv Infection ◽  
Avidity Index ◽  
Infection Group ◽  
Cutoff Value ◽  
Igg Avidity ◽  
Congenital Cmv Infection ◽  
Congenital Cmv

AbstractCytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates.To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection.The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study.Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation.The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.

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