Therapeutics to prevent congenital cytomegalovirus during pregnancy: what is available now and in the future?

2015 ◽  
Vol 36 (4) ◽  
pp. 156 ◽  
Author(s):  
Stuart T Hamilton ◽  
Corina Hutterer ◽  
Manfred Marschall
Keyword(s):  
Pregnant Women ◽  
Developed Countries ◽  
Fetal Malformation ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus ◽  
Fetal Infection ◽  
Congenital Cmv Infection ◽  
Social Importance ◽  
Cmv Disease ◽  
Congenital Cmv

Human cytomegalovirus (CMV) is the leading non-genetic cause of fetal malformation in developed countries. Congenital CMV infection can cause serious clinical sequelae, and in severe cases result in fetal or neonatal death. Despite the clinical and social importance of congenital CMV there is currently no standardised management strategy to prevent or treat maternal/fetal CMV infection during pregnancy and no evidence-based therapeutic for prenatally diagnosed CMV infection or disease. For pregnant women with a primary CMV infection during pregnancy, standard medical practise remains to offer no treatment at all or the option to terminate pregnancy. If intervention is requested, pregnant women may be offered a narrow range of medical therapies with limited evidence for efficacy and some with high risks of toxicity. However, there are several experimental and novel anti-CMV therapeutics currently being investigated that may provide a safe and effective therapeutic for use during pregnancy to prevent both fetal infection and reduce the risk of congenital CMV disease developing in the fetus once infected in utero.

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.

Congenital cytomegalovirus infection management; what is new?

2021 ◽  
Vol 1 (2) ◽  
pp. 001-007
Author(s):  
Therese-Mary William
Keyword(s):  
Pregnant Women ◽  
Screening Program ◽  
Dried Blood Spots ◽  
Cmv Infection ◽  
Pcr Assay ◽  
Assay Sensitivity ◽  
Congenital Cytomegalovirus ◽  
Congenital Cmv Infection ◽  
Specific Symptoms ◽  
Congenital Cmv

Congenital Cytomegalovirus (CMV) infection is one of major public health concerns and one of the most frequent congenital infections worldwide. Congenital CMV infection is under-diagnosed in the majority of asymptomatic pregnant women due to its self-limited non-specific symptoms and unimplemented screening program. It also can go undetected at birth because in affected newborns are often asymptomatic; however, they manifest serious morbidities later in life. Primary CMV infections are associated with the highest in-utero transmission with estimated rates of 30–35% . Transmission occurs less frequently in secondary maternal infections at approximately 1.1–1.7%. There are growing evidences that early treatment with the antiviral therapy in newborns with congenital CMV infection can reduce sensorineural hearing loss (SNHL) and the substantial long-term neurodevelopmental disabilities. There is increased interest in establishing a prophylactic CMV vaccines that can protect seronegative mothers from primary infection and also to augment the immune response in seropositive women in order to prevent reactivation or re-infection. Saliva PCR assay can be used to screen newborns within the first 3 weeks of age instead of Dried blood spots (DBS), liquid-saliva PCR assay sensitivity is “100%” higher than DBS sensitivity “35%-100%" as not all infants have detectable viraemia at birth. Suggestive strategies to reduce the burden of congenital CMV disease and ensure better outcomes are; establishing a screening programme for pregnant mothers, developing prophylactic CMV vaccines, early therapeutic intervention in pregnant women and newborns and to replace DBS with Saliva PCR assay in screening newborns.

scholarly journals Birth Prevalence of Congenital Cytomegalovirus (CMV) infection in a cohort of pregnant women in Bangladesh

2018 ◽  
Vol 43 (2) ◽  
pp. 77-81
Author(s):  
Munira Jahan ◽  
Nahida Sultana ◽  
Ridwana Asma ◽  
Shahina Tabassum ◽  
Md. Nazrul Islam
Keyword(s):  
Pregnant Women ◽  
Viral Infections ◽  
Congenital Infection ◽  
High Seroprevalence ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus ◽  
Birth Prevalence ◽  
Congenital Cmv Infection ◽  
Cmv Reactivation ◽  
Congenital Cmv

Cytomegalovirus (CMV) is a frequent cause of congenital infection in humans in all regions of the world. In contrast to most congenital viral infections, congenital CMV infection and disease have been consistently demonstrated in populations with a high seroprevalence. Three hundred pregnant women were studied prospectively in their 1st, 2nd and 3rd trimester to determine the seroprevalence and seroconversion of CMV in pregnancy. After birth, babies were also tested for anti CMV IgM to determine the rate of birth prevalence. Anti CMV IgG and IgM tests were performed by chemiluminescence methods. All 300 (100%) pregnant women were anti CMV IgG positive and 180 (60%) were subsequently anti CMV IgM positive during different trimesters of pregnancy. Birth prevalence of CMV IgM antibody was 1.3% among babies of anti CMV IgM positive mothers whereas none in CMV IgM negative mothers (OR 1.01, 95% CI .996-1.027).It may be concluded that CMV IgG seroprevalence is high among Bangladeshi pregnant women and the rate of CMV reactivation is also high during pregnancy. Despite protection by maternal immunity a certain percent of babies acquire congenital CMV infection.

Current practices of management of congenital Cytomegalovirus infection during pregnancy and childhood: systematic review protocol

2020 ◽  
Author(s):  
Claire Perillaud Dubois ◽  
Drifa Belhadi ◽  
Cédric Laouénan ◽  
Laurent Mandelbrot ◽  
Christelle Vauloup-Fellous ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pregnant Women ◽  
State Of The Art ◽  
Grey Literature ◽  
The State ◽  
Cochrane Library ◽  
Cmv Infection ◽  
Congenital Cmv Infection ◽  
Congenital Cmv ◽  
Current Practices

Abstract Background: Congenital CMV infection is the first worldwide cause of congenital viral infection and a major cause of sensorineural hearing loss and mental retardation. As systematic screening of pregnant women and newborns is still debated in many countries, this systematic review aims to provide the state of the art on current practices concerning management of congenital CMV infection.Methods: We will perform electronically searches on MEDLINE, EMBASE, Cochrane Library (CENTRAL), ClinicalTrials.gov, Web of Science and hand searches in grey literature. Interventions regarding biological, imaging, and therapeutic management of infected pregnant women, fetuses and neonates/children (from birth to 6 years old) will be studied in this systematic review. Study screening will be performed in duplicate by two independent reviewers and risk of bias will be evaluated with the ROBINS-I tool. Discussion: This review will provide the state of the art of current management of congenital CMV infection in pregnant women, fetuses, neonates and children until 6 years old, in order to have an overview of current practices of congenital CMV infection.Systematic review registration: PROSPERO CRD42019124342

Neonatal screening for congenital cytomegalovirus infection in Tehran, Iran, using Guthrie cards

2020 ◽  
Author(s):  
Samileh Noorbakhsh ◽  
Mohammad Farhadi ◽  
Faezeh Haghighi ◽  
Sara Minaeian ◽  
Morteza Haghighi Hasanabad
Keyword(s):  
Early Stage ◽  
Limited Data ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus ◽  
Congenital Cmv Infection ◽  
Effective Counseling ◽  
Total Dna ◽  
Guthrie Cards ◽  
Congenital Cmv

Background and Objectives: Cytomegalovirus (CMV) constitutes the most common viral cause of congenital infections in newborns worldwide. There are a significant number of asymptomatic newborns with congenital CMV infection in Iran, which may develop long-term sequelae of infection. Unfortunately, limited data exsists from Iran on the rate of congenital CMV infection among neonates. The current study was aimed to investigate the prevalence of congenital CMV infection among Iranian neonates by testing Guthrie cards. Materials and Methods: Guthrie cards were collected from infants within 2 weeks of life, and total DNA was extracted from samples by thermal shock and evaluated for CMV DNA using nested-PCR assay. CMV infection in newborns was confirmed through a commercial CMV PCR kit. Infected infants underwent further evaluation at the hospital. Results: CMV infection was identified in four of 1174 infants (0.34%) which is approximately 3 cases per 1000 live births. Infected infants were asymptomatic at birth and had a normal hearing status similar to other children. There were no factors in relation with CMV infection among newborns. Conclusion: According to the results of this study, infected infants with congenital CMV infection could identify at early stage by testing Guthrie cards (within 21 days of life). Furthermore, since there is a lack of CMV knowledge in our popula- tion, educating and effective counseling by obstetricians/ gynecologists to the pregnant women are recommended.  

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.

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.

Clinical and epidemiological features of congenital cytomegalovirus infection globally

2015 ◽  
Vol 36 (4) ◽  
pp. 153 ◽  
Author(s):  
Wendy J van Zuylen
Keyword(s):  
Vision Loss ◽  
Clinical Importance ◽  
Mental Disability ◽  
Cmv Infection ◽  
Congenital Cytomegalovirus Infection ◽  
Congenital Cytomegalovirus ◽  
Global Epidemiology ◽  
Congenital Cmv Infection ◽  
General Community ◽  
Congenital Cmv

Human cytomegalovirus (CMV) is the most common non-genetic cause of congenital disability. As a herpesvirus that infects the majority of the population, CMV is able to establish a lifelong latent infection in the host. Any time during pregnancy, a primary CMV infection, reactivation of latent CMV or a new viral strain can infect the placenta and the developing foetus, resulting in congenital CMV infection. Each year, an estimated 2000 children are born with congenital CMV infection in Australia, leaving ~500 children with permanent disabilities such as hearing or vision loss, or mental disability. Despite the clinical importance of congenital CMV, there is limited awareness and knowledge in the medical and general community about congenital CMV infection. This article reviews the global epidemiology and clinical features of maternal and congenital CMV infections.

First-line noninvasive management of cytomegalovirus primary infection in pregnancy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marie Denef ◽  
Laure Noel ◽  
Gaëlle Bruck ◽  
Justine Gudelj ◽  
Malek Tebache ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Primary Infection ◽  
Brain Mri ◽  
Neurodevelopmental Outcome ◽  
Fetal Outcome ◽  
Cmv Infection ◽  
First Line ◽  
Congenital Cmv Infection ◽  
Magnetic Resonance Imaging Mri ◽  
Congenital Cmv

Abstract Objectives To introduce a first-line noninvasive antenatal management of maternal cytomegalovirus (CMV) primary infection based on ultrasound (US) and magnetic resonance imaging (MRI). Amniocentesis (AC) is used as a second-line tool in cases of abnormalities compatible with fetal CMV infection on US and/or MRI screening. Methods Between January 2011 and October 2018, pregnant women referred with a CMV primary infection on antibody screening were followed up by monthly US scans and a brain MRI at approximately 32 weeks. In cases with US and/or MRI abnormalities compatible with congenital CMV infection, AC was performed to confirm the diagnosis. Results Ninety pregnant women with a primary CMV infection were included (89 singleton and one twin pregnancy). The first-line screening by US and/or MRI was normal for 72 of 91 fetuses (79%). At birth, 19 of these 72 neonates (26%) had a positive urine sample for CMV but were asymptomatic. US and/or MRI abnormalities were identified in 19 fetuses (21%). AC confirmed a fetal CMV infection in 16 fetuses (84%); 12 pregnancies were terminated, and four were continued, with three symptomatic neonates at birth and one poor neurodevelopmental outcome at postnatal follow-up. Conclusions First-line noninvasive management of maternal CMV primary infection based on serial US scans and brain MRI can be offered to identify fetuses with severe symptomatic congenital CMV infection and reduce the number of ACs without compromising the fetal outcome.

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