Congenital CYtoMEgalovirus Infection in VIEtnam (CYMEVIE)

Study Overview
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Brief Summary
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To estimate the prevalence of congenital CMV infection in Vietnamese neonates and relating morbidity within 2-year follow-up. Along with evaluating the predictive value of the presence and the level of CMV replication in the first trimester in a highly seropositive population

Detailed Description
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Congenital cytomegalovirus infection (cCMV) is the main non-genetic cause of sensorineural hearing loss (SNHL), and a major cause of neuro-disability. High maternal CMV prevalence seems to be consistently associated with high prevalence of cCMV infection but the associated morbidity might be different from one population to another. There exists no serologic marker useful to differentiate non-primary infection from primary infection. Since the morbidity of cCMV is similar between both primary and non-primary maternal infection, and to be infected in the first trimester is the major risk factor for long-term sequelae in neonates. Hence, it is needed to focus on finding markers that predict cCMV after maternal infection in the first trimester of pregnancy. To date, the epidemiology of cCMV, the morbidity related to cCMV in Vietnamese population and the predictive value of Cytomegalovirus Polymerase Chain Reaction (CMV PCR) in maternal blood and urine in the first trimester remain unknown. Therefore, it is necessary to conduct this study.

Official Title
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Congenital Cytomegalovirus Infection in Vietnam: Prevalence, Morbidity and Risk Factors

Conditions
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Prenatal Infection, Congenital Infection, Neonatal Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vietnamese pregnant women in the first trimester of pregnancy and at delivery and subsequent live neonates at birth. Informed consent Exclusion Criteria: Women under 18 years old. Miscarriages Stillbirths Premature delivery before 34th gestational week Loss to follow-up maternal monitoring. Participation in another interventional study that influences management of labour at delivery or perinatal morbidity or mortality.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of congenital CMV infection in Vietnamese neonates | Number of CMV positive neonates among all tested neonates | Within 7 days from birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the prevalence of symptomatic cCMV in neonates | Proportion of neonates presenting with at least one symptom related to cCMV in all cCMV neonates | Up to 25 months from recruitment | 
| To estimate the prevalence of cCMV related hearing loss in neonates | Proportion of cCMV related hearing loss in neonates in all cCMV neonates | Up to 25 months from recruitment | 
| To estimate the prevalence of cCMV related neurological sequelae in neonates | Proportion of cCMV related neurological sequelae in neonates in all cCMV neonates | Up to 25 months from recruitment | 
| To estimate CMV seroprevalence in pregnant Vietnamese women | Proportion of seropositive women in all tested pregnant women, including mother of CMV positive neonates and control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal whole blood in the first trimester to predict infection in the neonates | Comparison of the proportion of a positive CMV PCR in maternal whole blood in the first trimester between women who gave birth to an infected neonate and women gave birth to an uninfected neonate from control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine in the first trimester to predict infection in the neonates | Comparison of the proportion of a positive CMV PCR in maternal urine in the first trimester between women who gave birth to an infected neonate and women gave birth to an uninfected neonate from control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal saliva in the first trimester to predict cCMV infection in the neonates | Comparison of the proportion of a positive CMV PCR in maternal saliva in the first trimester between women who gave birth to an infected neonate and women gave birth to an uninfected neonate from control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal whole blood at delivery to predict infection in the neonates | Comparison of the proportion of a positive CMV PCR in maternal whole blood at delivery between women who gave birth to an infected neonate and women gave birth to an uninfected neonate from control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine at delivery to predict infection in the neonates | Comparison of the proportion of a positive CMV PCR in maternal urine at delivery between women who gave birth to an infected neonate and women gave birth to an uninfected neonate from control group | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in whole blood in the first trimester to predict the presence of symptomatic cCMV infection in neonates | Comparison of the proportion of a positive CMV PCR in maternal whole blood in the first trimester between symptomatic infected neonates and asymptomatic infected neonates | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine in the first trimester to predict a cCMV symptomatic infection in neonates | Comparison of the proportion of a positive CMV PCR in maternal urine in the first trimester between symptomatic infected neonates and asymptomatic infected neonates | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal saliva in the first trimester to predict the presence of symptomatic cCMV infection in neonates | Comparison of the proportion of a positive CMV PCR in maternal saliva in the first trimester between symptomatic infected neonates and asymptomatic infected neonates | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal whole blood at delivery to predict the presence of symptomatic cCMV infection in neonates | Comparison of the proportion of a positive CMV PCR in maternal whole blood at delivery between symptomatic infected neonates and asymptomatic infected neonates | Up to 25 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine at delivery to predict a cCMV symptomatic infection in neonates | Comparison of the proportion of a positive CMV PCR in maternal urine at delivery between symptomatic infected neonates and asymptomatic infected neonates | Up to 25 months from recruitment | 
| To evaluate the association between CMV PCR viral load in maternal whole blood at first trimester and at delivery in mothers with infected neonates | Evaluation the change of CMV PCR viral load in maternal whole blood at first trimester and at delivery in mothers with infected neonates | Up to 25 months from recruitment | 
| To evaluate the association between CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with infected neonates | Evaluation the change of CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with infected neonates | Up to 25 months from recruitment | 
| To evaluate the association between CMV PCR viral load in maternal whole blood at first trimester and at delivery in mothers with uninfected neonates in control group | Evaluation the change of CMV PCR viral load in maternal whole blood at first trimester and at delivery in mothers with uninfected neonates in control group | Up to 25 months from recruitment | 
| To evaluate the association between CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with uninfected neonates in control group | Evaluation the change of CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with uninfected neonates in control group | Up to 25 months from recruitment | 
| To calculate the false positive rate of CMV PCR on neonatal saliva versus on dry blood spot in screening congenital CMV infection | Calculation of the rate of positive CMV PCR on neonatal saliva with a negative result on CMV PCR on neonatal dry blood spot in all CMV positive on neonatal saliva | Up to 25 months from recruitment | 
| To calculate the false positive rate of CMV PCR on neonatal saliva versus on urine in screening congenital CMV infection | Calculation of the rate of positive CMV PCR on neonatal saliva with a negative result on CMV PCR on neonatal urine in all CMV positive on neonatal saliva | Up to 25 months from recruitment | 
| To evaluate risks factors for cCMV in Vietnamese women | Factors that may differ between mothers of uninfected neonates and mothers of infected ones regarding maternal age, parity, gestity, twin pregnancy, known health conditions including hypertension, diabetes, HIV, auto immune diseases and living conditions will be analyzed | Up to 25 months from recruitment | 
| To estimate the prevalence of symptomatic cCMV at 2 years of age | Proportion of infants presenting with at least one symptom related to cCMV at 2 years of age in all cCMV infants | Up to 48 months from recruitment | 
| To estimate the prevalence of cCMV related hearing loss at 2 years of age | Proportion of infants with cCMV related hearing loss at 2 years of age in all cCMV infants | Up to 48 months from recruitment | 
| To estimate the prevalence of cCMV related neurological sequelae at 2 years of age | Proportion of infants with cCMV related neurological sequelae at 2 years of age in all cCMV infants | Up to 48 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal whole blood in the first trimester to predict the cCMV long-term sequelae at the age of 2 years | Comparison of the proportion of a positive CMV PCR in maternal whole blood in the first trimester between infected infants with long-term sequelae at 2 years of age and infected infants without long-term sequelae at 2 years of age | Up to 48 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine in the first trimester to predict the cCMV long-term sequelae at the age of 2 years | Comparison of the proportion of a positive CMV PCR in maternal urine in the first trimester between between infected infants with long-term sequelae at 2 years of age and infected infants without long-term sequelae at 2 years of age | Up to 48 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal saliva in the first trimester to predict the cCMV long-term sequelae at the age of 2 years | Comparison of the proportion of a positive CMV PCR in maternal saliva in the first trimester between between infected infants with long-term sequelae at 2 years of age and infected infants without long-term sequelae at 2 years of age | Up to 48 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal whole blood at delivery to predict the cCMV long-term sequelae at the age of 2 years | Comparison of the proportion of a positive CMV PCR in maternal whole blood at delivery between between infected infants with long-term sequelae at 2 years of age and infected infants without long-term sequelae at 2 years of age | Up to 48 months from recruitment | 
| To evaluate the value of a positive CMV PCR in maternal urine at delivery to predict the cCMV long-term sequelae at the age of 2 years | Comparison of the proportion of a positive CMV PCR in maternal urine at delivery between between infected infants with long-term sequelae at 2 years of age and infected infants without long-term sequelae at 2 years of age | Up to 48 months from recruitment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMV PCR, CYMEVIE, Cytomegalovirus, Congenital Cytomegalovirus infection, CMV, cCMV