Congenital CYtoMEgalovirus Infection in VIEtnam (CYMEVIE)
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
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.
Study Design
Outcome Measures
Primary Outcome Measures
- Proportion of congenital CMV infection in Vietnamese neonates [Within 7 days from birth]
Number of CMV positive neonates among all tested neonates
Secondary Outcome Measures
- To estimate the prevalence of symptomatic cCMV in neonates [Up to 25 months from recruitment]
Proportion of neonates presenting with at least one symptom related to cCMV in all cCMV neonates
- To estimate the prevalence of cCMV related hearing loss in neonates [Up to 25 months from recruitment]
Proportion of cCMV related hearing loss in neonates in all cCMV neonates
- To estimate the prevalence of cCMV related neurological sequelae in neonates [Up to 25 months from recruitment]
Proportion of cCMV related neurological sequelae in neonates in all cCMV neonates
- To estimate CMV seroprevalence in pregnant Vietnamese women [Up to 25 months from recruitment]
Proportion of seropositive women in all tested pregnant women, including mother of CMV positive neonates and control group
- To evaluate the value of a positive CMV PCR in maternal whole blood in the first trimester to predict infection in the neonates [Up to 25 months from recruitment]
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
- To evaluate the value of a positive CMV PCR in maternal urine in the first trimester to predict infection in the neonates [Up to 25 months from recruitment]
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
- To evaluate the value of a positive CMV PCR in maternal saliva in the first trimester to predict cCMV infection in the neonates [Up to 25 months from recruitment]
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
- To evaluate the value of a positive CMV PCR in maternal whole blood at delivery to predict infection in the neonates [Up to 25 months from recruitment]
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
- To evaluate the value of a positive CMV PCR in maternal urine at delivery to predict infection in the neonates [Up to 25 months from recruitment]
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
- 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 [Up to 25 months from recruitment]
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
- To evaluate the value of a positive CMV PCR in maternal urine in the first trimester to predict a cCMV symptomatic infection in neonates [Up to 25 months from recruitment]
Comparison of the proportion of a positive CMV PCR in maternal urine in the first trimester between symptomatic infected neonates and asymptomatic infected neonates
- 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 [Up to 25 months from recruitment]
Comparison of the proportion of a positive CMV PCR in maternal saliva in the first trimester between symptomatic infected neonates and asymptomatic infected neonates
- 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 [Up to 25 months from recruitment]
Comparison of the proportion of a positive CMV PCR in maternal whole blood at delivery between symptomatic infected neonates and asymptomatic infected neonates
- To evaluate the value of a positive CMV PCR in maternal urine at delivery to predict a cCMV symptomatic infection in neonates [Up to 25 months from recruitment]
Comparison of the proportion of a positive CMV PCR in maternal urine at delivery between symptomatic infected neonates and asymptomatic infected neonates
- To evaluate the association between 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]
Evaluation the change of CMV PCR viral load in maternal whole blood at first trimester and at delivery in mothers with infected neonates
- To evaluate the association between CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with infected neonates [Up to 25 months from recruitment]
Evaluation the change of CMV PCR viral load in maternal urine at first trimester and at delivery in mothers with infected neonates
- 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 [Up to 25 months from recruitment]
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
- 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 [Up to 25 months from recruitment]
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
- To calculate the false positive rate of CMV PCR on neonatal saliva versus on dry blood spot in screening congenital CMV infection [Up to 25 months from recruitment]
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
- To calculate the false positive rate of CMV PCR on neonatal saliva versus on urine in screening congenital CMV infection [Up to 25 months from recruitment]
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
- To evaluate risks factors for cCMV in Vietnamese women [Up to 25 months from recruitment]
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
- To estimate the prevalence of symptomatic cCMV at 2 years of age [Up to 48 months from recruitment]
Proportion of infants presenting with at least one symptom related to cCMV at 2 years of age in all cCMV infants
- To estimate the prevalence of cCMV related hearing loss at 2 years of age [Up to 48 months from recruitment]
Proportion of infants with cCMV related hearing loss at 2 years of age in all cCMV infants
- To estimate the prevalence of cCMV related neurological sequelae at 2 years of age [Up to 48 months from recruitment]
Proportion of infants with cCMV related neurological sequelae at 2 years of age in all cCMV infants
- 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 [Up to 48 months from recruitment]
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
- 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 [Up to 48 months from recruitment]
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
- 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 [Up to 48 months from recruitment]
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
- 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 [Up to 48 months from recruitment]
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
- 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 [Up to 48 months from recruitment]
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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hanoi Obstetrics and Gynecology Hospital | Hanoi | Vietnam | 100000 |
Sponsors and Collaborators
- Hanoi Obstetrics and Gynecology Hospital
- Hôpital Necker-Enfants Malades
Investigators
- Study Chair: Yves Ville, MD.PhD, Hôpital Necker-Enfants Malades
- Study Director: Marianne Leruez-Ville, MD.PhD, Hôpital Necker-Enfants Malades
- Study Director: Anh Nguyen Duy, MD.PhD, Hanoi Obstetrics and Gynecology Hospital
- Principal Investigator: Ha Nguyen Thi Thu, MD.PhD, Hanoi Obstetrics and Gynecology Hospital
- Principal Investigator: Linh Dinh Thuy, MD.PhD, Hanoi Obstetrics and Gynecology Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Faure-Bardon V, Magny JF, Parodi M, Couderc S, Garcia P, Maillotte AM, Benard M, Pinquier D, Astruc D, Patural H, Pladys P, Parat S, Guillois B, Garenne A, Bussières L, Guilleminot T, Stirnemann J, Ghout I, Ville Y, Leruez-Ville M. Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy. Clin Infect Dis. 2019 Oct 15;69(9):1526-1532. doi: 10.1093/cid/ciy1128.
- Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007 Jul-Aug;17(4):253-76. Review.
- Leruez-Ville M, Magny JF, Couderc S, Pichon C, Parodi M, Bussières L, Guilleminot T, Ghout I, Ville Y. Risk Factors for Congenital Cytomegalovirus Infection Following Primary and Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using Polymerase Chain Reaction in Saliva. Clin Infect Dis. 2017 Aug 1;65(3):398-404. doi: 10.1093/cid/cix337.
- Mussi-Pinhata MM, Yamamoto AY, Aragon DC, Duarte G, Fowler KB, Boppana S, Britt WJ. Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: "The BraCHS Study". J Infect Dis. 2018 Sep 8;218(8):1200-1204. doi: 10.1093/infdis/jiy321.
- Puhakka L, Renko M, Helminen M, Peltola V, Heiskanen-Kosma T, Lappalainen M, Surcel HM, Lönnqvist T, Saxen H. Primary versus non-primary maternal cytomegalovirus infection as a cause of symptomatic congenital infection - register-based study from Finland. Infect Dis (Lond). 2017 Jun;49(6):445-453. doi: 10.1080/23744235.2017.1279344. Epub 2017 Jan 24.
- Ross SA, Fowler KB, Ashrith G, Stagno S, Britt WJ, Pass RF, Boppana SB. Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J Pediatr. 2006 Mar;148(3):332-6.
- Wang S, Wang T, Zhang W, Liu X, Wang X, Wang H, He X, Zhang S, Xu S, Yu Y, Jia X, Wang M, Xu A, Ma W, Amin MM, Bialek SR, Dollard SC, Wang C. Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China. Medicine (Baltimore). 2017 Feb;96(5):e6007. doi: 10.1097/MD.0000000000006007.
- Yamamoto AY, Anastasio ART, Massuda ET, Isaac ML, Manfredi AKS, Cavalcante JMS, Carnevale-Silva A, Fowler KB, Boppana SB, Britt WJ, Mussi-Pinhata MM. Contribution of Congenital Cytomegalovirus Infection to Permanent Hearing Loss in a Highly Seropositive Population: The Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study. Clin Infect Dis. 2020 Mar 17;70(7):1379-1384. doi: 10.1093/cid/ciz413.
- PSHN.0003.2021