Congenital CYtoMEgalovirus Infection in VIEtnam (CYMEVIE) (CYMEVIE)

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

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

Study Overview

• Status: Recruiting
• Conditions: Neonatal Disease; Prenatal Infection; Congenital Infection

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 Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

• Study Contact: Name: Ha Nguyen Thi Thu, MD.PhD; Phone Number: 0084989661093; Email: thuha.ivf@gmail.com
• Study Contact Backup: Name: Linh Dinh Thuy, MD.PhD; Email: drdinhlinhobgyn@gmail.com

Study Locations

• Vietnam
  • Hanoi, Vietnam, 100000
    • Recruiting
    • Hanoi Obstetrics and Gynecology Hospital
    • Contact: HA Nguyen Thi Thu, PhD.MD; Phone Number: 0084989661093; Email: thuha.ivf@gmail.com
    • Contact: LINH Dinh Thuy, PhD.MD; Phone Number: 0084936655779; Email: drdinhlinhhobgyn@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

5,000 mother/neonate pairs

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hanoi Obstetrics and Gynecology Hospital
• Collaborators: 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

Publications and helpful links

General Publications

• 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. doi: 10.1002/rmv.535.
• Leruez-Ville M, Magny JF, Couderc S, Pichon C, Parodi M, Bussieres 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.
• Puhakka L, Renko M, Helminen M, Peltola V, Heiskanen-Kosma T, Lappalainen M, Surcel HM, Lonnqvist 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.
• 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.
• 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. doi: 10.1016/j.jpeds.2005.09.003.
• 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.
• 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.
• 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, Bussieres 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 28, 2021
• First Posted (Actual): March 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Cytomegalovirus; CMV; CYMEVIE; Congenital Cytomegalovirus infection; CMV PCR; cCMV
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Infant, Newborn, Diseases
• Other Study ID Numbers: PSHN.0003.2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To be determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No