Prognostic Value of Neonatal Markers for the Development of Neurosensorial Sequelae in Children Infected by Cytomegalovirus in Utero (CYMEPEDIA)

Evaluation of the Prognostic Value of Clinical, Imaging, Immunological and Virological Markers in the Neonatal Period for the Development of Neurosensorial Sequelae at 1 Year in Children Infected by Cytomegalovirus in Utero.

The main objective of this study is to validate , in the neonatal period, a prognostic score for the development of neurosensorineural sequelae at 1 year and at 2 years in neonates infected in utero by cytomegalovirus. This score will be based on clinical, imaging and biological criteria .

The second objective of the study is to estimate the prevalence of this infection in France and to describe its epidemiology through the screening of 12,000 consecutive neonates.

Study Overview

• Status: Completed
• Conditions: Congenital Cytomegalovirus Infection
• Intervention / Treatment: Other: detection of CMV

Detailed Description

Infection with cytomegalovirus (CMV) is the most frequent cause of congenital neurological handicap of infectious origin in industrialized countries. Around 10% of infected neonates have symptoms and more than 50% of those will develop long term neurological sequelae and sensorineural hearing loss. Among asymptomatic infected neonates 10 to 15% will ultimately develop hearing loss. To establish the prognosis of infected neonates remains difficult and the purpose of the study is to better define early prognosis factors The true burden of CMV congenital infection is unknown in France: the prevalence of the infection as well as the description of its epidemiology (proportion of symptomatic and asymptomatic cases, rate of long term sequelae, proportion of cases following primary or secondary maternal infections) are unknown.

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 month (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Main objective: Neonate less than 1 month with congenital CMV infection at birth objectified by the detection of CMV in a urine sample, in saliva or blood (fresh or Guthrie card) obtained in the first 10 days life

• Whose parents accept regular monitoring by the paediatrician investigator
• For which a medical examination has been made
• Affiliated with a social security system
• And whose mother has given its written consent to the participation of their child to study

Exclusion Criteria:

- Children participating in an interventional study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: detection of CMV; Cohort of neonates less than 1 month with congenital CMV infection at birth objectified by the detection of CMV in a urine sample, in saliva or blood (fresh or Guthrie card) obtained in the first 10 days life	Other: detection of CMV; Clinical, radiological and laboratory (virological and immunological) standardized reports

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of neonatal markers (clinical, imaging and biological) for the development of neurosensorial sequelae at 1 year of age	Assessment will include standardised clinical evaluation, cerebral ultrasound, cerebral MRI, audiometric tests, developmental tests, virological tests (viral load in blood and saliva) and immunological tests (cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK) and cytokines).	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to evaluate the prevalence of congenital CMV in France:	screening by CMV PCR in a saliva sample collected in delivery room will be proposed to all mothers with a live birth neonate born in the Necker or Poissy	At birth
Prognosis value of antenatal imaging	To compare neurodevelopmental and sensorineural sequelae at one year with the result of antenatal imaging (ultrasound and MRI)	one year
Prognostic value of the periodic measurement of the kinetics of viral load shedding	To evaluate the prognostic value of the kinetics of CMV viral load in blood and in saliva from birth to 1 year old for the occurrence of neurodevelopmental and sensorineural sequelae	One year
neurodevelopmental and sensorineural sequelae according to the type of maternal infectionsequelae	Compare the proportion of neurodevelopmental and sensorineural sequelae according to the type of maternal infection (primary or secondary).	One year
Prevalence and description of congenital CMV infection in 10,000 French neonates	Screening of congenital CMV infection in a population of 10,000 consecutive newborns in 2 French maternities	1 week

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Laurence Bussieres, MD, APHP

Publications and helpful links

General Publications

• 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.
• Leruez-Ville M, Ren S, Magny JF, Jacquemard F, Couderc S, Garcia P, Maillotte AM, Benard M, Pinquier D, Minodier P, Astruc D, Patural H, Ugolin M, Parat S, Guillois B, Garenne A, Parodi M, Bussieres L, Stirnemann J, Sonigo P, Millischer AE, Ville Y. Accuracy of prenatal ultrasound screening to identify fetuses infected by cytomegalovirus which will develop severe long-term sequelae. Ultrasound Obstet Gynecol. 2021 Jan;57(1):97-104. doi: 10.1002/uog.22056.
• 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): September 9, 2013
• Primary Completion (ACTUAL): January 30, 2021
• Study Completion (ACTUAL): May 16, 2022

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: August 13, 2013
• First Posted (ESTIMATE): August 15, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 10, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Cytomegalovirus, congenital, handicap
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: P120114; AOM12196