Biomarkers of Cytomegalovirus Fetal Infection and Disease

Assistance Publique - Hôpitaux de Paris265 enrolled

Overview

The purposes of this study are to determine 1) if the diagnosis of CMV fetal infection could be done directly in the maternal blood instead of requesting an amniocentesis and 2) if innovative technologies such as proteomic, transcriptomic, methylomic and lipidomic applied in fetal samples could allow the discovery of new biomarkers of fetal infection.

Human cytomegalovirus (HCMV) is the most common cause of congenital infection worldwide. The diagnosis of CMV fetal infection relies on the detection of viral DNA in amniotic fluid by polymerase chain reaction after amniocentesis. Non-invasive diagnosis of fetal infection directly in maternal blood is not available. Symptoms develop in about 10% of HCMV-infected fetuses. Despite important advance in medical imaging, establishing the prognosis of an infected fetus remains challenging. Thrombocytopenia, blood HCMV DNA, anti-HCMV immunoglobulin M and β2-microglobulin are recognized biomarkers of symptomatic fetal infections. However, the predictive value of these individual markers is not. Omics technologies could help to establish multimarker signatures of symptomatic infections. The objective of the study is to: * validate fetal blood HCMV DNA, anti-HCMV immunoglobulin M , β2-microglobulin and platelet count as biomarkers of fetal disease; * identify new biomarkers of severe fetal disease using transcriptomic, methylomic and lipidomic analyses of fetal blood and of amniotic fluid. * validate a non-invasive CMV fetal infection diagnosis tool based on deep-sequencing of targeted CMV genes in maternal blood

Study Type

OBSERVATIONAL

Enrollment

265

Conditions

Cytomegalovirus Congenital

Interventions

Bio-specimen collectedBIOLOGICAL

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: CMV cases: * Informed consent obtained from the mother; * Pregnant women either with a history of primary CMV infection in pregnancy or carrying a fetus with ultrasound features compatible with CMV infection and willing to have amniocentesis for fetal diagnosis of CMV infection Control cases : \- Pregnant women carrying a fetus with aneuploidy-dysgonosomy Exclusion Criteria: CMV cases: * Fetuses older than the 26 weeks of gestation at the time of diagnosis of HCMV infection or impossibility to collect foetal samples by the end of the 26th week of gestation * Mother unable to understand the protocol * Absence of informed consent * Any clinical rationale not to perform cordocentesis * Mother \<18 years age * Administration of immunoglobulins or anti-viral therapy to the mother before the collection of fetal samples or before the diagnosis of symptomatic fetal infection * Administration of anti-HCMV drugs to the foetus before the collection of fetal samples or before the diagnosis of symptomatic fetal infection * Administration of immunosuppressive drugs to the mother during pregnancy * Maternal auto immune disorders * Multiple pregnancies. Control cases : * Mother unable to understand the protocol * Absence of informed consent

Locations (1)

Hôpital Necker Enfants-Malades

Paris, France

RECRUITING

Outcomes

Primary Outcomes

Number of Participants With Abnormal Laboratory Values in fetal blood

Fetal platelet in mm3/ml, β2 microglobulinein mg/L, proteins concentration in mg/L , Metabolites concentration in mmoles/l , Lipids concentration in mmoles/l , RNA messagers concentration in µg/ml profil

Time frame: At 23 weeks gestation +/- 3 weeks

Secondary Outcomes

Number of Participants With Abnormal Laboratory Values in amniotic fluid

CMV DNA quantification in UI/mL , protein concentration in mg/L, Metabolites concentration in mmoles/l , Lipids concentration in mmoles/l, RNAm concentration in µg/ml profil ,

Time frame: At 23 weeks gestation +/- 3 weeks

Non invasive diagnosis of fetal CMV infection in maternal blood in UI/mL.

CMV fetal DNA measurement in maternal blood

Time frame: At 23 weeks gestation +/- 5 weeks

Central Contacts

Marianne LERUEZ, MD, PhD

CONTACT

+33 (0) 1 44 49 49 49 62 marianne.leruez@aphp.fr

Hélène MOREL

CONTACT

+33 1 71 19 63 46 helene.morel@aphp.fr

Data from ClinicalTrials.gov

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