Biomarkers of Cytomegalovirus Fetal Infection and Disease

Biomarkers of Fetal Infection and Disease Following Maternal HCMV Infection

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

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