Metatranscriptomic Next Generation Sequencing in First Trimester Trophoblast With Increased Fetal Nuchal Translucency (METAHCN)

Assistance Publique - Hôpitaux de Paris

Status: Enrolling

Conditions: Increased Nuchal Translucency in the First Trimester of Pregnancy

Treatments: Diagnostic Test: Specific microbiologic diagnosis; Biological: Metatranscriptomic

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT05388968

APHP211328

Details and patient eligibility

About

The study is based on the hypothesis that increased nuchal translucency may be associated with a materno fetal infection and that the pathogen responsible for this infection could be identify with metatranscriptomic next-generation sequencing in the trophoblast tissue.

Full description

Nuchal translucency > 3.5 mm in the first trimester of pregnancy is due to fluid accumulation in the subcutaneous tissue in the nuchal area. This is seen in around 1% of all pregnancies. Increased nuchal translucency is explained by a chromosomic abnormality (mainly Down syndrome) in 30 to 40% of cases. Therefore, the state of the art is to perform an array CGH on chorionic villi sampling. Cases of nuchal translucency that are not explained by a chromosomic abnormality may be associated: with fetal defect (heart, congenital diaphragmatic hernia) in 10% of cases, with genetic disease in 4% of cases or with miscarriage or fetal death of unknown etiology in 18% of cases.

The etiology of increased nuchal translucency remains unknown in more than 50% of the cases. It could be linked to inflammation or reflect an infection but this latter association has been rarely studied. This association was suggested in a study reporting serology of CMV, toxoplasmosis or B19 parvovirus primary infections in pregnant women carrying a fetus with increased nuchal translucency. In those rare cases, the microorganism was not searched directly in the trophoblast tissue. In the investigators' center, the investigators describe in a context of maternal primary infection, one case of increased nuchal translucency with a positive CMV PCR in the trophoblast tissue collected at 12 weeks. Other pathogens yet not identified might be associated with increased nuchal translucency.

Metatranscriptomic next generation sequencing (mNGS) allows to search for any pathogens without a priori. It is therefore a powerful technic to study this potential association between increased nuchal translucency and infection.

Enrollment: 110 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Pregnant women
• Singleton pregnancy
• First trimester (11 GA+0D to 13 GA+6D)
• Carrying a fetus with a nuchal translucency > 3.5 mm for which a chorionic villi sampling is performed OR a suspicion of genetic abnormalities for which a chorionic villi sampling is performed
• Delivery planned at Necker hospital
• Not opposed to participation

Exclusion Criteria

• Age <18 years
• no health insurance
• difficulties in understanding the French language
• chronic infection (HIV, HBV, HVC and HTLV-1)

Trial design

110 participants in 3 patient groups

Nuchal translucency with no genetic abnormalities

Description:

Pregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency \> 3.5 mm and no genetic abnormalities with array CGH.

Treatment:

Diagnostic Test: Specific microbiologic diagnosis

Biological: Metatranscriptomic

Nuchal translucency with genetic abnormalities

Description:

Pregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency \> 3.5 mm and a genetic abnormalities at array CGH.

Treatment:

Diagnostic Test: Specific microbiologic diagnosis

Biological: Metatranscriptomic

Genetic abnormalities

Description:

Pregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency \< 3.5 mm and a suspicion of genetic abnormalities

Treatment:

Diagnostic Test: Specific microbiologic diagnosis

Biological: Metatranscriptomic