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

Recruiting

• Conditions: Increased Nuchal Translucency in the First Trimester of Pregnancy

• Registration Number: NCT05388968
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2022-05-02
• Study First Submitted QC: 2022-05-20
• Study First Posted: 2022-05-24
• Study Start: 2022-11-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-03
• Primary Completion: 2025-05
• Study Completion: 2026-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 110

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)

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
microorganisms (viruses, bacteria, or parasites) in trophoblast samples	At inclusion, 11-14 weeks of pregnancy	Identification by metatranscriptomic NGS, from women carrying a fetus with nuchal translucency (group 1) and in controls (group 2 and 3)

Secondary Outcome Measures

Name	Time	Method
intrauterine death	at termination of pregnancy (assessed up to 7 months)	Comparison in group 1 of the proportion of intrauterine death according to the presence or not of a microorganism in the trophoblast.
fetal abnormalities	at delivery	Comparison in group 1 of the proportion of fetal abnormalities, according to the presence or not of a microorganism in the trophoblast.
Miscarriage	at termination of pregnancy (assessed up to 7 months)	Comparison in group 1 of the proportion of miscarriageaccording to the presence or not of a microorganism in the trophoblast.
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples	at inclusion	specific serology to identify a maternal primary infection with the microorganism detected by metatranscriptomic NGS
birth weight	at delivery	Comparison in group 1 of birth weight, according to the presence or not of a microorganism in the trophoblast.
Gestational age	at delivery	Comparison in group 1 of gestational age at birth, according to the presence or not of a microorganism in the trophoblast.
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples	3 days after birth	specific serology to identify a maternal primary infection with the microorganism detected by metatranscriptomic NGS

Trial Locations

Locations (1)

Hopital Necker - Enfants malades; 🇫🇷 Paris, France