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

NCT ID: NCT05388968

Last Updated: 2024-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

110 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-11-07

Study Completion Date

2026-02-28

Brief Summary

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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

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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.

Conditions

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Increased Nuchal Translucency in the First Trimester of Pregnancy

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Nuchal translucency with no genetic abnormalities

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

Metatranscriptomic

Intervention Type BIOLOGICAL

Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling

Specific microbiologic diagnosis

Intervention Type DIAGNOSTIC_TEST

If a microorganism is detected by metatranscriptomic NGS, specific diagnosis (PCR and serology) will be done in maternal and neonatal samples (blood, urine, saliva)

Nuchal translucency with genetic abnormalities

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

Metatranscriptomic

Intervention Type BIOLOGICAL

Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling

Specific microbiologic diagnosis

Intervention Type DIAGNOSTIC_TEST

If a microorganism is detected by metatranscriptomic NGS, specific diagnosis (PCR and serology) will be done in maternal and neonatal samples (blood, urine, saliva)

Genetic abnormalities

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

Metatranscriptomic

Intervention Type BIOLOGICAL

Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling

Specific microbiologic diagnosis

Intervention Type DIAGNOSTIC_TEST

If a microorganism is detected by metatranscriptomic NGS, specific diagnosis (PCR and serology) will be done in maternal and neonatal samples (blood, urine, saliva)

Interventions

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Metatranscriptomic

Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling

Intervention Type BIOLOGICAL

Specific microbiologic diagnosis

If a microorganism is detected by metatranscriptomic NGS, specific diagnosis (PCR and serology) will be done in maternal and neonatal samples (blood, urine, saliva)

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Pathogen Discovery Laboratory

UNKNOWN

Sponsor Role collaborator

Institut Pasteur

INDUSTRY

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marianne LERUEZ-VILLE, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Yves Ville, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Hopital Necker - Enfants malades

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Jacques FOURGEAUD, PharmD

Role: CONTACT

01 44 49 56 11

Aminata TRAORE

Role: CONTACT

01 48 19 27 34

Facility Contacts

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Laurence BUISSIERES, PhD

Role: primary

01 44 49 43 26

References

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Sebire NJ, Bianco D, Snijders RJ, Zuckerman M, Nicolaides KH. Increased fetal nuchal translucency thickness at 10-14 weeks: is screening for maternal-fetal infection necessary? Br J Obstet Gynaecol. 1997 Feb;104(2):212-5. doi: 10.1111/j.1471-0528.1997.tb11047.x.

Reference Type BACKGROUND
PMID: 9070141 (View on PubMed)

Faure-Bardon V, Fourgeaud J, Guilleminot T, Magny JF, Salomon LJ, Bernard JP, Leruez-Ville M, Ville Y. First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS. Ultrasound Obstet Gynecol. 2021 Apr;57(4):568-572. doi: 10.1002/uog.23608. Epub 2021 Mar 9.

Reference Type BACKGROUND
PMID: 33533526 (View on PubMed)

Regnault B, Bigot T, Ma L, Perot P, Temmam S, Eloit M. Deep Impact of Random Amplification and Library Construction Methods on Viral Metagenomics Results. Viruses. 2021 Feb 7;13(2):253. doi: 10.3390/v13020253.

Reference Type BACKGROUND
PMID: 33562285 (View on PubMed)

Bilardo CM, Timmerman E, Pajkrt E, van Maarle M. Increased nuchal translucency in euploid fetuses--what should we be telling the parents? Prenat Diagn. 2010 Feb;30(2):93-102. doi: 10.1002/pd.2396.

Reference Type BACKGROUND
PMID: 20077440 (View on PubMed)

Other Identifiers

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APHP211328

Identifier Type: -

Identifier Source: org_study_id

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