Increased Nuchal Translucency in the First Trimester of PregnancyMETAHCNNCT05388968
Metatranscriptomic Next Generation Sequencing in First Trimester Trophoblast With Increased Fetal Nuchal Translucency (METAHCN)
An observational study of Increased Nuchal Translucency in the First Trimester of Pregnancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Increased Nuchal Translucency in the First Trimester of Pregnancy
- What is being tested?
- Metatranscriptomic and Specific microbiologic diagnosis
- How many people
- 78 participants
- Where
- 1 siteFrance
- Study dates
- 7 Nov 2022to 30 Sep 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Pregnant women consulting in the prenatal diagnosis Unit of the University Hospital Necker-Enfants-malades
Who may be able to join
- 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
Who cannot join
- Age <18 years
- no health insurance
- difficulties in understanding the French language
- chronic infection (HIV, HBV, HVC and HTLV-1)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pathogen Detection by Metatranscriptomic Next Generation Sequencing in the Trophoblast Collected in Women Carrying a Fetus With Increasing Nuchal Translucency in the First Trimester of Pregnancy
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.
Read the 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.
- Being tested
- Metatranscriptomic, Specific microbiologic diagnosis
- Keywords
- nuchal translucency, metatranscriptomic, next generation sequencing, metagenomic, trophoblast, high throughput sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetatranscriptomicBiological
Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling
Specific microbiologic diagnosisDiagnostic 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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Metatranscriptomic; Diagnostic Test: Specific microbiologic diagnosis | |
| 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. Receives: Biological: Metatranscriptomic; Diagnostic Test: Specific microbiologic diagnosis | |
| 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 Receives: Biological: Metatranscriptomic; Diagnostic Test: Specific microbiologic diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
microorganisms (viruses, bacteria, or parasites) in trophoblast samples
Identification by metatranscriptomic NGS, from women carrying a fetus with nuchal translucency (group 1) and in controls (group 2 and 3)
Measured: At inclusion, 11-14 weeks of pregnancy
Secondary outcomes (9)
Miscarriage
Comparison in group 1 of the proportion of miscarriageaccording to the presence or not of a microorganism in the trophoblast.
Measured: at termination of pregnancy (assessed up to 7 months)
intrauterine death
Comparison in group 1 of the proportion of intrauterine death according to the presence or not of a microorganism in the trophoblast.
Measured: at termination of pregnancy (assessed up to 7 months)
fetal abnormalities
Comparison in group 1 of the proportion of fetal abnormalities, according to the presence or not of a microorganism in the trophoblast.
Measured: at delivery
Gestational age
Comparison in group 1 of gestational age at birth, according to the presence or not of a microorganism in the trophoblast.
Measured: at delivery
birth weight
Comparison in group 1 of birth weight, according to the presence or not of a microorganism in the trophoblast.
Measured: at delivery
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
Amplification by real time PCR of the microorganism identified by metatranscriptomic NGS in maternal blood, urine, saliva and amniotic fluid if available
Measured: at inclusion
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
specific serology to identify a maternal primary infection with the microorganism detected by metatranscriptomic NGS
Measured: at inclusion
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
Amplification by real time PCR of the microorganism identified by metatranscriptomic NGS in neonatal blood, urine, saliva
Measured: 3 days after birth
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
specific serology to identify a maternal primary infection with the microorganism detected by metatranscriptomic NGS
Measured: 3 days after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2022
- Study start7 Nov 2022
- Primary completion3 Apr 2025
- Study completion30 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Increased Nuchal Translucency in the First Trimester of PregnancyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Pathogen Discovery Laboratory, Institut Pasteur, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Marianne LERUEZ-VILLE, MD, PhD, Study director, Assistance Publique - Hôpitaux de ParisYves Ville, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05388968
- Sponsor's protocol ID
- APHP211328
- Acronym
- METAHCN
- Status last verified
- Jun 2026
- First submitted
- 2 May 2022
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 9070141Faure-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.
PubMed 33533526Regnault 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.
PubMed 33562285Bilardo 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.
PubMed 20077440
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogen Detection by Metatranscriptomic Next Generation Sequencing in the Trophoblast Collected in Women Carrying a Fetus With Increasing Nuchal Translucency in the First Trimester of Pregnancy
- ClinicalTrials.gov ID
- NCT05388968
- Acronym / sponsor ID
- METAHCN / APHP211328
- Keywords
- nuchal translucency, metatranscriptomic, next generation sequencing, metagenomic, trophoblast, high throughput sequencing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Pathogen Discovery Laboratory, Institut Pasteur, URC-CIC Paris Descartes Necker Cochin
- Study start
- 7 Nov 2022 (actual)
- Primary completion
- 3 Apr 2025 (actual)
- Study completion
- 30 Sep 2025 (actual)
- First posted
- 24 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nuchal translucency with no genetic abnormalities | – | Biological: Metatranscriptomic, Diagnostic Test: Specific microbiologic diagnosisPregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency > 3.5 mm and no genetic abnormalities with array CGH. |
| Nuchal translucency with genetic abnormalities | – | Biological: Metatranscriptomic, Diagnostic Test: Specific microbiologic diagnosisPregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency > 3.5 mm and a genetic abnormalities at array CGH. |
| Genetic abnormalities | – | Biological: Metatranscriptomic, Diagnostic Test: Specific microbiologic diagnosisPregnant women between 11 and 14 weeks with a fetus showing a nuchal translucency < 3.5 mm and a suspicion of genetic abnormalities |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women consulting in the prenatal diagnosis Unit of the University Hospital Necker-Enfants-malades
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- Age <18 years
- no health insurance
- difficulties in understanding the French language
- chronic infection (HIV, HBV, HVC and HTLV-1)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetatranscriptomicAnalysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling | Biological | Genetic abnormalities, Nuchal translucency with genetic abnormalities, Nuchal translucency with no genetic abnormalities |
| Specific microbiologic diagnosisIf a microorganism is detected by metatranscriptomic NGS, specific diagnosis (PCR and serology) will be done in maternal and neonatal samples (blood, urine, saliva) | Diagnostic test | Genetic abnormalities, Nuchal translucency with genetic abnormalities, Nuchal translucency with no genetic abnormalities |
Primary outcome
microorganisms (viruses, bacteria, or parasites) in trophoblast samples
Time frame: 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)
9 secondary outcomes
Miscarriage
Time frame: at termination of pregnancy (assessed up to 7 months)
intrauterine death
Time frame: at termination of pregnancy (assessed up to 7 months)
fetal abnormalities
Time frame: at delivery
Gestational age
Time frame: at delivery
birth weight
Time frame: at delivery
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
Time frame: at inclusion
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
Time frame: at inclusion
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
Time frame: 3 days after birth
Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
Time frame: 3 days after birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Background: PubMed 9070141Sebire 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.
- Background: PubMed 33533526Faure-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.
- Background: PubMed 33562285Regnault 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.
- Background: PubMed 20077440Bilardo 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marianne LERUEZ-VILLE, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
Yves Ville, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Increased Nuchal Translucency in the First Trimester of Pregnancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
microorganisms (viruses, bacteria, or parasites) in trophoblast samples (time frame: At inclusion, 11-14 weeks of pregnancy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05388968, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.