Clinical trial NCT05388968: Metatranscriptomic Next Generation Sequencing in First Trimester Trophoblast With Increased Fetal Nuchal Translucency (METAHCN)
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Increased Nuchal Translucency in the First Trimester of Pregnancy
Keywords: nuchal translucency
metatranscriptomic
next generation sequencing
metagenomic
trophoblast
high throughput sequencing
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Pathogen Discovery Laboratory
name: Institut Pasteur
First posted: 2022-05-24
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women consulting in the prenatal diagnosis Unit of the University Hospital Necker-Enfants-malades

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.

Eligibility 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)

Primary outcomes:
measure: microorganisms (viruses, bacteria, or parasites) in trophoblast samples
timeFrame: At inclusion, 11-14 weeks of pregnancy
Secondary outcomes:
measure: Miscarriage
timeFrame: at termination of pregnancy (assessed up to 7 months)
measure: intrauterine death
timeFrame: at termination of pregnancy (assessed up to 7 months)
measure: fetal abnormalities
timeFrame: at delivery
measure: Gestational age
timeFrame: at delivery
measure: birth weight
timeFrame: at delivery
measure: Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
timeFrame: at inclusion
measure: Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in maternal samples
timeFrame: at inclusion
measure: Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
timeFrame: 3 days after birth
measure: Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples
timeFrame: 3 days after birth
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Necker - Enfants malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marianne LERUEZ-VILLE, MD, PhD
role: STUDY_DIRECTOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Yves Ville, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.