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| Name | Class |
|---|---|
| Pathogen Discovery Laboratory | UNKNOWN |
| Institut Pasteur | INDUSTRY |
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
| |
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metatranscriptomic | Biological | Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | At inclusion, 11-14 weeks of pregnancy |
| Measure | Description | Time Frame |
|---|---|---|
| Miscarriage | Comparison in group 1 of the proportion of miscarriageaccording to the presence or not of a microorganism in the trophoblast. | at termination of pregnancy (assessed up to 7 months) |
| intrauterine death |
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Inclusion Criteria:
Exclusion Criteria
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Pregnant women consulting in the prenatal diagnosis Unit of the University Hospital Necker-Enfants-malades
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| Name | Affiliation | Role |
|---|---|---|
| Marianne LERUEZ-VILLE, MD, PhD | Assistance Publique - Hôpitaux de Paris | Study Director |
| Yves Ville, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Necker - Enfants malades | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9070141 | Background | 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. | |
| 33533526 | Background | 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. |
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| Specific microbiologic diagnosis | 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) |
|
Comparison in group 1 of the proportion of intrauterine death according to the presence or not of a microorganism in the trophoblast.
| 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. | 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. | at delivery |
| birth weight | Comparison in group 1 of birth weight, according to the presence or not of a microorganism in the trophoblast. | 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 | 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 | 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 | 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 | 3 days after birth |
| 33562285 | Background | 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. |
| 20077440 | Background | 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. |