Increased Nuchal Translucency in the First Trimester of Pregnancy
Conditions
Keywords
nuchal translucency, metatranscriptomic, next generation sequencing, metagenomic, trophoblast, high throughput sequencing
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.
Interventions
DIAGNOSTIC_TESTSpecific 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)
BIOLOGICALMetatranscriptomic
Analysis with metatranscriptomic next generation sequencing of trophoblast obtained by chorionic villi sampling
Sponsors
Assistance Publique - Hôpitaux de Paris
Pathogen Discovery Laboratory
Institut Pasteur
URC-CIC Paris Descartes Necker Cochin
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| birth weight | at delivery | Comparison in group 1 of birth weight, 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 maternal samples | at inclusion | Amplification by real time PCR of the microorganism identified by metatranscriptomic NGS in maternal blood, urine, saliva and amniotic fluid if available |
| Detection of the microorganism identified by metatranscriptomic NGS by conventional diagnostic method in neonatal samples | 3 days after birth | Amplification by real time PCR of the microorganism identified by metatranscriptomic NGS in neonatal blood, urine, saliva |
Countries
France
Contacts
STUDY_DIRECTORMarianne LERUEZ-VILLE, MD, PhD
Assistance Publique - Hôpitaux de Paris
PRINCIPAL_INVESTIGATORYves Ville, MD, PhD
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed