Clinical trial NCT04308603: Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
Official title: Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops Fetalis by Massively Parallel Sequencing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Immune Hydrops Fetalis
Keywords: Non-immune hydrops fetalis
Multicentric prospective study
Next Generation Sequencing
Panel
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2020-03-16
Enrollment: 71
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: A fetal hydrops, also called a fetal anasarca, is the buildup of fluid in the serosa and / or fetal subcutaneous tissue. The diagnosis is made by ultrasound, possibly from the first trimester of pregnancy.

The etiologies of hydrops can be immune or non-immune. The historically classic immune causes are linked to fetal-maternal alloimmunizations in erythrocyte blood groups. The implementation of systematic prevention of these anti rhesus immunizations since the 1970s has significantly reduced the incidence of immune hydrops Non-immune hydrops (NIH) now represent 90% of fetal hydrops. Known causes of NIH can be classified in several ways depending on the mechanism or organ involved.

The prognosis for NIH is closely linked to the cause. Fetal anemia due to maternal-fetal infections can heal spontaneously or give rise to in utero transfusions. Cardiac rhythm abnormalities are accessible to medical treatment. Chylothorax compressions may benefit from in utero drainage, but chromosomal or metabolic causes cannot benefit from antenatal care. The term of pregnancy in which the hydrops is discovered also has an impact on survival, which however remains poor.

In France, certain pathologies can be considered as particularly serious without the possibility of treatment and give rise to a request for medical termination of pregnancy. This possibility is subject to acceptance by two practitioners who are members of a multidisciplinary prenatal diagnostic center (CPDPN). This preliminary multidisciplinary reflection participates in the development of prenatal counseling with the greatest precision in diagnostic hypotheses. This prenatal advice is essential for a couple on the decision to make a pregnancy in progress but also for future pregnancies, given the 25% risk of recurrence due to the autosomal recessive mode of transmission.

Thus the current screening strategy for inherited metabolic diseases on amniotic fluid is fragmented. The resulting subdiagnosis explains the objective of the study of using the new high throughput sequencing techniques (NGS) in this indication. This approach should make it possible to reduce the number of cases classified as idiopathic, to allow the parents concerned to receive suitable genetic counseling with a view to new pregnancies, and to refine the knowledge of the prenatal epidemiology of these pathologies.


Eligibility criteria: Inclusion Criteria:

* patient\> 18 years old
* Single Pregnancy
* Progressive pregnancy greater than 11 weeks: Fetal death in utero in a fetus previously known to be a carrier of non Immun Hydrops (NIH) is not an exclusion criterion.
* Presence of an ultrasound defined as follows and confirmed by a multidisciplinary prenatal diagnostic center CPDPN:
* Before 14 weeks: Generalized subcutaneous edema descending to the abdomen, associated or not with peri-visceral effusion
* After 14 weeks: presence of at least 2 of the following criteria: ascites, pleural effusion, pericardial effusion, subcutaneous edema, placental edema, hydramnios.
* Persistent hygroma after 14 weeks of amenorrhea
* Persistent isolated perivisceral effusions without etiologies found
* Patient having an invasive diagnostic sample (amniocentesis)
* Social insured in France
* Patient who signed the informed consent of the study

Exclusion Criteria:

* NIH whose diagnosis is known and confirmed as non-metabolic by a CPDPN
* Non-progressive pregnancy with Fetal Death in utero with normal previous ultrasound monitoring
* Refusal of invasive diagnostic sampling
* Patient under legal protection measure

Primary outcomes:
measure: Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis
timeFrame: during pregnancy after the 14th week of amenorrhea
Secondary outcomes:
measure: Comparison of percentage of etiology detected between the NGS technique and the biochemical technique.
timeFrame: during pregnancy after the 14th week of amenorrhea
measure: time to return the results in days of NGS techniques
timeFrame: during pregnancy after the 14th week of amenorrhea
measure: number of technical failure of these new tools of NGS techniques
timeFrame: during pregnancy after the 14th week of amenorrhea
measure: Number of cases where the interpretation of the genetic variants did not lead to a conclusion
timeFrame: during pregnancy after the 14th week of amenorrhea
measure: number of week of amenorrhea of gestation
timeFrame: immediately after the child birth
measure: issue of the pregnancy
timeFrame: immediately after the child birth
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU Besançon
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Clermont-Ferrand
country: France
facility: Hôpital d'Estaing
city: Dijon
country: France
facility: Hôpital Le Bocage
city: La Tronche
country: France
facility: CHU Grenoble
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Hopital Croix Rousse
city: Marseille
country: France
facility: Hopital Nord
city: Marseille
country: France
facility: CHU Marseille Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Nice
country: France
facility: Hôpital Archet 2
city: Paris
country: France
facility: APHP Trousseau
city: Pierre-Bénite
country: France
facility: Hopital Lyon Sud
city: Saint-Priest-en-Jarez
country: France
facility: CHU Saint Etienne
city: Toulouse
country: France
facility: Hôpital Paule de Viguier;
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Nancy Brabois,
Study officials:
References: