Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing

NCT04308603 | Completed

• 2 other identifiers: 69HCL19_05012019-A02338-49
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 17

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.

Conditions

Non-Immune Hydrops Fetalis

Keywords

Non-immune hydrops fetalis; Multicentric prospective study; Next Generation Sequencing; Panel

Outcome Measures

Primary Outcomes (1)

• Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops by Next Generation Sequencing (NGS) analysis

  Proportion of fetuses for which a genetic anomaly responsible for antenatal revelation Non Immun Hydrops can be detected by Next Generation Sequencing (NGS) analysis of the gene panel incriminated in inherited metabolic malformation compared to the proportion of fetuses for which a genetic anomaly has been identified by the technique current standard biochemical.

  during pregnancy after the 14th week of amenorrhea

Secondary Outcomes (6)

• Comparison of percentage of etiology detected between the NGS technique and the biochemical technique.

  during pregnancy after the 14th week of amenorrhea

• time to return the results in days of NGS techniques

  during pregnancy after the 14th week of amenorrhea

• number of technical failure of these new tools of NGS techniques

  during pregnancy after the 14th week of amenorrhea

• Number of cases where the interpretation of the genetic variants did not lead to a conclusion

  during pregnancy after the 14th week of amenorrhea

• number of week of amenorrhea of gestation

  immediately after the child birth

Study Arms (1)

pregnant patient whose fetuses have an antenatal NIH

EXPERIMENTAL

All pregnant patients whose fetuses have an antenatal revelation of NIH from the first trimester ultrasound scan will be included in this study.

Diagnostic Test: NON-IMMUNE HYDROPS FETALIS diagnosis

Interventions

NON-IMMUNE HYDROPS FETALIS diagnosis DIAGNOSTIC_TEST

Amniotic liquid of each selected patients will be tested by both technic to describe and detect etiological information. Each patient will be tested using the current procedure with a defined panel of genes as well as with the NGS procedure. The results of both procedures will be compared.

pregnant patient whose fetuses have an antenatal NIH

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patient\> 18 years old
• Single Pregnancy
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (17)

CHU Besançon

Besançon, 25000 Besancon, France

Location

CHU Pellegrin

Bordeaux, 33076, France

Location

Hôpital Femme Mère Enfant

Bron, 69500, France

Location

Hôpital d'Estaing

Clermont-Ferrand, 63003, France

Location

Hôpital Le Bocage

Dijon, 21079, France

Location

CHU Grenoble

La Tronche, 38700, France

Location

CHU Limoges

Limoges, 87042, France

Location

Hopital Croix Rousse

Lyon, 69004, France

Location

Hopital Nord

Marseille, 13000, France

Location

CHU Marseille Timone

Marseille, 13005, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Hôpital Archet 2

Nice, 06200, France

Location

APHP Trousseau

Paris, 75012, France

Location

Hopital Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Hôpital Paule de Viguier;

Toulouse, 31059, France

Location

CHU de Nancy Brabois,

Vandœuvre-lès-Nancy, 54511, France

Location

MeSH Terms

Conditions

Hydrops Fetalis

Condition Hierarchy (Ancestors)

Erythroblastosis, Fetal; Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; alpha-Thalassemia; Thalassemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Immune System Diseases; Edema; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 16, 2020
• Study Start: April 12, 2021
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (17)