Antenatal Investigation of Fetuses With Complex Congenital Heart Defects Using multiOMICS

NCT ID: NCT06705543

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2026-12-31

Brief Summary

This study will use multiOMICS study on fetuses with complexe congenital heart defects (CHD) to identify etiological epigenetic factors of these cardiac malformations, related to environmental factors during pregnancy.

Detailed Description

Congenital heart defects (CHDs) are a very heterogeneous group of heart diseases in terms of embryonic mechanisms, phenotypes and aetiologies. In isolated forms, genetic causes are identified in only 19% of cases, linked to chromosomal abnormalities (8%) or gene variants (11%). Environmental causes such as infection, exposure to toxic substances or ingestion of teratogenic substances may also favour the onset of MCC. Although in the majority of cases the aetiology remains unknown, the discovery of MCC in the ante-natal period almost systematically leads to a genetic aetiological work-up using amniotic fluid for karyotype, Array-CGH and, more recently, exome analysis. With regard to environmental causes, recent data in the literature report a link between environmental exposures (occupational, extra-occupational or medicinal) and congenital anomalies.

Objectives: The low percentage of genetic abnormalities and toxic factors identified as causal in patients with non-syndromic CHD prompts a search for more complex causes such as epigenetic modifications linked to an interaction between genes and environmental factors.

Methods: The multi-omics study approach, using high-throughput sequencing technologies (exome, RNASeq, methylSeq), provides a wealth of information on cellular and/or tissue signaling pathways in response to exposure. Integrated analysis of transcriptomes and methylomes has demonstrated the occurrence of combined defects in gene expression and methylation following toxic exposure. The period of CHD formation during embryonic development prompts us to look for epigenetic modifications during prenatal period, as close as possible to the pathophysiological mechanisms leading to this malformation.

Expected results: the multi-omics analysis applied to fetuses with non-syndromic complex CHD, combined with the characterization of occupational and non-occupational environmental exposures, will enable us to extend the etiological search for these malformations, to identify biomarkers linked to the occurrence and severity of these malformations and gain a better understanding of the pathophysiological mechanisms linked to CHD.

In the longer term, this study will serve as a basis for large-scale studies to enable the development of prevention policies, based on exhaustive, multicenter cohorts. In addition, multi-omics studies could identify gene markers, by exome, transcriptome and/or methylome, which could then be studied in a targeted manner.

Conditions

Congenital Heart Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Congenital Heart Defects population

Group Type: ACTIVE_COMPARATOR

multi-omics genetic analyses included exome

Intervention Type: GENETIC

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit. These genetic analyses will include :

• Study of free RNA circulating in the LA,
• Methylome study.
• Trio exome study (parents-fetus).

control population

Group Type: PLACEBO_COMPARATOR

multi-omics genetic analyses

Intervention Type: GENETIC

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit; These genetic analyses will include :

• Study of free RNA circulating in the LA,
• Methylome study.

Interventions

multi-omics genetic analyses included exome

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit. These genetic analyses will include :

• Study of free RNA circulating in the LA,
• Methylome study.
• Trio exome study (parents-fetus).

Intervention Type: GENETIC

multi-omics genetic analyses

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit; These genetic analyses will include :

• Study of free RNA circulating in the LA,
• Methylome study.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

Fetuses with congenital heart disease :

• Pregnant women aged 18 and more
• Single foetal pregnancy in which the foetus has a complex non-syndromic congenital heart defect, with no identified chromosomal abnormality, gene syndrome or infection.
• Patient for whom the indication for amniocentesis has been accepted by the CPDPN and accepted by the couple/patient
• Gestational age between 20 and 28 weeks' gestation.
• Person affiliated to or benefiting from a social security scheme.
• Free, informed and express consent (confirmed in writing) (at the latest on the day of inclusion and before any examination required by the research).

Control Population for RNAseq and MéthlySeq

• Pregnant women aged 18 and more
• Patient in whom the indication for amniocentesis has been retained by the CPDPN and accepted by the couple/patient, for a non-malformative ultrasound anomaly (hyperechoic bowel, idiopathic hydramnios, increased risk of trisomy 21, agenesis of the OPN, suspected toxoplasmosis/CMV seroconversion), with no chromosomal anomaly, gene syndrome or infection identified.
• Gestational age between 20 and 28 weeks' gestation.
• Person affiliated to or benefiting from a social security scheme.
• Free, informed and express consent (confirmed in writing) (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria

For both populations (cases and controls) :

• Female minors,
• Patients not affiliated to the social security system,
• Patients who do not understand French,
• Patients under guardianship
• Multiple pregnancies, or where the foetus has associated malformations

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Caroline ROORYCK-THAMBO, PROF

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

CHU de Bordeaux

Bordeaux, , France

Site Status: RECRUITING

CHU de Nantes

Nantes, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Caroline ROORYCK-THAMBO, PROF

Role: CONTACT

caroline.rooryck-thambo@chu-bordeaux.fr

+335 56 79 59 81

Facility Contacts

Caroline ROORYCK-THAMBO, PROF

Role: primary

caroline.rooryck-thambo@chu-bordeaux.fr

Marie VINCENT, DR

Role: primary

0240087516

Other Identifiers

CHUBX 2024/30

Identifier Type: -

Identifier Source: org_study_id