ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis (AnddiPrenatome)

January 30, 2026 updated by: Centre Hospitalier Universitaire Dijon

Prenatal diagnosis of genetic diseases is a real medical challenge. The discovery of antenatal abnormalities on ultrasound is frequent (5 to 10% of pregnancies), and when an abnormalities is seen on ultrasound, it raises the possibility of an underlying developmental anomaly. Currently, in France, when abnormalities are discovered with an ultrasound scan, the etiological diagnosis is based on additional imaging tests (cerebral MRI, 3D bone tomography, fetal CT, fetal CT) or diagnostic tests such as invasive chorionic villus sampling, amniocentesis or fetal blood for infectious, metabolic, immunological and genetic investigations (standard karyotype, FISH (fluorescence in situ hybridization) for the rapid detection of aneuploidy, Chromosome Analysis on DNA Chip (ACPA or CGH-array) and possible sequencing of targeted genes when they are available within a time frame compatible with pregnancy). NIPT (Non-invasive prenatal testing) on cell free fetal DNA circulating in maternal blood has more limited indications, allowing, from an early stage of pregnancy, the determination of fetal sex and fetal rhesus factor and the search for aneuploidy.

However, establishing an etiological diagnosis during pregnancy has many benefits for the parents: clarifying the cause, obtaining a more precise prognosis to determine future management and outcome of the pregnancy, and establishing the risks of recurrence.

Over the past decade, medical genetics has undergone a real technological revolution, leading to the development of high throughput genome-wide, exome (ES) and genome (GS) sequencing. However, few countries have currently embarked on ES/GS in prenatal care, due to the constraints of time and the difficulty of interpreting genomic data when the clinical data is limited to antenatal imaging data.

In 2016, France launched the France Medicine Genomics 2025 Plan (PFMG2025) to deploy GS, particularly in the diagnosis of rare diseases. It is thus becoming essential to define the modalities of prescription of this testing, in particular during prenatal diagnosis. In parallel, from the first publications, the applications of genomic analysis on circulating fetal DNA seem to be able to extend to genome sequencing for research of SNVs responsible for developmental diseases.

The AnDDI-rares health network therefore proposes this ANDDI-PRENATOME pilot project to study the feasibility of a "rapid" analysis of ES in prenatal diagnosis from 61 fetuses with ultrasound abnormalities, as a first step before considering future cost-effectiveness (PRME) or care system performance (PREPS) studies in conjunction with the PFMG2025.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

149

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Dijon, France, 21079
        • CHU Dijon Bourgogne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Pregnant women with antenatal discovery of at least two obstetrical ultrasound abnormalities

Description

Inclusion Criteria:

  • Pregnant women with antenatal discovery of at least two obstetric ultrasound abnormalities (2 major malformations, or 1 major malformation and 1 minor malformation, or 1 isolated malformation with a high probability of a genetic condition) : who undergo invasive antenatal sampling for CGH-array diagnosis ; who has already had an invasive antenatal sampling for the diagnosis of CGH-array and for which the fetal CGH-array has been found to be normal (sufficient fetal DNA or amniotic fluid should be available to allow exome sequencing to be performed without further amniotic fluid puncture).
  • Pregnant woman and father aged 18 years or more
  • Written consent provided by the pregnant woman and the father of the fetus
  • Possibility of sufficient fetal specimen (amniotic fluid or fetal blood) to collect an additional sample for the pilot project
  • Possibility of sampling the pregnant woman and the father of the foetus (peripheral blood)
  • Pregnant woman and father of the fetus able to understand the study

Pilot Organizational Study:

In addition to the inclusion & exclusion criteria of the main study:

  • Pregnant woman and biological father of fetus who provided oral consent to be interviewed
  • Professionals (obstetrician, midwife, geneticist, biologist) agreeing to be interviewed

Exclusion Criteria:

  • Diagnostic hypothesis considered highly probable that can be confirmed by an available molecular or cytogenetic test with a lower cost than ES (e. g. 22q11 microdeletion) or high suspicion of fetal infection (e. g. toxoplamosis seroconversion)
  • Refusal of pregnant woman or father of fetus to participate in the study
  • Pregnancy earlier than 15 weeks of amenorrhea or later than 34 weeks of amenorrhea
  • Pregnant woman and father of the foetus not covered by the national health insurance system
  • Pregnant woman and/or father of the fetus under partial judicial protection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
control
fetus with at least 2 ultrasound abnormalities and both parents
Biological: Invasive fetal sampling, blood sampling of mother and father
to perform an exome sequencing analysis in trio
Other: Parent interviews (optional organizational study)
Interview with a sociologist or psychologist to explore perceptions of ES and the impact of the results, expectations regarding certain types of results not currently available, the emotional situation, and position regarding the continuation of the pregnancy At 4 different times: at inclusion, at the time of the CGA-array results, at the time of the ES results and at a distance from the ES results
Other: parent questionnaire (optional organizational study)
To evaluate the experience, perceptions, the impact of the analyses on the decision, satisfaction and concerns regarding the ES and its results, opinions on certain types of results not currently available, as well as anxiety and possible psychological distress At 4 different points in time: at inclusion, at the delivery of the CGA-array results, at the delivery of the ES results and at a distance from the delivery of the ES results
comparison
fetus with at least 2 ultrasound abnormalities with ES diagnosis on invasive fetal sampling
Biological: Invasive fetal sampling, blood sampling of mother and father
to perform an exome sequencing analysis in trio
Other: Parent interviews (optional organizational study)
Interview with a sociologist or psychologist to explore perceptions of ES and the impact of the results, expectations regarding certain types of results not currently available, the emotional situation, and position regarding the continuation of the pregnancy At 4 different times: at inclusion, at the time of the CGA-array results, at the time of the ES results and at a distance from the ES results
Other: parent questionnaire (optional organizational study)
To evaluate the experience, perceptions, the impact of the analyses on the decision, satisfaction and concerns regarding the ES and its results, opinions on certain types of results not currently available, as well as anxiety and possible psychological distress At 4 different points in time: at inclusion, at the delivery of the CGA-array results, at the delivery of the ES results and at a distance from the delivery of the ES results
Biological: blood sampling from the mother to recover the circulating cell free fetal DNA
to perform a sequencing analysis of the genome of circulating free fetal DNA
professional
obstetrician, midwife, geneticist, biologist
Other: professional interviews (optional organizational study)
interview to understand how the decision is formed
Other: Focus group for professionals (optional organizational study)
interview to specify whether variants of unknown significance) VUS will potentially be returned to the clinicians, or even to the patient via the clinician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time required to return ES results to patients and their families in a context prenatal diagnosis
Time Frame: Through study completion, an average of 12 months
Through study completion, an average of 12 months
number of discrepancies between ES and WGS
Time Frame: Through study completion, an average of 12 months
Through study completion, an average of 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Questionnaire to understand the expectations of couples and their a priori perception of ES
Time Frame: Through study completion, an average of 12 months
To define feelings and to know better how couples perceive ES and its implications and in particular the risk of discovery of VUS (variants of unknown significance) and ID (incidental data).
Through study completion, an average of 12 months
Questionnaire to evaluate the organization of health professionals involved in the decision-making process
Time Frame: Through study completion, an average of 12 months
Through study completion, an average of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire Dijon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2019

Primary Completion (Actual)

December 20, 2021

Study Completion (Actual)

January 25, 2024

Study Registration Dates

First Submitted

May 22, 2019

First Submitted That Met QC Criteria

May 22, 2019

First Posted (Actual)

May 28, 2019

Study Record Updates

Last Update Posted (Actual)

February 3, 2026

Last Update Submitted That Met QC Criteria

January 30, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • THAUVIN AnDDI rares 2018

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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