NCT03964441: AnddiPrenatome

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

Completed Last updated 3 February 2026

What this trial tests

trial testing Invasive fetal sampling, blood sampling of mother and father in Prenatal in 149 participants. Completed in 25 January 2024.

Timeline

20 June 2019

Primary endpoint
20 December 2021

25 January 2024

Quick facts

Lead sponsor	Centre Hospitalier Universitaire Dijon
Status	Completed
Study type	OBSERVATIONAL
Enrollment	149
Start date	20 June 2019
Primary completion	20 December 2021
Estimated completion	25 January 2024
Sites	1 location across France

Drugs / interventions tested

• Invasive fetal sampling, blood sampling of mother and father — full drug profile →
• blood sampling from the mother to recover the circulating cell free fetal DNA — full drug profile →
• Parent interviews (optional organizational study)
• parent questionnaire (optional organizational study)
• professional interviews (optional organizational study)
• Focus group for professionals (optional organizational study)

Conditions studied

• Prenatal — all drugs for Prenatal →
• Genome-wide High Throughput Sequencing — all drugs for Genome-wide High Throughput Sequencing →

Sponsor

Centre Hospitalier Universitaire Dijon

Who can join

18 and older, female only, with Prenatal or Genome-wide High Throughput Sequencing. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool.
   Tran Mau-Them F, Delanne J, Denommé-Pichon AS, Safraou H, et al · · 2023 · cited 18× · PMID 37035737 · DOI 10.3389/fgene.2023.1099995
2. Reanalysis of unsolved prenatal exome sequencing for structural defects: diagnostic yield and contribution of postnatal/postmortem features.
   Thauvin-Robinet C, Garde A, Favier M, Delanne J, et al · · 2025 · cited 3× · PMID 40186013 · DOI 10.1038/s41431-025-01823-y
3. Gain-of-function MYCN causes a megalencephaly-polydactyly syndrome manifesting mirror phenotypes of Feingold syndrome.
   Nishio Y, Kato K, Tran Mau-Them F, Futagawa H, et al · · 2023 · cited 3× · PMID 37710961 · DOI 10.1016/j.xhgg.2023.100238