A Pilot Study to Assess the Feasibility and Acceptability of Newborn Screening Using in Silico Panel-based Solo Genome Sequencing in France

NCT ID: NCT06875089

Last Updated: 2025-11-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 5000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-05-05
• Study Completion Date: 2031-07-31

Brief Summary

Newborn Screening (NBS) based on genome sequencing (GS) is currently the subject of particular attention at both European and international levels. Over the past three years, several publications have discussed the opportunities and challenges of using GS for NBS. To date, only two Chinese programs have published their results, the first on a series of 29,601 healthy newborns and the second on a series of 10,334 healthy newborns and 668 high-risk infants. Globally, more than twenty pilot projects are underway, although none has been initiated within the French context thus far. Across the different pilot projects, various study designs are used. Most have opted for a targeted GS-based analysis to screen for pediatric-onset diseases. Some projects focus solely on diseases for which effective drugs or interventions exist to prevent or reduce symptoms. In contrast, others offer parents the option to screen their newborns for diseases without current treatment options, but for which a treatment is underdevelopment, or with interest in early management, a choice exercised by most parents. Indeed, early diagnosis of these diseases can help to introduce treatments or interventions when they become available, to participate in research trials on new treatments and to receive early management and genetic counseling.

In France, the national NBS program has long been recognized worldwide for its organizational quality and comprehensiveness, although, until recently, it has one of the lowest numbers of diseases screened in Europe. As of mid-2024, the French NBS only includes 14 serious diseases. Recently, the French bioethics law has evolved to allow the use of genetic testing as a first-line procedure for NBS. At the same time, the development and efficiency of genomic techniques and the rapid increase in the number of treatable rare diseases (RDs) raise questions about the acceptability and relevance of these genomic methods for NBS and its possible extension. The extension of NBS to many RDs of early onset represents a real public health challenge as RDs, 80% of which are of genetic origin, account for 10% of deaths before the age of 5.

The FHU TRANSLAD has elaborated the PERIGENOMED Project, a large-scale project which aims to assess the relevance of pGS-NBS in France (analytical and clinical validity, clinical utility and psychosocial, ethical and organizational issues).

The pGS-NBS (also known as in silico panel-based GS, i.e. an analysis carried out entirely using informatic tools) consists of bioinformatics filtering steps that return only selected variants and/or rare variants from targeted genes issued from GS. So, even if the source data comes from the GS, it is possible to configure the pipeline to return only those variations known to be responsible for specific RDs.

the PERIGENOMED Project will be led in two steps. The first pilot step (PERIGENOMED-CLINICS 1 - PGC1 Study), presented in this protocol, aims to evaluate the feasibility and acceptability of pGS-NBS France. This pilot study plans to screen 2,500 newborns using pGS-NBS targeting two lists of genes (1 corresponding to genes variables responsible of treatable rare diseases, 2 including genes variation leading to actionable rare diseases). In both lists only RDs of early onset are considered. PGC1 study will be carried in 5 healthcare centers in France, with results expected to be returned to clinicians within less than 4 weeks. It will also provide an understanding of the optimal information and analytical pathways, and the possible organizational repercussions of pGS-NBS as well as a first insight about the validity of the pGS-NBS and about the clinical course of newborns screened positive and with a confirmed RD Two studies in humanities and social sciences (HSS) will also be linked to PGC1 Study. The first will focus on the reasons given by decliners and on the medical and socio-economic characteristics (at the individual and contextual level) of decliners versus participants. The second will assess the psychosocial impact of result disclosure on families of positive newborns, comparatively of negative ones.

These initial results will provide the first outcomes before the launch of a second larger phase PERIGENOMED-CLINICS 2 (PGC2 Study - 22,000 newborns), designed for studying the implementation of such pGS-NBS in routine on a regional level.

Conditions

Newborn Screening Programmes for Rare Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

No participants

future families not taking part in the pGS- NBS study

Satisfaction questionnaire

Intervention Type: OTHER

questionnaire on information process of parents informed about pGS-NBS

interview with HSS researcher

Intervention Type: OTHER

interview with a member of the HSS team on reasons for declining /accepting pGS-NBS

Participants

future families who take part the pGS-NBS

pGS-NBS

Intervention Type: GENETIC

Collection of a second DBS card if the parents accept the pGS-NBS for their newborn

Satisfaction questionnaire

Intervention Type: OTHER

questionnaire on information process of parents informed about pGS-NBS

interview with HSS researcher

Intervention Type: OTHER

interview with a member of the HSS team on reasons for declining /accepting pGS-NBS

satisfaction questionnaire

Intervention Type: OTHER

questionnaire on results delivery in parents having accepted the pGS-NBS

Qualitative and quantitative longitudinal exploration

Intervention Type: OTHER

validated anxiety and depression scales to assess the psychosocial impact and perceived utility for families whose child screened negative among which 30 families will be interviewed. Interviews and validated anxiety and depression scales will be suggested to all families receiving positive screening results

Medical follow up

Intervention Type: OTHER

follow-up of true positives and false negatives based on medical records (vital status, care pathways) until 5 years after results delivery

Interventions

pGS-NBS

Collection of a second DBS card if the parents accept the pGS-NBS for their newborn

Intervention Type: GENETIC

Satisfaction questionnaire

questionnaire on information process of parents informed about pGS-NBS

Intervention Type: OTHER

interview with HSS researcher

interview with a member of the HSS team on reasons for declining /accepting pGS-NBS

Intervention Type: OTHER

satisfaction questionnaire

questionnaire on results delivery in parents having accepted the pGS-NBS

Intervention Type: OTHER

Qualitative and quantitative longitudinal exploration

validated anxiety and depression scales to assess the psychosocial impact and perceived utility for families whose child screened negative among which 30 families will be interviewed. Interviews and validated anxiety and depression scales will be suggested to all families receiving positive screening results

Intervention Type: OTHER

Medical follow up

follow-up of true positives and false negatives based on medical records (vital status, care pathways) until 5 years after results delivery

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

For satisfaction study about the information & identification of determinants of acceptability :

• All future parents approached for whom the unborn child will be cared for in the participating maternity unit
• At least one parent/legal guardian who received information about the study
• Future parents/legal guardian who do not object to the use of their data
• Parent(s) or legal guardian(s) affiliated to a social security system or beneficiaries of such a system

For pGS-NBS :

• All babies born in one of the participating centers or born by chance outside the maternity but whom care will be carried out in the participating center
• Newborn who are less than 28 days at the date of the collection of PGC1 blotting paper

• At least one biological parent who received information about the study
• Parent(s) or legal guardian(s) who do not object to "conventional" NBS
• At least one parent/legal guardian able to provide consent for testing the infant
• Informed consent signed by at least one parent/legal guardian
• Agreement of the second parent/legal guardian for testing the infant (unless he is unknown or loss of contact) obtained from the first parent/legal guardian if his written informed consent has not been obtained
• Parent(s) or legal guardian(s) affiliated to a social security system or beneficiaries of such a system

• Babies born under anonymous birth according to the French law, known as "nés sous X"

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU d'Angers

Angers, , France

Site Status: NOT_YET_RECRUITING

CHU Besançon

Besançon, , France

Site Status: NOT_YET_RECRUITING

CHU Dijon Bourgogne

Dijon, , France

Site Status: RECRUITING

CHU Hôtel Dieu

Nantes, , France

Site Status: NOT_YET_RECRUITING

CHU Rennes - Hôpital Sud

Rennes, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Laurence OLIVIER-FAIVRE

Role: CONTACT

laurence.faivre@chu-dijon.fr

0380295313 ext. +33

Facility Contacts

Estelle COLIN

Role: primary

escolin@chu-angers.fr

0241353470 ext. +33

Nicolas MOTTET

Role: primary

N1mottet@chubesancon.fr

0381218505 ext. +33

Laurence OLIVIER-FAIVRE

Role: primary

laurence.faivre@chu-dijon.fr

0380295313 ext. +33

Sandra MERCIER

Role: primary

sandra.mercier@chu-nantes.fr

0240083245 ext. +33

Laurent PASQUIER

Role: primary

laurent.pasquier@chu-rennes.fr

0299266744 ext. +33

References

Level C, Thauvin-Robinet C, Binquet C, Duffourd Y, Davoine E, Chevarin M, Tran-Mau-Them F, Lemaitre M, Bruel AL, Safraou H, Salvi D, Tisserant E, Lecommandeur E, Charreton A, Hassine A, de Tayrac M, Redon R, Barc J, Schmitt S, Piard J, Kuentz P, Cormier C, Malbos M, Racine C, Chabrol B, Cheillan D, Tardy V, Colin E, Bris C, Mercier S, Nizon M, Gaudillat L, Loizeau V, Lenelle C, Mottet N, Simon E, Arnoux JB, Carpentier M, Renaud C, Ziegler A, Lejeune C, Jannot AS, Asensio ML, Rollier P, Odent S, Bezieau S, Pasquier L, Huet F, Faivre L. PERIGENOMED-CLINICS 1-the first study on feasibility, acceptability and psychosocial impact of PERIGENOMED: a pilot project aimed at providing initial concrete evidence on the relevance of panel-based genome sequencing for newborn screening (NBS) in France. BMJ Open. 2025 Oct 23;15(10):e105752. doi: 10.1136/bmjopen-2025-105752.

Reference Type: DERIVED

PMID: 41130699 (View on PubMed)

Other Identifiers

OLIVIER FAIVRE AFM 2023

Identifier Type: -

Identifier Source: org_study_id