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Bros-Facer et al. Rare Dis Orphan Drugs J 2023;2:21 https://dx.doi.org/10.20517/rdodj.2023.26 Page 3 of 14

METHODS
A web-based survey, using the free online Survey Monkey platform, was developed by several members of a
dedicated working group on NBS set up by IRDiRC to gather information about newborn sequencing
initiatives in Europe that are using NGS as a first-tier test. NGS approaches include whole-exome
sequencing (WES), whole-genome sequencing (WGS), and/or classic NGS gene panels. First-tier NGS test
was defined as the first test to be used for screening newborns for a list of early-onset, severe, and treatable
genetic conditions. The survey contained 57 questions inquiring about different aspects of each initiative,
including study design and methodology, testing technology, confirmatory testing, test validation, data
analysis and follow-up, cost-effectiveness, and vision for the future. The full questionnaire can be found in
supplementary materials. A link to the online survey was disseminated via email and responses were
analyzed qualitatively. Several of the initiatives requested that their data remain anonymous as they are still
in the planning phase and have yet to secure funding for their studies. Therefore, for the purposes of this
article, the identity of some of the initiatives is not presented and only aggregated results are presented to
preserve confidentiality.

Initially, we planned to distribute the survey to the lead and co-lead investigators of 17 NBS initiatives in
Europe in April and May 2023. However, prior to survey distribution, we learned that three of the selected
initiatives did not use (or plan to use) NGS for NBS as a first-tier test. Thus, the total number of surveys
distributed by email was 14. The IRDiRC NBS working group was asked to compile a list of European NGS-
based NBS initiatives and surveys were distributed accordingly via email. It is important to note that our
survey pool does not represent a comprehensive landscape review, and that caution should be exercised
with regard to the interpretation of survey results.

RESULTS
General information
Respondents
All surveys were completed and returned with one respondent per initiative. Twelve respondents provided
the name of their initiatives: Baby Detect, FirstSteps, Genome-wide Screening Pilot Study (GSP Study),
Generation Study, GenNatal, NGSf4NBS, Neonatal genomic screening: feasibility, expectations, definition
of the diagnostic pathway, and public health implications, PeriGenoMed, PROGETTO GENOMA PUGLIA,
Responsible Implementation of Newborn Genome Screening (RINGS), Screen4Care and Shifting
Perspective on scReening for Inborn errors of immunity with Neonatal Genetics (SPRING). All initiatives
were considered research pilot projects focused on the technical feasibility of selected NGS approaches (i.e.,
WES, WGS, and/or classic gene panels) in NBS as a first-tier test and are or will be carried out in parallel to
the existing NBS programs.

Most laboratories participating in this survey were genetic (6), followed by NBS (3), clinical (2), and
immunological (1). Two initiatives were part of a government organization. Six initiatives are ongoing or
about to start enrollment, while the remaining eight are still in a preparatory phase. One initiative had
concluded the first part of a two-stage study at the time of writing (manuscript in preparation). Several
aspects of the research pilots are either yet to be fully defined or subject to change with study progression.

Regional breakdown and catchment/scope
Apart from one pan-European research study with two pilot trials planned in Germany and Italy (i.e.,
multi-national), all other initiatives are focused within one European country and include three initiatives in