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Page 2 of 6 Tsipouras et al. Rare Dis Orphan Drugs J 2023;2:17 https://dx.doi.org/10.20517/rdodj.2023.15

[3]
dietary intervention prevents serious mental deficiency . In the past fifty years, mandated NBS has
expanded to include other, mostly Mendelian, diseases where early therapeutic intervention has been
effective in preventing and/or ameliorating irreversible tissue damage. In many countries, states, and
regions of the world, public health programs are in place to collect blood specimens from babies soon after
birth . Analytes extracted from dried blood spots collected on filter paper are assayed using gas
[4]
chromatography/mass spectrometry (GC/MS) or tandem MS.

A second layer of screening based on Next-Generation Sequencing (NGS) technology could expand the
[5,6]
scope of the existing NBS programs . This additional layer of screening will not replace what is currently
used, but it will increase the current offering substantially to include a broader spectrum of disorders not
detectable by tandem MS.

Newborn genome sequencing could evolve to become the new paradigm for healthcare delivery, where early
detection could result in better clinical outcomes. Rapid Whole Genome Sequencing (rWGS) has been
shown to be an effective diagnostic test linked to decreased infant mortality and improved outcomes in
babies admitted to Neonatal Intensive Care Units (NICU) .
[7,8]
Extending the use of genome sequencing as a screening test to all newborns is only a matter of time.
However, before newborn genome screening is widely adopted, several factors will need to be carefully
considered, including:

1. Accurate definition of pathogenic genomic variants in diverse populations.

2. Defined care paths for the follow-up of a screen-positive finding.

3. Evidence that early intervention leads to improved clinical outcomes.

4. Detailed cost analysis.

Persuasive answers to the above will be required by the key stakeholders whose support is essential, i.e.,
parents, health care providers, public health policymakers, and the pharmaceutical industry.

Several newborn genome screening (including whole genome sequencing and whole exome sequencing)
initiatives have been launched, or they will be launched soon [9-11] .

We anticipate that no one project will have the necessary solutions to satisfactorily address all or some of
the above-mentioned problems. Thus, aggregation of information collected from different sources could
provide part of the solution for critical mass and momentum.

Data aggregation of such magnitude presents significant legal, ethical, and technical challenges related to (i)
the security and privacy of sensitive information; (ii) the size and varied nature of stored genomic data; and
(iii) legal requirements for data sharing. A viable near- and mid-term solution that can help address these
issues will be using trusted research environments (TREs) and data federation for secure storage, access, and
analysis of genomic data . A comparison of risks and benefits between existing and federated databases for
[12]
genomic data is shown in Table 1.