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Ji et al. Rare Dis Orphan Drugs J 2023;2:26 https://dx.doi.org/10.20517/rdodj.2023.30 Page 11 of 19

information beyond their clinical results. Interestingly, parents of infants younger than three months were
the least likely to request additional findings, and a significant proportion changed their decision regarding
[73]
information disclosure over the study period . This lower uptake by parents of young infants has been
replicated across other studies and poses a potential and substantial barrier when using gNBS to expand
current NBS programs .
[74]
Alternative models for the delivery of genetic information, such as using gNBS data as a “lifetime
repository” to be accessed at relevant time points in an individual’s life, merit consideration. However, with
such an approach, we must also consider the ongoing relevance and consistency in the interpretation of
genetic variants and population health literacy and the ability to allocate resources for the management of
this “lifetime resource” [58,65] . The cost and infrastructure required for routine storage of newborn data also
need to be considered.

While there is intra- and interjurisdictional debate on which conditions are amenable, useful, and feasible
for gNBS, Australian stakeholders are striving to develop pathways in which conditions can be efficiently
considered for incorporation into routine panels, based on the merits of screening for each condition. One
existing mechanism to promote the utility of genomic sequencing is PanelApp, deployed by Australian
Genomics in 2019. This crowdsourced, publicly available knowledge-generating platform was developed to
facilitate the sharing and evaluation of gene panels, contributing toward national and international efforts to
establish standards of gene selection and consensus on genotype-phenotype relationships . Further efforts
[75]
to curate appropriate gene panels for NBS include Baby Screen +, with the proposed research criteria for
condition selection including analytical and clinical validity and clinical utility (disease onset exclusively or
predominantly in childhood (before five years of age), disease severity, and diseases with an effective
treatment available that alters the natural history of the disease). Nongenetic functional assays are
considered desirable, serving to confirm the expected phenotype and probability of symptom manifestation
[76]
and reduce uncertainties associated with genes of incomplete penetrance . Knowledge from international
studies and other screening strategies such as RGCS will also inform gene selection curation, noting that
[57]
the suitability for inclusion may vary between program objectives.
Capacity building for a potential new model of newborn bloodspot screening
Capacity building will be integral to shaping a health system that is able to sustainably offer and manage
increased genomic information arising from potential new models of NBS. This will include but is not
limited to follow-up clinical and genetic services, public and family engagement and education to optimise
genomic health literacy. Although paediatric tertiary services are situated in over half of Australian states,
areas such as Tasmania and the Northern Territory rely on interstate mutual healthcare agreements for the
management of children who require access to specialist genetic and clinical services. Thus, ratifying and
strengthening referral pathways is essential so that no child falls through the gap of an evolving NBS
program. This should include access to specialist services and coordinated management in the community.

Underpinning these needs is the imperative to engage stakeholders from genomics, NBS, rare diseases,
health system, and health policy, as well as the broader community. Links between these groups should be
embedded both within and between states, nationally and internationally, so that Australia can move in line
with the international pace of change, embed new technologies of (newborn) screening in a health system
that is ready to receive it and can overcome the obstacles that are common globally while acknowledging the
uniqueness of Australia’s health system.