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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 5 of 19

THE EVOLUTION OF NEWBORN BLOODSPOT SCREENING TECHNOLOGIES IN
AUSTRALIA
NBS in the tandem mass spectrometry (tMS) age included screening for conditions of amino acid, organic
acid, and fatty acid oxidation metabolism, with Australia being a leader among international tMS
programs . The era of tMS was perhaps the first time when well-established screening principles had been
[32]
challenged, with the possibility of adding a myriad of conditions (pathogenic and non-pathogenic) onto the
NBS panel with a negligible increase in the cost of case finding.

The pitfalls of “counting of conditions” in newborn bloodspot screening programs
The naming and counting of conditions on NBS panels varies between programs nationally and
internationally. This is related to a range of factors, including the nomenclature used to identify conditions
and the emergence of systems that count screened tMS analytes versus identified conditions. This has led to
varying perceptions of how many conditions were being screened within each program and questionable
comparisons between programs as to “best practice” [32-38] [Figure 1].

Australian programs continue to focus on conditions that are medically actionable. For instance, while
ornithine transcarbamylase (OTC) deficiency, an X-linked urea cycle disorder, is included in international
routine NBS panels, the fact that males with the condition often present and require urgent treatment
within the first days of life (before DBS samples can be collected and analysed), precluding this as an
[39]
actionable condition to be screened for with Australian NBS programs . To set Australian NBS programs
within the scope of international best practice, the HGSA has provided recommendations on how disorders
[1]
are classified [Table 1] . These recommendations are consistent with requests by the Australian rare disease
community, which advocates for meaningful and consistent patient- and family-centred terms and
language, rather than a focus on “counting of conditions” to guide best practice.

Incorporating genetics within existing newborn bloodspot screening programs
Beyond tMS, first-tier genetic testing for selected monogenic conditions has been recommended for
national incorporation into Australian NBS programs since July 2022, after the successful state-wide
implementation of pilot programs for SMA and primary immunodeficiencies in New South Wales (NSW)
and the Australian Capital Territory (ACT).

The effectiveness of NBS, however, goes beyond the availability of an accurate test. Regardless of the ability
of genetic testing to identify at-risk newborns, the success of screening for a particular condition remains
intricately linked with processes for diagnosis and healthcare delivery. This is evidenced by the Australian
experience of integration of NBS for SMA into current healthcare systems [Figure 2]. Here, the co-
development of an efficient referral pathway and model of care has been imperative to facilitate equitable
SMA diagnosis and optimise opportunities for early intervention, specialist, and social care to mitigate
health inequities due to financial, geographical, cultural, or linguistic barriers .
[28]
Lessons learnt from the recent NBS for SMA program include challenges with delays in establishing an
evidence base for NBS in rare conditions and developing the infrastructure on a state-by-state basis to
incorporate genetic first-tier screening within existing NBS services. These challenges have led to current
disparities in diagnostic and therapeutic interventions between newborns across Australia [45,46] . Babies born
in NSW/ACT since July 2022 have been screened for SMA through NBS, while other states and territories
are at various stages of implementing this screening. This experience has underlined the importance of
horizon scanning for emergent therapies for rare conditions (a key factor in the Ministerial decision to
recommend screening for SMA), so that the future expansion of Australian NBS programs is better
coordinated with the availability of new therapies that are safe, effective and cost-effective [25,47] .