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Adding genomic testing to newborn screening programs can expand them to cover hundreds of conditions and is getting closer to reality with multiple pilot studies internationally publishing early results.
Australian newborns have been screened for rare conditions since the mid-1960s, with over 99% of 300,000 Australian babies now tested for 32 conditions each year. Newborn screening is highly effective. But it is struggling to keep pace with the rapid growth of precision treatments that are now available for hundreds of severe, early-onset rare conditions. Screening for these conditions gives us the opportunity to intervene early, potentially preventing critical illness, death and disability.
Adding genomic sequencing to newborn screening programs can quickly add hundreds of new conditions, using a single assay across a range of disease areas, not just those with readily available biochemical markers. While genomic newborn screening (gNBS) has been discussed for over 20 years, falling sequencing costs and growing testing capacity have brought the concept closer to reality. Many governments worldwide are investing in large-scale research projects to investigate the role of genomics in preventative healthcare, including in newborns. Some have gone as far as announcing ambitious plans to make genomic newborn screening standard within the decade.
Does the evidence support implementation?
Over the past 12 months, we have seen the publication of early results from several gNBS studies, now totalling over 10,000 newborns. This includes the GUARDIAN and Early Check studies from the USA, the BabyDetect study from Belgium and now our BabyScreen+ study in Victoria. The study enrolled 1,000 newborns and performed genome sequencing using existing NBS cards, looking for 605 early-onset, severe but treatable rare conditions. Results were available within 13 days on average. Sixteen babies received a diagnosis. Standard newborn screening, which proceeded in parallel, only identified one of these. The clinical impacts of the results ranged from giving preventative advice such as avoiding certain foods and medications in G6PD deficiency through to prompt bone marrow transplant in a baby with a severe immunodeficiency.
Given the early stage of the research, one of the key questions was that of feasibility. Ideally gNBS would leverage existing sample collection infrastructure without the need for additional samples. However, extracting sufficient high-quality DNA from newborn screening (Guthrie) cards is technically challenging. While we found the DNA extraction process needed optimisation, ultimately only 3% of samples required recollection, which supports adding genomic sequencing to existing processes without the need for substantial redesign of the sample collection pathway. From a technical perspective, gNBS would also require very high volumes of DNA samples to be sequenced and analysed, with a relatively quick turnaround time as many of the conditions screened require intervention in the first weeks of life. We delivered gNBS results within 13 days on average, which compares favourably with standard NBS; however, this was not anywhere near at the scale and pace that would be required for a national rollout to 300,000 newborns each year. Many questions about feasibility and scalability of the laboratory component therefore remain.
Parents of newborns enrolled in the study generally reported they found the decision to have gNBS easy to make and supported future public funding. We delivered education about gNBS using an online decision support tool in the third trimester of pregnancy, with parents objectively demonstrating good understanding of key concepts and knowledge retention. However, given the relatively small size of the study, it is likely to have attracted those enthusiastic about research and new technologies. We saw an over-representation of parents with higher levels of education and under-representation of those who speak a language other than English at home. As we consider scaling up, it will be important to address issues of equity, both in terms of access to the screening test itself, as well as access to downstream clinical pathways.
What’s next for genomic newborn screening in Australia?
These early results from us and from others internationally are certainly promising. However, gNBS is undeniably both complex and costly, and many unresolved issues remain including absence of data on long-term outcomes and cost-effectiveness. The scale of the practical challenges ahead is daunting. If we commit to exploring this as a public health program, we will require substantial investment in sequencing and computing infrastructure as well workforce expansion to provide high quality test interpretation, manage the results, support families and provide downstream healthcare across a wide range of rare conditions. We will also need to achieve national consistency and make sure Australian babies and families benefit equitably, including those from Indigenous and other traditionally disadvantaged communities.
In addition to the practical challenges, ethical issues surrounding consent models, data storage, privacy and reuse will need to be resolved by trialling out different solutions and carefully assessing the associated benefits and risks. Realistically, it will take another 10 years of carefully planned and executed large-scale research nationally and internationally before genomic newborn screening could be incorporated into standard public health programs. Australia needs to plan for this future. Engaging proactively with the transformative potential of population genomic screening across all life stages now requires us to move beyond pilot studies and into evidence generation at scale, within our own healthcare system and for the benefit of our own diverse populations.
Professor Zornitza Stark is a clinical geneticist at the Victorian Clinical Genetics Services, Murdoch Children’s Research Institute and professor at the Department of Paediatrics, University of Melbourne.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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