Bruce Bennetts^1
1The Children's Hospital at Westmead

Newborn Bloodspot Screening (NBS) is the only viable mechanism to ensure universal identification of newborns who need early treatment for rare health conditions. The TRAIL study is one of several Medical Research Futures Funds studies established to explore genomic newborn screening. 

Through six cohorts the TRAIL study will explore the themes of sensitivity and specificity; data security, scale; speed; and acceptability: workforce, population and public policy. What level of information families require to make informed decisions on genomic NBS is also being explored. We will undertake a needs assessment of nurses and midwives to understand their comfort level with consenting models, as well as their understand of genomic NBS

The main cohort are de-identified NBS cards, mixed with the NBS cards from consented patients with a known genetic diagnosis to assess the sensitivity of the TRAIL bioinformatics pipeline.  This also opens the potential for future analysis of WGS data, enabling rapid and efficient genetic diagnosis beyond the newborn period - potentially for life. 

In the last phase of the TRAIL study, we will undertake prospective recruitment of pregnant women, to test learnings from earlier cohorts to assess gNBS in a real-time piloted approach.

Zornitza Stark^1
1Victorian Clinical Genetics Services, Murdoch Children's Research Institute

Rare diseases are a leading cause of infant mortality and lifelong disability in high income countries. Incorporating genomic sequencing into newborn screening programs raises the prospect of being able to detect hundreds of early-onset, severe, but treatable genetic conditions at birth, potentially improving clinical outcomes, with genomic data stored to benefit health over lifetime and support further research. However, the challenges of implementing genomic newborn screening at scale are formidable, spanning technical, clinical and ethical aspects with the need for large, carefully designed studies to inform policy and practice. The BabyScreen+ pilot study  provided genomic newborn screening to a cohort of 1,000 Victorian infants for over 600 genetic conditions with the aim of determining the feasibility and acceptability of this approach. Testing was successfully completed for 95% of cases using dried bloodspot cards. The screen-positive rate was 1.6%, including treatable conditions that are not currently included in NBS. 99.5% of enrolled families believed genomic NBS should be universally available.

Karin S Kassahn^1,2, Lucy T Anastasi¹, Ayesha Chowdhury¹, Alex Ashenden³, Stephanie Skinner⁶,  Tomas Rozek³, Khoa Lam^2,3, Enzo Ranieri^3,4, Tracy Merlin⁵, Drago Bratkovic⁶, Ben Saxon⁶, Nicholas Smith⁶, Hamish Scott^1,2, Jennie Louise^2,7, Christopher Barnett^2,6, Carol Wai-Kwan Siu^2,3, Jovanka King^2,6,8
 

¹Department of Molecular Pathology, SA Pathology, Adelaide, SA 5000 Australia
²Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, SA 5000, Australia
³Department of Biochemical Genetics, SA Pathology, SA 5006, Australia
⁴Present address: Sydney Children’s Hospital at Westmead, Sydney NSW Australia
⁵School of Public Health, The University of Adelaide, SA 5000, Australia
⁶Women’s and Children’s Hospital, Adelaide, SA 5006, Australia
⁷Present address: South Australian Health and Medical Research Institute, SA 5000, Australia
⁸Immunology Directorate, SA Pathology, Adelaide, SA 5000, Australia
 

The NewbornsInSA research project explores a novel model of newborn screening by integrating metabolomic and genomic analyses into a multi-omics screen. Recruitment is conducted through health care professional referral or self-enrolment during pregnancy until shortly after birth. Complementing the metabolomic analyses, genomic newborn screening is performed by whole-genome sequencing with analysis and reporting restricted to a virtual panel of approximately 600 genes. Prospective recruitment for genomic newborn screening was first opened to families referred via health care professionals in the setting of post-natal complications, with an uptake of almost 50%. Broader recruitment directly from the general public is opening in late 2024, leveraging social media platforms, collection centres and birthing hospitals to distribute study information. This study provides examples of challenges faced in variant review and reporting in a genomic newborn screening context.