{ "abstract": "Introduction Newborn bloodspot screening (NBS) is freely and universally available to babies born in Australia, with nearly 300 000 newborns screened each year. The NBS programme screens for approximately 30 conditions; however, there are hundreds of childhood conditions that could be treated if identified earlier and asymptomatically. Contemporary screening platforms have relied on mass spectrometry-based technologies, limiting surveillance to conditions with validated biomarkers detectable within the neonatal period. Advancements in metabolic techniques and genomics have expanded the range of conditions that could be detected. The NewbornsInSA research study will develop, validate and evaluate a novel multi-omic model of newborn screening, integrating metabolomic and genomic newborn screening as complementary methodologies.Methods Parents can opt in to additional NBS through NewbornsInSA during pregnancy or shortly after birth. One thousand prospectively recruited families will be offered genomic NBS by whole-genome sequencing, including analysis of a virtual gene panel of over 600 genes, and concurrent metabolomic screening. Clinically actionable pathogenic or likely pathogenic genetic variants will be reported to parents and whole genome sequencing data will be available on request for diagnostic reanalysis, if required later in life.Acceptability of the NewbornsInSA programme will be evaluated through stakeholder engagement activities with healthcare professionals, members of the public and patient advocacy groups. Family experiences will be assessed using online surveys. The diagnostic yield, accuracy and the costs and consequences of the multi-omic NBS model will be assessed by comparison to standard-of-care NBS.NewbornsInSA will investigate the acceptability, feasibility and cost-effectiveness of a multi-omic newborn screening model in a prospectively recruited South Australian population. We hypothesise that this approach will increase the number of conditions identified, reduce the time to diagnosis and facilitate earlier care with better outcomes for newborns with genetic conditions.Ethics and dissemination This research study has been ethically approved by the Women’s and Children’s Health Network Human Research Ethics Committee (2022/HRE00258 and 2023/HRE00236). Findings will be disseminated through peer-reviewed publication and conferences.", "authors": [ { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia" ], "name": "Lucy Anastasi" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia" ], "name": "Ayesha Chowdhury" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "South Australia Neonatal Screening Centre, SA Pathology at Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Alex Ashenden" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "South Australia Neonatal Screening Centre, SA Pathology at Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Tomas Rozek" }, { "affiliations": [ "South Australian Health and Medical Research Institute Limited, Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Jennie Louise" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "South Australia Neonatal Screening Centre, SA Pathology at Women’s and Children’s Hospital, North Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Khoa Lam" }, { "affiliations": [ "Paediatric and Reproductive Genetics Unit, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Stephanie Skinner" }, { "affiliations": [ "Paediatric and Reproductive Genetics Unit, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Kirsty Stallard" }, { "affiliations": [ "AHTA, School of Public Health, University of Adelaide, Adelaide, South Australia, Australia", "Adelaide Health Technology Assessment (AHTA), The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Tracy Merlin" }, { "affiliations": [ "Adelaide Health Technology Assessment (AHTA), The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Camille Schubert" }, { "affiliations": [ "Adelaide Health Technology Assessment (AHTA), The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Arlene Vogan" }, { "affiliations": [ "Flinders Medical Centre, Bedford Park, South Australia, Australia" ], "name": "Scott Morris" }, { "affiliations": [ "Flinders University Institute for Mental Health and Wellbeing, Bedford Park, South Australia, Australia", "Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia" ], "name": "Sarah Cohen-Woods" }, { "affiliations": [ "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia", "Neurology and Clinical Neurophysiology, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Nicholas Smith" }, { "affiliations": [ "Sydney Children’s Hospital at Westmead, Sydney, New South Wales, Australia" ], "name": "Enzo Ranieri" }, { "affiliations": [ "Haematology and Oncology Clinic, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Benjamin Saxon" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia", "Centre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, University of South Australia, Adelaide, South Australia, Australia" ], "name": "Hamish S Scott" }, { "affiliations": [ "Metabolic Clinic, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Drago Bratkovic" }, { "affiliations": [ "Paediatric and Reproductive Genetics Unit, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia" ], "name": "Christopher P Barnett" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "South Australia Neonatal Screening Centre, SA Pathology at Women’s and Children’s Hospital, North Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Carol Wai-Kwan Siu" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia", "Allergy and Clinical Immunology, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia", "Immunology Directorate, SA Pathology, Adelaide, South Australia, Australia" ], "name": "Jovanka King" }, { "affiliations": [ "Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia", "Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia" ], "name": "Karin S Kassahn" } ], "title": "NewbornsInSA multi-omic newborn screening: protocol for a prospective cohort study", "uid": "f2b646a4-ff4c-5837-973f-a2c97585775e" }