Current State and Innovations in Newborn Screening: Continuing to Do Good and Avoid Harm International Journal of Neonatal Screening
Abstract In 1963, Robert Guthrie’s pioneering work developing a bacterial inhibition assay to measure phenylalanine in dried blood spots, provided the means for whole-population screening to detect phenylketonuria in the USA. In the following decades, NBS became firmly established as a part of public health in developed countries. Technological advances allowed for the addition of new disorders into routine programmes and thereby resulted in a paradigm shift. Today, technological advances in immunological methods, tandem mass spectrometry, PCR techniques, DNA sequencing for mutational variant analysis, ultra-high performance liquid chromatography (UPLC), iso-electric focusing, and digital microfluidics are employed in the NBS laboratory to detect more than 60 disorders. In this review, we will provide the current state of methodological advances that have been introduced into NBS. Particularly, ‘second-tier’ methods have significantly improved both the specificity and sensitivity of testing. We will also present how proteomic and metabolomic techniques can potentially improve screening strategies to reduce the number of false-positive results and improve the prediction of pathogenicity. Additionally, we discuss the application of complex, multiparameter statistical procedures that use large datasets and statistical algorithms to improve the predictive outcomes of tests. Future developments, utilizing genomic techniques, are also likely to play an increasingly important role, possibly combined with artificial intelligence (AI)-driven software. We will consider the balance required to harness the potential of these new advances whilst maintaining the benefits and reducing the risks for harm associated with all screening. Keywords: neonatal screening, next-generation sequencing, biochemical analysis, SCID screening, cystic fibrosis screening, proteomics, metabolomics, quality control, 2nd-tier testing, NGS in NBS
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Giancarlo la Marca, Rachel S Carling, Stuart J Moat et al.. Current State and Innovations in Newborn Screening: Continuing to Do Good and Avoid Harm. International Journal of Neonatal Screening. (2023). https://doi.org/10.3390/ijns9010015 Giancarlo la Marca, Rachel S Carling, Stuart J Moat, Raquel Yahyaoui, Enzo Ranieri, James R Bonham, Peter C J I Schielen
1Newborn Screening, Clinical Chemistry and Pharmacology Lab, IRCCS Meyer Children’s University Hospital, 50139 Florence, Italy 2Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy 3Biochemical Sciences, Viapath, Guys & St Thomas’ NHSFT, London SE1 7EH, UK 4GKT School of Medical Education, Kings College London, London SE1 1UL, UK 5Department of Medical Biochemistry, Immunology & Toxicology, University Hospital Wales, Cardiff CF14 4XW, UK 6School of Medicine, Cardiff University, University Hospital Wales, Cardiff CF14 4XW, UK 7Laboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, Málaga Regional University Hospital, Institute of Biomedical Research in Malaga (IBIMA-Plataforma BIONAND), Avenida Arroyo de los Angeles s/n, 29011 Malaga, Spain 8Biochemical Genetics, Genetics and Molecular Pathology, SA Pathology, Women’s & Children’s Hospital, Adelaide 5043, Australia 9Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK 10International Society for Neonatal Screening, Reigerskamp 273, 3607 HP Stichtse Vecht, The Netherlands 