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Current state and innovations in newborn screening: continuing to do good and avoid harm

la Marca, Giancarlo, Carling, Rachel. S., Moat, Stuart. J., Yahyaoui, Raquel, Ranieri, Enzo, Bonham, James. R. and Schielen, Peter. C. J. I. 2023. Current state and innovations in newborn screening: continuing to do good and avoid harm. International Journal of Neonatal Screening 9 (1) , 15. 10.3390/ijns9010015

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: MDPI
Date of First Compliant Deposit: 6 April 2023
Date of Acceptance: 13 March 2023
Last Modified: 17 May 2023 08:27

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