Current State and Innovations in Newborn Screening: Continuing to Do Good and Avoid Harm.
Giancarlo la MarcaRachel S CarlingStuart J MoatRaquel YahyaouiEnzo RanieriJames R BonhamPeter C J I SchielenPublished in: International journal of neonatal screening (2023)
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.
Keyphrases
- tandem mass spectrometry
- ultra high performance liquid chromatography
- artificial intelligence
- simultaneous determination
- public health
- machine learning
- high performance liquid chromatography
- liquid chromatography
- big data
- gas chromatography
- high resolution
- deep learning
- high resolution mass spectrometry
- escherichia coli
- solid phase extraction
- human health
- type diabetes
- dna methylation
- mass spectrometry
- copy number
- metabolic syndrome
- climate change
- cystic fibrosis
- pseudomonas aeruginosa
- adipose tissue