Current State and Innovations in Newborn Screening: Continuing to Do Good and Avoid Harm

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.

Future of Dutch NGS-Based Newborn Screening: Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy

“…Gained knowledge on these kind of variants can later be used to decide whether these variants should still be reported in NBS in the future. An interesting approach to further decreasing the number of FPs is to combine both biochemical and genetic techniques, usually with NGS as second tier, but also in a procedure where both NGS and biomarkers are used in a first-tier setting [ 27 , 28 , 29 ].…”

Prospects for Expansion of Universal Newborn Screening in Bulgaria: A Survey among Medical Professionals

“…Coupled with artificial intelligence, this creates a great window of opportunity for NBS [ 47 ]. Nevertheless, this anticipated development must be cautious and balanced in order to harness the potential of these new advances while maximizing the benefits and minimizing the risks of NBS activities [ 10 ]. Prior research must be conducted to determine and analyze the ethical, legal, organizational, and social repercussions [ 48 ].…”

“…Following the success of the first universal NBS for phenylketonuria in the 1960s, tests for other conditions were gradually added to NBS programs [ 8 , 9 , 10 ]. This expansion varied across different countries, depending on their healthcare systems and policy priorities, as well as the availability of human, physical, and financial resources [ 1 , 3 , 7 ].…”

A Metabolic Biomarker Panel for Congenital Heart Disease Assessment with Newborn Dried Blood Spots

“…Routine neonatal screening serves as a tool to identify diseases that could potentially impact a child's long-term health or survival. Each year, millions of infants in the United States undergo newborn screening (NBS), where substances in dried blood spots (DBS) are measured to check for certain genetic, endocrine, and metabolic disorders 19 . Early detection, diagnosis, and intervention can avert death or disability, enabling children to reach their full potential.…”