Transitioning from laboratory-developed tests to a single commercial reagent kit in a national newborn screening program: impact on analytical performance and harmonization
Carling, Rachel S Barclay, Zoe J Ward, Sophie C Appleton, Marie Barski, Robert Benn, Harry Chambers, Kelly Coakley, Paul Kemp, Helena Crabbe, Nicola
Carling, Rachel S
Barclay, Zoe J
Ward, Sophie C
Appleton, Marie
Barski, Robert
Benn, Harry
Chambers, Kelly
Coakley, Paul
Kemp, Helena
Crabbe, Nicola
Abstract
Newborn screening in England is a national program with laboratories adhering to common screening algorithms. Until recently, screening for inherited metabolic disorders was provided by ten laboratories using laboratory-developed tests (LDTs) and three using commercial assays: harmonization of results proved challenging. Introduction of hereditary tyrosinemia type 1 screening meant LDTs required modification to include the measurement of succinylacetone, and subsequent re-validation. This provided an opportunity to implement a single commercial reagent kit in all laboratories. It was anticipated that this would improve analytical performance and harmonization. This study aimed to determine whether these goals were achieved. Verification across the 13 laboratories revealed that the commercial kit reduced inter-laboratory variation for all analytes demonstrating improved harmonization. However, this was achieved by applying instrument-specific correction factors to all analytes, the magnitude of which were significant, indicating a lack of standardization. Performance of succinylacetone was limited by instrument-dependent background interference from the methionine stable isotope label, underscoring the need to establish evidence-based screening cut-off values (COV) rather than adopting published thresholds. This study emphasizes the need for traceable reference materials to improve laboratory quality and the value of screening outcome data.
MIDER Authors
Affiliations
Date
2026-06-09
Type
Article
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Citation
Carling RS, Barclay ZJ, Ward SC, Appleton M, Barski R, Benn H, Chambers K, Coakley P, Kemp H, Crabbe N, Dowden S, Greenfield T, Hogg SL, Hussein S, Marr R, Parkes O, Powell D, Ramgoolam T, Ssali J, Taj N, Wright K, Wu THY, Bonham JR. Transitioning from Laboratory-Developed Tests to a Single Commercial Reagent Kit in a National Newborn Screening Program: Impact on Analytical Performance and Harmonization. Int J Neonatal Screen. 2026 Jun 9;12(2):41. doi: 10.3390/ijns12020041.