Evaluation of a Common Internal Standard Material to Reduce Inter-Laboratory Variation and Ensure the Quality, Safety and Efficacy of Expanded Newborn Screening Results When Using Flow Injection Analysis Tandem Mass Spectrometry with Internal Calibration
Open Access
- 19 November 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Neonatal Screening
- Vol. 6 (4), 92
- https://doi.org/10.3390/ijns6040092
Abstract
In 2015, the newborn screening (NBS) programmes in England and Wales were expanded to include four additional disorders: Classical Homocystinuria, Isovaleric Acidemia, Glutaric Aciduria Type 1 and Maple Syrup Urine Disease, bringing the total number of analytes quantified to eight: phenylalanine, tyrosine, leucine, methionine, isovalerylcarnitine, glutarylcarnitine, octanoylcarnitine and decanoylcarnitine. Post-implementation, population data monitoring showed that inter-laboratory variation was greater than expected, with 90th centiles varying from 17% to 59%. We evaluated the effect of stable isotope internal standard (IS) used for quantitation on inter-laboratory variation. Four laboratories analysed routine screening samples (n > 101,820) using a common IS. Inter-laboratory variation was determined for the eight analytes and compared with results obtained using an in-house common IS (n > 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p < 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory “calibration factors”. For screening programmes where laboratories adhere to single analyte cut-off values (COVs), it is important that inter-laboratory variation is minimised, primarily to prevent false positive results. Whilst the use of a common IS helps achieve this, it is evident that instrument set-up also contributes to inter-laboratory variation.Keywords
This publication has 6 references indexed in Scilit:
- Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with phenylketonuriaJournal of Inherited Metabolic Disease, 2019
- The Importance of Assay Imprecision near the Screen Cutoff for Newborn Screening of Lysosomal Storage DiseasesInternational Journal of Neonatal Screening, 2019
- Effect of Dried Blood Spot Quality on Newborn Screening Analyte Concentrations and Recommendations for Minimum Acceptance Criteria for Sample AnalysisClinical Chemistry, 2016
- Enhanced interpretation of newborn screening results without analyte cutoff valuesGenetics in Medicine, 2012
- The Horwitz Ratio (HorRat): A Useful Index of Method Performance with Respect to PrecisionJournal of AOAC International, 2006