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

Rachel S Carling; Catharine John; Philippa Goddard; Caroline Griffith; Simon Cowen; Christopher Hopley; Stuart J Moat

doi:10.3390/ijns6040092

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

Int J Neonatal Screen. 2020 Nov 19;6(4):92. doi: 10.3390/ijns6040092.

Authors

Rachel S Carling^{1

2}, Catharine John¹, Philippa Goddard³, Caroline Griffith⁴, Simon Cowen⁵, Christopher Hopley⁵, Stuart J Moat^{6

7}

Affiliations

¹ Biochemical Sciences, Viapath, Guys & St Thomas' NHSFT, London SE1 7EH, UK.
² GKT School Medical Education, Kings College London, London SE1 1UL, UK.
³ Newborn Screening & Biochemical Genetics, Birmingham Children's Hospital, Birmingham B4, UK.
⁴ Specialist Laboratory Medicine, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK.
⁵ LGC, Teddington, Middlesex TW11 0LY, UK.
⁶ Department of Medical Biochemistry, Immunology & Toxicology, University Hospital Wales, Cardiff CF14 4XW, UK.
⁷ School of Medicine, Cardiff University, University Hospital Wales, Cardiff CF14 4XW, UK.

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: dried blood spots; expanded screening; flow injection analysis tandem mass spectrometry; inter-laboratory variation; internal calibration; isotope dilution.