{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:20:38Z","timestamp":1781115638722,"version":"3.54.1"},"reference-count":9,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>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 &gt; 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 &gt; 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p &lt; 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory \u201ccalibration factors\u201d. 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.<\/jats:p>","DOI":"10.3390\/ijns6040092","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T10:46:26Z","timestamp":1605782786000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1988-3088","authenticated-orcid":false,"given":"Rachel S.","family":"Carling","sequence":"first","affiliation":[{"name":"Biochemical Sciences, Viapath, Guys &amp; St Thomas\u2019 NHSFT, London SE1 7EH, UK"},{"name":"GKT School Medical Education, Kings College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine","family":"John","sequence":"additional","affiliation":[{"name":"Biochemical Sciences, Viapath, Guys &amp; St Thomas\u2019 NHSFT, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Goddard","sequence":"additional","affiliation":[{"name":"Newborn Screening &amp; Biochemical Genetics, Birmingham Children\u2019s Hospital, Birmingham B4, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Griffith","sequence":"additional","affiliation":[{"name":"Specialist Laboratory Medicine, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Cowen","sequence":"additional","affiliation":[{"name":"LGC, Teddington, Middlesex TW11 0LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hopley","sequence":"additional","affiliation":[{"name":"LGC, Teddington, Middlesex TW11 0LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Moat","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Immunology &amp; Toxicology, University Hospital Wales, Cardiff CF14 4XW, UK"},{"name":"School of Medicine, Cardiff University, University Hospital Wales, Cardiff CF14 4XW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","unstructured":"NHS Newborn Blood Spot Screening Programme (2020, September 15). A Laboratory Guide to Newborn Blood Spot Screening for Inherited Metabolic Diseases, Available online: https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/642333\/IMD_laboratory_handbook_2017.pdf."},{"key":"ref_2","unstructured":"Association of Public Health Laboratories (2010, September 15). Overview of Cutoff Determinations and Risk Assessment Methods Used in Dried Blood Spot Newborn Screening-Role of Cutoffs and other Methods of Data Analysis. Available online: https:\/\/www.aphl.org\/programs\/newborn_screening\/Documents\/Overview%20on%20Cutoff%20Determinations%20and%20RIsk%20Assessment%20Methods_final.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Robinson, B., and Gelb, M. (2019). The importance of assay imprecision near the screen cutoff for newborn screening of lysosomal storage diseases. Int. J. Neonatal. Screen, 5.","DOI":"10.3390\/ijns5020017"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/gim.2012.2","article-title":"Enhanced interpretation of newborn screening results without analyte cutoff values","volume":"14","author":"Marquardt","year":"2012","journal-title":"Genet. Med."},{"key":"ref_5","unstructured":"Carling, R., and John, C. Personal communication."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1373\/clinchem.2015.247668","article-title":"Effect of dried blood spot quality on newborn screening analyte concentrations and recommendations for minimum acceptance criteria for sample analysis","volume":"62","author":"George","year":"2016","journal-title":"Clin. Chem."},{"key":"ref_7","unstructured":"Carling, R.S. Personal communication."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/jaoac\/89.4.1095","article-title":"The horwitz ratio (HorRat): A useful index of method performance with respect to precision","volume":"89","author":"Horwitz","year":"2006","journal-title":"J. AOAC Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/jimd.12163","article-title":"Performance of laboratory tests used to measure blood phenylalanine for the monitoring of patients with phenylketonuria","volume":"43","author":"Moat","year":"2019","journal-title":"J. Inherit. Metab. Dis."}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/92\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:34:26Z","timestamp":1760178866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/6\/4\/92"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":9,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijns6040092"],"URL":"https:\/\/doi.org\/10.3390\/ijns6040092","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]}}}