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The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism

The expansion of the recommend uniform screening panel to include more than 50 primary and secondary target conditions has resulted in a substantial increase of false positive results. As an alternative to subjective manipulation of cutoff values and overutilization of molecular testing, here we des...

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Autores principales: Gavrilov, Dimitar K., Piazza, Amy L., Pino, Gisele, Turgeon, Coleman, Matern, Dietrich, Oglesbee, Devin, Raymond, Kimiyo, Tortorelli, Silvia, Rinaldo, Piero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423003/
https://www.ncbi.nlm.nih.gov/pubmed/33073028
http://dx.doi.org/10.3390/ijns6020033
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author Gavrilov, Dimitar K.
Piazza, Amy L.
Pino, Gisele
Turgeon, Coleman
Matern, Dietrich
Oglesbee, Devin
Raymond, Kimiyo
Tortorelli, Silvia
Rinaldo, Piero
author_facet Gavrilov, Dimitar K.
Piazza, Amy L.
Pino, Gisele
Turgeon, Coleman
Matern, Dietrich
Oglesbee, Devin
Raymond, Kimiyo
Tortorelli, Silvia
Rinaldo, Piero
author_sort Gavrilov, Dimitar K.
collection PubMed
description The expansion of the recommend uniform screening panel to include more than 50 primary and secondary target conditions has resulted in a substantial increase of false positive results. As an alternative to subjective manipulation of cutoff values and overutilization of molecular testing, here we describe the performance outcome of an algorithm for disorders of methionine, cobalamin, and propionate metabolism that includes: (1) first tier screening inclusive of the broadest available spectrum of markers measured by tandem mass spectrometry; (2) integration of all results into a score of likelihood of disease for each target condition calculated by post-analytical interpretive tools created byCollaborative Laboratory Integrated Reports (CLIR), a multivariate pattern recognition software; and (3) further evaluation of abnormal scores by a second tier test measuring homocysteine, methylmalonic acid, and methylcitric acid. This approach can consistently reduce false positive rates to a <0.01% level, which is the threshold of precision newborn screening. We postulate that broader adoption of this algorithm could lead to substantial savings in health care expenditures. More importantly, it could prevent the stress and anxiety experienced by many families when faced with an abnormal newborn screening result that is later resolved as a false positive outcome.
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spelling pubmed-74230032020-10-15 The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism Gavrilov, Dimitar K. Piazza, Amy L. Pino, Gisele Turgeon, Coleman Matern, Dietrich Oglesbee, Devin Raymond, Kimiyo Tortorelli, Silvia Rinaldo, Piero Int J Neonatal Screen Article The expansion of the recommend uniform screening panel to include more than 50 primary and secondary target conditions has resulted in a substantial increase of false positive results. As an alternative to subjective manipulation of cutoff values and overutilization of molecular testing, here we describe the performance outcome of an algorithm for disorders of methionine, cobalamin, and propionate metabolism that includes: (1) first tier screening inclusive of the broadest available spectrum of markers measured by tandem mass spectrometry; (2) integration of all results into a score of likelihood of disease for each target condition calculated by post-analytical interpretive tools created byCollaborative Laboratory Integrated Reports (CLIR), a multivariate pattern recognition software; and (3) further evaluation of abnormal scores by a second tier test measuring homocysteine, methylmalonic acid, and methylcitric acid. This approach can consistently reduce false positive rates to a <0.01% level, which is the threshold of precision newborn screening. We postulate that broader adoption of this algorithm could lead to substantial savings in health care expenditures. More importantly, it could prevent the stress and anxiety experienced by many families when faced with an abnormal newborn screening result that is later resolved as a false positive outcome. MDPI 2020-04-10 /pmc/articles/PMC7423003/ /pubmed/33073028 http://dx.doi.org/10.3390/ijns6020033 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gavrilov, Dimitar K.
Piazza, Amy L.
Pino, Gisele
Turgeon, Coleman
Matern, Dietrich
Oglesbee, Devin
Raymond, Kimiyo
Tortorelli, Silvia
Rinaldo, Piero
The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title_full The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title_fullStr The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title_full_unstemmed The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title_short The Combined Impact of CLIR Post-Analytical Tools and Second Tier Testing on the Performance of Newborn Screening for Disorders of Propionate, Methionine, and Cobalamin Metabolism
title_sort combined impact of clir post-analytical tools and second tier testing on the performance of newborn screening for disorders of propionate, methionine, and cobalamin metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423003/
https://www.ncbi.nlm.nih.gov/pubmed/33073028
http://dx.doi.org/10.3390/ijns6020033
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