Enhanced interpretation of newborn screening results without analyte cutoff values

Gregg Marquardt, Robert Currier, David M S McHugh, Dimitar Gavrilov, Mark J. Magera, Dietrich Matern, Devin Oglesbee, Kimiyo Raymond, Piero Rinaldo, Emily H. Smith, Silvia Tortorelli, Coleman T. Turgeon, Fred Lorey, Bridget Wilcken, Veronica Wiley, Lawrence C. Greed, Barry Lewis, François Boemer, Roland Schoos, Sandrine MarieMarie Françoise Vincent, Yuri Cleverthon Sica, Mouseline Torquado Domingos, Khalid Al-Thihli, Graham Sinclair, Osama Y. Al-Dirbashi, Pranesh Chakraborty, Mark Dymerski, Cory Porter, Adrienne Manning, Margretta R. Seashore, Jonessy Quesada, Alejandra Reuben, Petr Chrastina, Petr Hornik, Iman Atef Mandour, Sahar Abdel Atty Sharaf, Olaf Bodamer, Bonifacio Dy, Jasmin Torres, Roberto Zori, David Cheillan, Christine Vianey-Saban, David Ludvigson, Adrya Stembridge, Jim Bonham, Melanie Downing, Yannis Dotsikas, Yannis L. Loukas, Vagelis Papakonstantinou, Georgios S A Zacharioudakis, Kos Baráth, Eszter Karg, Leifur Franzson, Jon J. Jonsson, Nancy N. Breen, Barbara G. Lesko, Stanton L. Berberich, Kimberley Turner, Margherita Ruoppolo, Emanuela Scolamiero, Italo Antonozzi, Claudia Carducci, Ubaldo Caruso, Michela Cassanello, Giancarlo La Marca, Elisabetta Pasquini, Iole Maria Di Gangi, Giuseppe Giordano, Marta Camilot, Francesca Teofoli, Shawn M. Manos, Colleen K. Peterson, Stephanie K. Mayfield Gibson, Darrin W. Sevier, Soo Youn Lee, Hyung Doo Park, Issam Khneisser, Phaidra Browning, Fizza Gulamali-Majid, Michael S. Watson, Roger B. Eaton, Inderneel Sahai, Consuelo Ruiz, Rosario Torres, Mary A. Seeterlin, Eleanor L. Stanley, Amy Hietala, Mark McCann, Carlene Campbell, Patrick V. Hopkins, Monique G. De Sain-Van Der Velden, Bert Elvers, Mark A. Morrissey, Sherlykutty Sunny, Detlef Knoll, Dianne Webster, Dianne M. Frazier, Julie D. McClure, David E. Sesser, Sharon A. Willis, Hugo Rocha, Laura Vilarinho, Catharine John, James Lim, S. Graham Caldwell, Kathy Tomashitis, Daisy E. Castĩeiras Ramos, Jose Angel Cocho De Juan, Inmaculada Rueda Fernández, Raquel Yahyaoui MacÍas, José María Egea-Mellado, Inmaculada González-Gallego, Carmen Delgado Pecellin, Maria Sierra García-Valdecasas Bermejo, Yin Hsiu Chien, Wuh Liang Hwu, Thomas Childs, Christine D. McKeever, Tijen Tanyalcin, Mahera Abdulrahman, Cecilia Queijo, Aída Lemes, Tim Davis, William Hoffman, Baker Mei, Gary L. Hoffman

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.

Original languageEnglish (US)
Pages (from-to)648-655
Number of pages8
JournalGenetics in Medicine
Volume14
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Tandem Mass Spectrometry
Reference Values
Differential Diagnosis
Fatty Acids
Software
Databases
Guidelines

Keywords

  • cutoff values
  • false-positive rate
  • inborn errors of metabolism
  • newborn screening
  • positive predictive value

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Marquardt, G., Currier, R., McHugh, D. M. S., Gavrilov, D., Magera, M. J., Matern, D., ... Hoffman, G. L. (2012). Enhanced interpretation of newborn screening results without analyte cutoff values. Genetics in Medicine, 14(7), 648-655. https://doi.org/10.1038/gim.2012.2

Enhanced interpretation of newborn screening results without analyte cutoff values. / Marquardt, Gregg; Currier, Robert; McHugh, David M S; Gavrilov, Dimitar; Magera, Mark J.; Matern, Dietrich; Oglesbee, Devin; Raymond, Kimiyo; Rinaldo, Piero; Smith, Emily H.; Tortorelli, Silvia; Turgeon, Coleman T.; Lorey, Fred; Wilcken, Bridget; Wiley, Veronica; Greed, Lawrence C.; Lewis, Barry; Boemer, François; Schoos, Roland; Marie, Sandrine; Vincent, Marie Françoise; Sica, Yuri Cleverthon; Domingos, Mouseline Torquado; Al-Thihli, Khalid; Sinclair, Graham; Al-Dirbashi, Osama Y.; Chakraborty, Pranesh; Dymerski, Mark; Porter, Cory; Manning, Adrienne; Seashore, Margretta R.; Quesada, Jonessy; Reuben, Alejandra; Chrastina, Petr; Hornik, Petr; Atef Mandour, Iman; Atty Sharaf, Sahar Abdel; Bodamer, Olaf; Dy, Bonifacio; Torres, Jasmin; Zori, Roberto; Cheillan, David; Vianey-Saban, Christine; Ludvigson, David; Stembridge, Adrya; Bonham, Jim; Downing, Melanie; Dotsikas, Yannis; Loukas, Yannis L.; Papakonstantinou, Vagelis; Zacharioudakis, Georgios S A; Baráth, Kos; Karg, Eszter; Franzson, Leifur; Jonsson, Jon J.; Breen, Nancy N.; Lesko, Barbara G.; Berberich, Stanton L.; Turner, Kimberley; Ruoppolo, Margherita; Scolamiero, Emanuela; Antonozzi, Italo; Carducci, Claudia; Caruso, Ubaldo; Cassanello, Michela; La Marca, Giancarlo; Pasquini, Elisabetta; Di Gangi, Iole Maria; Giordano, Giuseppe; Camilot, Marta; Teofoli, Francesca; Manos, Shawn M.; Peterson, Colleen K.; Mayfield Gibson, Stephanie K.; Sevier, Darrin W.; Lee, Soo Youn; Park, Hyung Doo; Khneisser, Issam; Browning, Phaidra; Gulamali-Majid, Fizza; Watson, Michael S.; Eaton, Roger B.; Sahai, Inderneel; Ruiz, Consuelo; Torres, Rosario; Seeterlin, Mary A.; Stanley, Eleanor L.; Hietala, Amy; McCann, Mark; Campbell, Carlene; Hopkins, Patrick V.; De Sain-Van Der Velden, Monique G.; Elvers, Bert; Morrissey, Mark A.; Sunny, Sherlykutty; Knoll, Detlef; Webster, Dianne; Frazier, Dianne M.; McClure, Julie D.; Sesser, David E.; Willis, Sharon A.; Rocha, Hugo; Vilarinho, Laura; John, Catharine; Lim, James; Caldwell, S. Graham; Tomashitis, Kathy; Castĩeiras Ramos, Daisy E.; Cocho De Juan, Jose Angel; Rueda Fernández, Inmaculada; Yahyaoui MacÍas, Raquel; Egea-Mellado, José María; González-Gallego, Inmaculada; Delgado Pecellin, Carmen; García-Valdecasas Bermejo, Maria Sierra; Chien, Yin Hsiu; Hwu, Wuh Liang; Childs, Thomas; McKeever, Christine D.; Tanyalcin, Tijen; Abdulrahman, Mahera; Queijo, Cecilia; Lemes, Aída; Davis, Tim; Hoffman, William; Mei, Baker; Hoffman, Gary L.

In: Genetics in Medicine, Vol. 14, No. 7, 07.2012, p. 648-655.

Research output: Contribution to journalArticle

Marquardt, G, Currier, R, McHugh, DMS, Gavrilov, D, Magera, MJ, Matern, D, Oglesbee, D, Raymond, K, Rinaldo, P, Smith, EH, Tortorelli, S, Turgeon, CT, Lorey, F, Wilcken, B, Wiley, V, Greed, LC, Lewis, B, Boemer, F, Schoos, R, Marie, S, Vincent, MF, Sica, YC, Domingos, MT, Al-Thihli, K, Sinclair, G, Al-Dirbashi, OY, Chakraborty, P, Dymerski, M, Porter, C, Manning, A, Seashore, MR, Quesada, J, Reuben, A, Chrastina, P, Hornik, P, Atef Mandour, I, Atty Sharaf, SA, Bodamer, O, Dy, B, Torres, J, Zori, R, Cheillan, D, Vianey-Saban, C, Ludvigson, D, Stembridge, A, Bonham, J, Downing, M, Dotsikas, Y, Loukas, YL, Papakonstantinou, V, Zacharioudakis, GSA, Baráth, K, Karg, E, Franzson, L, Jonsson, JJ, Breen, NN, Lesko, BG, Berberich, SL, Turner, K, Ruoppolo, M, Scolamiero, E, Antonozzi, I, Carducci, C, Caruso, U, Cassanello, M, La Marca, G, Pasquini, E, Di Gangi, IM, Giordano, G, Camilot, M, Teofoli, F, Manos, SM, Peterson, CK, Mayfield Gibson, SK, Sevier, DW, Lee, SY, Park, HD, Khneisser, I, Browning, P, Gulamali-Majid, F, Watson, MS, Eaton, RB, Sahai, I, Ruiz, C, Torres, R, Seeterlin, MA, Stanley, EL, Hietala, A, McCann, M, Campbell, C, Hopkins, PV, De Sain-Van Der Velden, MG, Elvers, B, Morrissey, MA, Sunny, S, Knoll, D, Webster, D, Frazier, DM, McClure, JD, Sesser, DE, Willis, SA, Rocha, H, Vilarinho, L, John, C, Lim, J, Caldwell, SG, Tomashitis, K, Castĩeiras Ramos, DE, Cocho De Juan, JA, Rueda Fernández, I, Yahyaoui MacÍas, R, Egea-Mellado, JM, González-Gallego, I, Delgado Pecellin, C, García-Valdecasas Bermejo, MS, Chien, YH, Hwu, WL, Childs, T, McKeever, CD, Tanyalcin, T, Abdulrahman, M, Queijo, C, Lemes, A, Davis, T, Hoffman, W, Mei, B & Hoffman, GL 2012, 'Enhanced interpretation of newborn screening results without analyte cutoff values', Genetics in Medicine, vol. 14, no. 7, pp. 648-655. https://doi.org/10.1038/gim.2012.2
Marquardt G, Currier R, McHugh DMS, Gavrilov D, Magera MJ, Matern D et al. Enhanced interpretation of newborn screening results without analyte cutoff values. Genetics in Medicine. 2012 Jul;14(7):648-655. https://doi.org/10.1038/gim.2012.2
Marquardt, Gregg ; Currier, Robert ; McHugh, David M S ; Gavrilov, Dimitar ; Magera, Mark J. ; Matern, Dietrich ; Oglesbee, Devin ; Raymond, Kimiyo ; Rinaldo, Piero ; Smith, Emily H. ; Tortorelli, Silvia ; Turgeon, Coleman T. ; Lorey, Fred ; Wilcken, Bridget ; Wiley, Veronica ; Greed, Lawrence C. ; Lewis, Barry ; Boemer, François ; Schoos, Roland ; Marie, Sandrine ; Vincent, Marie Françoise ; Sica, Yuri Cleverthon ; Domingos, Mouseline Torquado ; Al-Thihli, Khalid ; Sinclair, Graham ; Al-Dirbashi, Osama Y. ; Chakraborty, Pranesh ; Dymerski, Mark ; Porter, Cory ; Manning, Adrienne ; Seashore, Margretta R. ; Quesada, Jonessy ; Reuben, Alejandra ; Chrastina, Petr ; Hornik, Petr ; Atef Mandour, Iman ; Atty Sharaf, Sahar Abdel ; Bodamer, Olaf ; Dy, Bonifacio ; Torres, Jasmin ; Zori, Roberto ; Cheillan, David ; Vianey-Saban, Christine ; Ludvigson, David ; Stembridge, Adrya ; Bonham, Jim ; Downing, Melanie ; Dotsikas, Yannis ; Loukas, Yannis L. ; Papakonstantinou, Vagelis ; Zacharioudakis, Georgios S A ; Baráth, Kos ; Karg, Eszter ; Franzson, Leifur ; Jonsson, Jon J. ; Breen, Nancy N. ; Lesko, Barbara G. ; Berberich, Stanton L. ; Turner, Kimberley ; Ruoppolo, Margherita ; Scolamiero, Emanuela ; Antonozzi, Italo ; Carducci, Claudia ; Caruso, Ubaldo ; Cassanello, Michela ; La Marca, Giancarlo ; Pasquini, Elisabetta ; Di Gangi, Iole Maria ; Giordano, Giuseppe ; Camilot, Marta ; Teofoli, Francesca ; Manos, Shawn M. ; Peterson, Colleen K. ; Mayfield Gibson, Stephanie K. ; Sevier, Darrin W. ; Lee, Soo Youn ; Park, Hyung Doo ; Khneisser, Issam ; Browning, Phaidra ; Gulamali-Majid, Fizza ; Watson, Michael S. ; Eaton, Roger B. ; Sahai, Inderneel ; Ruiz, Consuelo ; Torres, Rosario ; Seeterlin, Mary A. ; Stanley, Eleanor L. ; Hietala, Amy ; McCann, Mark ; Campbell, Carlene ; Hopkins, Patrick V. ; De Sain-Van Der Velden, Monique G. ; Elvers, Bert ; Morrissey, Mark A. ; Sunny, Sherlykutty ; Knoll, Detlef ; Webster, Dianne ; Frazier, Dianne M. ; McClure, Julie D. ; Sesser, David E. ; Willis, Sharon A. ; Rocha, Hugo ; Vilarinho, Laura ; John, Catharine ; Lim, James ; Caldwell, S. Graham ; Tomashitis, Kathy ; Castĩeiras Ramos, Daisy E. ; Cocho De Juan, Jose Angel ; Rueda Fernández, Inmaculada ; Yahyaoui MacÍas, Raquel ; Egea-Mellado, José María ; González-Gallego, Inmaculada ; Delgado Pecellin, Carmen ; García-Valdecasas Bermejo, Maria Sierra ; Chien, Yin Hsiu ; Hwu, Wuh Liang ; Childs, Thomas ; McKeever, Christine D. ; Tanyalcin, Tijen ; Abdulrahman, Mahera ; Queijo, Cecilia ; Lemes, Aída ; Davis, Tim ; Hoffman, William ; Mei, Baker ; Hoffman, Gary L. / Enhanced interpretation of newborn screening results without analyte cutoff values. In: Genetics in Medicine. 2012 ; Vol. 14, No. 7. pp. 648-655.
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title = "Enhanced interpretation of newborn screening results without analyte cutoff values",
abstract = "Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88{\%} of known false-negative events. Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1{\%} and a positive predictive value above 60{\%}.",
keywords = "cutoff values, false-positive rate, inborn errors of metabolism, newborn screening, positive predictive value",
author = "Gregg Marquardt and Robert Currier and McHugh, {David M S} and Dimitar Gavrilov and Magera, {Mark J.} and Dietrich Matern and Devin Oglesbee and Kimiyo Raymond and Piero Rinaldo and Smith, {Emily H.} and Silvia Tortorelli and Turgeon, {Coleman T.} and Fred Lorey and Bridget Wilcken and Veronica Wiley and Greed, {Lawrence C.} and Barry Lewis and Fran{\cc}ois Boemer and Roland Schoos and Sandrine Marie and Vincent, {Marie Fran{\cc}oise} and Sica, {Yuri Cleverthon} and Domingos, {Mouseline Torquado} and Khalid Al-Thihli and Graham Sinclair and Al-Dirbashi, {Osama Y.} and Pranesh Chakraborty and Mark Dymerski and Cory Porter and Adrienne Manning and Seashore, {Margretta R.} and Jonessy Quesada and Alejandra Reuben and Petr Chrastina and Petr Hornik and {Atef Mandour}, Iman and {Atty Sharaf}, {Sahar Abdel} and Olaf Bodamer and Bonifacio Dy and Jasmin Torres and Roberto Zori and David Cheillan and Christine Vianey-Saban and David Ludvigson and Adrya Stembridge and Jim Bonham and Melanie Downing and Yannis Dotsikas and Loukas, {Yannis L.} and Vagelis Papakonstantinou and Zacharioudakis, {Georgios S A} and Kos Bar{\'a}th and Eszter Karg and Leifur Franzson and Jonsson, {Jon J.} and Breen, {Nancy N.} and Lesko, {Barbara G.} and Berberich, {Stanton L.} and Kimberley Turner and Margherita Ruoppolo and Emanuela Scolamiero and Italo Antonozzi and Claudia Carducci and Ubaldo Caruso and Michela Cassanello and {La Marca}, Giancarlo and Elisabetta Pasquini and {Di Gangi}, {Iole Maria} and Giuseppe Giordano and Marta Camilot and Francesca Teofoli and Manos, {Shawn M.} and Peterson, {Colleen K.} and {Mayfield Gibson}, {Stephanie K.} and Sevier, {Darrin W.} and Lee, {Soo Youn} and Park, {Hyung Doo} and Issam Khneisser and Phaidra Browning and Fizza Gulamali-Majid and Watson, {Michael S.} and Eaton, {Roger B.} and Inderneel Sahai and Consuelo Ruiz and Rosario Torres and Seeterlin, {Mary A.} and Stanley, {Eleanor L.} and Amy Hietala and Mark McCann and Carlene Campbell and Hopkins, {Patrick V.} and {De Sain-Van Der Velden}, {Monique G.} and Bert Elvers and Morrissey, {Mark A.} and Sherlykutty Sunny and Detlef Knoll and Dianne Webster and Frazier, {Dianne M.} and McClure, {Julie D.} and Sesser, {David E.} and Willis, {Sharon A.} and Hugo Rocha and Laura Vilarinho and Catharine John and James Lim and Caldwell, {S. Graham} and Kathy Tomashitis and {Castĩeiras Ramos}, {Daisy E.} and {Cocho De Juan}, {Jose Angel} and {Rueda Fern{\'a}ndez}, Inmaculada and {Yahyaoui Mac{\'I}as}, Raquel and Egea-Mellado, {Jos{\'e} Mar{\'i}a} and Inmaculada Gonz{\'a}lez-Gallego and {Delgado Pecellin}, Carmen and {Garc{\'i}a-Valdecasas Bermejo}, {Maria Sierra} and Chien, {Yin Hsiu} and Hwu, {Wuh Liang} and Thomas Childs and McKeever, {Christine D.} and Tijen Tanyalcin and Mahera Abdulrahman and Cecilia Queijo and A{\'i}da Lemes and Tim Davis and William Hoffman and Baker Mei and Hoffman, {Gary L.}",
year = "2012",
month = "7",
doi = "10.1038/gim.2012.2",
language = "English (US)",
volume = "14",
pages = "648--655",
journal = "Genetics in Medicine",
issn = "1098-3600",
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TY - JOUR

T1 - Enhanced interpretation of newborn screening results without analyte cutoff values

AU - Marquardt, Gregg

AU - Currier, Robert

AU - McHugh, David M S

AU - Gavrilov, Dimitar

AU - Magera, Mark J.

AU - Matern, Dietrich

AU - Oglesbee, Devin

AU - Raymond, Kimiyo

AU - Rinaldo, Piero

AU - Smith, Emily H.

AU - Tortorelli, Silvia

AU - Turgeon, Coleman T.

AU - Lorey, Fred

AU - Wilcken, Bridget

AU - Wiley, Veronica

AU - Greed, Lawrence C.

AU - Lewis, Barry

AU - Boemer, François

AU - Schoos, Roland

AU - Marie, Sandrine

AU - Vincent, Marie Françoise

AU - Sica, Yuri Cleverthon

AU - Domingos, Mouseline Torquado

AU - Al-Thihli, Khalid

AU - Sinclair, Graham

AU - Al-Dirbashi, Osama Y.

AU - Chakraborty, Pranesh

AU - Dymerski, Mark

AU - Porter, Cory

AU - Manning, Adrienne

AU - Seashore, Margretta R.

AU - Quesada, Jonessy

AU - Reuben, Alejandra

AU - Chrastina, Petr

AU - Hornik, Petr

AU - Atef Mandour, Iman

AU - Atty Sharaf, Sahar Abdel

AU - Bodamer, Olaf

AU - Dy, Bonifacio

AU - Torres, Jasmin

AU - Zori, Roberto

AU - Cheillan, David

AU - Vianey-Saban, Christine

AU - Ludvigson, David

AU - Stembridge, Adrya

AU - Bonham, Jim

AU - Downing, Melanie

AU - Dotsikas, Yannis

AU - Loukas, Yannis L.

AU - Papakonstantinou, Vagelis

AU - Zacharioudakis, Georgios S A

AU - Baráth, Kos

AU - Karg, Eszter

AU - Franzson, Leifur

AU - Jonsson, Jon J.

AU - Breen, Nancy N.

AU - Lesko, Barbara G.

AU - Berberich, Stanton L.

AU - Turner, Kimberley

AU - Ruoppolo, Margherita

AU - Scolamiero, Emanuela

AU - Antonozzi, Italo

AU - Carducci, Claudia

AU - Caruso, Ubaldo

AU - Cassanello, Michela

AU - La Marca, Giancarlo

AU - Pasquini, Elisabetta

AU - Di Gangi, Iole Maria

AU - Giordano, Giuseppe

AU - Camilot, Marta

AU - Teofoli, Francesca

AU - Manos, Shawn M.

AU - Peterson, Colleen K.

AU - Mayfield Gibson, Stephanie K.

AU - Sevier, Darrin W.

AU - Lee, Soo Youn

AU - Park, Hyung Doo

AU - Khneisser, Issam

AU - Browning, Phaidra

AU - Gulamali-Majid, Fizza

AU - Watson, Michael S.

AU - Eaton, Roger B.

AU - Sahai, Inderneel

AU - Ruiz, Consuelo

AU - Torres, Rosario

AU - Seeterlin, Mary A.

AU - Stanley, Eleanor L.

AU - Hietala, Amy

AU - McCann, Mark

AU - Campbell, Carlene

AU - Hopkins, Patrick V.

AU - De Sain-Van Der Velden, Monique G.

AU - Elvers, Bert

AU - Morrissey, Mark A.

AU - Sunny, Sherlykutty

AU - Knoll, Detlef

AU - Webster, Dianne

AU - Frazier, Dianne M.

AU - McClure, Julie D.

AU - Sesser, David E.

AU - Willis, Sharon A.

AU - Rocha, Hugo

AU - Vilarinho, Laura

AU - John, Catharine

AU - Lim, James

AU - Caldwell, S. Graham

AU - Tomashitis, Kathy

AU - Castĩeiras Ramos, Daisy E.

AU - Cocho De Juan, Jose Angel

AU - Rueda Fernández, Inmaculada

AU - Yahyaoui MacÍas, Raquel

AU - Egea-Mellado, José María

AU - González-Gallego, Inmaculada

AU - Delgado Pecellin, Carmen

AU - García-Valdecasas Bermejo, Maria Sierra

AU - Chien, Yin Hsiu

AU - Hwu, Wuh Liang

AU - Childs, Thomas

AU - McKeever, Christine D.

AU - Tanyalcin, Tijen

AU - Abdulrahman, Mahera

AU - Queijo, Cecilia

AU - Lemes, Aída

AU - Davis, Tim

AU - Hoffman, William

AU - Mei, Baker

AU - Hoffman, Gary L.

PY - 2012/7

Y1 - 2012/7

N2 - Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.

AB - Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.

KW - cutoff values

KW - false-positive rate

KW - inborn errors of metabolism

KW - newborn screening

KW - positive predictive value

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