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Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net

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Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net. / Sommerburg, Olaf; Stahl, Mirjam; Hämmerling, Susanne; Gramer, Gwendolyn; Muckenthaler, Martina U; Okun, Jürgen; Kohlmüller, Dirk; Happich, Margit; Kulozik, Andreas E; Mall, Marcus A; Hoffmann, Georg F.

In: J CYST FIBROS, Vol. 21, No. 3, 05.2022, p. 422-433.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sommerburg, O, Stahl, M, Hämmerling, S, Gramer, G, Muckenthaler, MU, Okun, J, Kohlmüller, D, Happich, M, Kulozik, AE, Mall, MA & Hoffmann, GF 2022, 'Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net', J CYST FIBROS, vol. 21, no. 3, pp. 422-433. https://doi.org/10.1016/j.jcf.2021.10.007

APA

Sommerburg, O., Stahl, M., Hämmerling, S., Gramer, G., Muckenthaler, M. U., Okun, J., Kohlmüller, D., Happich, M., Kulozik, A. E., Mall, M. A., & Hoffmann, G. F. (2022). Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net. J CYST FIBROS, 21(3), 422-433. https://doi.org/10.1016/j.jcf.2021.10.007

Vancouver

Sommerburg O, Stahl M, Hämmerling S, Gramer G, Muckenthaler MU, Okun J et al. Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net. J CYST FIBROS. 2022 May;21(3):422-433. https://doi.org/10.1016/j.jcf.2021.10.007

Bibtex

@article{d7a47900b8584fbc8931cb33fa78e812,
title = "Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net",
abstract = "BACKGROUND: Previous studies suggest that PAP-based CF protocols are suitable for newborn screening (NBS) for cystic fibrosis (CF) when newborns designated as CFSPID should not be detected. However, there are still discussions about the performance of IRT/PAP algorithms. We present the final results of a pilot study evaluating a IRT/PAP protocol with an IRT-dependent safety net (SN) conducted from 2008 to 2016 in southwestern Germany on nearly 500,000 newborns.METHODS: To achieve reliable data, all newborns were screened using both the PAP-based and a DNA-based CFNBS algorithm. PAP quantification and genetic analysis of the four most common CFTR mutations in Germany were performed in all newborns with IRT≥99.0 percentile. NBS was rated positive if either PAP was ≥1.6 µg/l and/or at least one CFTR mutation was detected. In addition, an IRT-dependent SN resulted in positive rating for both protocols if IRT was ≥99.9 percentile. To evaluate the IRT/PAP protocol, its performance was compared to that of the IRT/DNA protocol.RESULTS: The IRT/PAP protocol with IRT-based SN used in the study achieved a sensitivity of 94%, if false-negative detected neonates with meconium ileus and those designated as CFSPID were excluded from analysis. CF/CFSPID ratio was 92. However, PPV of the IRT/PAP+SN protocol was with 10.3% very low.CONCLUSIONS: PAP-based CFNBS protocols can be used, if less detection of CFSPID is desired. The IRT/PAP protocol with IRT-dependent SN evaluated here achieved adequate sensitivity but should probably be used in combination with a third-tier test to also achieve an acceptable PPV.",
keywords = "Cystic Fibrosis/diagnosis, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Germany, Humans, Infant, Newborn, Neonatal Screening/methods, Pancreatitis-Associated Proteins/analysis, Pilot Projects, Sensitivity and Specificity, Trypsinogen/analysis",
author = "Olaf Sommerburg and Mirjam Stahl and Susanne H{\"a}mmerling and Gwendolyn Gramer and Muckenthaler, {Martina U} and J{\"u}rgen Okun and Dirk Kohlm{\"u}ller and Margit Happich and Kulozik, {Andreas E} and Mall, {Marcus A} and Hoffmann, {Georg F}",
note = "Copyright {\textcopyright} 2021. Published by Elsevier B.V.",
year = "2022",
month = may,
doi = "10.1016/j.jcf.2021.10.007",
language = "English",
volume = "21",
pages = "422--433",
journal = "J CYST FIBROS",
issn = "1569-1993",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Final results of the southwest German pilot study on cystic fibrosis newborn screening - Evaluation of an IRT/PAP protocol with IRT-dependent safety net

AU - Sommerburg, Olaf

AU - Stahl, Mirjam

AU - Hämmerling, Susanne

AU - Gramer, Gwendolyn

AU - Muckenthaler, Martina U

AU - Okun, Jürgen

AU - Kohlmüller, Dirk

AU - Happich, Margit

AU - Kulozik, Andreas E

AU - Mall, Marcus A

AU - Hoffmann, Georg F

N1 - Copyright © 2021. Published by Elsevier B.V.

PY - 2022/5

Y1 - 2022/5

N2 - BACKGROUND: Previous studies suggest that PAP-based CF protocols are suitable for newborn screening (NBS) for cystic fibrosis (CF) when newborns designated as CFSPID should not be detected. However, there are still discussions about the performance of IRT/PAP algorithms. We present the final results of a pilot study evaluating a IRT/PAP protocol with an IRT-dependent safety net (SN) conducted from 2008 to 2016 in southwestern Germany on nearly 500,000 newborns.METHODS: To achieve reliable data, all newborns were screened using both the PAP-based and a DNA-based CFNBS algorithm. PAP quantification and genetic analysis of the four most common CFTR mutations in Germany were performed in all newborns with IRT≥99.0 percentile. NBS was rated positive if either PAP was ≥1.6 µg/l and/or at least one CFTR mutation was detected. In addition, an IRT-dependent SN resulted in positive rating for both protocols if IRT was ≥99.9 percentile. To evaluate the IRT/PAP protocol, its performance was compared to that of the IRT/DNA protocol.RESULTS: The IRT/PAP protocol with IRT-based SN used in the study achieved a sensitivity of 94%, if false-negative detected neonates with meconium ileus and those designated as CFSPID were excluded from analysis. CF/CFSPID ratio was 92. However, PPV of the IRT/PAP+SN protocol was with 10.3% very low.CONCLUSIONS: PAP-based CFNBS protocols can be used, if less detection of CFSPID is desired. The IRT/PAP protocol with IRT-dependent SN evaluated here achieved adequate sensitivity but should probably be used in combination with a third-tier test to also achieve an acceptable PPV.

AB - BACKGROUND: Previous studies suggest that PAP-based CF protocols are suitable for newborn screening (NBS) for cystic fibrosis (CF) when newborns designated as CFSPID should not be detected. However, there are still discussions about the performance of IRT/PAP algorithms. We present the final results of a pilot study evaluating a IRT/PAP protocol with an IRT-dependent safety net (SN) conducted from 2008 to 2016 in southwestern Germany on nearly 500,000 newborns.METHODS: To achieve reliable data, all newborns were screened using both the PAP-based and a DNA-based CFNBS algorithm. PAP quantification and genetic analysis of the four most common CFTR mutations in Germany were performed in all newborns with IRT≥99.0 percentile. NBS was rated positive if either PAP was ≥1.6 µg/l and/or at least one CFTR mutation was detected. In addition, an IRT-dependent SN resulted in positive rating for both protocols if IRT was ≥99.9 percentile. To evaluate the IRT/PAP protocol, its performance was compared to that of the IRT/DNA protocol.RESULTS: The IRT/PAP protocol with IRT-based SN used in the study achieved a sensitivity of 94%, if false-negative detected neonates with meconium ileus and those designated as CFSPID were excluded from analysis. CF/CFSPID ratio was 92. However, PPV of the IRT/PAP+SN protocol was with 10.3% very low.CONCLUSIONS: PAP-based CFNBS protocols can be used, if less detection of CFSPID is desired. The IRT/PAP protocol with IRT-dependent SN evaluated here achieved adequate sensitivity but should probably be used in combination with a third-tier test to also achieve an acceptable PPV.

KW - Cystic Fibrosis/diagnosis

KW - Cystic Fibrosis Transmembrane Conductance Regulator/genetics

KW - Germany

KW - Humans

KW - Infant, Newborn

KW - Neonatal Screening/methods

KW - Pancreatitis-Associated Proteins/analysis

KW - Pilot Projects

KW - Sensitivity and Specificity

KW - Trypsinogen/analysis

U2 - 10.1016/j.jcf.2021.10.007

DO - 10.1016/j.jcf.2021.10.007

M3 - SCORING: Journal article

C2 - 34764021

VL - 21

SP - 422

EP - 433

JO - J CYST FIBROS

JF - J CYST FIBROS

SN - 1569-1993

IS - 3

ER -