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, Jahrgang 21, Nr. 3, 05.2022, S. 422-433.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -