Final results of the southwest German pilot study on cystic fibrosis newborn screening – Evaluation of an IRT/PAP protocol with IRT-dependent safety net
| Autor: | Olaf Sommerburg, Margit Happich, Georg F. Hoffmann, Jürgen G. Okun, Dirk Kohlmüller, Marcus A. Mall, Mirjam Stahl, Susanne Hämmerling, Martina U. Muckenthaler, Gwendolyn Gramer, Andreas E. Kulozik |
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| Rok vydání: | 2022 |
| Předmět: |
Pulmonary and Respiratory Medicine
Percentile medicine.medical_specialty Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Pancreatitis-Associated Proteins Pilot Projects PAP protocol Sensitivity and Specificity behavioral disciplines and activities Cystic fibrosis Neonatal Screening Germany Internal medicine medicine Humans Immunoreactive trypsinogen Genetic testing Newborn screening medicine.diagnostic_test business.industry Infant Newborn medicine.disease Dried blood spot Cftr mutation Pediatrics Perinatology and Child Health Trypsinogen business psychological phenomena and processes |
| Zdroj: | Journal of Cystic Fibrosis. 21:422-433 |
| ISSN: | 1569-1993 |
| DOI: | 10.1016/j.jcf.2021.10.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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