Cystic Fibrosis Newborn Screening in Austria Using PAP and the Numeric Product of PAP and IRT Concentrations as Second-Tier Parameters
Maximilian Zeyda,
Andrea Schanzer,
Pavel Basek,
Vera Bauer,
Ernst Eber,
Helmut Ellemunter,
Margit Kallinger,
Josef Riedler,
Christina Thir,
Franz Wadlegger,
Angela Zacharasiewicz,
Sabine Renner
Affiliations
Maximilian Zeyda
Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
Andrea Schanzer
Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
Pavel Basek
University Clinic for Paediatric and Adolescent Medicine, University Hospital Salzburg, 5020 Salzburg, Austria
Vera Bauer
Department of Pediatrics and Adolescent Medicine, Klinikum Wels-Grieskirchen, 4600 Wels, Austria
Ernst Eber
Division of Pediatric Pulmonology and Allergology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria
Helmut Ellemunter
Department of Child and Adolescent Health, Division of Cardiology, Pulmonology, Allergology, and Cystic Fibrosis, Cystic Fibrosis Centre, Medical University of Innsbruck, 6020 Innsbruck, Austria
Margit Kallinger
PEK Hospital Steyr Department of Pediatrics and Adolescent Medicine, 4400 Steyr, Austria
Josef Riedler
Department of Pediatrics and Adolescent Medicine, Kardinal Schwarzenberg Hospital Schwarzach, 5620 Schwarzach, Austria
Christina Thir
Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, 4040 Linz, Austria
Franz Wadlegger
Division of Pediatric Pulmonology and Allergology, Department of Pediatrics and Adolescent Medicine, Hopital Klagenfurt am Wörthersee, 9020 Klagenfurt am Wörthersee, Austria
Angela Zacharasiewicz
Department of Pediatrics and Adolescent Medicine, Klinikum Ottakring, Wilhelminenspital, Teaching Hospital of the University of Vienna, 1010 Vienna, Austria
Sabine Renner
Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria
In Austria, newborns have been screened for cystic fibrosis (CF) by analyzing immunoreactive trypsinogen (IRT) from dried blood spots (DBS)s for nearly 20 years. Recently, pancreatitis-associated protein (PAP) analysis was introduced as a second-tier test with the aim of reducing recalls for second DBS cards while keeping sensitivity high. For 28 months, when IRT was elevated (65–130 ng/mL), PAP was measured from the first DBS (n = 198,927) with a two-step cut-off applied. For the last 12 months of the observation period (n = 85,421), an additional IRT×PAP cut-off was introduced. If PAP or IRT×PAP were above cut-off, a second card was analyzed for IRT and in case of elevated values identified as screen-positive. Above 130 ng/mL IRT in the first DBS, newborns were classified as screen-positive. IRT analysis of first DBS resulted in 1961 (1%) tests for PAP. In the first 16 months, 26 of 93 screen-positive were confirmed to have CF. Two false-negatives have been reported (sensitivity = 92.8%). Importantly, less than 30% of families compared to the previous IRT-IRT screening scheme had to be contacted causing distress. Adding IRT×PAP caused a marginally increased number of second cards and sweat tests to be requested during this period (15 and 3, respectively) compared to the initial IRT-PAP scheme. One case of confirmed CF was found due to IRT×PAP, demonstrating an increase in sensitivity. Thus, the relatively simple and economical algorithm presented here performs effectively and may be a useful model for inclusion of CF into NBS panels or modification of existing schemes.
