title: Measurement of fecal elastase improves performance of newborn screening for cystic fibrosis.
abstract: The aim of newborn screening (NBS) for CF is to detect children with 'classic' CF where early treatment is possible and improves prognosis. Children with inconclusive CF diagnosis (CFSPID) should not be detected, as there is no evidence for improvement through early treatment. No algorithm in current NBS guidelines explains what to do when sweat test (ST) fails. This study compares the performance of three different algorithms for further diagnostic evaluations when first ST is unsuccessful, regarding the numbers of children detected with CF and CFSPID, and the time until a definite diagnosis.
  
  
  
  In Switzerland, CF-NBS was introduced in January 2011 using an IRT-DNA-IRT algorithm followed by a ST. In children, in whom ST was not possible (no or insufficient sweat), 3 different protocols were applied between 2011 and 2014: in 2011, ST was repeated until it was successful (protocol A), in 2012 we proceeded directly to diagnostic DNA testing (protocol B), and 2013-2014, fecal elastase (FE) was measured in the stool, in order to determine a pancreas insufficiency needing immediate treatment (protocol C).
  
  
  
  The ratio CF:CFSPID was 7:1 (27/4) with protocol A, 2:1 (22/10) with protocol B, and 14:1 (54/4) with protocol C. The mean time to definite diagnosis was significantly shorter with protocol C (33days) compared to protocol A or B (42 and 40days; p=0.014 compared to A, and p=0.036 compared to B).
  
  
  
  The algorithm for the diagnostic part of the newborn screening used in the CF centers is important and affects the performance of a CF-NBS program with regard to the ratio CF:CFSPID and the time until definite diagnosis. Our results suggest to include FE after initial sweat test failure in the CF-NBS guidelines to keep the proportion of CFSPID low and the time until definite diagnosis short.
authors.affiliation: Division of Pediatric Pulmonology, Children's Hospital of Eastern Switzerland, St.Gallen, Switzerland. Electronic address: juerg.barben@kispisg.ch.
authors.forename: Juerg
authors.initials: J
authors.lastname: Barben
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Health Sciences and Health Policy, University of Lucerne, Lucerne, Switzerland.
authors.forename: Corina S
authors.initials: CS
authors.lastname: Rueegg
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Jurca
authors.affiliation: Division of Pediatric Gastroenterology, Department of Paediatrics, Cantonal Hospital Lucerne, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Spalinger
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Kuehni
mesh_terms: D000465:Algorithms; D002985:Clinical Protocols / Q000145:classification / Q000592:standards; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D042241:Early Diagnosis; D061345:Early Medical Intervention / Q000379:methods; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods / Q000592:standards; D010196:Pancreatic Elastase / Q000032:analysis*; D011379:Prognosis; D058996:Quality Improvement; D013542:Sweat / Q000378:metabolism; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors; D014362:Trypsinogen / Q000032:analysis
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014362:Trypsinogen; D010196:Pancreatic Elastase
keywords: CFSPID; Cystic fibrosis; Fecal elastase; Newborn screening