{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:41:55Z","timestamp":1786974115167,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In Denmark, newborn screening (NBS) for cystic fibrosis (CF) was introduced on 1 May 2016. The implementation and results from the first 2 years of the national newborn CF screening program are presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The screening included immunoreactive trypsinogen (IRT), followed by evaluation for the F508del mutation when a value at or above the 50\u2009ng\/mL cutoff was present. In cases with a single F508del mutation or a very high IRT value above 145\u2009ng\/mL, next\u2010generation sequencing of the CF transmembrane conductance regulator gene (<jats:italic>CFTR<\/jats:italic>) was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 126\u2009522 newborn infants 126\u2009338 were tested (99.85%), and 4730 samples (3.7%) were assessed for <jats:italic>CFTR<\/jats:italic> mutations. Twenty\u2010six infants were screen\u2010positive and referred for diagnostic follow\u2010up of whom 22 were confirmed to have a CF diagnosis, four had one known and one <jats:italic>CFTR<\/jats:italic> allele with unknown pathogenicity, classified as cystic fibrosis screening positive inconclusive diagnosis (CFSPID), PPV 84.6%. One of the four children classified as CFSPID was later found to carry the two identified <jats:italic>CFTR<\/jats:italic> variants in cis and was reclassified as a carrier of CF. We found two false negatives; one exhibited an IRT level above the 50\u2009ng\/mL cutoff but was below the 145\u2009ng\/mL very high cutoff and with no F508del mutation present. The second false\u2010negative fell below the 50\u2009ng\/mL IRT cutoff but was diagnosed shortly after birth on the basis of meconium ileus. Screening sensitivity, 91.7%. Two hundred thirty\u2010two children were identified as carriers of CF, which is twofold above the estimated annual number of carriers. All but one carrier were heterozygous for the F508del <jats:italic>CFTR<\/jats:italic> mutation. Sixteen percent of the sequenced samples revealed rare <jats:italic>CFTR<\/jats:italic> variants, which were classified as nonpathogenic in relation to CF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>During the first 2 years of NBS CF screening in Denmark, we identified close to the expected number of infants with CF using an algorithm based on IRT, presence of F508del mutation and comprehensive genetic analysis. CFSPID accounted for only a small minority, despite comprehensive <jats:italic>CFTR<\/jats:italic> sequencing, whereas more carriers than initially expected were identified.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.24564","type":"journal-article","created":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T14:25:35Z","timestamp":1572877535000},"page":"549-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Cystic fibrosis newborn screening in Denmark: Experience from the first 2 years"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-8548","authenticated-orcid":false,"given":"Marianne","family":"Skov","sequence":"first","affiliation":[{"name":"Department of Pediatrics, CF Center Copenhagen, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"B\u00e6kvad\u2010Hansen","sequence":"additional","affiliation":[{"name":"Department for Congenital Disorders, Center for Neonatal Screening Statens Serum Institut Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Hougaard","sequence":"additional","affiliation":[{"name":"Department for Congenital Disorders, Center for Neonatal Screening Statens Serum Institut Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Skogstrand","sequence":"additional","affiliation":[{"name":"Department for Congenital Disorders, Center for Neonatal Screening Statens Serum Institut Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan M.","family":"Lund","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Clinical Genetics, Center for Inherited Metabolic Diseases, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Pressler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CF Center Copenhagen, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne V.","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, CF Center Aarhus Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Duno","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Molecular Genetics Laboratory, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2017.0206"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710023371403"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","unstructured":"Southern KW Merelle MME Dankert\u2010Roelse JE Nagelkerke AD. 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