{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:55:07Z","timestamp":1791266107808,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cystic fibrosis (CF) newborn screening in T\u00fcrkiye uses a two\u2010step immunoreactive trypsinogen (IRT\/IRT) algorithm with fixed cutoffs. The infants missed by fixed\u2010cutoff screening remain poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective single\u2010center cohort (2015\u20132025), 90 children with confirmed CF were classified as IRT\u2010positive (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200978; IRT\u20101\u2009\u2265\u200990\u2009ng\/mL) or IRT\u2010negative (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912; IRT\u20101\u2009&lt;\u200990\u2009ng\/mL). CFTR variants were re\u2010evaluated (ACMG\/AMP) and stratified by Welsh\u2013Smith class and residual\u2010function status. Clinical, perinatal, pre\u2010analytical, microbiological and genotype data were compared with standardized effect sizes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IRT\u2010negative patients were diagnosed later (median 12 vs. 2 months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and had higher early Pseudomonas aeruginosa colonization (33.3% vs. 9.0%; unadjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037). Height standard deviation score was higher in IRT\u2010negative patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004; Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      = \u22120.77; not retained after false\u2010discovery\u2010rate adjustment). Mean IRT\u20101 was four\u2010fold lower (44.5 vs. 189.1\u2009ng\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Class IV\u2013V variants accounted for 33.3% of classified IRT\u2010negative versus 11.1% of IRT\u2010positive alleles; IRT\u2010negative patients were enriched for residual\u2010function and splicing variants, including 2789\u2009+\u20095\u2009G\u2009&gt;\u2009A (9.5% vs. 2.0%), R334W and Y1032C. Pre\u2010analytical and perinatal factors did not differ.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In every missed case, the first\u2010tier IRT value fell below the fixed national cutoff, without evidence of pre\u2010analytical or perinatal contributions. Missed cases clustered among carriers of residual\u2010function and splicing CFTR variants, whose attenuated pancreatic injury may keep neonatal IRT below the cutoff. Because the Turkish protocol forgoes second\u2010tier testing in IRT\u20101\u2013negative infants, this subgroup is invisible to the current algorithm; the fixed cutoff warrants optimization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71864","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:27:14Z","timestamp":1791264434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Residual\u2010Function and Splicing CFTR Variants Characterize False\u2010Negative IRT Newborn Screening: A Ten\u2010Year Single\u2010Center Cohort From T\u00fcrkiye"],"prefix":"10.1002","volume":"61","author":[{"given":"\u00c7i\u011fdem","family":"Korkmaz","sequence":"first","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman Talha","family":"Akp\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cerrahpa\u015fa Faculty of Medicine Istanbul University\u2010Cerrahpa\u015fa Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysel","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cerrahpa\u015fa Faculty of Medicine Istanbul University\u2010Cerrahpa\u015fa Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serap Din\u00e7er","family":"Kartkaya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cerrahpa\u015fa Faculty of Medicine Istanbul University\u2010Cerrahpa\u015fa Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6956-8820","authenticated-orcid":false,"given":"Abdurrahman Zarif","family":"G\u00fcney","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furkan","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5649-8045","authenticated-orcid":false,"given":"Berrak","family":"\u00d6ztosun","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abd\u00fclhamit","family":"\u00c7ollak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe Ayz\u0131t K\u0131l\u0131n\u00e7","family":"Sakall\u0131","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Department of Pediatrics Istanbul University\u2010Cerrahpa\u015fa, Cerrahpa\u015fa Faculty of Medicine Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2475911"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-149810.1542\/peds.2006-1498"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.107.1.1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/ijns6030057","article-title":"Newborn Screening for Cystic Fibrosis: over the Hump, Still Need to Fine\u2010Tune It","volume":"6","author":"Castellani C.","year":"2020","journal-title":"International Journal of Neonatal Screening"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(79)90825-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns11020024"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jcf.2018.02.006","article-title":"ECFS Best Practice Guidelines: The 2018 Revision","volume":"17","author":"Castellani C.","year":"2018","journal-title":"Journal of Cystic Fibrosis"},{"key":"e_1_2_10_9_1","unstructured":"Ministry of Health of T\u00fcrkiye General Directorate of Public Health Department of Child and Adolescent Health. 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