{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:52:34Z","timestamp":1784843554390,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014177","name":"Legacy of Angels Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014177","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Newborn screening\u00a0for cystic fibrosis (CF) has been underway universally in the United States\u00a0for more than a decade, as well in most European countries, and algorithms have been evolving throughout this period with quality improvement projects as immunoreactive trypsinogen (IRT) determinations alone have been transformed to a 2\u2010tier strategy with DNA analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To apply next generation sequencing (NGS) as a screening method to expand the DNA tier and identify substantially more variants in the CF transmembrane conductance regulator (<jats:italic>CFTR<\/jats:italic>) gene to enhance sensitivity and equity while minimizing incidental findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Sequential evaluation and improvement plan in three phases using algorithm modifications coupled to statewide follow up and analysis of screening outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After demonstrating feasibility in the first phase, we studied an IRT\/NGS algorithm that included <jats:italic>CFTR<\/jats:italic> Variants with Varying Clinical Consequences (VVCCs). This revealed a high identification of CF patients with 2\u2010variants detected through screening, but for every CF case there were 1.4 with CF metabolic syndrome\/CF screen positive, inconclusive diagnosis (CRMS\/CFSPID). This led us to a third phase of improvement in which the VVCCs were eliminated except for R117H, resulting in 94% 2\u2010variant detection of patients and 0.44:1 ratio of CRMS\/CFSPID to CF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NGS can be used with IRT as an effective method of identifying infants at risk for CF without an appreciable increase in detection of carriers. Its potential added value includes facilitating equity, enhancing sensitivity and detecting more CF patients with 2\u2010variants during the screening process.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.26253","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T08:35:33Z","timestamp":1669192533000},"page":"778-787","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Refinement of newborn screening for cystic fibrosis with next generation sequencing"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-1737","authenticated-orcid":false,"given":"Michael J.","family":"Rock","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene University of Wisconsin school of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-120X","authenticated-orcid":false,"given":"Nicholas","family":"Antos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-7016","authenticated-orcid":false,"given":"Philip M.","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns6010008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.55.1.35"},{"key":"e_1_2_9_4_1","first-page":"445","article-title":"Newborn screening for cystic fibrosis. 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