{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:27:34Z","timestamp":1792517254746,"version":"4.5.0"},"reference-count":18,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ersjournals.com"],"crossmark-restriction":true},"short-container-title":["Breathe"],"accepted":{"date-parts":[[2021,8,11]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>Newborn bloodspot screening (NBS) for cystic fibrosis (CF) is an effective strategy for the early recognition of infants with a CF diagnosis. Some infants with a positive NBS result for CF have an inconclusive diagnosis and evidence suggests the number of these infants is increasing, as more extensive gene analysis is integrated into screening protocols. There is an internationally agreed, but complex, designation for infants with an unclear diagnosis after a positive screening result: cystic fibrosis transmembrane conductance regulator (CFTR)-related metabolic syndrome\/cystic fibrosis screen positive, inconclusive diagnosis (CRMS\/CFSPID). Infants with a CRMS\/CFSPID designation have no clinical evidence of disease and do not meet the criteria for a CF diagnosis, but the NBS result indicates some risk of developing CF or a CFTR-related disorder. In this review, we describe the accurate designation of these and reflect on emerging management pathways, with particular attention given to clear and consistent communication.<\/jats:p><jats:sec><jats:title>Educational aims<\/jats:title><jats:list list-type=\"bullet\"><jats:list-item><jats:p>To clarify the definition of the global harmonised designation: cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (CRMS)\/cystic fibrosis screen positive, inconclusive diagnosis (CFSPID).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>To understand what impact a CRMS\/CFSPID result has for the patient and their family.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:sec>","DOI":"10.1183\/20734735.0088-2021","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T11:30:39Z","timestamp":1635852639000},"page":"210088","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cystic fibrosis transmembrane conductance regulator-related metabolic syndrome\/cystic fibrosis screen positive, inconclusive diagnosis (CRMS\/CFSPID)"],"prefix":"10.1183","volume":"17","author":[{"given":"Aditi","family":"Sinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Southern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"2024101703585195000_17.3.210088.1","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/ppul.23478","article-title":"Novel insights into the diagnostic and therapeutic challenges of the CFTR metabolic syndrome\/CF screen positive indeterminate diagnosis","volume":"51","author":"Machogu","year":"2016","journal-title":"Pediatr Pulmonol"},{"key":"2024101703585195000_17.3.210088.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2015.01.001"},{"key":"2024101703585195000_17.3.210088.3","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.jcf.2020.11.006","article-title":"Updated guidance on the management of children with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome\/cystic fibrosis screen positive, inconclusive diagnosis (CRMS\/CFSPID)","volume":"20","author":"Barben","year":"2021","journal-title":"J Cyst Fibros"},{"key":"2024101703585195000_17.3.210088.4","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.jcf.2019.04.010","article-title":"Inconclusive diagnosis after a positive newborn bloodspot screening result for cystic fibrosis; clarification of the harmonised international definition","volume":"18","author":"Southern","year":"2019","journal-title":"J Cyst Fibros"},{"key":"2024101703585195000_17.3.210088.5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/ijns6010019","article-title":"Inconclusive diagnosis after newborn screening for cystic fibrosis","volume":"6","author":"Munck","year":"2020","journal-title":"Int J Neonatal Screen"},{"key":"2024101703585195000_17.3.210088.6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3390\/ijns5020023","article-title":"Psychological impact on parents of an inconclusive diagnosis following newborn bloodspot screening for cystic fibrosis: a qualitative study","volume":"5","author":"Johnson","year":"2019","journal-title":"Int J Neonatal Screen"},{"key":"2024101703585195000_17.3.210088.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.09.066"},{"key":"2024101703585195000_17.3.210088.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.09.003"},{"key":"2024101703585195000_17.3.210088.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2008.09.005"},{"key":"2024101703585195000_17.3.210088.10","first-page":"21","article-title":"The implications and management of cystic fibrosis screen positive, inconclusive diagnosis patients","volume":"31","author":"Krishnananthan","year":"2019","journal-title":"Paediatr Respir Rev"},{"key":"2024101703585195000_17.3.210088.11","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jpeds.2016.09.064","article-title":"Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation","volume":"181S","author":"Farrell","year":"2017","journal-title":"J\u00a0Pediatr"},{"key":"2024101703585195000_17.3.210088.12","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jcf.2018.11.014","article-title":"The increasing challenge of genetic counseling for cystic fibrosis","volume":"18","author":"Foil","year":"2019","journal-title":"J Cyst Fibros"},{"key":"2024101703585195000_17.3.210088.13","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.jpeds.2016.09.063","article-title":"Applying cystic fibrosis transmembrane conductance regulator genetics and CFTR2 data to facilitate diagnoses","volume":"181S","author":"Sosnay","year":"2017","journal-title":"J Pediatr"},{"key":"2024101703585195000_17.3.210088.14","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.arcped.2017.07.015","article-title":"Guidelines for the clinical management and follow-up of infants with inconclusive cystic fibrosis diagnosis through newborn screening","volume":"12","author":"Sermet-Gaudelus","year":"2017","journal-title":"Arch Pediatr"},{"key":"2024101703585195000_17.3.210088.15","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2081"},{"key":"2024101703585195000_17.3.210088.16","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/ppul.24634","article-title":"Phenotype of children with inconclusive cystic fibrosis diagnosis after newborn screening","volume":"55","author":"Munck","year":"2020","journal-title":"Pediatr Pulmonol"},{"key":"2024101703585195000_17.3.210088.17","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-1993(11)60014-3"},{"key":"2024101703585195000_17.3.210088.18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.pan.2016.03.021","article-title":"CFTR and\/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients","volume":"16","author":"Gaitch","year":"2020","journal-title":"Pancreatology"}],"container-title":["Breathe"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/20734735.0088-2021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T11:42:45Z","timestamp":1729165365000},"score":1,"resource":{"primary":{"URL":"http:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/20734735.0088-2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":18,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,11,2]]},"published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1183\/20734735.0088-2021"],"URL":"https:\/\/doi.org\/10.1183\/20734735.0088-2021","relation":{},"ISSN":["1810-6838","2073-4735"],"issn-type":[{"value":"1810-6838","type":"print"},{"value":"2073-4735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]}}}