Evaluating CRMS/CFSPID phenotypes and outcomes: A retrospective study from a large UK cystic fibrosis centre.

Background: Cystic fibrosis transmembrane conductance regulator metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID) is a designation given following a positive newborn screen for cystic fibrosis (CF) when CF is not excluded but cannot be confirmed. We describe the long-term clinical outcomes of a CRMS/CFSPID cohort. Methods: A retrospective, single centre study of children with a current or previous diagnosis of CRMS/CFSPID. Study period extended from February 1, 2007 to August 1, 2022. Baseline and longitudinal data were assessed. Results: 30 children were designated as CRMS/CFSPID between 2007 and 2021. At baseline, 13 CFTR variants were identified, of which F508del and R117H 7T/9T were most common (occurring in 25 and 20 children respectively). Initial mean immunoreactive trypsinogen and sweat chloride were 82.8 mmol/L and 34.3 mmol/L respectively. During longitudinal assessment (n = 27), occurring over a mean duration of 8.5 years, five children progressed to CF at a mean age of 9.5 years. All children were pancreatic sufficient except one who reclassified to CF. Four isolated Conclusions: Most children with CRMS/CFSPID remained well with a low progression rate to CF. This supports a less intensive medical surveillance approach. Our results highlight the importance of assessment in a dedicated CRMS/CFSPID clinic during adolescence to detect progression to CF after 6 years of age.