Background and Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010-2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. Results: From 2010-2020, there were 8,765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7,591 children had a clinical diagnosis of CF and 1,174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1-9.1% after the first year of life. Conclusions: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Background: Newborn screening (NBS) for cystic fibrosis (CF) has been underway universally in the USA for 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 determinations alone have been transformed to a 2-tier strategy with DNA analyses. Objective: To apply next generation sequencing (NGS) as a method for expanding the DNA tier for identifying variants in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene with minimization of unintended outcomes. Design: Sequential quality improvement project in three phases using plan coupled to statewide follow up and analysis of screening outcomes in comparison to other NBS programs that use CFTR sequencing. Results: After demonstrating feasibility in the first phase, we studied an IRT/NGS algorithm that included CFTR Variants with Varying Clinical Consequences (VVCCs). This revealed a high identification of CF patients with 2-variants detected through screening, but for every CF case there were 1.4 with cystic fibrosis metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID). This led us to a third phase of quality improvement in which the VVCCs were eliminated except for R117H, resulting in 94% 2-variant detection of patients and 0.44:1 ratio of CRMS/CFSPID to CF. Conclusion: NGS can be used with IRT as an effective method of identifying infants at risk for CF without an appreciable increase in detection of either carriers or CRMS/CFSPID cases.