Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age
Tanja Gonska1,2, Katherine Keenan2, Jacky Au3
1Divisions of Gastroenterology, Hepatology.
Insights
Cystic fibrosis screen-positive, inconclusive diagnosis (CFSPID) infants show good health outcomes. An initial sweat chloride test can predict CF risk in these children, aiding targeted clinical follow-up.
Area of Science:
- Pediatrics
- Genetics
- Pulmonology
Background:
- Cystic fibrosis screen-positive, inconclusive diagnosis (CFSPID) infants lack clear diagnostic resolution via sweat testing and genetic analysis.
- Uncertainty regarding CFSPID health outcomes complicates clinical management and follow-up strategies.
- Identifying early predictive biomarkers is crucial for risk stratification and personalized care in CFSPID.
Purpose of the Study:
- To evaluate the long-term health outcomes of infants with CFSPID.
- To determine the predictive value of initial diagnostic tests for CF development in CFSPID.
- To assess the utility of sweat chloride levels as a biomarker for CF risk in CFSPID.
Main Methods:
- A prospective, longitudinal, multicenter, Canada-wide cohort study.
- Inclusion criteria: CF-screened newborns with 1-2 CFTR gene variants and/or sweat chloride 30-59 mmol/L.
- Monitoring for CF diagnosis conversion, pulmonary, and nutritional outcomes over a mean of 7.7 years.
Main Results:
- 21% of CFSPID children were reclassified as CF, often due to genotype reinterpretation or increased sweat chloride (≥60 mmol/L).
- An initial sweat chloride of ≥40 mmol/L predicted CF conversion.
- Pancreatic-sufficient CFSPID children exhibited normal growth, and pulmonary function was comparable to healthy controls.
Conclusions:
- CFSPID children generally have favorable nutritional and pulmonary outcomes by school age.
- Diagnostic reclassification rates remain significant in the CFSPID population.
- Initial sweat chloride testing serves as a valuable biomarker for predicting CF risk in CFSPID, guiding clinical decisions.
Background And Objectives:
Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children.
Methods:
Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes.
Results:
The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls.
Conclusions:
Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:24Cystic Fibrosis: Management
Sinus disease and chronic...