Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

Carlo Castellani, MD; Barry Linnane, MB, BCh, BAO, DCH, MRCPI, MRCPCH, MD; Iwona Pranke, PhD; Federico Cresta, MD; Isabelle Sermet-Gaudelus, MD, PhD; Daniel Peckham, MD


Semin Respir Crit Care Med. 2019;40(6):701-714. 

In This Article

The CF NBS Process

All CF NBS programs begin with a measurement of IRT to identify infants at an increased risk of CF in a population, and end, ultimately, with a sweat test to make the diagnosis of CF in an individual. IRT is sensitive in detecting CF but not specific, and so all CF NBS programs have a second step (tier) of testing to reduce the number of false positives, and hence improve the positive predictive value and minimize the numbers the program refers for clinical assessment. Broadly, programs adopt two different approaches for the second tier, either repeating the IRT (IRT/IRT), or running a DNA analysis for disease causing CF variants (mutations) (IRT/DNA). Local factors such as budget, resources, prevalence of CF, genetic heterogeneity, limitations on genetic testing, etc., result in further refinement and adaptations to these core models.[46]

All modern CF NBS programs measure IRT in dried blood spots taken as a part of established population-based public health screening of newborns, typically in the first 3 to 5 days of life.[45–47] IRT is the first step (tier) of testing and dictates the sensitivity of the screening program. The lower the IRT cut-off value is set the more sensitive the test, hence the likelihood of missing a case (false negative) reduces, although it never reaches zero. However, this comes at the costs of identifying more unaffected infants (false positives), which have significant organizational and resource implications. If it ultimately results in a family being contacted for repeat testing, it risks a significant psychological harm.[70]