Newborn screening for cystic fibrosis

Abstract

Newborn screening for cystic fibrosis (CF NBS) has been introduced in almost all of the Western countries, and most of the children with CF are now being identified via CF NBS before disease-related symptoms develop. This review summarizes the evidence that has been generated to date to support the benefit of CF NBS and the various screening algorithms that are used in different jurisdictions. A special focus is directed towards the challenges arising from false-negative and -positive screening results. Finally, we review the emerging data reporting on positively-screened newborns, in whom confirmatory sweat testing resulted in an inconclusive diagnosis for CF.

Keywords:

• cystic fibrosis
• nbs
• positive screened newborns with inconclusive diagnosis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Over the last 5 years, cystic fibrosis (CF) has been added to newborn screening (NBS) panels in almost all Western countries.

• Although the strength of evidence regarding clinical benefit of CF NBS is not perfect, emerging CFTR-modifying drugs in the therapeutic field provide additional rationale for early identification of patients at risk for CF.

• Most of CF NBS programs have adapted an IRT–DNA algorithm.

• A newly introduced IRT–PAP algorithm showed equally good performance compared to IRT–DNA, but at a cost of higher false positive rates.

• The rate for false-negative screens and carrier detection depends on the individual screening algorithms, and seems to be minimal in screening programs, which are based on three-tier testing rather than extensive genetic analysis.

• Screened positive newborns with a consequent inconclusive diagnosis of Cystic Fibrosis (CFSPID) form a significantly large and newly recognized group as a side product of CF NBS.

• Some of these CFSPID patients will meet diagnostic criteria later on, and repeated sweat testing at 2–3 years of age is suggested.

• For a subset of CFSPID patients, CF-specific lung pathogens can be isolated in throat swabs, warranting further clinical monitoring to not miss early signs for lung disease.