Follow the evidence pathway

CF evaluation joins a compatible presentation with objective evidence of CFTR dysfunction. A positive NBS, symptoms, or family history can provide the compatible presentation. Elevated sweat chloride is the primary objective evidence, while genotype helps explain and refine the finding. No single stream should replace the others.

IRT is a screening analyte, not a measure of sweat chloride or direct proof of CFTR dysfunction. The state program controls the reflex algorithm, cutoff, and panel composition. Because targeted panels have ancestry-dependent coverage, some programs use a very-high-IRT safety net to preserve follow-up when a panel misses a disease-causing variant; this is not a shared feature of all state algorithms.

A positive NBS should move the infant to diagnostic sweat testing, and an intermediate result should keep uncertainty visible. CFTR testing can move from a targeted panel to sequencing and deletion or duplication analysis when fewer than two disease-causing variants are found, with every result traced to the specimen, method, and question it was designed to answer.