Non-invasive prenatal diagnosis for cystic fibrosis: detection of paternal mutations, exploration of patient preferences and cost analysis

Objectives: We aim to develop non-invasive prenatal diagnosis (NIPD) for cystic fibrosis (CF) and determine costs and implications for implementation.

Methods: A next-generation sequencing assay was developed to detect ten common CF mutations for exclusion of the paternal mutation in maternal plasma. Using uptake data from a study exploring views on NIPD for CF, total test-related costs were estimated for the current care pathway and compared with those incorporating NIPD.

Results: The assay reliably predicted mutation status in all control and maternal plasma samples. Of carrier or affected adults with CF (n = 142) surveyed, only 43.5% reported willingness to have invasive testing for CF with 94.4% saying they would have NIPD. Using these potential uptake data, the incremental costs of NIPD over invasive testing per 100 pregnancies at risk of CF are £9025 for paternal mutation exclusion, and £26,510 for direct diagnosis.

Conclusions: We have developed NIPD for risk stratification in around a third of CF families. There are economic implications due to potential increased test demand to inform postnatal management rather than to inform decisions around termination of an affected pregnancy.