title: Non-invasive prenatal diagnosis for cystic fibrosis: detection of paternal mutations, exploration of patient preferences and cost analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.|Genetics and Genomic Medicine, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hill
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Twiss
authors.affiliation: Research Department of Applied Health Research, University College London, London, UK.
authors.forename: Talitha I
authors.initials: TI
authors.lastname: Verhoef
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Drury
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Fiona
authors.identifier: http://orcid.org/0000-0003-3626-764X
authors.initials: F
authors.lastname: McKay
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mason
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Jenkins
authors.affiliation: Research Department of Applied Health Research, University College London, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Morris
authors.affiliation: North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.|Genetics and Genomic Medicine, UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK.
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Chitty
mesh_terms: D003365:Costs and Cost Analysis; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000191:economics; D006801:Humans; D008297:Male; D062145:Maternal Serum Screening Tests / Q000191:economics / Q000379:methods*; D009154:Mutation; D057240:Patient Preference / Q000706:statistics & numerical data