title: Preconceptional screening of couples for carriers of cystic fibrosis: a prospective evaluation of effects, costs and savings for different mutation detection methods.
abstract: OBJECTIVE
  The aim of this study was to perform a prospective evaluation of the effects, costs and savings of a preconceptional screening programme of couples for carriers of cystic fibrosis (CF).
  
  
  METHODS
  A decision model for both single-entry two-step (SETS) and double-entry two-step (DETS) couple screening was constructed. Two mutation detection methods were considered: allele-specific oligonucleotide (ASO) hybridisation screening of 32 mutations, with a sensitivity of 90%, and denaturing gradient gel electrophoresis (DGGE), with a sensitivity of 98%. In our model, the following combinations were used: (1) ASO for both steps; (2) DGGE for both steps, and (3) ASO for the first step and DGGE for the second step. The model is demonstrated using figures from the Netherlands, where there is a carrier frequency of 1:30. We estimated the value of different choices and probabilities in a decision tree and determined the costs of screening for CF and the costs of the illness itself.
  
  
  RESULTS
  We found that with most of the combinations of mutation detection methods, SETS couple screening could offer positive net savings in the Netherlands. The ASO/DGGE combination resulted in the highest net savings. DETS couple screening for all combinations, including testing with DGGE in both steps, did not show a positive cost-savings balance at all, not even with an uptake rate of 100%. The maximum number of carrier couples identified when screening 100,000 couples with the ASO/DGGE combination was 98 (SETS). This could result in about 25 fewer children born with CF each year in the Netherlands, under the following assumptions: (1) each couple has two children and 10% of couples are unable to have children; (2) of detected carrier couples, 15% decide not to have children and 85% make use of prenatal diagnosis; (3) of those fetuses diagnosed with CF, 80% are aborted, and (4) prenatal diagnosis carries a 0.75% risk of iatrogenic abortion.
  
  
  CONCLUSIONS
  The results of this evaluation show that there are no financial objections to the preconceptional screening of couples in the Netherlands when the above-mentioned assumptions apply; thus, further evaluation can concentrate on the balance of the non-economic consequences of screening for participants and for society.
authors.affiliation: Department of Medical Genetics, University of Groningen, Groningen, The Netherlands. j.verheij@medgen.azg.nl
authors.forename: J B
authors.initials: JB
authors.lastname: Verheij
authors.forename: M F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: R M
authors.initials: RM
authors.lastname: Hofstra
authors.forename: G
authors.initials: G
authors.lastname: Pals
authors.forename: J D
authors.initials: JD
authors.lastname: Habbema
authors.forename: L P
authors.initials: LP
authors.lastname: ten Kate