title: Performance of antenatal reflex DNA screening for Down's syndrome.
abstract: OBJECTIVE
  Maternal plasma DNA analysis has a high but imperfect antenatal Down's syndrome screening performance. We aimed to determine the effect of combining DNA testing with current tests.
  
  
  METHODS
  In our modelled screening protocol, women provide two samples, one serum sample for a Combined test, and a plasma sample for a possible DNA test. Women with a Combined test risk above a specified level have a DNA test using the plasma sample without the need to recall them for another sample and counselling (ie. in a reflex manner). Women with a failed DNA test after a second attempt using a fresh plasma sample have an Integrated test. Screening performance was estimated according to the proportion of women reflexed to DNA testing and compared with universal DNA testing.
  
  
  RESULTS
  Reflexing 10% of women to a DNA test yields a 91% detection rate (DR) for a 0.025% false-positive rate (FPR) and no failed tests, compared with a 98% DR, 0.2% FPR and a 2.5% test failure rate with universal DNA testing (94% for 0.046% if 20% reflexed). DNA test failure rate has little influence on screening performance
  
  
  CONCLUSIONS
  Reflex DNA testing substantially reduces the FPR with a relatively small loss in detection compared with universal DNA testing, and reduces patient anxiety by avoiding the recall of women for DNA testing.
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ n.j.wald@qmul.ac.uk.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wald
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bestwick
mesh_terms: D000328:Adult; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests / Q000379:methods / Q000592:standards; D015999:Multivariate Analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards; D017422:Sequence Analysis, DNA / Q000592:standards*
keywords: DNA analysis; Down’s syndrome; antenatal screening; maternal plasma; reflex testing