Performance of antenatal reflex DNA screening for Down's syndrome. (December 2015)

• Record Type: Journal Article
• Authors: Wald, Nicholas J; Bestwick, Jonathan P
• Is Part Of: Journal of medical screening. Volume 22:Number 4(2015)
• Page Start: 168
• Page End: 174
• Publication Date: 2015-12
• Subjects: Down's syndrome -- antenatal screening -- DNA analysis -- reflex testing -- maternal plasma; Medical screening -- Periodicals; 362.177
• DOI: 10.1177/0969141315581005
• Languages: English
• ISSNs: 0969-1413

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 Conclusion: 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.