Performance of antenatal reflex DNA screening for Down's syndrome.

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.