Improved DNA Analysis Reduces False Positive Prenatal DNA Testing For Trisomy Conditions Interview with:

Professor Sir Nicholas Wald FRCP FRS Professor of Preventive Medicine Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of London London

Prof. Wald

Professor Sir Nicholas Wald FRCP FRS
Professor of Preventive Medicine
Wolfson Institute of Preventive Medicine
Barts and The London School of Medicine and Dentistry
Queen Mary University of London
London What is the background for this study?

Response: Prenatal screening for Down’s syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) by maternal plasma DNA analysis has an improved screening performance compared with conventional screening but is too expensive to be performed routinely and has a technical failure rate.

The aim of the study was to take advantage of the improved screening performance of the DNA analysis in conjunction with the existing methods thereby providing a seamless testing interface between the “old” and the “new” methods that would detect a larger proportion of affected pregnancies with a much lower false-positive rate, at a much reduced cost compared with universal DNA testing and with no failed tests. The novel approach was to conduct a conventional screening test using a screening cut-off level that identifies about 10% of women with the highest risks of having an affected pregnancy (much higher than in conventional screening) and then to perform a DNA test using a portion of the original blood sample collected for the conventional test. Progressing to the DNA test was automatic for these high risk women without their having to be recalled for counseling and a fresh blood sample (ie as a reflex response hence the term “reflex DNA screening”). What are the main findings?

Response: The application of prenatal reflex DNA screening in five hospitals in the UK was successful in demonstrating a high detection rate and a very low false-positive rate with many fewer women with unaffected pregnancies requiring an invasive diagnostic test, either an amniocentesis or a chorionic villus sampling (CVS). Of the 22,812 women screened there were 106 with affected pregnancies, 95% of which were detected by screening and only 2 in 10,000 (0.02%) being given a false-positive screening result. Had conventional screening been carried out fewer affected pregnancies would have been detected (81%) with over 100 times more being given a false-positive result (2.42%). What should clinicians and patients take away from your report?

Response: Prenatal reflex DNA screening is a highly effective method of screening, substantially reducing both the need to worry women with positive screening results and reducing the number of women requiring an invasive diagnostic test. The cost of the DNA test is higher than conventional testing and the reflex DNA screening method captures the cost-effectiveness of conventional screening, limits the cost of the DNA testing to about 10% of women and saves substantially on the cost of providing patient counseling and invasive diagnostic testing. What recommendations do you have for future research as a result of this study?

Response: Research is needed to simplify DNA testing, reduce its cost and reporting time, and reduce the number of technical failures that can arise with this form of testing. As these aims begin to be achieved the proportion of women reflexed to DNA testing can increase. Is there anything else you would like to add?

Response: Those responsible for prenatal screening programmes throughout the world considering DNA testing can now give serious consideration to prenatal reflex DNA screening as a method of choice.

Disclosures: As given in the paper, Nicholas Wald is a Director of Logical Medical Systems which produces software for the interpretation of prenatal screening tests. Thank you for your contribution to the community.



Nicholas J Wald, Wayne J Huttly, Jonathan P Bestwick, Robert Old, Joan K Morris, Ray Cheng, Joe Aquilina, Elisabeth Peregrine, Devender Roberts, Zarko Alfirevic. Prenatal reflex DNA screening for trisomies 21, 18, and 13GENETICS in MEDICINE, 2017; DOI: 10.1038/GIM.2017.188

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.


[wysija_form id=”1″]






Last Updated on November 10, 2017 by Marie Benz MD FAAD