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UK Study Finds Reflex NIPT After Combined Screening Detects Most Trisomies, Avoids Invasive Tests

This article has been updated to add information about the failure rate of Premaitha's test.

NEW YORK (GenomeWeb) – Employing noninvasive prenatal testing (NIPT) for fetal trisomies 21, 18, and 13 as a reflex test after first-trimester combined screening results in few invasive diagnostic tests, a high detection rate, and a low false-positive rate, compared to conventional screening, according to a new study by researchers in the UK.

The study, published in Genetics in Medicine today, involved almost 23,000 pregnant women who were screened at five UK hospitals. About 10 percent ended up receiving a DNA reflex test, which detected 95 percent of all trisomies present, with a false-positive rate of 0.02 percent. Using NIPT also avoided up to 530 invasive diagnostic tests that would likely have been ordered after a positive conventional screening result. 

For the project, which took place in 2015 and 2016, researchers led by Nicholas Wald at the Wolfson Institute of Preventive Medicine at Queen Mary University in London used a reflex DNA screening protocol in which women provided two blood samples. The first sample was used for the first-trimester combined screen, which measures nuchal translucency and two blood markers. If that test showed a combined risk of trisomy 21, trisomy 18, or trisomy 13 higher than 1 in 800, an NIPT was automatically triggered and the two test results were reported together. This procedure, the authors noted, meant that women did not have to be recalled to give another blood sample for DNA testing and thus avoided the anxiety that is often associated with such a recall.

Of the 22,812 women obtaining the combined test, 2,480, or 10.9 percent, had a high enough risk to trigger an NIPT. For the first part of the study, the researchers sent those samples to Sequenom in the US, a total of 715.

Later on, NIPT testing was performed at the Wolfson Institute using Premaitha Health's test. For that platform, the researchers tracked the technical failure rate, which was 8.7 percent in their hands (152 of 1,756 samples failed). Almost all of the failed samples were retested using a back-up sample, which again had some failures, and 31 women, or 1.7 percent, needed to provide a second blood sample. Just a single sample still yielded no result after testing that second sample twice.

In total, NIPT yielded 105 screen-positive results, among them 101 true positives and four false positives. Altogether, 106 pregnancies were affected by trisomy, for a detection rate of 95 percent — the combined screen initially missed three and the reflex DNA test missed another two cases. Of the 101 women who were true positives, 88 had an invasive diagnostic test, and 83 terminated their pregnancy. Three of the four women with a false-positive result had an invasive diagnostic test. The positive predictive value of the screening procedure – the odds of being affected after obtaining a positive result – was 25:1.

Reflex DNA screening, the authors concluded, lowers the false-positive rate compared to other screening methods and avoids recall-induced anxiety, while delivering a detection rate that is almost as high as that of universal NIPT – 95 percent compared to 99 percent. "These clinical benefits, together with the reduced cost compared with universal DNA testing, make the reflex approach a preferred method of screening," they wrote.