New screening tests are far better predictors of fetal genetic conditions compared with previous methods, a new study published April 1 in the New England Journal of Medicine notes, but other studies in the same issue underscore that the tests should never be considered diagnostic.
The tests, conducted through a simple blood draw of a mother as early as nine weeks into a pregnancy, predict the risk a fetus will have Down syndrome or a growing suite of other genetic issues. The screening tests are popular among older pregnant women whose fetuses face a greater risk of having a genetic condition, but the screens are now being rolled out to women of all ages.
The Journal published three studies on the tests, known as noninvasive prenatal tests. One large, industry-funded study confirmed that the tests could be used for women of all ages, but the other two focused on test results that were incorrect. One of the other studies, led by Baylor College of Medicine researchers in Texas, found a significant percentage of false positive results; for one rare genetic condition 62 percent of women told that their fetus likely had the condition actually did not have it.
“There is a lot of misconception out there that this is a diagnostic test and it is not,’’ said Sau W. Cheung, the lead Baylor author of the study that examined 294 positive screening results, of which 56, or about 19 percent, were incorrect for various chromosomal conditions. False positive test results occur with greater frequency the more rare a genetic condition. As companies now roll out tests for ever more rare conditions to younger women, “the potential for harm is increasing,’’ the paper concludes. C
heung and other researchers said the tests should be called “DNA-based noninvasive prenatal screening” to convey the message that positive results need to be followed up with a diagnostic test.
The New England Center for Investigative Reporting found in December that doctors and patients were misunderstanding screening test results, in part because of some companies’ marketing techniques that overstated the accuracy of screenings. Meanwhile, the largest study in the New England Journal on prenatal tests, funded primarily by the prenatal testing company Ariosa Diagnostics, further confirms that the tests are far better predictors than traditional screening methods such as blood tests and ultrasounds for women of all ages.
The tests were originally designed for older, higher-risk women. “If one is interested in detection of Down syndrome, this test is clearly far better than previous screening that has been performed,’’ said Dr. Mary Norton, the first author of the study and vice chair of genetics in the department of obstetrics, gynecology and reproductive sciences at the University of California San Francisco.
But she cautioned that Down syndrome is more rare in young women than those over 35, and other tests are needed if women want to fully examine the risk to fetuses of intellectual disability.
“Whether this is the best test for low-risk women will remain a topic of discussion,’’ Norton said. The study also found that 3 percent of women fail to get a result at all from the blood screens, and in those women there is often a high rate of chromosomal problems. In another University of Washington-led study, researchers examined one possibility of false positives: genetic variations in a mother.
In an email, Drs. Hilary Gammill and Jay Shendure said they decided to lead the study in part because the "impact of an abnormal result on families seemed to be particularly substantial...We believed that understanding the reasons for false positives might help alleviate some anxiety and provide a way to eliminate some of the false positive results."
While false positive results can occur for a variety of reasons, the genetic variation cause could possibly be lessened by changing some aspects of the prenatal tests algorithms, they said. "Though it is difficult to estimate the proportion of false positive tests that are due to (this form of genetic variation) we expect that it is a significant contributor," the two wrote.