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New and improved prenatal screening: do expecting parents understand what these tests mean?

“It’s your pregnancy. Demand the accuracy of the MaterniT21 PLUS test.” “No confusion. Just simple, clear results.” So reads Sequenom Laboratories’ website, speaking to prospective parents and health care providers. The MaterniT21 test is marketed as a noninvasive prenatal test (NIPT) screening for trisomies 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patu syndrome) by analyzing DNA It also includes other chromosomal abnormalities and can identify gender. Older tests for genetic errors like Down syndrome rely on less specific biomarkers in maternal blood and are not as sensitive or specific. The website boasts to health care providers about the tests sensitivity rates above 99% and very low false positive rates. “The test has been validated in the largest of its kind, independently designed, analyzed, and published clinical study,” the site claims. “The robust data is derived from testing more than 2,800 pregnant women’s blood samples, which included 375 trisomies. No other test comes close in terms of scale.”

So, this sounds great! New technology offering safe testing with a low risk of self positives. The statistics on the website were from a study that focused on women at risk to have these types of genetic abnormalities occur, a high risk population. A study published in the New England Journal of Medicine last year looking at a similar test revealed similar results for lower risk women more reflective of the general population. (Bianchi) Not only was the false positive rate better in this new NIPT when compared to older screening methods, but the authors also confirmed the positive predictive value was much better than standard testing and consistent with what would be expected in a low risk population (for trisomy 21, the positive predictive value was 45.5% with the newer DNA tests, only 4.2% with standard testing). Clearly, this is a huge step forward in screening for these genetic conditions.

Testing companies differ in how they report the results, but Sequenom advertises “The MaterniT21 PLUS test reports positive or negative results for trisomy 21, 18, and 13. For other fetal chromosomal abnormalities, we report it as an Additional Finding.” What these kinds of tests actually report, however, is not a “Yes, trisomy 21 is present” or “No, there are no problems”, they report a risk of a problem being present. The tests are very sensitive, meaning they don’t miss many of the chromosomal defects they are meant to detect, and it has a low false positive rate which means few false alarms (tests that come back showing a defect when there isn’t one). Remember, the positive predictive value in the Bianchi study above showed the positive predictive value (the probability that subjects with a positive screening test truly have the chromosomal defect) was 45% for trisomy 21 in a low-risk population. Of all the tests that came back showing a high probability of the condition, only 45% of the infants born did actually have the abnormality (1912 women, 6 positive tests, 3 false positive tests, 5 infants born with trisomy 21).

These tests are intended to be screening tests and are not considered to be diagnostic and as screening tests they are far superior to the testing that has been used over the past few decades. The recommendation is that follow-up diagnostic testing is done when a NIPT shows a risk of chromosomal abnormality. This information, combined with the woman’s risk factors, will give a much more accurate picture of the true risk. This can be a hard concept for expectant parents to understand, but their understanding is extremely important. The New England Center for Investigative Reporting (NECIR) reveals:

…evidence is building that some women are terminating pregnancies based on the screening tests alone. A recent study by another California-based testing company, Natera Inc., which offers a screen called Panorama, found that 6.2 percent of women who received test results showing their fetus at high risk for a chromosomal condition terminated pregnancies without getting a diagnostic test such as an amniocentesis.

Data from Stanford has also captured this phenomenon and in one case a woman underwent an abortion even after a confirmatory test which showed no problems because she felt the initial NIPT could not be wrong. (Daley)

Ideally, genetic counseling could be provided to prospective parents to explain this type of testing but this might be difficult to do practically. The family’s obstetrical providers might be able to provide some information, but in a standard obstetrical practice it is probably difficult for most providers to spend an adequate amount of time explaining the value and significance of such test. Fortunately, Kuppermann et al published a study in the Journal of the American Medical Association which found even use of a “computerized, interactive decision-support guide” lead to less use if prenatal screening and diagnostic tests and users of the decision-support guide demonstrated more informed decision making. While this study did not look specifically at NIPT, it shows that such a tool might be helpful for educating families about testing options and the value and use of prenatal testing.

As I discussed in my post on direct to consumer (DTC) genetic testing, the companies that produce these tests should ensure that the tests are being marketed responsibly. Certainly the strengths of the testing can be promoted, they are superior to older tests, but the actual clinical importance of the test and it’s role in screening, not diagnosis, should be clear to both patients and health care providers alike. Like the DTC genetic tests, these are not regulated by the FDA so there little if any oversight of the claims made in promotional material. Right now it appears advances in this technology are occurring faster than professional groups like the American Medical Association and American College of Obstetrics and Gynecology can adapt their practice guidelines and ensure that health care providers understand themselves the role these tests should play. As these tests must be ordered by a health care provider, it is up to that provider to ensure that the expectant parents receive true informed consent so the parents understand the screening nature, the strengths and the weaknesses of the testing options available to them.

The science of Results you can trust: MaterniT21 Plus. (n.d.) Sequenom Laboratories. Retrieved from:

Bianchi, D.W., Parker, RL, Wentworth, J. et al. (27 Feb 2014) DNA Sequencing versus Standard Aneuploidy Screening. New England Journal of Medicine. 370(9):799-808. doi: 10.1056/NEJMoa1311037

Daley, B. (n.d.) Oversold and misunderstood: Prenatal screening tests prompt abortions. New England Center for Investigative Reporting. Retrieved from:

Kuppermann, M, Pena S, Bishop JT, et al. (Sept 2014) Effect of Enhanced Information, Values Clarification, and Removal of Financial Barriers on Use of Prenatal Genetic Testing: A Randomized Clinical Trial. JAMA. 312(12):1210-1217. doi:10.1001/jama.2014.11479.


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