cell free DNA is NOT Diagnostic

SMFM logo imageWhile this point has been made in multiple professional statements and news reports–including here–the Society for Maternal-Fetal Medicine (SMFM) felt it worth reminding the world that cell free DNA is NOT diagnostic.

At the close of 2014, a bombshell report appeared in the Boston Globe by the New England Center for Investigative Reporting (NECIR) about the newest form of Down syndrome prenatal testing. Non-invasive prenatal screening (NIPS) has been hailed as the “holy grail” of prenatal testing: able to provide more accurate results with no risk to the mother or the pregnancy. But all this hype has led to mass misunderstanding on what NIPS results actually mean and women are making irrevocable decisions based on false information.

The SMFM felt the NECIR report justified an updated statement in the hopes of clearing up this misunderstanding on what NIPS results really mean and how NIPS testing should be administered.

From the statement:

It is important for providers to remember that cell free DNA is a screening test, and does not have the diagnostic accuracy of amniocentesis.  By its very nature, a screening test does not tell with 100% certainty whether or not a fetus will be affected by a given disorder. Unfortunately, in part because of the high stakes in this very competitive market, the tests are being presented as having >99% accuracy, the same accuracy as is used to describe amniocentesis and CVS. 

Links in the quote are to relevant posts further expanding on the points made in the statement.

The SMFM provides a helpful bullet list for providers and patients to understand about NIPS:

  • cfDNA tests are screening tests, not diagnostic tests.
  • Abnormal results must be confirmed with diagnostic testing via CVS or amniocentesis before irreversible action, such as pregnancy termination, is undertaken.
  • Although cfDNA tests have greater sensitivity and specificity than traditional serum screening, false positives and false negatives still occur.
  • The likelihood that a patient with a positive cfDNA has an affected fetus – the positive predictive value – is lower if her background risk is low. For low risk women and for rare disorders, a positive test is more likely to be a false positive.
  • cfDNA testing is therefore not recommended for low-risk women.
  • Because the background risk for microdeletions is extremely low, a high-false positive rate is associated with cfDNA detected microdeletions.
  • Genetic counseling services are an important part in providing information in the care for patients.  The SMFM recommends payers provide adequate reimbursement for these services to provide ideal care for patients.

While these points have been made before, in professional statements and in other publications, the NECIR report that women are aborting their pregnancies on the misunderstanding of NIPS’ accuracy justifies the SMFM’s recent statement.

The SMFM further calls on the NIPS laboratories to take specific measures to improve understanding of their NIPS offerings:

Companies offering cfDNA should take steps to ensure that providers and patients interpret test results correctly. The Society suggests the following steps:

  • Test results should be reported with a positive-predictive value or patient-specific risk, as is done with traditional serum screening.
  • Given the risk of false positives with screening for rare disorders such as microdeletions, these tests should be offered as “opt-in,” rather than “opt-out” options, ideally only after counseling by a genetic counselor.

Practitioners and women are are misunderstanding that NIPS remain a “maybe” and before any decision is made to terminate a pregnancy, NIPS results should be confirmed by diagnostic testing. Further, SMFM emphasizes the role for genetic counseling and the need for that counseling to be reimbursed. And, perhaps most pointedly, the SMFM calls out the NIPS laboratories, like Sequenom’s MaterniT21, Ariosa’s Harmony, Illumina’s verifi, and Natera’s Panorama, for their responsibility in creating the misunderstanding and their role in improving accurate understanding of their testing products.

We’ll see as 2015 progresses if practitioners and the NIPS labs heed the SMFM’s call for ethical, responsible care to be provided expectant mothers when offering them NIPS testing.


  1. kweansmom says:

    I’m a mom of a child with Down Syndrome and I’m on several online forums. Anecdotally, I hear stories of doctors offering to terminate, even strongly recommending it, based on Quad Screenings and tests which are much less accurate than NIPS. I don’t know if this is true but I hear it a lot. And this is in the 21st century, not a generation or two ago.

  2. I see a lot on false positives but what about false negatives? I am 39 and will be 40 when I deliver. I had the cell free DNA test through labcorp at 10 weeks and came back negative. My dr doesn’t recommend the first trimester bloodwork if you do the cffdna test but I did have the nuchal ultrasound and all looks good. The only other test they will do is the AFP. My concern is that last year I had a miscarriage due to Trisomy 21. Between my age and last experience I am wondering if I should do an amnio. My dr seems to think that we can rely on the cffdna test and not do amnio due to risk of miscarriage. Based on your read of the literature, what is likelihood of a false negative?

    • While false negatives do occur, they are far rarer than false positives. Moreover, you still had cfDNA from your previous miscarriage in your blood stream and I would have instead thought that may have resulted in a false positive for your current pregnancy. The clear nuchal and the screen-negative cfDNA result suggests a high probability that your baby does not have one of the tested-for conditions. From the beginning, an amnio was the only way to know for sure, but given the increased chance that you had from your prior miscarriage and your age, the fact that you have two negative screens means your likelihood of NOT having a child with one of the tested-for conditions is actually more likely given the screen results.


  1. […] were made based solely on a NIPS result. In response, the Society for Maternal Fetal Medicine issued a statement emphasizing that a NIPS result is […]

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