Advertising is the art of making whole lies out of half truths. ~Edgar A. Shoaff

Every few years a new screening technology comes zooming down the prenatal pike, sometimes arriving more quickly than we might like. First there was maternal age, with the magical age of 35 as the cut-off. Low maternal serum AFP arrived in the 1980s and the OB community embraced it virtually overnight when ACOG’s Committee on Professional Liability issued a statement that practitioners could be held legally liable if they had not offered this screen to a patient who had given birth to a child with Down syndrome. This was followed in short order by the Triple Screen, The Quad Screen, nuchal thickening, Integrated Screening, etc., each one a statistical notch above its predecessor. The latest iteration – cell-free fetal DNA or Non-Invasive Prenatal Screening (NIPS)  – stands head and shoulders above the rest. Two of our colleagues have already discussed the limitations and strengths of NIPS here on The DNA Exchange.*

NIPS is big, as in global big. One lab makes its brochure available in more 20 languages, from Afrikaans to Xhosa (the pregnancy gods must be crazy, dropping pamphlets out of The Cloud). Tens of millions of women around the world are likely to undergo NIPS in the near future. And pregnant women are a “renewable resource” –  a whole new batch pops up every day and many women will have two, three, or more children. Competition for market share among labs is stiff and there is little incentive to dissuade women from undergoing prenatal screening. It’s not that labs coerce women to undergo screening, advocate eugenic agendas, or run roughshod over personal autonomy. All labs would support a woman’s right to decline prenatal screening and Lord knows they stay away from the abortion discussion. But if enough women decline, then there is no incentive to offer the screen. The companies have something to sell and will spin their product to attract customers.

Which brings me to the subtly misleading implications of the name Non-Invasive Prenatal Screening. Sure, NIPS is non-invasive. But so is ultrasound, AFP, HCG, etc. All of these screening tests are non-invasive and therefore do not carry a direct risk of fetal loss. NIPS  is no different from the rest in that sense. It is superior to other screens in terms of having a very low first positive rates, high positive predictive value, and high sensitivity. But NIPS is still an alternative to other screening tests, not to amniocentesis or CVS.

Yet the websites of companies that offer NIPS communicate a different message that subtly suggests that NIPS is in fact an alternative to amniocentesis/CVS instead of an alternative to, say, the Integrated Screen:

First we thought the PC was a calculator. Then we found out how to turn numbers into letters with ASCII – and we thought it was a typewriter. Then we discovered graphics, and we thought it was a television. With the World Wide Web, we’ve realized it’s a brochure. ~Douglas Adams

The suggestion that NIPS is a diagnostic test is further reinforced by reassuring text in large, appealing fonts – Comprehensive, Accurate, Trustworthy, and, my personal favorite, No Confusion. Such wording conflates screening tests with diagnostic tests. Who could resist a test that boasts to be >99% accurate, especially when combined with images of smiling, beautiful parents and babies so cute that you wish your touch screen would allow you to hug them? It is easy to see why parents might be confused and some genetic counselors feel that 75% of their patients may think that NIPS is diagnostic. Yes, the labs also offer comparison to other screens, information about the conditions being screened for, links to disability focused websites, and acknowledge the role of diagnostic testing. But information does not sell products; images and impressions do.

The Treachery of Images by René Magritte

NIPS is a pretty good screening tool that can help patients decide if they want to proceed to diagnostic testing such as amniocentesis or CVS. However, the first step in the process of considering any testing should be a soul-searching and difficult discussion between parents and with their care providers about views on disability, parenthood, expectations for their children, and beliefs about pregnancy termination (I can’t prove it, but I am pretty sure that discussion is not taking place anywhere near as frequently as it should). For parents who feel it is important to know the chromosomal status of their baby, the next step is to outline the pros and cons of screening tests, emphasizing that a screen only provides a probability that a child may have a particular chromosomal disorder. The risk estimate provided by the screening test may help parents decide if they wish to undergo diagnostic testing.

One might counter that labs are commercial entities engaging in good old American advertising, which everybody knows is not exactly a strictly honest business. But prenatal screening is not like trying to sell Coke vs. Pepsi or Ford vs. Toyota or Chia Pet vs., well, whatever it is that Chia Pets are in competition with. We are talking about babies, our deepest hopes and dreams, and the core values that define our humanity. This demands a higher standard and this is where genetic counselors need to work with their laboratory employers to elevate the discussion.


* Missing from much of the professional  discussion about NIPS has been the viewpoint of people with disabilities, their families, and their advocates. As Rachel Adams points out, the Down syndrome community in particular might feel particularly targeted by a test named Maternit21 – but that thorny topic is for another day.


Filed under Robert Resta

11 responses to “NIPS SPIN

  1. Melanie Hardy

    A colleague pointed out to me that the cell-free fetal DNA companies did a really good job in naming their product… NON-INVASIVE prenatal testing. It’s interesting that genetic counselors and other health care professionals have spent so much energy debating the end of that title: NIPS (screening), NIPT (testing), NIPD (diagnosis – the one that makes us cringe…). However, it’s really the beginning of the title that counts to patients. The first words out of our mouths are “non-invasive” – as in: this test does not cause *imminent harm* to your baby and is a safe alternative to those (scary! scary!) invasive tests. Saying the name causes us to further accentuate the invasive nature of diagnostic testing which, in reality, is a rather safe method for getting comprehensive diagnostic information about a pregnancy.

    A student I was supervising the other day asked, “Do I have to tell the patient exactly what NIPT stands for?” I thought that was a really great question – I mean, how often do we take the time to outline the acronym “CVS”? If I call cell-free fetal DNA testing simply by an acronym (NIPT), then describe the benefits and limitations of the testing without the label of “non-invasive prenatal (whatever you prefer)”, I eliminate the NIPT-versus-amnio issue. It becomes, simply, one of several testing options that may be useful for the patient in their particular situation, and with pros and cons, just like the other test options.

  2. Katie Stoll

    Great article, Bob! Marketing for prenatal genetic tests does demand a higher standard and I think all in our profession (lab-employed or not) should continue to raise the questions and concerns you bring up here. For related read on this topic from a different perspective check out “Anatomy of a Webpage: Marketing Fetal Gene Tests and Sequenom’s MaterniT21” by George Estreich

  3. Emma

    Thanks for this article. I work with an ultrasound clinic. I am offering two different companies for the NIPS:-
    (Harmony- Ariosa) for the standard (T21, 18, 13 & sex chromosomes) and (Panorama – Natera) for the extended panel to rule out (22q, Cri-du-chat, Angelman, Prader-Willi and 1p36).
    I use my genetic counselling session to discuss the limitations and emphasise the fact that here in Australia, no-one would terminate a pregnancy on the basis of NIPS alone. So I try (without being directive) to encourage the use of NIPS at 10 weeks, so if a NIPS comes back high risk and CVS is required, this still allows them decision making time. However, in using NIPS in the case of an increase risk at the 12wk ultrasound and MSS – this then turns into an amniocentesis.
    I am working very closely with the OB and Sonologist in trying to educate the GP shared care physicians in offering the NIPS as an option at 10 weeks.

  4. Brianne Kirkpatrick

    Rob, wouldn’t you agree NIPS is in a category of its own, not really *screening* like the other screens and not really *diagnostic* like the diagnostic options?

    How can we call CVS a diagnostic test and consider it superior to NIPS when the rate of confined placental mosaicism is around 2% and the results received from CVS might reflect the chromosomal makeup of the placenta rather than the fetus? Not that we need to complicate prenatal genetic counseling sessions and confuse our patients any further(!), but I feel that NIPS is in a category of its own (“near-diagnostic”) and should be explained as such during prenatal counseling sessions.

  5. Robert Resta


    While I think that NIPS is clearly superior in most situations to other forms of prenatal screening, it is still a screening test (refinements in the technology may one day change that, of course). Just because it looks like a pipe does not mean that it is a pipe.

    For now, the only thing in common between CVS and NIPS is that both analyze placental DNA. CVS mosaicism is a different phenomenon than the positive predictive value of NIPS. No diagnostic test is perfect; even blood and skin karyotyping of a live born individual have inaccuracies stemming from mosaicism (See for example “Trisomy 21 mosaicism: We may all have a touch of Down syndrome” by Hulten MA et al Cytogenetics and Genomic Research 2013;139:189-92). In my views, lab websites can lead one to confuse sensitivity with accuracy.

    At some point the medical community agrees that the accuracy of a test is never 100% but as close to it as you will ever get in a less than perfect world and that it is acceptable to label the test diagnostic. Amnio & CVS are there; NIPS is not there, unless you wanted to describe NIPS as an inferior diagnostic test.

    It only confuses patients and everyone else to call a test “near diagnostic,” especially when the positive predictive value varies so widely with the a priori risk, from ~10% to >80% in typical clinical practice. Ceci n’est pas un test diagnostique.

    • Katie Stoll

      The limitations of CVS are being highlighted with increasing use of NIPS, and I predict this will continue. The acceptance of using CVS as a diagnostic tests came from studies of tens of thousands of women – pretty big studies. But still when we are trying to figure out the diagnostic accuracy for some really rare conditions, how big does the N have to be to really understand how frequently the fetal and placental cells are discordant for any given aneuploidy? NIPS is being much more widely used than CVS ever has been and through this I believe our understanding of the cytogenetics of the placenta will expand. My stomach sank when I started investigating the limitations of CVS as false positive NIPS results started emerge ( ). I think we need to seriously consider how we think and talk about the accuracy of CVS as a profession. Brianne, I can understand your concern about confusing patients with too much information about these complicated testing options, but I really feel it is our responsibility to be sure we understand the limitations of these tests and that we convey this in some way to patients who are putting their trust in us as the experts. CVS results do not always represent the fetal chromosomes and this should be made clear.

      • Brianne Kirkpatrick

        Bob and Katie,
        Thank you both for your responses. You provided deeper insight into the complicated issues surrounding NIPS and CVS and how these options are (mis)understood by genetic counselors and patients. I hope other readers gain as much from your replies as I did.

        Also, apologies to you, Bob, for getting your name wrong in my first post! I tried to go back and correct it when I realized my mistake, but there is no option to edit a post once it is up.

  6. Sarah

    Just a quick point- most of these tests are being marketed as ‘accurate’ or ‘having hgh accuracy’ when in fact it’s sensititvity and specificity they have high values for, not accuracy. This can be seen on some of the results where accuracy is given for some conditions but not all, and sensitivity and specifity is gven for all conditions.
    I’m still not 100% comfortable with the expanded screening (22q11 for example) in the absence of a anomaly on ultrasound – especially with highly variable conditions. I don’t think there has been enough thought about how to counsel women about these rare conditions and possible outcomes. And when it expands even further what do we do? There were some great lessons about this with how to give prenatal microarray results (Women’s experiences receiving abnormal prenatal chromosomal microarray testing results, Bernhardt et al) that I think we need to address asap!

  7. Leslie

    What is interesting to me is that there are, in my experience, patients that are ready to proceed with termination following positive NIPT/NIPS results and patients that essentially see this test as no different that a Quad screen. My dilemma with the test is based on more than one issue: on the one hand, for women who are using the test purely to get as much information as they can without the risk of an invasive procedure (the majority of the population at my clinic), it’s very useful. Women see the test as a way to find out that important information (knowledge is power!), and if by chance there is a false positive, then all the better for them. The woman was prepared for the “worst case scenario” (for want of a better phrase).
    I have also had those that I think actually grossly underestimate the power of the test, and remain quite skeptical until after delivery. I’ve had patient do their own research and actually become even more skeptical about the test. Though, to some degree, I imagine this is often a coping mechanism – it’s easier to say, “Well, it’s just screening,” than to accept the very high risk for a fetal chromosome abnormality.

    On the other hand, there are those who use the test because maybe they would like to avoid an invasive procedure, if possible, but they are using their test results for decision-making, and not purely for information to prepare for a child with special needs or a lethal condition. For these women, there are some ready to terminate just with the NIPS results because they did research and found how very low the false-positive rates are. There are others who may see the necessity to confirm with CVS or amnio because high accuracy is not the same as 100% accuracy, without any discussion from me. Still, often, it seems that no matter how clear I try to be about this test not being 100%, there are still women who are ready to make permanent decisions based on this screening. So far, I have been able to help these women see the reasoning behind confirming with traditional invasive procedures, but I dread the day when one of my patients goes forward with a termination against medical advice and recommendations.

    • Sarah

      Leslie- I completely agree that it’s concerning how many women are making decisions about termination solely based on NIPS results. I’ve heard from one of the cyto labs in the city I’m in that they are receiving products of conception for karyotyping after TOP based on NIPS results. They luckily have not had discrepant results but it’s only a matter of time. I’m not sure whether there’s people unergoing TOP based on first trimester screening results but I susect it would be a lot less likely because there’s more knowledge around that test and the false positive rate.

  8. Robert Resta

    Sarah and Leslie
    You both make good and worrisome points which further highlight the need – no, the ethical imperative – for labs to advertise their products honestly, openly, and accurately.

    Bob Resta

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