By Lisa Demers
Lisa Demers is a certified genetic counselor working in a prenatal diagnosis program at Dartmouth-Hitchcock in Nashua, NH. She graduated from the Arcadia Genetic Counseling Program in 2003. Lisa has been president of the New England Regional Genetics Group, is a member of the New Hampshire Perinatal Loss Taskforce, and is the proud mother of two little boys who teach her more and more about Star Wars every day.
I feel like it’s time to show some appreciation for the amazing screening test that has truly enhanced the prenatal screening world. Non-invasive prenatal screening (NIPS) has taken our prenatal world by storm and is rapidly infiltrating university hospitals and private practices alike. This is a change (who really likes change?) and it’s fast. Testing has jumped out of the controlled hands of research laboratory scientists and into the lucrative playing field of investor-backed industry. But is this a bad thing?
NIPS has taken traditional screening and made it better. There is no denying that NIPS is a superior screening test. The benefit of NIPS over traditional screening is acknowledged by the rapid approval of coverage by major insurance plans. I applaud Katie Stoll in her eloquent summary of the discrepant positive predictive value (PPV), but I do not think this area of ambiguity should overshadow the benefits of testing. The PPV for a “high risk” (or whatever language the report contains) sample, even if it is 11% (using the data in Katie’s initial post), is about the same as a 1 in 9 risk for trisomy 18 using traditional methods. So is the counseling really very different? “This screening test suggests a very high risk for trisomy 18, diagnostic testing will tell us for sure”.
Our knowledge about how to best utilize this test and interpret the results is an ongoing process. This is completely on par with other technologies. At one point, supernumary rings were identified on karyotype with little way to identify the origin. The argument that we shouldn’t use a technology until we completely understand it is unreasonable. We need large testing numbers to give us these uncertain results so that we can learn from them. Ambiguity with test results is hardly a new concept for us. Genetic counselors deal with this all the time! Our counseling isn’t really changing; it’s just the same uncertainty coming from a different test.
I argue that this test provides much LESS ambiguity since most women are getting reassuring results. The number of women who are screen positive is dramatically decreased. Fewer women being anxious, fewer amnios being considered and performed, and fewer losses of otherwise normal babies. And why wouldn’t an informed patient want the BEST screening test? And why wouldn’t providers want to offer it?
I absolutely acknowledge that not all patients are fully informed about NIPS prior to testing, and I hate to think about the ignorance that providers may pass along to patients. But what genetic counselor hasn’t had a patient arrive at their office with an abnormal screening result thinking that their baby is, in fact, affected? We hear this endlessly. And how long has traditional screening been around? And those results even have a risk estimate listed! Sometimes I like being the hero in these situations “You mean my pregnancy is at a one percent risk for Down syndrome? What a relief!” The misinterpretation of testing results is inevitable. We should not back away from better testing simply because some people do not understand.
While I agree that I would prefer that the commercial labs present their results with some more obvious notation of the limitations of the testing, no report can eliminate ignorance. So perhaps our focus can be a shift to better education. After all, isn’t that we do? We need to talk with providers in our area and help them understand the test more clearly. Review with the nursing staff when a referral is sent to us that the results are screening and not diagnostic. I can tell you that in my own experience, education isn’t always successful because I still have providers who offer universal SMA and Fragile X testing without being able to interpret the results. *Sigh* But these patients are ultimately referred for counseling, and I consider that a success.
Education at the patient level is important too. Group counseling sessions can be an effective way to inform the pregnant population, especially about universal topics like screening. The overwhelming task of education is not unique to prenatal genetic counselors, but to the profession as a whole. Rather than hold back on a test that is truly superior because providers misunderstand it, why don’t we try to tackle the larger issue of provider education?
What I hope is that the consumers of NIPS can work closely with the industry providers to further study the performance of this technology to better understand cell free fetal DNA and its utility in pregnancy screening. Let’s work together in educating providers about the testing and the importance of pre-test counseling. Patients deserve it. Without the cooperation and participation from genetic counselors we risk delaying universal acceptance of NIPS. Let’s all jump aboard and steer this train.
The DNA Exchange 
Thank you for this thoughtful post, Lisa. I agree that NIPS is a very good screening test, and that genetic counselors are well equipped to lead the way in education regarding this and other new genetic testing technologies. I am also passionate about considering innovative ways to reach people with accurate and balanced information, like group appointments, http://www.ncbi.nlm.nih.gov/pubmed/23662746 . As you point out, genetic counselors have decades of experience to draw from in managing uncertainty and as genetic counselors, we can look at a “high risk” NIPS result and recognize it as a screening test which in some ways is similar to an increased risk with analyte screening. The reality though is that much of the counseling being done about NIPS results is taking place outside of the genetic counselor’s office and with good reasons (like limited access to genetic counseling services in their community) https://thednaexchange.com/2013/11/04/nips-and-the-threat-to-informed-decision-making/ . In my observations, it is not always clear to patients or providers that this is a screening test, and it appears that the marketing of these tests has led some to believe that this is diagnostic or nearly-diagnostic (http://www.ncbi.nlm.nih.gov/pubmed/24375317 ). So yes, it is important for us as genetic counselors to take the lead on education regarding both the benefits and limitations of NIPS in our communities and as part of a national conversation. In order to steer the train in the direction we want it to go (i.e. to support patients making informed and value consistent decisions) we need to have a significant role in laying the tracks and not just be passengers on a commercial agenda. I look forward to further discussion and collaboration.
I am concerned about the bias demonstrated in this post. I fully understand the excitement that so many people have for cell free DNA and the potential of the technology. However, I’m reluctant to jump on the NIPS-is-the-new-MSS bandwagon without deeper consideration of what NIPS *doesn’t* tell us. Down syndrome, T18, T13 and gender chromosome anomalies are NOT the only genetic conditions that may affect a pregnancy.
One of the things that I still appreciate about traditional MSS (especially when combined with first-trimester sonography for markers/anomalies) is the presentation of a risk estimation. For the patient with a 1:10 risk for Down syndrome, I’m thinking strongly about the potential for other genetic conditions as well. Even if that patient follows with negative NIPS testing, I can have a really impactful conversation about further test options that may continue to be considered to look for other possible genetic conditions. Compare that patient to another patient with a 1:10,000 MSS risk. If both patients had only a negative NIPS result (ie, they never did the MSS) and had no other risk indicators, they appear the same in regards to genetic risk. With only NIPS, we may have now lost the opportunity to further evaluate the 1:10 patient through detailed US or other testing.
A follow-up conversation about “there is always a chance for other genetic conditions not detectable by NIPS” is lost on NIPS-only patients because their HCP reported the NIPS result with “everything looks good” – and that patient (surprisingly?) took that to mean that *everything* is okay with their baby. Even if the result is presented more accurately, it still sounds to the patient like *everything* is okay because there is nothing to alert them to other genetic possibilities besides some HCP who is raining on their pregnancy parade with a very obligatory-sounding statement like “this test cannot detect all possible genetic conditions”.
Genetic counselors are obligated to fully evaluate genetic tests for their benefits, risks and limitations. Other HCPs often lack the time or training to do this to the extent that we GCs should be. If we jump so easily to the belief that the shiny newness and potential performance of NIPS is all that is required to fully embrace it as the ultimate replacement for other screening tests, how can we expect other HCPs to present this testing or its results in an unbiased fashion to their patients?
Very true, Melanie! I also feel a longing for the “hidden” implications in the traditional maternal serum screening of analytes (and NT ultrasound). It’s hard ignore the value that we have held onto by fully evaluating each biochemical marker.
In my opinion, your comment hasn’t really highlighted a weakness in my thesis, but rather supports it. My point is that NIPS is a far superior screening test for trisomies 21, 18, and 13. There is no doubt about that. How we use this test, how we present it to patients, and how we “role model” for other providers is what is critical here. So thank you for reiterating that point! The education needs to be there that this is a SCREENING test, and only for the conditions listed (because it’s expanding all the time these days!). The “off label” uses of biochemical screening (the secondary information gained from MSS aside from the intended use for screening for Down syndrome, trisomy 18, and ONTDs) are still out there — will they remain in strong contention for pregnancy screening? I think we have to wait and see. I look forward to learning how this all will be incorporated.
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