Americans’ public understanding of science is woefully inadequate. We are remarkably ill informed on issues as wide ranging as evolution and climate change, rendering us uniquely vulnerable to manipulation by special interest groups and startlingly gullible when it comes to the peddling of pseudoscience “cures” by quacks and charlatans.
That’s why it is especially disappointing to see a mainstream publication featuring a piece that actually increases public misunderstanding of science instead of ameliorating it. Unfortunately, Libby Copeland’s article The Alarming Inaccuracy of Prenatal Testing displays a remarkable lack of understanding of science, explaining nothing, confusing everything, and creating unnecessary fear for pregnant women.
According to Copeland:
The New England Center for Investigative Reporting has a story out that should alarm every woman who’s recently had blood drawn for a prenatal screening. Beth Daley reports that, “sparked by the sequencing of the human genome a decade ago, a new generation of prenatal screening tests…has exploded onto the market in the past three years. The unregulated screens claim to detect with near-perfect accuracy the risk that a fetus may have Down or Edwards syndromes, and a growing list of other chromosomal abnormalities.”
The problem is, they don’t.
Copeland’s central claim is utterly false.
Copeland, who is generally an excellent writer, falls into a common trap that afflicts the unwary. She fails to recognize the difference between the colloquial meaning of words and the meaning within scientific discourse. Because she utterly misunderstands the use of words like “screening,” “accuracy” and “predictive,” she has produced a breathless piece of baseless fear mongering.
Before we can understand what’s wrong with Copeland’s piece, we need to understanding the meaning of those words in scientific discourse. Let’s start by framing the problem.
Most expectant parents want to know if their unborn child is afflicted with a serious genetic problem. With the information in hand, they may choose to terminate the pregnancy or to consult with appropriate specialists to prepare for the birth of the child. Amniocentesis (putting a needle into the uterus and drawing off amniotic fluid for analysis) can provide a nearly 100% accurate diagnosis of the major genetic problems of interest such as Down’s syndrome.
Amniocentesis is a diagnostic test, because it provides a diagnosis. The problem with amniocentesis is that it is invasive, expensive and increases the risk of miscarriage. If all 4 million pregnant women had amniocentesis each year, there would be hundreds of miscarriages and the cost would be astronomical. Obviously we don’t want to do that. What we’d like to do is restrict the use of amniocentesis only to those women at high risk of carrying a baby with a serious genetic problem.
How do we find out who is at high risk? We offer all 4 million pregnant women a screening test.
The critical difference between a diagnostic test and a screening test is this:
A screening test can never provide a diagnosis.
Never!
What do we mean then when we talk about the accuracy of a screening test if a screening test, by definition, can NEVER give us a diagnosis?
The perfect screening test would mean that everyone who has a positive test result actually is at high risk (positive predictive value = 100%) and everyone who has a negative result is actually at low risk (negative predictive value = 100%). However, and this is the critical point, even a perfect test with 100% positive predictive value and 100% negative predictive value could NEVER tells us which child has Down’s syndrome or any other major genetic problem. It can ONLY tell us who ought to have amniocentesis; that’s it, nothing more.
Copeland clearly does not understand this when she writes:
… [W]hile these non-invasive prenatal tests are more accurate than the combination of blood test and ultrasound … they nevertheless can lead to false alarms as much as half the time. The rarer the condition, the greater the risk of false alarm. And yet they promise things like “99% Accurate, Simple & Trusted.”
The test promises that is is 99% accurate AT IDENTIFYING WOMEN AT RISK, not at diagnosing major chromosomal problems.
Copeland concludes her piece with a bit of information that she believes is a scathing indictment of the test, but it actually a scathing indictment of her understanding:
Three of the labs returned results indicating that the women were pregnant with healthy female fetuses.
The catch? The women who gave their blood samples weren’t pregnant at all.
That’s only to be expected from a screening test. A false positive means that the test indicates high risk for a major genetic problem when no major genetic problem exists. Therefore, a non-pregnant woman could have a false positive test. This is not news to people who understanding screening tests.
Copeland had a perfect opportunity to educate people about what screening tests can and cannot do, and she blew it. But she could redeem herself and her piece. Copeland could write a revision explaining her error and why expectant parents shouldn’t make the same error that she did. That would increase the public understand of this specific area of science, which, presumably was the reason for writing the piece in the first place.
The fact is pre-natal screening is encouraging mothers to perform medical procedures that are dangerous to the fetus. Would you walk into a room if you knew there is 1 in a 100 chance that you will die in there?
Let’s look at the numbers. If we take the statistics for the quad test with NT (the most accurate at the moment)
– The test gives 1.6% false positives
– the number of children born with Down syndrome is 1:1000
– the risk of miscarriage following amnio is 1:100
– the number of pregnancies per year 4,000,000
If we assume that every mother in US will get the screening test, and if the result is positive, will do amnio, we will get 6394 dead babies per year, who would have been alive and healthy if the test did not exist.
In addition, T21, T13 and T18 are relatively common, but most babies born with genetic abnormalities, particularly to mothers under 40, will not have these particular disorders – they will have something else, that the tests don’t see. So, a negative test does not really mean that the mother is significantly more likely to have a healthy baby, compared to one where the results are not known.
Where are you getting your numbers? Amnio increases your miscarriage risk by 0.25%. Most sources put the risk of loss related to amnio at one in 400. And the risk of Down Syndrome is heavily age-dependent. 1in 350 at age 35 and 1 in 30 by age 45. So your analysis is WAAAY off
and besides most of us are not using the quad test with NT. We’ve moved on to much more sophisticated approaches, like ultra screen with NT or cell-free fetal DNA from mom’s blood.
There is a lot of misunderstanding about the application of a test to a low-prevalence population (such as Copeland’s comment about the women who weren’t pregnant).
According to Bayesian reasoning, the lower the pre-test probability of the condition being tested for, the greater the chance of false-positives. This is just one of the issues with the over-use of testing that results from risk-aversion.
It’s Down Syndrome, not Down’s, but yeah.
I’ve encountered a lot of pushback against genetic screening in the NCB crowd, as well as from the disability activists. I wanted the screening, and if necessary, diagnostic testing, because there are certain conditions that I would have wanted an abortion for. I couldn’t even get my doctors to do the blood tests early enough that I could still have a first trimester abortion, nor could I talk to anyone about it online because instead of support, I got a lot of “Oh, *we* would *never* do the testing because we would love our child for whatever length of time he or she was with us.” There was A LOT of emphasis on how often the tests are wrong. And from the disability folks, a lot of talk about how their lives are devalued whenever anyone aborts a fetus because of genetic abnormalities that aren’t endangering the health of the mother.
I understand the disability activists’ point of view, particularly w/r/t Down’s Syndrome, but no one was ever supportive of what the mother goes through.
Definitely. It’s one thing to be willing to raise a child with a disability, for example, but another thing to carry a pregnancy to term after a fatal or most likely fatal diagnosis. Some women choose to do that, but none should ever be forced to.
Don’t forget the pushback from people who have had miscarriages. I recently learned that I am a horrible person who minimizes others’ suffering because I believe that life starts at birth, and therefore it is abusive to force someone to go through a pregnancy they don’t want.
I have friend raising a son who has Down Syndrome, he is a joy to his family, but her life is not one I would choose for myself and my family.
I know what it is like to go through painful surgeries, and physio, and OT, to have a good outcome and the intellectual ability to understand that the pain was worthwhile.
Would I want to subject my child to a life of pain and disability with few positive gains and little chance that they would ever understand why the pain was necessary? No.
Would I opt to continue a pregnancy affected by a lethal abnormality if I had the opportunity to end it before my child could feel pain? No.
I have lost wanted pregnancies. Has that changed my beliefs? No.
I expect other people will have different values and beliefs and that these may guide them to make different choices. It is their life to live, the best they know how, and if they make different choices, well, that’s ok.
I would like them to afford me the same respect and assume that just as their choices are based on sincerely held personal beliefs and ethics, so are mine.
“Worst of all, Daley reports cases where women aborted based on those screening results alone, without getting confirmation from amniocentesis.”
A bit of the author’s bias on having an abortion for the “right” reason showing through in that phrasing. There are giant swaths of the country where abortions aren’t available after 12 weeks pregnancy. So waiting for a confirmatory test (which may or may not confirm anything) can actually mean waiting until an abortion is prohibitively expensive due to time and travel expense.
Second trimester abortion may not be available or the woman might not be comfortable with it. There’s a sizable group of people that would have an abortion at 8 weeks but not at 18 weeks, and almost everyone agrees that sooner is better than later for a whole host of reasons.
“In one of the three Stanford cases, the woman actually obtained a confirmatory test and was told the fetus was fine, but aborted anyway because of her faith in the screening company’s accuracy claims. “She felt it couldn’t be wrong,” Cherry [Athena Cherry, a professor of pathology at Stanford] said.”
This woman is an idiot. There’s no cure for that. I can’t imagine the conversation she had with her doctor.
It could be that she wanted to terminate for other reasons, but thought that this may be a more socially acceptable excuse.
that’s true.
All the crap that is in the media makes me wonder why it’s so hard to write about this topic with any sort of accuracy. I don’t think you have to be a doc to do it, or a genius, just have a working knowledge of the topic and a willingness to ask experts when needed.
I guess I shouldn’t be surprised, the media writes wonderful puff pieces about how pit bulls are perfect pet for families, too. (Just don’t look at the pile of mangled (500+) and dead (27) bodies in 2014)!
Okay, y’all. I literally JUST got back from my genetic counseling and first trimester screening/cell-free DNA test, and I am here to report that the genetic counselor and sonographer were EXPLICIT in their insistence that these tests were SCREENING tests, and to be absolutely sure, amnio/CVS must be performed. so the journalist is being disingenuous, at best. I find it difficult to imagine that a woman could walk out of these counseling sessions misinformed.
PS: NT’s looking good.
I don’t think it’s a matter of being misinformed. It’s a matter of being scared shitless. I’m a former scientist and current attorney and actually quite smart and you could tell me til you’re blue in the face that it’s screening blah blah blah. All you think about is how you did this test to look for scary things and the test shows a strong likelihood of scary things. And you gotta now wait 6 long weeks. Thank goodness for sequenom my second time around.
I am a genetic counsellor and it’s amazing what people recall from appointments- the confusion around screening and diagnostic tests is the bane of my existence and part of my PhD
Studies have shown that very large numbers of people “mis-hear” whenever they are under stress — for example, when given instructions in the ER, something like 80% later either cannot recall what they are told, or get it wrong, which is why it’s important to get written instructions [that assumes the patient has basic literacy; too often instructions are quite complex and full of jargon]
The patient nods, and says he understands, and all the time his/her mind is still trying to absorb something else entirely.
We often *would* understand if our brains weren’t still circling around WTF happened? After my last trip I had to call the friend who drove me to ask about how long the doc I should wait to change it, ’cause I couldn’t remember. Not rocket science
Okay, now I’m starting to panic. Had the blood screening, came back as low risk for everything. Is there still a chance something could be wrong? 36 IVF pregnancy. He does have water on his kidneys…
Yes, there’s still a chance that something could be wrong. Screening tests are not diagnostic. If you’re worried, talk to your doctor or genetic counselor. Good luck.
The tests probably also include the probability of a false negative result, what it is depends on your age and on exactly which tests were done. Ask your doctor if it wasn’t provided. It’s very small, but not zero.
That being said, there are far less serious reasons for a reading of water on the kidneys.
One of my sons had bilateral pyelectasis at our 24 week scan, still had it (but milder) at 36 weeks. They scanned his kidneys the day after he was born and things had resolved.
I was terrified at the results from the first scan, but my OB told me it is not all that uncommon (especially for boys), typically resolves on it’s own, and if they know about beforehand there’s a lot they can do once baby’s out if it’s not resolved.
There’s always a chance, however tiny, something could be wrong. Good prenatal care and delivering at an appropriate hospital are your best bet for reducing risk and managing any complications.
Mildly dilated kidneys and/or ureters are really common, especially in boys. If mild, it is likely to be nothing at all. Obviously your situation is best discussed with your doctor, as this is just a general statement and something I learned on my ob/gyn rotation
This is a great example of the state of journalism today. This sort of thing should never happen, because you should have fact checkers on staff whose job it is to make sure that the facts are all correct, and ideally you should have any article written by a lay person checked by someone who actually understands the science. But you get less and less of that in journalism these days because news agencies either can’t afford to pay for good journalism or they just don’t want to. I feel really bad for the author … she was trying to do her job, got misinformed, and had no one on staff who could help her avoid making a really embarrassing mistake.
That’s what I was wondering? Surely there are doctors/scientists/academics that can give an educated opinion on what you’ve written? My physics lecturer from uni was regularly on the news giving his expert opinion on the ‘alien sighting’ stories (generally a slow news state here).
It seems like Dunning-Kruger mentality meets the whole flattery of encountering “insider knowledge” – in blog posts from lay people it is largely expected, but on a website that claims some credibility for news it would surely be inexcusable?
I got a journalism degree back in 1997. Fact checking was taught as a part of the process, not as an afterthought or something you just do if you have the time and the resources. You had to do it, just like you had to do research and interviews. I did some work as a fact checker when I was young and I fact checked everything–even facts that weren’t relevant to the main subject of the article. If it was presented as a fact, I checked it. The idea of allowing an article to go to press that contained information that wasn’t true was something I had nightmares about. It honestly boggles my mind that an article like this would ever make it out into the world. But then, I don’t work as a journalist. (Most) journalists make a really poor living, which really does explain why the quality of journalism is just not very good. I’m betting (though I don’t know) that a lot of publications no longer employ fact checkers, but just require the writers themselves to do their own fact checking … which is a really, really bad idea.
Embarrassing? I doubt anyone else even notices.
This is what you get when you quit paying journalists.
Thank you for this, Dr. Amy. I am a layperson who has had both screening and diagnostic testing during pregnancy. The misconceptions around both are astounding, and this article is woefully inaccurate.
Here is the scenario I faced with my one successful pregnancy: 1. I am a carrier for Hemophilia A. Any son I have has a 1 in 2 chance of being a hemophiliac. I would not terminate for hemophilia, but I did want to know if I was having a hemophiliac, because it would have significantly altered my prenatal care and mode of delivery (I would have opted for a section).
2. I was also AMA during all of my pregnancies and a month shy of 40 during my successful pregnancy. Two of my prior pregnancies were lost to aneuploidy. I wanted to know if I was having a euploid baby, and I would have terminated for T18, T13, was undecided on T21. The point is, I wanted to know what I was facing so that my husband and I could be aware and informed.
I skipped the first trimester screening, with the exception of NT ultrasound, as it can be useful in screening cardiac issues. CVS was performed at 12 weeks by a perinatologist with a loss rate of 1/800 for this procedure. 46XX, and we were overjoyed.
We faced a number of questions and criticisms from people who just didn’t understand (“why don’t you just do the blood work?”) or were not in agreement with our choice (“why risk a miscarriage? what if you lose a healthy baby? would you really terminate for _____?”)
Ultimately, screening and diagnostics are a personal decision. But it’s not one that can be accurately made without the right information. This article is just depressing. I hope Copeland is willing and able to correct her errors.
I am enormously grateful that these screening tests were not available 10 years ago, because I have a beautiful, healthy, chromosomally-abnormal female child taking a shower right now in our bathroom. Her condition is rare, published information suggests scary outcomes, and the pressure to terminate would have been high. We need much better information in the scientific literature on the full range of potential outcomes associated with different conditions (positive and negative), so parents can make informed choices.
Among two of the most common aneuploidies most likely to result in a live birth (Edwards syndrome and Patau syndrome) the information in the scientific literature doesn’t cover positive outcomes because they are quite rare. With the most common aneuploidy, Down syndrome, the full range of outcomes is well covered. The thing is, with a prenatal T21 diagnosis, you don’t know where your child will fall on the spectrum of outcomes with respect to health, intellect, and development.
When you refer to “pressure to terminate”, I assume you are referring to family and friends, because that is not the role of genetic counselors. My sisters and I have had extensive genetic counseling due to our family situation (uncle with severe hemophilia A and two out of three of us are carriers) and though termination has been discussed, none of us have ever felt pressure to do so.
Screening and diagnostics are a personal choice. I am happy that they exist, even if some choose not to avail themselves.
I am glad your daughter is well.
In our case, the “pressure to terminate” would absolutely have come from family and friends. I respect that these are highly personal decisions and every family situation and genetic condition has its own unique aspects.
Our reality is that coming from over-educated families full of PhDs, we probably would have terminated for a genetic diagnosis that looked to have a high probability of moderate to severe intellectual disability. And if we had done that, the world would be worse off. For example, our daughter has a unique connection to an elderly woman with dementia and her regular visits to the “memory care facility” bring the residents there absolute delight. This is not a relationship that would have developed if our daughter was neurotypical.
So it’s a conundrum. I am glad that screening and diagnostics exist and I know they have saved people from a lot of heartbreak. But I don’t think genetic screening and diagnosis are an unalloyed good in every case.
But you don’t have a retrospectoscope. You see things now through the lens of having a beautiful and healthy daughter, and I am happy for you. But you don’t know what you would have done. It’s why it pains me to read things like, “I would never terminate”, because until you are there, you truly don’t know.
I lost two aneuploid babies, one was T18 and the other was T16. From the start, those pregnancies were fraught. I don’t know how to describe this very well, but watching your baby on the screen during a 7 week ultrasound, watching its heart just struggle to beat — something so fundamental to us all that we take for granted — it was so very painful. I wanted that baby to live, no matter what, in that moment. But once I knew what his life was likely to be like, should he make it out of me alive, my ultimate choice a little bit down the road was to terminate. In the end, I didn’t have to make the call, because I lost him anyway.
Everyone has an opinion, don’t they? Some don’t know when to keep their mouths shut. My husband and I spent tens of thousands on ART, had multiple losses, we were almost 40 and 42 when our daughter was born, AND I carry the gene for a pretty serious disease. Yes, people have opinions.
Another side of the coin — my uncle is a severe hemophiliac. He was born in the early 50s. He suffers from spontaneous bleeds and spent the majority of his childhood at the Hospital for Sick Children in Toronto.
My grandfather was a dentist, my grandparents were upper-middle class. My uncle’s illness bankrupted them, my grandfather eventually lost his practice and my grandparents had to sell their home at a loss. It robbed my mother, the eldest child, of any real semblance of a childhood, because she had to care for her younger siblings as my grandmother spent most of her time with my uncle at the hospital. My grandparents marriage suffered, everyone suffered. There were times when my uncle was near death and he was given Extreme Unction more than once.There was no conundrum, it all just really sucked.
As my uncle grew and aged his illness slowly became somewhat more manageable. He went to university, had a career, married, had children. He also contracted Hep C from tainted blood, and will likely not live much beyond his next birthday.
His daughter is an obligate carrier. She is no stranger to hemophilia, she lived it, yet she chose to have a child. Opinions? Lots of them. Her only child, a son, was born with a less serious expression of the disease – there’s a host of things he cannot do (contact sports, for one) but he is nowhere near as sick as his grandfather was at the same age and treatment/understanding/management options have improved. And we have socialized medicine, so my cousin has never had to pay out of pocket for her son’s care.
But here’s the big thing, the one thing my cousin had that my grandmother didn’t that mattered more to her than anything else — she had time to prepare. She knew ahead of time that her son would be a hemophiliac. She knew what that could look like, that the odds were >60% that her son would have the most serious expression of the disease, like her father does. She got lucky, and he does not. But she had time, information, knowledge. I just cannot see how that is a bad thing.
With all due respect, how do you know people aren’t making informed choices? It seems your issue is more that people are not making the choice *you* would have made.
Well, our daughter has a substantial deletion on chromosome #9. After she was diagnosed at age 3, the geneticist gave us a copy of everything he could find in the literature on her syndrome. Every study said “global developmental delay”, “moderate to severe mental retardation”, “life-long care”, etc. Does she have learning and social challenges? Sure. But she also has above-average verbal intelligence, reads, rides a bike, and brings a lot of joy to the world. So in our case, for HER specific syndrome, we could not have made an informed decision about continuing or terminating the pregnancy based on the scientific literature, because kids like her are not represented in the descriptions of her syndrome.
Davidah “because kids like her are not represented in the descriptions of her syndrome”
Have you considered asking anyone responsible for her medical care to write up a case study?
If your complaint is that the information isn’t out there – well, get yours out there.
Davidah, I am glad your daughter is so well.
However, imagine you were to tell your story to a family who has just got the same diagnosis, who know that they do not feel able to care for a severely disabled child. They are given hope that their baby turns out like your daughter and decide to proceed with the pregnancy.
Their baby then, sadly, turns out to have a very short, limited life, they are bankrupted by medical bills and their marriage collapses under the stress.
Is that a good outcome either?
People need to know the most likely outcomes, to hope for the best but to be prepared for the worst.
If doctors paint a bleak picture, and the parents say “ok, we can still cope” and things turn out better than expected it is far, far more ethical than if they paint a rosy picture to people who would choose differently if faced with a bleak outlook, and then these people end up living a life they would never have chosen if the hopeful predictions turn out to be too optimistic.
I have Spina Bifida on the milder end of the spectrum, my sister died at a day old from undiagnosed Congenital Diaphragmatic Hernia. I have had miscarriages of wanted pregnancies, and I would still end a pregnancy affected by severe Spina Bifida, fatal abnormalities or trisomy.
I am so happy that your daughter is exceeding expectations, but giving people less information or falsely hopeful information is not a good response to her story.
Also, the new screening tests actually DON’T pick up on the rarer partial duplications or mosaic trisomies . . . they just pick up on abnormalities of 13, 18, and 21 (and X and Y).
If you tell doctors before hand that you don’t want any mention of termination in the case of Down Syndrome, they won’t mention it. My son’s NT screening came back borderline and my OBGYN only gave us information on caring for people with DS and resources for help and support should we need it. We opted not to do the amnio, and figured we’d just assume he would be born with DS and prepare for that. My son was born without Down Syndrome and is chromosomally normal, but my doctors and care team were incredibly kind and supportive towards us and didn’t pressure us at all. The only “pressure” we faced were from some friends and family who didn’t think we were making the right decision to not have the amnio and not terminate if he did have DS.
I’m a parent of a kid that hit the genetic lottery – he has a ridiculously rare syndrome that is generally incompatible with life, and yet here I sit bumming around on the internet while I watch build a lego marble maze around the cat. I’m a bit nervous about the fact that when you google his ridiculously rare syndrome (and another one that has a similar name but is much, much worse) you get a bunch of pictures of him having fun, being not dead, and having a normal(ish) childhood (for a kid who sucks at breathing).
I get an email every few months from moms with prenatal test results or new infants diagnosed with the syndrome. And I’m not selling them anything, I’m just a stranger with a blog, but they’re seeing my son and buying hope. But the odds are cruel, and about half of the pregnancies don’t make it to term, and about a third of the babies die in the first few days or weeks. And it breaks my heart every time.
Theres definitely a gap in the information that parents are getting from genetic counselors, because they all go home and google. They told me not to google. I googled. Of course I googled. Got a whole lot of autopsized dead babies on the image search, so I guess I’m glad that my kid’s cute pictures are bumping those off the google image search.
To me, what you articulate is exactly the conundrum. If we had a prenatal diagnosis for our daughter, choosing to terminate the pregnancy would have been an eminently reasonable decision and probably the decision we would have made (although there’s no way to know for sure). And our lives would probably be easier if we had a second neurotypical child. But I truly believe that the world is a better place because of the joy that our younger daughter spreads.
It is also true that many children with my daughter’s syndrome have severe health problems as well as more significant learning disabilities. Seeing our daughter’s positive life could spread false hope to parents who get the same diagnosis but their child has worse outcomes.
So is it better to be spared that potential pain but lose the joy and richness that our daughter brings to the world with her quirky way of being? I have neither answers nor judgment, but I think the questions are worth asking.
“So is it better to be spared that potential pain but lose the joy and richness that our daughter brings to the world with her quirky way of being? I have neither answers nor judgment, but I think the questions are worth asking.”
When you phrase the question that way, you have already supplied both answer and judgment.
Eh, every choice you make stops a potential child from being born. If you had terminated, then gone on to have another kid, would that kid have been less precious?
To make that call, you’d have to also be pleased with every abortion that happens before a term pregnancy, because if that abortion had not happened, neither would that wonderful, unique later child. I mean, I was originally part of triplets, but only me and my twin survived to term. Is the world a better place because of this spontaneous abortion because, damn, I’m awesome? I mean, imagine how much it would have sucked if I were the triplet that didn’t make it, and some less special triplet were born in my place.
Since we are asking questions and all.
I agree that the Slate article is poorly written. But I think there is cause for concern with those new fetal DNA tests. They ARE being marketed as almost akin to diagnostic tests, and they don’t have to be approved by the FDA using a loophole that allows labs that develop & analyze their own proprietary tests to sidestep FDA approval rules. (Although the FDA has recently announced they are going to look at such tests more carefully.) Furthermore, Sequenom, the creator of the Materniti21 test, engaged in fraud misprepresenting the accuracy of an earlier version of the test. http://www.nytimes.com/2009/09/29/business/29drug.html?_r=0
The care providers do share some of the blame. They are the ones who should be explaining to their patients the differences between a diagnostic and screening test, and explaining the risks of false positives and false negatives.
But if the publicly traded companies creating these tests are lying about the results and marketing them deceptively, while escaping FDA scrutiny, then that’s the bigger issue!
When I did mine, my OB gave me a glossy brochure printed by the test’s marketer that appeared to explain the benefits and limitations of the test accurately. If other companies are selling these screening tests as something they aren’t, I agree, that’s a problem!
I think the actual marketing material is clear if you can understand it. But when the doctor explains it saying that they filter out the placental DNA from your blood and test it, it makes it sound more certain.
I think you raise an interesting point. I declined all diagnostic/screening tests other than u/s during my pregnancy; we were fairly young at the time and had gone through a decent amount of genetic testing for IVF ourselves. I read up as much as I could on pregnancy issues…but still had zero idea that there was a difference between diagnostic and screening tests (until I read it in this blog post nearly 3 years later!). I imagine there are a lot of others out there similarly confused.
A big thanks to Dr. Amy for clearly explaining the confusion.
I worry that any OB would agree to a termination without a confirmatory diagnostic test first.
That seems foolhardy.
It’s happening though- unfortunately even some GPs don’t understand that 99.9% sensitivity does not equal a 99.9% positive predictive value. I wrote about this in my paper in ANZJOG published in October about clinical implications of NIPT
Unfortunately, the confusion is shared by the reps for the company that makes the test. We have had reps in our office telling us that we ‘don’t need’ to use a genetic counseling/MFm team any more—just use the test!
Umm, no.
What do they think happens if the results come back with something abnormal?
Ok, haven’t read the article. Former scientist here. Have to agree with the notion that the prenatal screen leaves something to be desired. We did CCS testing at ccrm. 95% accurate (probably higher but I think they used that # to cya). We transferred a normal embryo and did the prenatal screen in california. Came back 1:6 chance if downs. My life was a living hell for 6 wks until the amnio. 6 yrs, 5 IVFs, etc, finally pregnant, we did the CCS testing to avoid this scenario, and now we’re looking at having to terminate? (Yes, that would’ve been our decision). Thank goodness the amnio showed all ok. For #2, also a CCS normal, we skipped the prenatal screen and just did materniT21 blood test. OB was on board since she saw how distraught I was the last time. Long story but in my opinion the prenatal screen is not accurate enough to be worth doing. Thankfully blood tests like M21 are now widely available. I totally get screen vs diagnosis but that’s of little comfort while waiting 6 weeks for amnio. And we chose not to do cvs b/c risk of mosaicism which would’ve required doing amnio anyway. Btw I think it was the very low PappA that skewed the test. Turns out we as IUGR, vci, and vasa previa, prob all related. But that 6 wks was hell. M21 wasn’t available then (summer 2010).
Ok having read it it seems like she is criticizing th M21 type tests not the traditional prenatal screen I was referring to. I read up on sequenom quite a bit and their method of testing is quite different than the prenatal screen–actual DNA testing vs running several hormones and plugging into database to see where that combo of values might fall risk-wise. So what is the concern people have here with sequenom et al? That it might be non-fetal DNA that is tested? Beyond that issue, why would that DNA testing be any less accurate than that used in amnio?
Obv if I had a positive m21 test done I’d do amnio too to confirm. But with a negative I was very confident that this plus CCS test results plus no issues seen on multiple high level ultrasounds was enough to not do amnio as well with my #2. And doing the test at 10 weeks gave me many more weeks of reassurance.
Cervical smear tests are another screening test that the general public has a hard time understanding.
I have had women with symptoms and an abnormal looking cervix on examination get upset that I “refuse” to do a smear test.
I explain, very carefully, that I am referring for colposcopy, which is the diagnostic test and skipping the smear test, because I already know something is not right.
Women with symptoms of cervical cancer need colposcopies and biopsies. They do not need smears.
Smears are a screening test for women without symptoms, to risk assess who should have colposcopy. This message is not getting through as well as it could.
Screening is not diagnosis, screening is about throwing the majority of people out of the pool before you run a more difficult, more expensive or more invasive test on the remaining group. A positive screening test does not mean you have the disease, it means the probability that you have it is high enough to justify the next-tier test.
Also…once you have symptoms and signs, a smear test is no longer helpful because a negative is much more likely to be a false negative than a true one…
Often times you have to tease it out with a thought exercise
“I think there is something wrong, so I am referring you for colposcopy. If I do a smear test and it is negative…I still think there is something wrong and I will refer you. If I do a smear test and it is positive, it tells me something I already suspect…and I still refer you to colposcopy. A smear test will not change the management plan, and so I’m not going to do it, because, for you, today, it simply doesn’t add anything.”
Hilariously, all the commenters on the Slate article agree with Dr. Amy, that the article is pretty dumb.
Awesome. I was wondering if anyone made the author aware of her error. At least a lot of the Slate readers understand the difference between screening and diagnostic.
I would hope that every OB would explain that to her/his patients prior to doing the test, but I suspect, due to time constraints and/or lack of curiosity of the patient, this doesn’t happen. Of course, for the patients that DID have screening tests, and DID have the tests explained, they know the difference, and since so many women get these tests every year, that’s a decent portion of the population.
Slate’s comment engine is twelve kinds of screwed up.
Yes, I was embarrassed for Copeland. Her last part, reporting on sending in blood samples of non-pregnant women, was an especially bad failure. Obviously this test cannot work on a non-pregnant woman. It works based on the fun fact that maternal circulation contains not just the woman’s own cells but also rare cells that have sloughed off the fetus and have leached into her bloodstream. If there are no fetal cells in circulation, it will frequently report on the woman’s own cells: normal 46 XX (healthy female). This is a known “weakness” of the test, but one easily overcome by *not sending in a blood sample when you are not pregnant*.
The blood test I had was last year pretty accurate, like 99% for downs, and 90%+ for a couple other trisomies that are much rarer to begin with. We were comfortable with those odds. I think it was called fetal free cell, it’s only been around about 2 years. And of course I was pregnant! I wonder how it’d mess up the test if you sent in male blood.
Well, there occasionally are people with XY chromosomes who present with entirely female phenotype, sometimes including a functioning uterus. There are also doctors with a taste for practical jokes. So, I’m sure the company has seen that before.
There is another problem with older moms and the Harmony test. There is a slow rate of loss of one of our X chromosomes as we age. Therefore, there is a fairly high rate of false positives for Turner’s syndrome (XO) when the non-invasive tests are used – not because the the baby is missing an x chromosome, but mom has lost some in her peripheral cells. However, we ALWAYS recommend confirmation with an amiocentesis before proceeded with any termination of pregnancy.
Could a woman receive a bone marrow transplant from a male donor and then go on to get pregnant? That would give her XY blood.
Would a male be likely to be a bone marrow match?
Yes, siblings often match each other. I have a relative who just received a bone marrow transplant with his sister as the donor.
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Got it. That makes sense.
Are you asking if she could get pregnant or if it would screw up the blood test? Not that I know the answer to either, I’m just an unemployed history teacher. its an interesting question though
Only the blood cells would be XY, the rest of the cells would have the normal XX (including the gametes). There would be circulating fragments of the Y chromosome in her blood though – it would make it harder to interpret NIPT. Similarly, NIPT is not validated for women pregnant via donor eggs, the fetus must have some shared DNA for the test to work properly.
However, many women who had childhood cancers requiring bone marrow transplants have infertility secondary to the chemotherapy they received – not 100%, but definitely higher than age related.
I wonder if the author is lumping in various tests as all in the same category–for example, the Counsyl family prep test which is intended for use prior to reproduction.
I had this test. The company refused to be in network so I still have to pay $500 of a $750 bill . . . If I hadn’t had coverage at all though the bill would have been reduced to $250. I always understood it to be a screening test. And it is WAY better than the Quad screen, IMO. I didn’t want to tempt myself to end a pregnancy, so I had it at 20 weeks instead of 9-11. I was going to skip all screening but when MFM was telling me ‘we just don’t know’ regarding my baby’s heart, I couldn’t take it any more. Turns out his heart is fine, the test came back very fast too.
I also accessed a similar test for Rh status of my fetus this time. Having had an Rh- child despite having a Rh+ husband, I knew another Rh- child was possible. That test was covered & I didn’t have to pay anything. And my fetus was in fact Rh-
It is sorta funny how that shook out because strictly speaking the first test was more indicated than the second.
I would never have an abortion, but I still had the screening, too. Why? Because if our baby had a heart or other organ defect, or spinal bifida, or one of the trisomies, I would want to know so we could arrange for appropriate treatment at birth, if not (in the case of spinal bifida) sooner. It’s as simple as that. As DH and I say, more information is always a good thing.
(Well, perhaps not in some of the more…interesting…corners of the Internet.)
The test we are talking about *cannot* screen for anything but Chromosomal issues. It certainly cannot screen for Spina Bifida. It also cannot screen for heart or organ defects (it could increase the index of suspicion but that is not the same) that are unrelated to Chromosomes. Just like the anatomy scan can’t really screen for chromosomal issues. Isn’t that nice that ‘you would never have an abortion’. I don’t have the luxury of saying that, I have had one. Most women who say that, don’t truly know in fact that they would never ever. But I qualified my comment to say that I didn’t want to be *personally tempted*. I posted to illustrate that this screening test is flexible (unlike AFP/quad) and can be used after you have already attached to the fetus, rather than near the embryonic stage where termination is theoretically easier to contemplate, if one, like me, understands that while I don’t want to consider termination an option, early in a pregnancy diagnosed with an Anomoaly, the appeal may be greater.
So if the test had come back saying you had a 1% chance that the baby had a genetic issue, would you have arranged to have appropriate treatment at birth based on this 1% chance or would you have undergone an amniocentesis and risk miscarriage to confirm for sure whether further treatment was needed? What if arranging appropriate treatment was not an easy task and would require to relocate to another city for the last month of pregnancy or so?
This is actually a classic problem in conditional probability. I’ve usually seen it used for the tuberculosis skin test in a population where TB is rare, but it can be used for any screening test for a relatively uncommon condition.
-Assume that 99% of people without the condition will correctly test negative.
-Assume 99% of people WITH the condition will correctly test positive.
Now your test is 99% accurate!
Next, assume that one person in 1,000 actually has the condition, and assume that YOU just tested positive! What’s the probability that you actually have the condition?
Most people ignore the third assumption, jump straight to 99%, and panic. In fact, the answer is: P(true positive)/(P(true positive OR false positive) =
(.001*.99)/(.001*.99 +.01*.999)=
0.09 or 9%.
Drop the incidence of the disease to 1 in 10,000, and it’s less than 1%.
Now, when I went for my chromosomal disorder screening a couple years ago, I was given a lovely glossy brochure that explained, in simple language that left out all the calculations, that even if I tested positive, my baby was still most likely OK and I’d just need to go for follow-up tests.
The story is that the featured woman’s doctor didn’t read up on the test properly before administering it, that’s all.
Which featured woman?
Sorry, I was thinking of a different article.
Yep, you MUST do the positive predictive value calculation. The sensitivity of a test is meaningless without it.
I remember the first time I was introduced to this concept in a class. The prof did exactly what you did and gave us a theoretical test with very high specificity and sensitivity for a condition that was relatively rare and then just as you did, said “Ok your test came back positive, what is the chance you really have the disease?” and had us guess. I went out on a limb and estimated that the chance was only 50%. Mine was the lowest guess of anyone in the class, but I was not even close. Then she introduced us to the calculation and had us do it and it was like an eye opening shock how low the number was. I doubt any of us has forgotten it.
This is one of the reasons positive HIV tests are ALWAYS repeated before telling the patient the results.
I always have to grit my teeth at the folks who tell me about “false positives” they got at diagnostic screening tests — particularly for GD. It’s a screening tests, not a diagnostic.
It depends how it’s being said.
“Oh, sorry you tested positive on the 1-hour, but it doesn’t necessarily mean you have GD, I tested positive on the 1 hour but was fine. Good luck on the 3-hour!”
That’s reasonable.
“I had a false positive on the one-hour test! That one-hour test is so stupid, it lies all the time.” That’s missing the point.
I know not everyone is adopting it but this is just one reason I LOVE the two hour.
I feel like, at that point, you may just as well start out with the 3-hour, which may be why it isn’t being adopted.
I did a lot of teeth-gritting on the pregnancy forums. Why don’t other countries report the results they way they do in Israel? I got a piece of paper after the NT scan that showed the odds of Down Syndrome solely based on age, and then adjusted for the NT results. That was then further updated based on the blood test results. None of this “positive” and “negative” confusion.
That’s what I got, in the USA. The probability that my baby had Down Syndrome based on my age and on my completely negative NT scan, along with a recommendation NOT to get amniocentesis.
Now, those results turned out to be really useful later in pregnancy when my baby’s growth slowed down. Since we had the sure due date and the negative NT test, we knew it almost certainly wasn’t a chromosomal disorder, which meant it was easier to make the diagnosis of probable placental insufficiency.
If some women AREN’T getting proper explanations, BEFORE the test is done, that’s the problem.
I get your point but technically once the baby’s growth is no longer normal, you are no longer part of the normal population where everything looks fine.Your new population isn’t everybody, it’s “IUGR babies”, so the negative predictive value of your normal NT and blood tests go down.
I saw an example of this during my NICU rotation. There was a baby from a teen mother who had had a negative quad screen (only non-invasive test available at that time) and a normal ultrasound. Risk of chromosomal abnormalities based on these + her very young age was low. But it turned out to be trisomy 21 anyway.
This case is similar to the Edwards case that Copeland linked to. Screening results obtained during early pregnancy when everything looked fine lose a good deal of their helpfulness if new data pointing to a problem arrive.
Definitely. Still, IUGR + no other data means a much higher probability of chromosomal disorders than IUGR + normal screening test. (Especially if the IUGR is following a classic placental-insufficiency pattern.)
These tests weren’t available 6yrs ago when I was pregnant, but I did get the quad screen. We knew there was a low likelihood of Down Syndrome or other chromosomal disorder that are often linked with age, but with ID twins, if one had it, so did the other (to my understanding). The screen came back as expected, and my boys are fine.
(looked it up, must confess that even though I often run qpcr based on cdna reverse transcribed from rna, I do not really understand this article.)
http://nextgenseek.com/2014/05/rna-seq-on-identical-twins-discordant-for-downs-syndrome-reveal-genome-wide-expression-dysregulation/
At the time, quad screens were considered fairly inaccurate for fraternal twins, because even if something pinged, it would be impossible to tell which baby, and amnio would have to be done on both. My impression is that the new tests are better, and can narrow it down better, at least if the fraternal twins are boy/girl. If they are same sex, well, I guess there’s still the same issue.
When I read her article, not being familiar with the tests she was talking about, I thought that she was referring to inadequately validated tests being marketed as diagnostic. My misunderstanding.
Have you written to her, perchance? This is definitely an issue of science education, as you say and a correction would mean a lot!