How Down syndrome prenatal screening’s administration is about elimination … & what’s needed to change that

Forbes_Icon_400x400In her column in Forbes, Kavin Senapathy, a self-styled scientific mythbuster, took on claims that prenatal genetic testing has as its purpose eliminating those with Down syndrome. Unfortunately, her column retold myths and she based her mythbusting on fantasy.

What is being tested

Senapathy’s column focuses on a prenatal test for Down syndrome, but her second paragraph misstates what is being tested.

Senapathy wrote that the test measures “levels of fetal DNA floating in the mother’s bloodstream during pregnancy, also known as cell-free fetal DNA.” She can be forgiven for this description since this is what the testing laboratories misleadingly say on their websites. But, it has been known for years that what is being tested is not fetal DNA, but DNA derived from the placenta.

As a result, what is being screened is not cell-free fetal DNA, but cell-free DNA or “cfDNA.” Understanding this distinction—that it is not fetal DNA—helps explain why cfDNA screening has false positives and false negatives.

How accurate is cfDNA screening? 

Senapathy further confuses the accuracy of cfDNA screening. She explains that conventional screening provides a risk score, such as a 1-in-70 chance that the tested pregnancy actually is carrying a child with Down syndrome. As though it is a good thing, Senapathy describes how cfDNA laboratories instead “unambiguously report whether or not an aneuploidy was detected.” Reporting screen results in this way, though, is misleading and contrary to professional recommendations.

Cell-free DNA screens are marketed as having a greater than 99% ability to detect Down syndrome prenatally. But, as the National Society of Genetic Counselor’s fact sheet on cfDNA cautions: “A >99% risk score does not mean there is a greater than 99% chance that the pregnancy is affected with a condition.  A ‘Positive’ or ‘Aneuploidy Detected’ does not mean the fetus definitively has a chromosome condition.” The claimed 99% accuracy concerns cfDNA screening’s “sensitivity” or ability to detect affected pregnancies. But, screening tests also have what is called “specificity,” which is the test’s ability to rule out pregnancies which are not affected. Combining these results provide screening test’s “positive predictive value” or “PPV.”

PPV provides the probability that a screening test is a true or false positive and can vary widely depending on the mother’s age. According to the American College of Obstetricians & Gynecologists (ACOG) committee opinion on cfDNA screening, receiving an “aneuploidy detected” result for Down syndrome can mean for a 40-year old mom a PPV of 87%, but the younger the mother, the lower the PPV. A 25-year old mom receiving a “positive” cfDNA screen really means she has a PPV of 33%, or, put another way, two-thirds of a chance that her cfDNA screen is actually a false positive.

There are no prenatal treatments for Down syndrome … and there never have been.

Having misunderstood the nature of cfDNA screening, Senapathy then critiques the concern that prenatal testing will lead to the extinction of Down syndrome based on possible prenatal therapies–the key word here being “possible.”

She quotes a single individual in her column, Dr. Diana Bianchi, who she rightly notes is a well-regarded researcher in the field of prenatal genetics. Senapathy cites the prenatal treatments Dr. Bianchi is working on to defend prenatal testing as simply providing information on which patients may exercise options.

Near the end, Senapathy quotes Dr. Bianchi as saying that she “routinely get[s] emails from expectant couples from all over the world who are asking if any prenatal treatment currently exists for Down syndrome.” Note what is missing: an answer saying that prenatal treatments do currently exist. This is because there are no prenatal treatments for Down syndrome, nor have there ever been.

Prenatal genetic testing for Down syndrome has been around since amniocentesis in the 1970’s and alpha fetoprotein screening in the 1980’s. Without any prenatal treatments, the information prenatal testing provides limits parents’ choices: continue the pregnancy knowing their child will have Down syndrome (with adoption being an option if the pregnancy is continued), or abort. After a prenatal diagnosis, abortion is the most often selected option. Given this result of prenatal testing, relying on non-existent prenatal treatments renders Senapathy’s defense of prenatal testing fanciful and her critique of the very real elimination of children with Down syndrome disingenuous.

How prenatal testing’s administration eliminates Down syndrome

The column that Senapathy is critiquing was written by Tim Stanley, which had the headline “Down’s syndrome people risk ‘extinction’ at the hands of science, fear and ignorance.” In fact, Senapathy’s criticism is technically correct. Down syndrome is a naturally occurring condition at or near-in-time to conception without any preventive method developed to keep it from occurring. Therefore, so long as children will be conceived, a certain percentage will have Down syndrome, and, so long as some couples decide to continue a pregnancy after a prenatal diagnosis (or forego prenatal testing altogether), then there will always be children with Down syndrome born. So, yes, prenatal testing will not result in the “extinction” of Down syndrome.

But what Senapathy does not cover is that how prenatal testing is being administered is not only resulting in the elimination of Down syndrome, but that its administration relies on the elimination of Down syndrome.

To counter the concern about possible extinction, Senapathy mischaracterizes the reported termination rate in the United States. Citing a study from 2012, she represents that a prenatal diagnosis “leads to over half of American women choosing to terminate.” “Over half” could be as slight as 51%, but the study is of three states that have a termination rate that ranges from a low of 61% (California) to a high of 93% (Maine), with a weighted average of 74%. “Over half” is more accurately stated as “almost 75%” of expectant women terminate following a prenatal diagnosis.

However, that percentage pales in comparison to what is happening in the country and neighboring continent from which Stanley was writing.

Stanley was commenting on Britain’s National Health Service (“NHS”) recommending that cfDNA screening be offered to “high risk” moms. In Britain, with just conventional screening, half of all pregnancies carrying a child with Down syndrome have been aborted. (See Table 4 of this study). Stanley need look only across the English Channel to see the likely future: in France, 86% of all pregnancies carrying a child with Down syndrome are aborted; in Switzerland, it’s 87%; and, in Denmark, which introduced conventional screening nationwide only in recent years, the Copenhagen Post ran a report wondering whether Denmark “could be a country without a single citizen with Down’s syndrome in the not too distant future.”

And note that these figures are not modified with “after a prenatal diagnosis.” In the United States it remains that less than half of all expectant moms carrying a child with Down syndrome have a prenatal diagnosis, and therefore when almost 75% terminate, that remains a minority of all pregnancies positive for Down syndrome. In the countries just cited, almost all women carrying a child with Down syndrome have a prenatal diagnosis and therefore France’s 86%, Switzerland’s 87%, and Denmark’s termination rates are of all pregnancies carrying a child with Down syndrome. Put another way, if there were 100 pregnant women carrying a child with Down syndrome, given those numbers in Western Europe, less than 15 would be born each year.

Call it what you will–extinction/elimination–but prenatal testing is what enables this decimation of Down syndrome.

And, prenatal testing’s funding depends on it.

The funding of decimating Down syndrome

Prenatal testing in Western European countries and England is largely at no-cost to parents. Similarly, here in the United States, every state covers prenatal testing as part of Medicaid, it is increasingly being covered through private health plans due to the Affordable Care Act’s “essential health benefits” requirement including prenatal care as part of covered services, and states like California and Iowa have had for years state-administered prenatal testing programs for Down syndrome.

While coverage renders prenatal testing low- or no-cost to parents, that does not mean it costs nothing. Conventional screening has a relatively low cost, however, cfDNA screening and diagnostic testing can cost in the thousands for each test. Meaning, if an expectant mother has prenatal testing through to a prenatal diagnosis, the public or private insurer will pay thousands of dollars.

When you add the costs up of prenatal screening and prenatal diagnostic testing when only about 1-in-800 babies are born with Down syndrome, how are all those costs to the public health care system justified?

The way economists, physicians, and, in the case of Ariosa’s (the maker of cfDNA screen Harmony) CEO Ken Song make the argument is that the costs are justified by the “savings” to the health system afforded by prenatal testing.

What “savings” are those?

The claimed added costs of a life with Down syndrome that are avoided through abortion.

These studies are called cost-effectiveness analyses. The costs of prenatal testing being offered to all women is shown to be “effective” when prenatal testing identifies enough pregnancies carrying a child with Down syndrome that are then aborted, “saving” the health system the claimed added medical costs of that life with Down syndrome. Therefore, in order for Medicaid, private insurance and health systems, and public health systems like the NHS to justify the scarce health care dollars going to pay for prenatal screens–the vast majority of which will be negative–thousands of Down syndrome selective abortions are required.

Presenting these cost-effectiveness analyses in no way endorses their methodology or their conclusions, both of which are as deeply flawed as are their motivations and expressive statement they make about Down syndrome and about the role for prenatal testing.

But, the fact is, these noxious studies do exist and insurers and public officials rely on them to justify spending millions upon millions of dollars to cover prenatal testing, justifying it by the thousands of abortions that these officials are counting on will result after a prenatal diagnosis.

Common ground on the role for prenatal testing

All this said, despite glossing over how the administration of prenatal testing is resulting in the elimination of Down syndrome, it is Senapathy’s conclusion on which we can agree and remains the best hope for ultimately proving her argument correct.

Senapathy concludes that prenatal testing’s goal is not to extinguish Down syndrome but, instead, “Ultimately, a woman needs facts to empower an informed decision, whatever that choice may be, when faced with a Down syndrome diagnosis.” Here is where we agree.

Prenatal testing remains “just” technology and it is not going to cease being performed. It has no intent or purpose beyond what we humans apply in how we use it. Prenatal testing, therefore, does just provide information about the chances of having a child with Down syndrome.

But prenatal testing alone does not empower a woman to make an informed decision.

Prenatal testing for Down syndrome does not take place in a vacuum.

verinata months ahead of the curveInstead, it is administered in a system currently justified and even marketed to lead to the abortion of children with Down syndrome. Dr. Bianchi’s company, Verinata, which developed the cfDNA screen verifi, even marketed its test with the tagline “We’re months ahead of the curve.” The tagline appeared across a photo of a woman’s mid-section to highlight how the earlier cfDNA result could allow an expectant woman to choose a more private abortion before her pregnancy had begun to show.

Professional medical guidelines recognize the challenge posed by prenatal genetic testing, which is why they do not just recommend that women receive prenatal testing, but also professional and educational support throughout the process.

Recognizing the advances made by cfDNA screening, professional recommendations changed in 2013 to emphasize the need for pre-test counseling. This is so expectant women can make their first informed choice about prenatal testing, whether to even have it to begin with, understanding what it tests for, what its results mean, and what would follow depending on those results,

Professional recommendations have long recommended post-test counseling but this, too, has been improved in light of cfDNA screening. Whereas before, genetic counseling and written materials were recommended after a diagnosis, recognizing the higher accuracy of cfDNA screening, these supportive resources are now recommended after a cfDNA screen result.

Newer resources have been developed to help expectant mothers. The ACMG identified three distinct resources to be provided expectant mothers receiving a cfDNA screen result; the NSGC produced fact sheets on cfDNA screening and on Down syndrome; and ACOG refers in its most recent committee opinion on cfDNA screening to additional resources for expectant mothers.

However, despite insurance coverage decisions being based on professional guidelines, and professional behavior changing based on these guidelines, still the emphasis in funding and clinical practice remains just on offering prenatal testing and reporting its results and not on providing expectant mothers with the professional and educational supports to empower informed decisions. Moreover, despite every cfDNA laboratory knowing who is receiving a screen positive result, they still have not committed to delivering the identified written resources.

This imbalance in information joins the imbalance in funding and perpetuates the elimination of Down syndrome.

When will prenatal testing be done right?

The challenges posed by the administration of prenatal testing has been well-known among those engaged in developing prenatal testing and in drafting professional recommendations about it. However, despite recognizing the need for better counseling and supportive resources to empower expectant mothers, still the systematic bias towards offering testing which leads to selective abortion persists.

In response, in 2008, the Prenatally & Postnatally Diagnosed Conditions Awareness Act was passed unanimously by both houses of Congress and signed into law. Its language, while recognizing the need for accurate, up-to-date information to be provided patients, remained permissive and the responsible agency, Health & Human Services, has largely ignored it. Since 2012, twelve states have passed laws providing for the delivery of accurate information about Down syndrome and referral to local support organizations, but, these too, have had little impact since money has not been appropriated for the laws’ full implementation (with the exception of Massachusetts). Recognizing the challenge posed particularly by cfDNA screening, Congresswoman Jamie Herrera-Beutler has introduced an appropriations bill for funding to develop physician and patient educational materials.

Like Dr. Bianchi’s potential prenatal treatments, though, these measures also remain promises that have not resulted in the needed change.

Unless a change is made professionally by obstetricians and others delivering prenatal care, women will continue to be offered just prenatal testing, and not the needed pre- and post-test counseling.

Unless a change is made in the funding, such that private and public insurers that base coverage decisions on professional guidelines but only fund the cost of prenatal testing, and not the costs of genetic counseling and educational materials, then women will continue just to be told a prenatal test result and be left to find the rest of the information they need for informed decisions.

Now, though, is a unique time in the administration of prenatal testing. With the advances made with cfDNA screening, it is at the forefront of practitioner and patient minds and prenatal testing is receiving more media and political attention than ever before. Perhaps if the changes are made in professional practice and insurance coverage to follow all of the guidelines, and not just the offer of prenatal testing, then Senapathy’s critique and conclusion will both be true. Should professional practice and insurance coverage be made to follow all of the guidelines’ recommendations, then prenatal testing will not be administered to eliminate children with Down syndrome, but rather will be administered to empower women to make informed decisions.

Mark W. Leach serves as the bioethics specialist for the National Center for Prenatal & Postnatal Down Syndrome Resources, which provides resources recognized by the professional medical guidelines. He blogs about Down syndrome and prenatal testing at http://www.downsyndromeprenataltesting.com/. Mark is the father to a daughter who has Down syndrome and a son who has curly, blonde hair. You can tweet him @MarkWLeach

Comments

  1. It’s little wonder that a magazine focused on money would print this article. The part that makes me saddest is the continuing attitude towards Down syndrome that “if we’re testing for it, it must be bad.”

    For your readers, here is a website to check out the UK campaign for better implementation of this screening: dontscreenusout.org.
    From the site:
    “Many parents whose children have been given a diagnosis or prognosis of fetal disability have experienced a lack of clarity in how this has been communicated to them. Additionally, many have experienced a presumption of the medical profession that they would opt for abortion, and a lack of information and support for the option of bearing and raising their disabled baby, receiving palliative care for newborn children, or even considering adoption.

    All of this constitutes a lack of accommodation, inclusion, and support for disability, and causes a culture in which parents feel pressure to abort their babies if they have Down’s Syndrome or other disabilities. If the right medical reforms were brought about that enabled support for parents, cfDNA implementation can be implemented as an uncomplicated benefit.”

    Lastly, the verinata ad disgusts me. They don’t even try to sugarcoat it, do they?

  2. While it’s certainly possible medical technology could be the reason the numbers of people with Down Syndrome will drop, there will likely never be a time when the condition becomes extinct because there will always be women willing and able to bring them to term.

    • I’m guessing you didn’t make it to this part which is in the middle of the post: “Therefore, so long as children will be conceived, a certain percentage will have Down syndrome, and, so long as some couples decide to continue a pregnancy after a prenatal diagnosis (or forego prenatal testing altogether), then there will always be children with Down syndrome born. So, yes, prenatal testing will not result in the “extinction” of Down syndrome.”

  3. Ashley Johnson says:

    I think you may be misinterpreting the “months ahead of the curve” advertisement, or at least I see it in a very different way. The reason a woman would want test results as early as possible is not to conceal their shame at choosing abortion in the case of a positive test. There is no shame. If abortion is the chosen option, it is in the best interest of everyone, fetus included, to have it done as early as possible. I have made the difficult choice to terminate two pregnancies affected by T21, and I made large efforts to inform myself before making my choice. I feel no shame for the choices my husband and I made, and the only reason I’d want to conceal our choice is for fear of pro-life zealots who would want to harm us. My termination at 15.5 weeks was much more difficult emotionally and physically than my termination at 12 weeks. I’m so thankful these NIPS can be done at ten weeks.

    • Ashley, thank you for sharing your experience, but I think you’re responding to a point that I don’t make in either the main article or in the post linked regarding the advertisement. Regardless, if the point of the tagline was, as you say, to allow for earlier terminations which are safer, then why not say that? Instead, it says, “months ahead of the curve,” highlighting that before the pregnancy is physically showing, women can have the verifi test and then end their pregnancy, if they so choose. The selling point of the tagline is not safety, but privacy.

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