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Human beings are not capable of deciding whether to continue with the pregnancy of their unborn child based on statistics and percentages

Posted in Diagnostic testing, Media, Screening, Statistics, This blog by Matt at WelcometoIllinois on October 29, 2009

The UK’s coverage of Down’s syndrome screening and statistics continues following the publication of a report in the BMJ.

Tom Shakespeare, research fellow at the Institute for Policy and Practice at Newcastle University, has written an interesting and provocative piece looking beyond the statistics to the human cost of screening for Down’s.

I started off submitting a quick comment but it quickly became the spelling error-packed diatribe I have been considering writing for some time. I’m not sure where I am going with this in all honesty, but I think I am building to something here…

Having been through the process of dealing with a pre-natal diagnosis of Down’s syndrome I have come to the conclusion that human being are simply not capable of deciding whether to continue with the pregnancy of their unborn child based on statistics and percentages. I agree with Tom that we need more research into the long-term emotional consequences of these difficult decisions but would go further and suggest that we need to radically rethink how we as a society approach screening.

In my experience, johnthewayne is correct: “we test for downs, not because it is the worst thing in the world, but simply because it is possible”. The result is that parents are supplied with information that is supposed to be “accurate” but tells them nothing.

These were ours: “a one in 11 chance based on the nuchal fold; one in 4,000 based on the blood; one in 76 in total, compared to one in 300 on average for my wifes age; a 95% accuracy rate for the combined test, compared to 85% for just the nuchal fold measurement; a one in 100 chance that the next test could result in a miscarriage.”

If you think you know what you would do faced with these statistics think again. You cannot possibly know until it is your own child you are deciding the fate of.

Then there is the fact that the effects Down’s syndrome are a spectrum. Will your child have heart problems, thyroid problems, gastrointestinal problems, hearing problems, leukemia, hypotonia? None of the above? How severe will the learning impairment be?

The screening process asks all of these questions and provides answers for none of them, and yet we are expecting would-be parents to use the results of screening to decide the fate of their unborn child. Counselling can help parents understand what Down’s syndrome is, but it does nothing to help them make the most important decision in the life of their child.

In this context it does not surprise me that so many people decide to terminate following a pre-natal diagnosis (aside from the fact that they may decide they do not want to or not capable of raising a child with Down’s syndrome, which is an entirely valid response).

In my experience the decision to terminate is the only choice facing parents that enables them to regain control of the situation. As we considered out options we were drawn almost inevitably towards termination by the fact that it was the only decision that provides a definitive outcome, rather than more chance.

I say almost – in the end we decided that Downs syndrome, in and of itself, was not enough to justify abortion, and that we would take that chance. Our son is now one year old and healthy and happy and I have not regretted our decision for a second.

However, my desire to rethink the screening process is not based on ensuring more parents take the same decision as us – that is for them to decide – it is a desire to ensure that the process itself reflects the severity and long-term implications of the decision itself.

UK NHS developing non-invasive diagnosis tests

Posted in Diagnostic testing, Genetics, Scientific research, Screening by Matt at WelcometoIllinois on August 9, 2009

The Guardian reports that the UK’s National Health Service has begun a program to develop non-invasive blood tests that will reduce the risk of ante-natal testing for a number of conditions, including Down’s syndrome.

I’ve written about non-invasive diagnostic tests a number of times, including the news that the UK’s Medical Research Council (MRC) is investing £7m in a national network of centres dedicated to DNA testing research.

The latest new concerns a £2m grant from UK National Institute for Health Research (NIHR) to a study entitled Reliable Accurate Prenatal non-Invasive Diagnosis (RAPID), which will run for 5 years from April 2009 and test non-invasive alternatives to amniocentesis and CVS.

Specifically the program will investigate the use of circulating cell-free fetal nucleicacid (cffNA) technology for non-invasive prenatal diagnosis (NIPD).

Interestingly, the Guardian reports, and this report (PDF) from the working group considering the potential use of NIPD confirms, that tests based on the analysis of cffNA have been available as a service to hospital trusts since 2001 for “rhesus negative women whose baby is at high risk of having potentially fatal anaemia or jaundice.”

However, the potential use of cffNA as part of the national screening programme is a different matter – one that could potentially increase the accuracy of ante-natal testing for genetic abnormalities and other conditions, but also one that raises significant practical and ethical concerns.

These concerns were not lost on the working group investigating the increased use of cffDNA. The working group report suggests that the national implementation of cffNA for Down’s syndrome screening could be possible in five years but also notes that “a possible consequence of increased testing is more terminations, which could in turn result in increased social pressure to terminate, particularly if the diagnosed conditions were to become rarer in society resulting in a decline of support services.”

The working group report adds:

“It is therefore important to ensure that policies in this area are genuinely motivated by concern for parental autonomy, rather than any sense of reducing financial and social ‘burden’, and that the experiences of disabled people and their families be fairly reflected when framing policy and educational materials.”

In particular, given blood tests are a routine part of any pregnancy, the working group reports that it will be important to ensure that any NIPD tests are not taken lightly.

“If cffNA tests were made available to all pregnant women early in pregnancy as a replacement technology, there would be a need to move towards the rigorous informed consent model commonly used for diagnostic testing, where an active decision is made following discussion with a health care professional.”

Non-invasive Down’s syndrome tests make progress

Posted in Diagnostic testing, Scientific research, Screening by Matt at WelcometoIllinois on January 29, 2009

Genetic analysis company Sequenom has announced that it is making progress towards commercialising its non-invasive test for Down’s syndrome and other chromosomal abnormalities.

Based on an expanded sample of 858 tests “the Sequenom SEQureDx RNA-based technology demonstrated a 100% positive predictive value (PPV) and a 99.9% negative predictive value (NPV).”

As The Street notes, that last figure indicates that the company is no longer able to repeat its
previous claim to no false positives.

“Until today, Sequenom’s test had a 100% detection rate for Down syndrome and a 0% false positive rate when used in just under 400 pregnant women — a perfect record. While Wednesday’s disclosure of one false positive test in more than 858 total samples mars that flawless performance, Sequenom CEO Harry Stylli says an overall false positive rate of one-tenth of 1% is significantly better than current prenatal screening methods for Down syndrome, which can have a false positive rate of around 5%.”

UPDATE – It turns out the test results were wrong – UPDATE

According to The Street, the test works like this:

“The Sequenom test relies on new technology that can detect minute amounts of fetal RNA in a mother’s bloodstream. Using a small sample of blood taken from the mother, Sequenom isolates fetal RNA [ribonucleic acid] and determines whether there are two copies of chromosome 21 (a healthy baby) or an extra copy of the chromosome, which would indicate Down syndrome.”

Sequenom is coming to make its test available in the US in June, although as Xconomy reports “The medical audience will demand evidence published in peer-reviewed journals, and loads of it, before they give their full stamp of approval.”

Detailed results should be published in peer-reviewed journal in mid-2009, according to the company. Recommendation from American College of Obstetricians and Gynecologists will likely not come until 2010 or 2011, at the earliest.

Sequenom is not the only company developing new non-invasive testing techniques. I previously wrote about similar testing technology under development at Stanford University being licensed to a company called Fluidigm.

A company called Artemis Health has also acquired a license from Stanford University to develop cell-free fetal DNA prenatal diagnostic tests.

Meanwhile a company called Lenetix announced that it is making progress with maternal serum test developed at the University of Vermont that make use of methylation-sensitive amplification (MSA) of fetal nucleic acid markers.

Debate on ethics of antenatal screening is long overdue

Posted in Attitudes to disability, Ethics, Screening by Matt at WelcometoIllinois on January 12, 2009

The director of the UK’s Autism Research Centre, Professor Simon Baron-Cohen, has called for an ethical debate in the UK over the potential use of antenatal screening to test for autism after he led a group of scientists at Cambridge University to discover that high levels of testosterone are linked to autism.

According to The Guardian, Baron-Cohen said:

“If there was a prenatal test for autism, would this be desirable? What would we lose if children with autistic spectrum disorder were eliminated from the population? We should start debating this. There is a test for Down’s syndrome and that is legal and parents exercise their right to choose termination, but autism is often linked with talent. It is a different kind of condition.”

Baron-Cohen is no doubt correct about the contribution to society of people with autism compared to people with Down’s syndrome, but his apparent desire to separate the debate over screening for autism from screening for other birth defects is unfortunate.

As Sharon over at The Voyage notes:

“It’s also irrelevant that autistic people can have special talents that benefit society and that if there was a way of telling if a child could grow up to be (sarcasm) a useful, clever autist or a wasteful, stupid autist with absolutely nothing to offer (/sarcasm) the test would be more useful. Heck, if everyone had to prove their usefulness to society to be allowed to exist, the world’s population would take a big drop.”

Given the history of institutionalization and the ongoing ignorance of Down’s syndrome, society is only now beginning to understand what people with Down’s syndrome are capable of. In any case the debate over screening for autism cannot possibly occur in isolation.

The Guardian quotes Vivienne Nathanson, head of ethics at the British Medical Association, as saying. “The question, then, is are we comfortable with [testing] for a disorder which is life-limiting in terms of opportunities and experience, rather than life-ending?”

That description could be applied to Down’s syndrome as much as autism and yet there has never been a debate over the rights and wrongs of screening for Down’s or other chromosomal abnormalities. As Professor Joan Morris, director of the National Down Syndrome Cytogenetic Register, put it: “”There is no new argument here.”

I previously covered a research study on the attitudes of research ethics committee members towards screening for Down’s syndrome. As noted in that report “screening was introduced [in the UK] based on small scale preliminary studies and without ethical review.”

Indeed as Frank Buckley of DownsEd noted in November “there has been no parliamentary discussion or law on screening in Britain”.

I am sure that screening for Down’s syndrome is here to stay – medical advances cannot be reversed, but it is important that we as a society consider why that screening occurs and whether the results are desirable.

The great unasked question in Down’s syndrome screening

Posted in Attitudes to disability, Ethics, Screening by Matt at WelcometoIllinois on December 8, 2008

“Australia urgently needs a national screening policy for Down syndrome, experts say, after international research showed it could halve the number of babies born with the incurable genetic condition,” reports the Sydney Morning Herald.

“Every pregnant woman should be offered screening for Down syndrome regardless of age, and screening should be co-ordinated by a national policy, according to experts,” says The Age.

“Experts say Australia needs a national screening policy for Down syndrome as research shows it could halve the number of babies born with the genetic condition,” states News-Medical.net.

The medical experts are responding to this story from Denmark in which a national screening programme halved the number of children born with Down’s syndrome since it was introduced in 2000.

What none of the reports addresses, however is why Australian medical experts would like to produce similar results over there. The experts talk encouragingly about lowering risk and improving detection rates but none of them is quoted as explaining why they would want to do this in the first place.

It is as if the benefits are self-explanatory. But are they?

This is of course not an Australian peculiarity. The media’s focus on statistics in the UK also invariably sees a reduction in the number of children being born with Down’s syndrome being reported as a good thing, without any discussion of why that should be the case.

Why is it that reducing the number of people born with Down’s syndrome is a good thing in the eyes of medical experts? Yes there is the fact that Down’s syndrome can limit the abilities and lives of those affected, but does society help these people by reducing their number?

The call for more widespread an accurate screening for Down’s syndrome has little to do with quality of life. In a recent comment in the Independent, Dominic Lawson noted: “the NHS Down Syndrome screening process is hugely expensive, justifiable on cost-benefit grounds purely on the basis that it will detect and destroy children who would otherwise cost the Health Service much more as survivors”.

All of which would be fine if society had come to some kind of conclusion that the benefits of reducing the number of people with Down’s syndrome outweighed the cost of doing so.

As Michael Bérubé stated in his 2007 article for Globe and Mail (also available here) “the possible eradication of Down syndrome just isn’t something our species has achieved, or should achieve, any consensus about”.

Quoting a report from Nursing Ethics, Frank Buckley from DownsEd recently pointed out that “there has been no parliamentary discussion or law on screening in Britain”.

As I previously covered, there are real doubts among research ethics committee members as to whether screening for Down’s syndrome is even ethical.

The support we have received since our son was born has been fantastic and there are a great many services available to us, but they remained a secret until after he was born.

The information we were given in the run up to deciding whether to keep him or not seemed adequate at the time. In hindsight, it was very one sided. As Frank Buckley pointed out:

“The NHS’ so-called ‘best practice’ information leaflet devotes less than 3 pages to informing parents about Down syndrome. Most of this limited information is about maternal age and chromosomes rather than people. People who have Down syndrome are not featured talking about how they view their lives. Nor are their families. There are no photographs of people who have Down syndrome. This ‘best practice’ guidance then devotes 12 pages to describing the screening and diagnostic process in detail. The message? On balance, parents should be far more interested in learning about the screening process than the condition actually being screened for.”

If you are going to advocate reducing the number of a specific population of society the least you can do is be prepared to provide a coherent and honest argument as to why it is necessary, or even desirable, to do so. That’s not too much to ask, is it?

The use of DNA chips in diagnostic testing

Posted in Diagnostic testing, Scientific research by Matt at WelcometoIllinois on December 1, 2008

I previously wrote about the use of “‘microarrays’ or gene chips in the genetic testing process and a new DNA test called array comparative genomic hybridization (aCGH). MIT Technology Review has an overview of the technology.

The DNA chip used in the study performs a process known as array comparative genomic hybridization (aCGH), which involves looking for an abnormal number of copies of particular segments of DNA. Normally, humans have two copies of each segment. Having extra or missing copies can result in serious medical problems. Each DNA chip contains hundreds of single-stranded DNA segments, each embedded in a piece of glass at a precise location. The researchers then add single-stranded, fetal DNA segments, usually taken from amniotic fluid. These strands are labeled red. Single-stranded DNA reference segments, which act as a control group and are labeled green, are also added to the chip. Once the fetal and control strands are bound with the embedded DNA, the arrangement of colors on the chip is imaged and analyzed by a computer.

“Basically we measured the color signal intensity,” said [Sau Wai Cheung, director of Baylor College of Medicine’s Cytogenetics Laboratory]. If the fetus has an extra copy of a particular segment of DNA, then the spot on the chip that corresponds to that DNA segment will appear more red than green. If the fetus is missing a DNA segment, the corresponding spot on the chip will appear more green than red. And if the fetus has the correct number of copies of the DNA segment, then the spot should appear yellow.

To put this in some context:

“The process normally used for prenatal diagnosis is karyotyping, which looks at the overall size and shape of chromosomes to identify problems. [Cheung] says the new research shows that DNA chips can reliably detect far smaller chromosomal abnormalities than karyotyping allows. And while these abnormalities may be small in size, they can have a big impact. “A lot of the diseases that we tested for [in this study] cause mental delays and problems with physical development,” said Cheung. Angelman syndrome, for example, can result in significant developmental problems and seizures.”

The study at Baylor included 300 cases and identified seven cases where the aCGH results provided new information about the risk of disease, “including two cases that would otherwise have been missed”. On the downside still requires an invasive testing procedure and has not been widely studied at this stage.

In fact, I previously mentioned the technique in the context of a warning from Leslie G. Biesecker of the federal government’s National Human Genome Research Institute, that the tests do not provide enough information to know whether genetic abnormalities will actual cause a disorder, or how severe the effects might be.

The MIT Technology Review story raises the same issue, as Diana Bianchi, professor of pediatrics, obstetrics, and gynecology at Tufts University School of Medicine and the editor in chief of Prenatal Diagnostics (which published details of the Baylor study): “The downside of aCGH is you pick up these copy-number variants that may or may not have clinical significance, and in the worst case [the impact] may be unknown.”

The reports adds: “Knowing that an unborn child has genetic abnormalities but not knowing how those might affect the child’s development could leave many parents scared and confused, Bianchi says.”

Of course that is the exact same issue that impact parents receiving screening and diagnostic test results today, but no one seems to bother about that.

Cases of Down’s syndrome halved by Danish screening programme

Posted in Diagnostic testing, Screening by Matt at WelcometoIllinois on November 27, 2008

A Danish national screening programme has apparently halved the number of children born with Down’s syndrome since it was introduced in 2000, according to this Press Association report.

The story, which is unfortunately light on medical details states that “British attempts to instigate a similar programme have been hampered by disagreements over screening techniques”.

It is not clear what techniques are used in the Danish programme, but the story states that “Danish women were offered a risk assessment for Down’s in their first trimester of pregnancy based on their age as well as simple medical tests” and “Before the new system the decision on whether to test a pregnant woman for Down’s was based only on their age and diagnostic tests were offered mainly to women older than 35.”

Either way the result of the screening programme is that “the number of babies diagnosed with the syndrome before birth… increased by 30%” while “the number of babies born with Down’s syndrome fell from 55-65 per year during 2000-4, to 31 in 2005 and 32 in 2006.”

In utero treatment for Down’s syndrome?

Posted in Scientific research, Screening, Therapeutic treatments by Matt at WelcometoIllinois on November 26, 2008

New Scientist is among a number of news sources reporting that it may one day be possible to treat the symptoms of Down’s syndrome before a child in born via a protein injection.

The report indicates that injecting proteins could make up for malfunctions in glial cells and protect neurons that would otherwise be impacted by Down’s syndrome. According to the report:

“Catherine Spong and colleagues at the National Institutes of Health in Bethesda, Maryland, injected NAP and SAL into mice pregnant with trisomic pups in the middle of their pregnancy. When the pups were born, they reached developmental milestones such as grasping a rod, righting themselves and responding to tactile stimulation at the same time as normal mice.”

There are no guarantees that the treatment would have the same effect on humans, of course, but it does raise an interesting scenario where screening tests can also be used to enable treatment, rather than termination.

See also NHS Behind the Headlines’ take on this story: “It is unclear whether the improvements seen in mice would be seen in humans, and whether such improvements would significantly alter the impact of Down’s syndrome on the individual.”

Genetic complications

Posted in Genetics, Screening by Matt at WelcometoIllinois on November 10, 2008

There’s an excellent editorial in the Ottawa Citizen about the complications involved in dealing with the results of a pre-natal screening test.

I’m tempted to include the entire report as it is not long and should probably be read in its entirety but I’ll settle for a link and an excerpt:

“Knowledge is usually an asset, though it can at times be a burden. And in some cases, as expectant parents with access to new prenatal tests have discovered, it can be both.

Doctors can now screen fetuses for up to 200 genetic abnormalities, but the test results can be ambiguous. Sometimes they reveal that a fetus has a genetic glitch. How serious is the glitch?
Unfortunately, the tests can’t always say with any specificity.

A test may uncover a genetic variation that is associated with a disease. What are the odds that the child will have the disease? How severe will it be if the child does? Will it cause physical problems, intellectual problems or both? Will it affect the child’s lifespan? All good questions, but the answers are unknown.”

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Legal action and ante-natal screening

Posted in Diagnostic testing, Legal issues, Screening, Support services by Matt at WelcometoIllinois on November 5, 2008

A report from Canada.com on the potential for doctors to face legal action if they don’t provide genetic testing to all pregnant mothers highlights the need for adequate processes and support.

    “Canadian physicians may face more wrongful-birth lawsuits if they don’t start adhering to guidelines introduced one year ago recommending all pregnant woman be offered prenatal screening for chromosomal abnormalities, according to an article to be published today by the Canadian Medical Association Journal.

    But one of the authors says not all doctors are aware of the guidelines, nor are there enough medical practitioners in Canada to provide the lengthy counselling pregnant women should be getting.”

It’s pretty sad to think that someone’s reaction to having a baby with Down’s syndrome is to sue the doctor but if screening tests are being mandating without enough thought being put into whether the medical and counselling staff are available then legal action is somewhat inevitable.