Welcome to Illinois

The practical and ethical implications of non-invasive diagnostic testing

Posted in Diagnostic testing, Ethics by Matt at WelcometoIllinois on May 27, 2009

The Journal of the American Medical Association has published a commentary written by two doctors from the University of Connecticut Health Center, Farmington, on the practical and ethical implications of new non-invasive diagnostic testing for Down’s syndrome.

The article is only available to existing subscribers or those willing to shell out $25, but Patricia E. Bauer has the details:

“Among other concerns, the authors cite these:

– Women currently receiving fetal Down syndrome screening often receive only limited information prior to the screening and are rarely asked to provide inormed consent. Many women are unaware that this screening may ultimately lead to questions about further invasive testing and possible termination of the pregnancy.

– The use of noninvasive testing “may be encouraged” by for-profit laboratories, insurance companies and governmental health agencies that could derive economic benefits from the use of the testing, potentially undercutting individual patient choice.

– The reduced prevalence of people with identifiable genetic disabilities in the population could “subtly alter public attitudes toward the acceptability of continuing an affected pregnancy.” This attitude shift could “diminish understanding and support for affected individuals and their families and increase the stigma associated with having a genetic disorder.”

The authors call for the public, medical professional societies, and the government to be proactively involved in shaping the future of this testing.”

NHS screening head admits to accuracy failure of Down’s syndrome screening

Posted in Screening, Statistics by Matt at WelcometoIllinois on May 16, 2009

The head of the UK’s screening programmes has admitted that the NHS has failed to roll-out more accurate screening tests for Down’s syndrome and that as a result a number of healthy foetuses are unnecessarily lost due to miscarriage triggered by diagnostic testing.

Dr Anne Mackie, the director of programmes at the UK National Screening Committee (UKNSC), told The Guardian that an “estimated 146 babies a year in England who do not have any abnormality are lost as a result” of attempting to detect Down’s syndrome.

That death rate is higher than it should be as only 30% of hospitals offer the combined test for Down’s syndrome, despite it being “introduced by the NHS 10 years ago and declared best method in 2003”.

As previously covered, last year Down syndrome Education International estimated that current screening practice in England and Wales reduces annual live births of babies with Down’s syndrome by around 660 and leads to the losses of 400 babies without Down’s syndrome.

“Mackie blamed the problem on a lack of sonographers, who perform ultrasound scans. The reason is not money but a high burnout rate and the fact that sonographers are not recognised as a separate profession – many start as radiographers – making it an unappealing career option.

The NHS was meant to be ready to offer every woman the combined test by the end of March 2010.”

Kypros Nicolaides, professor of foetal medicine at King’s College London, and inventor of the combined test described the NHS’s failure to roll-out the test nationwide as “scandalous and disgraceful” and stated that “the NHS is failing 70% of women in Britain and causing the death of normal babies.”

While the focus on the unnecessary deaths of healthy foetuses is understandable, I would also suggest that the inaccuracy of the testing process also results in the unnecessary deaths of a number of foetuses with Down’s syndrome – either through miscarriage or through confusion and fear resulting in parents that might otherwise be capable of raising a child with Down’s syndrome choosing to terminate.

The problems caused by the lack of accuracy are highlighted by a follow-up story in The Guardian:

“The difficulty for women and their partners is that the statistical chance of Down’s, for example one in 200, is very comparable to the quoted miscarriage risk of an amniocentesis test, which is between 0.5% and 1%,” explained Jane Fisher of the charity Antenatal Results and Choices.

Sally Hill, a sonographer in Surrey who works both privately and for the NHS, added:

“The consequences of inaccurate Down’s screening are serious and are being ignored. We should be encouraging high standards rather than accepting minimum standards. [There is] considerable variation in different risk calculation software available and this can mean the difference between being deemed high risk or low risk, which is unacceptable.”

UK invests in DNA testing research

Posted in Diagnostic testing, Scientific research by Matt at WelcometoIllinois on May 13, 2009

The Times is reporting that the UK’s Medical Research Council (MRC) is investing £7m in a national network of centres dedicated to DNA testing research, including the use of DNA testing for the prenatal diagnosis of Down’s syndrome.

Projects include genetic sequencing for transplant matching, “identifying inherited genetic mutations that can cause breast cancer, colon cancer and kidney and eye disorders”, and “studying the genetic factors that contribute to mental illnesses, and infectious diseases such as malaria and the antibiotic-resistant bacteria Clostridium difficile.”

As far as Down’s syndrome is concerned, a “project at the Cambridge hub will evaluate methods of testing the blood of pregnant women for foetal DNA. This could potentially allow prenatal diagnosis of Down’s syndrome without amniocentesis, an invasive test that can cause miscarriage,” The Times reports.

I’ve written about DNA testing for prenatal diagnosis of Down’s syndrome before. In particular Sequenom appeared to making good progress but has subsequently admitted that the data was mishandled by employees.

Test for birth defects may cause birth defects

Posted in Diagnostic testing, Scientific research, Surveys by Matt at WelcometoIllinois on January 5, 2009

Damned if you do…

I read this report back before Christmas on the risks related to chorionic villus sampling (CVS), a common prenatal diagnostic test for Down’s syndrome, but I didn’t really take it in.

A study by Dr. Lewis B. Holmes of Massachusetts General Hospital for Children has reviewed past research on the possible link between CVS and birth defects and indicated that CVS may increase the risk of that the baby will be born with a birthmark, or “infantile hemangioma” or even limb defects.

According to this report from Reuters:

“In one study, Holmes reports, researchers found “cavernous or strawberry hemangiomas” in 12 of 95 (12.6 percent) CVS-exposed infants compared with 3 of 87 (3.4 percent) infants who had been exposed to amniocentesis, which is typically performed later in pregnancy.

In another study, hemangiomas were seen in 21.1 percent in 578 CVS-exposed infants versus 7.4 percent in 445 amniocentesis-exposed infants. Some babies in the CVS group, but none in the amniocentesis group, had multiple hemangiomas.

Holmes also looked at the evidence for an association between CVS and birth defects involving the limbs, especially the fingers, and found some “clear” correlations. The evidence suggests that these risks are greater when CVS is performed earlier in pregnancy, such as at 8 to 9 weeks gestation.”

The Editor-in-Chief of the Journal of Craniofacial Surgery points out that “CVS is generally done for prenatal detection of serious genetic diseases like Down’s syndrome in pregnancies at high risk” and that “the benefits of knowing the test results could outweigh the possible risk of hemangiomas or other abnormalities”.

Which is probably true, but the risk of birth defects should also be factored into any cost/benefit analysis of diagnostic testing. I certainly don’t remember it being mentioned when we were preparing for our CVS test.

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.

Down’s syndrome births up 25% in UK in last 15 years

Posted in Charities, Screening, Statistics, Surveys by Matt at WelcometoIllinois on September 18, 2008

Here are some interesting statistics about Down’s syndrome:

* “Around 750 babies are born with Down syndrome each year in England and Wales – up 25% from around 600 annual births in the early 1990s.

* Around 6,000 babies are born with Down syndrome each year in the North America and around 10,000 across Europe.

* Approximately 220,000 babies are born with Down syndrome worldwide each year. Over 200,000 of these babies are born in less developed regions of the world.

* Over 40,000 people with Down syndrome live in the UK today, around 350,000 in North America and perhaps 400,000 across Europe.

* An estimated 3-4 million people are living with Down syndrome worldwide. As global healthcare improves, the population of people with Down syndrome may double over the next 30 years.”

They have been published by Down Syndrome Education International in conjunction of the findings I noted earlier that indicated that invasive testing for Down’s syndrome carries a much higher risk causing the miscarriage of healthy babies than previously thought.

When you also consider that according to DownsEd, “successful management and treatment of health conditions has raised average life expectancy dramatically for people with Down syndrome from around 12 years in 1950 to around 60 years today” it’s doubly understandable why the charity has called (PDF) on the UK Government to “to consider an urgent review of its approaches to supporting people with Down syndrome and their families and its policies concerning the genetic screening of unborn babies.”

More on that research at the BBC, The Telegraph, ITN and The Observer.

Reassessing the risks of invasive testing

Posted in Screening, Statistics, Surveys by Matt at WelcometoIllinois on September 15, 2008

Invasive testing for Down’s syndrome carries a much higher risk of causing the miscarriage of healthy babies than previously thought, according to new research due to be published in the UK this week.

“The research claims that, in detecting and preventing the birth of 660 Down’s babies, 400 healthy foetuses are lost,” reports The Guardian. Currently the National Health Service cites a a miscarriage rate of between 1 and 2% following the invasive amniocentesis and chorionic villus sampling (CVS) tests.

However, no research has been done on the number of babies without Down’s syndrome that are lost due to invasive testing, according to The Guardian. The new research, to be published in the Down’s Syndrome Research and Practice journal, is a best-guess due to the lack of accurate statistics.

Details of the research are due to be broadcast by the UK’s Channel 4 News at 7pm on Tuesday. According to The Guardian the research’s authors are concerned “about how well qualified the staff are who carry out the invasive testing and about their ability to use ultrasound”.

The Foundation for People with Learning Difficulties pointed out in July that “pregnant women and their partners do not always receive the information they need to help them to make decisions about antenatal screening” and that “midwives and obstetricians often feel they lack vital information about disability to guide expectant parents through the screening for fetal abnormality.”

The threshold for the recommendation of invasive testing is also criticised: “To detect as many Down’s babies as possible, the initial screening threshold is set wide, which means that more than 95 per cent of women defined as ‘high risk’ will not be carrying a baby with the disorder, yet most go on to have the amniocentesis or CVS tests.”

If the research results are accurate they will certainly cast a new light on the decision of expectant mothers to decide whether or not to go through with invasive testing. It will be interesting to see how the researchers’ estimates stand up to scrutiny.

The report states that about 750 Down’s babies are born every year in England and Wales.

More on this research.