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On terminations and survival rates

Posted in Scientific research, Termination by Matt at WelcometoIllinois on January 24, 2010

I recently wrote about the theory that an increase in the quality of care and medication had contributed to the increased number of children born with Down’s syndrome in the US and UK (along with higher maternal age of course).

A recent study of survival rates of children with congenital abnormalities backs that up. According to a Medscape report based on a story in the Lancet, “medical advances from 1985 through 2003… increased in the likelihood of survival.”

While that seems pretty straightforward another finding of the study has me perplexed.

“Pregnancy termination played a significant role in boosting survival rates. ‘The proportion of terminations of pregnancy for fetal anomaly increased throughout the study period (from 12.4% in 1985 to 18.3% in 2003) and, together with year of birth, was an independent predictor of increased survival,’ the authors write.”

Now I can fully understand how increased terminations of babies with congenital abnormalities would have an impact on the overall infant mortality rate but are the researchers, or the reporter, seriously suggesting that there is a causal relationship between increased terminations and increased survival rates?

The statement “pregnancy termination played a significant role in boosting survival rates” suggests so. As does the headline: “Treatment Advances, Early Terminations Contribute to Higher Survival Rates in Children With Congenital Anomalies”.

I’ve been racking my brains trying to work out how increased terminations could lead to the babies that are born with congenital abnormalities being more likely to live longer, but I can’t see it. Without access to the Lancet report it is hard to tell whether the original research supports the Medscape headline, but my guess is that Medscape has taken a statement that was true for the general population and applied it specifically to the population of children with congenital abnormalities.

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The difference between treatment and cure

Posted in Scientific research, Therapeutic treatments by Matt at WelcometoIllinois on January 12, 2010

A few months ago I briefly mentioned some research underway at the Stanford University School of Medicine and Lucile Packard Children’s Hospital that could eventually lead to treatments that could improve cognition in people with Down’s syndrome, or at least delay the decline of cognitive function.

The research has hit the headlines this week thanks to a New York Times post questioning the need for a “cure” for Down’s syndrome.

The NYT post concludes by asking “if there were a cure for your child that would fundamentally change who he is, would you welcome it?” It’s an interesting theoretical question, but one that is unlikely to be raised by the research.

As Dr. Ahmad Salehi, M.D., Ph.D., the lead researcher on the Stanford University study, noted in response to a similar question, “restoring a rather limited aspect of learning and memory in a mouse model of Down syndrome is far from being a cure”.

It also only addresses cognitive function, which is one of many potential effects of Down’s syndrome. Others, such as heart defects and thyroid problems, are already treated by medical science, Why would you not also treat cognitive ability, were that possible?

I do understand, however, why some parents would be wary of a theoretical cure. I previously mentioned, twice, that while I am in favour of using drugs to improve life for people with Down’s syndrome, gene therapy (or praying to remove the effects of Down’s syndrome in the latter example) feels like quite a different proposition as it raises questions about fundamentally changing the personality of the recipient.

Research contradicts Down’s syndrome stereotypes

Posted in Attitudes to disability, Scientific research, Support services by Matt at WelcometoIllinois on November 3, 2009

Anyone who’s had anything to do with Down’s syndrome will have heard the stereotypes about people with DS: they’re very loving; they’re very happy; they’re very stubborn. G had been alive less than five minutes before I was told by a paediatrician that “They are very happy babies”.

Is there any truth in the suggestion that all people with Down’s syndrome share certain personality traits?

Recent research would suggest not, according to a blog post I just stumbled upon written by Pierce J Howard PhD, Managing Director of Research and Development at the Center for Applied Cognitive Studies in Charlotte.

Howard and his colleagues have taken their personality assessment for adolescents, and translated it into a form to rate the personalities of people with Down’s syndrome. The early results suggest that people with Down’s syndrome – or Down’s syndrome individuals (DSIs) as the research put it – exhibit more varied personalities than developmentally typical individuals (DTIs).

“The standard deviations for N, E, O, and A are higher among DSIs, suggesting that there is more variability in these four areas than is found among DTIs—more extremes in behavior. More extremely neurotic individuals, and more extremely calm ones; more extremely extraverted as well as more extremely introverted; more extremely imaginative and more extremely literal; more who are extremely deferential, and more who are extremely defiant, in comparison to the DTIs.”

As Dr Howard goes on to explain, “the only supertrait that suggests LESS variability among DSIs is C, suggesting that DSIs as a group show less extremely ambitious behavior, as well as less of the opposite”. It would be interesting, as Rickismom notes in the comments, to research whether that potential lower will to achieve is natural or the result of “a society-induced resignation or hopelessness”.

The mean responses do suggest that people with Down’s syndrome are more likely to exhibit certain personality traits such as:

– “a somewhat lower level of creativity, complexity, and comfort with change”
– “a noticeably lower preference for perfectionism, focus, ambition, concentration, and methodicalness”
– “a somewhat stronger tendency to defer to others and be comfortable in the background”

However, when it comes to the big stereotype, that of happiness, the research suggests that people with Down’s syndrome are no happier than anyone else:

“the means on N and E show no difference between the DSIs and the DTIs, suggesting that levels of happiness (positive emotions dominating negative emotions) are similar.”

As Dr Howard explains, if continued research supports these early results it could have a significant impact in the way in which support services are provided to people with Down’s syndrome.

“Historically, people have assumed that DSIs were all similar behaviorally—that they all like repetition, were all moderately sociable, and so forth. This data clearly challenges those assumptions. Hence, among DSIs, we need to take individual differences into account with respect to career choices, roles in group homes, managing conflict, teaching/learning style, relationship management, motivational strategies, therapy modes, and, in short, we need to employ the same individual difference sensitivities with DSIs that we use with our developmentally typical friends, family, and associates.”

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.”

What’s up Bub?

Posted in Genetics, Scientific research by Matt at WelcometoIllinois on July 21, 2009

Scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory and the University of Tennessee, Knoxville think they may have come up with a solution to the problem of what causes chromosomal abnormalities such as Down’s syndrome.

According to ScienceBlog, researchers think it could be down to a gene called Bub1:

“Usually, both copies of a gene in a chromosome must carry the same mutation in order for an organism to be adversely effected.

‘But we found that a mutation in a single copy of the Bub1 gene can have an impact — and this is not the case with most genes. With Bub1, if you have one bad gene and one healthy gene, there’s a problem,’ says Francesco Marchetti of Berkeley Lab’s Life Sciences Division.”

ScienceBlog adds:

“It’s rare for humans to have mutations in both copies of a gene, while it is quite common to have a mutation in only one copy. Usually, the healthy gene overrides the mutated gene ?- but not in Bub1, at least in mice.”

Research points to potential in utero treatment for Down’s syndrome

Posted in Scientific research, Therapeutic treatments by Matt at WelcometoIllinois on June 3, 2009

Researchers from Tufts Medical Center and Tufts University have published a paper that suggests it may be possible to develop prenatal therapies for Down’s syndrome.

According to the press release, the research suggests that “amniotic fluid surrounding Down syndrome fetuses shows oxidative stress, a condition that could harm fetal cells and play a role in affected individuals”.

The research prompted some surprising new findings:

“The longstanding assumption has been that proteins produced by the additional copy of chromosome 21 were almost exclusively responsible for the atypical development and function associated with the syndrome. A surprising aspect of the findings was that the molecular abnormalities observed were predominantly produced by genes on the other chromosomes.”

The release continues: “Researchers are examining amniotic cells to determine if they show similar genomic profiles to the cell-free material in the fluid. If that is the case, they will begin to look at the effectiveness of anti-oxidant compounds as potential treatment in vitro.”

Of course, any potential treatment is years away, but this is an interesting development nonetheless. I previously covered the potential for in utero treatment here.

Down’s syndrome and cancer

Posted in Genetics, Scientific research by Matt at WelcometoIllinois on May 21, 2009

I meant to write about this the other day but I didn’t have time. Now it has been reported everywhere it is easier just to link to the reports: Nature has published a report explaining why people with Down’s syndrome are less susceptible to cancer.

“A gene on the extra chromosome that causes Down’s syndrome helps to protect those with the disorder from some types of cancer.

Sandra Ryeom, a vascular biologist at Children’s Hospital Boston in Massachusetts, and her colleagues experimented with mice and with human cells to show that an additional third copy of the DSCR1 gene (also known as RCAN1) can suppress the growth of the blood vessels that feed cancerous tumours.”

I previously reported on how a better understanding of Down’s syndrome may aid breast cancer therapy.

More on this from the BBC, MIT Technology Review, and Forbes.

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.

Court ruling on (lack of) autism-vaccine link

Posted in Legal issues, Off topic, Scientific research by Matt at WelcometoIllinois on February 12, 2009

Following up on my earlier post.

The Washington Post reports:

Thousands of parents who claimed that childhood vaccines had caused their children to develop autism are wrong and not entitled to federal compensation, a special court ruled today in three decisions with far-reaching implications for a bitterly fought medical controversy.

The New York Times adds:

These three decisions, each looking into a different theory as to how vaccines might have injured the children, are expected to guide the outcomes of all [5,000 similar] claims.

The judges ruled that the families seeking compensation had not shown that their children’s autism was brought on by the presence of thimerosal, a mercury vaccine preservative, by the weakened measles virus used in the measles/mumps/rubella vaccine, or by a combination of the two.

The Washington Post continues:

The decision by three independent special masters is especially telling because the special court’s rules did not require plaintiffs to prove their cases with scientific certainty — all the parents needed to show was that a preponderance of the evidence, or “50 percent and a hair,” supported their claims. The vaccine court effectively said today that the thousands of pending claims represented by the three test cases are on extremely shaky ground.

In his ruling on one case, special master George Hastings said the parents of Michelle Cedillo — who had charged that a measles, mumps and rubella (MMR) vaccine caused their child to develop autism — had “been misled by physicians who are guilty, in my view, of gross medical misjudgment.”

Hastings said that he was deeply moved by the suffering autism imposed on families such as the Cedillos, but that “the evidence advanced by the petitioners has fallen far short of demonstrating . . . a link.”

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MMR-autism report author fixed results

Posted in Off topic, Scientific research by Matt at WelcometoIllinois on February 8, 2009

This is a bit off-topic but I think it is important to spread the word given that the health of children is at stake. The Sunday Times reports:

“The doctor who sparked the scare over the safety of the MMR vaccine for children changed and misreported results in his research, creating the appearance of a possible link with autism, a Sunday Times investigation has found.

Confidential medical documents and interviews with witnesses have established that Andrew Wakefield manipulated patients’ data, which triggered fears that the MMR triple vaccine to protect against measles, mumps and rubella was linked to the condition.”

I find it fascinating – not to mention alarming – that Wakefield’s report continues to dominate thinking about the MMR jab over ten years after it was published, despite the countless subsequent reports that have either disproved or failed to support its claims.

It would be funny if the impact on our children wasn’t so potentially tragic. As The Guardian reported this week:

“Measles cases have risen to a record high as children who were never vaccinated against the disease become ill, the Health Protection Agency said yesterday.

Last year there were 1,348 cases of the disease in England and Wales, the HPA said, up from 990 in 2007. Those numbers may yet rise as more reports come in.

The agency blamed the increase on a paper from Dr Andrew Wakefield and colleagues published in the Lancet in 1998 which hypothesised a link between the MMR vaccine and autism. Although that claim has been demolished, the fallout continues.”

As a report from the British Medical Journal, also in The Guardian pointed out:

“Children occasionally die from measles. These are usually children who have not been vaccinated. In the early 1990s, more than 150 children died in the US because of a measles outbreak among young children who hadn’t been vaccinated.”

Today’s Sunday Times report states:

“The research was published in February 1998 in an article in The Lancet medical journal. It claimed that the families of eight out of 12 children attending a routine clinic at the hospital had blamed MMR for their autism, and said that problems came on within days of the jab…

However, our investigation, confirmed by evidence presented to the General Medical Council (GMC), reveals that: In most of the 12 cases, the children’s ailments as described in The Lancet were different from their hospital and GP records. Although the research paper claimed that problems came on within days of the jab, in only one case did medical records suggest this was true, and in many of the cases medical concerns had been raised before the children were vaccinated.”

Along with two other professors, Wakefield is defending himself against allegations of serious professional misconduct brought by the General Medical Council related to ethical aspects of the study, rather than its findings.

However, ten of the original 13 authors of the report retracted their findings in 2004, while the editor of The Lancet admitted that in hindsight it should not have been published due to conflicts of interest.

Just last month the senior vice-president of communications and strategy at Autism Speaks, resigned from the charity in a dispute over the continued funding of research into the original report’s findings.

“If you keep looking under the same rock, you’re going to keep finding the same thing,” said Singer. “Over and over, the science has shown there is no causal link between vaccines and autism. It’s time to look for answers in new and different places.”

The position of the Down’s Syndrome Association on MMR, incidentally, states:

“The vast majority of independent research bodies, who have looked into the evidence relating to MMR and autism, have found no good quality evidence linking the two. There is no reason to suggest that children with Down’s syndrome would be any more at risk of adverse side effects. The diseases which MMR protects against would be likely to be serious for a child with the syndrome, and single vaccines would leave the child at risk from these diseases for longer.”

I should perhaps note that The Sunday Times report concludes:

“Through his lawyers, Wakefield this weekend denied the issues raised by our investigation, but declined to comment further.”