Wednesday, January 14, 2009

Soaring autism rates in California not an artifact

NEW YORK (Reuters Health) – The increasing number of autism cases seen in California since the 1990s is in large part real, not simply the result of changes in diagnostic criteria or in how autism cases are counted, new research suggests.

This study is the first to assess whether the autism trends in California might be explained by changes in age at diagnosis or by inclusion of milder cases, Dr. Irva Hertz-Picciotto and Dr. Lora Delwiche, from the University of California, Davis, note.

Using data from the California Department of Development Services, the researchers found that autism rates among children aged 5 years or younger rose steadily from 0.8 per 10,000 children born in California in 1990 to 11.2 per 10,000 children born in 2006.

The cumulative incidence per 10,000 births climbed from 6.2 in 1990 to 42.5 in 2001.

The proportion of cases that were diagnosed by 5 years of age rose only slightly from 54 percent to 61 percent for 1990 to 1996 births, according to a report in the January issue of Epidemiology.

A change in the age at diagnosis could explain 12 percent of the increase in autism rates, while inclusion of milder cases could explain 56 percent.

"With evidence of a leveling off, the possibility of a true increase in (autism) incidence deserves serious consideration," the investigators emphasize.

"It's time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California," Hertz-Picciotto added in a statement.

SOURCE: Epidemiology, January 2009.

New Study: Autism Linked to Environment

By Marla Cone

California's sevenfold increase in autism cannot be explained by changes in doctors' diagnoses and most likely is due to environmental exposures, University of California scientists reported Thursday.

The scientists who authored the new study advocate a nationwide shift in autism research to focus on potential factors in the environment that babies and fetuses are exposed to, including pesticides, viruses and chemicals in household products.

"It's time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California," said Irva Hertz-Picciotto, an epidemiology professor at University of California, Davis who led the study.

Throughout the nation, the numbers of autistic children have increased dramatically over the past 15 years. Autistic children have problems communicating and interacting socially; the symptoms usually are evident by the time the child is a toddler.

More than 3,000 new cases of autism were reported in California in 2006, compared with 205 in 1990. In 1990, 6.2 of every 10,000 children born in the state were diagnosed with autism by the age of five, compared with 42.5 in 10,000 born in 2001, according to the study, published in the journal Epidemiology. The numbers have continued to rise since then.

To nail down the causes, scientists must unravel a mystery: What in the environment has changed since the early 1990s that could account for such an enormous rise in the brain disorder?

For years, many medical officials have suspected that the trend is artificial--due to changes in diagnoses or migration patterns rather than a real rise in the disorder.

But the new study concludes that those factors cannot explain most of the increase in autism.

Hertz-Picciotto and Lora Delwiche of the UC Davis Department of Public Health Sciences analyzed 17 years of state data that tracks developmental disabilities, and used birth records and Census Bureau data to calculate the rate of autism and age of diagnosis.

The results: Migration to the state had no effect. And changes in how and when doctors diagnose the disorder and when state officials report it can explain less than half of the increase.

Dr. Bernard Weiss, a professor of environmental medicine and pediatrics at the University of Rochester Medical Center who was not involved in the new research, said the autism rate reported in the study "seems astonishing." He agreed that environmental causes should be getting more attention.

The California researchers concluded that doctors are diagnosing autism at a younger age because of increased awareness. But that change is responsible for only about a 24 percent increase in children reported to be autistic by the age

"A shift toward younger age at diagnosis was clear but not huge," the report says.

Also, a shift in doctors diagnosing milder cases explains another 56 percent increase. And changes in state reporting of the disorder could account for around a 120 percent increase.

Combined, Hertz-Picciotto said those factors "don't get us close" to the 600 to 700 percent increase in diagnosed cases.

That means the rest is unexplained and likely caused by something that pregnant women or infants are exposed to, or a combination of genetic and environmental factors.

"There's genetics and there's environment. And genetics don't change in such short periods of time," Hertz-Picciotto, a researcher at UC Davis' M.I.N.D. Institute, a leading autism research facility, said in an interview Thursday.

Many researchers have theorized that a pregnant woman's exposure to chemical pollutants, particularly metals and pesticides, could be altering a developing baby's brain structure, triggering autism.

Many parent groups believe that childhood vaccines are responsible because they contained thimerosal, a mercury compound used as a preservative. But thimerosal was removed from most vaccines in 1999, and autism rates are still rising.

Dozens of chemicals in the environment are neurodevelopmental toxins, which means they alter how the brain grows. Mercury, polychlorinated biphenyls, lead, brominated flame retardants and pesticides are examples.

While exposure to some--such as PCBs--has declined in recent decades, others--including flame retardants used in furniture and electronics, and pyrethroid insecticides--have increased.

Mothers of autistic children were twice as likely to use pet flea shampoos, which contain organophosphates or pyrethroids, according to one study that has not yet been published. Another new study has found a link between autism and phthalates, which are compounds used in vinyl and cosmetics. Other household products such as antibacterial soaps also could have ingredients that harm the brain by changing immune systems, Hertz-Picciotto said.

In addition, fetuses and infants might be exposed to a fairly new infectious microbe, such as a virus or bacterium, that could be altering the immune system or brain structure. In the 1970s, autism rates increased due to the rubella virus.

The culprits, Hertz-Picciotto said, could be "in the microbial world and in the chemical world."

"I don't think there's going to be one smoking gun in this autism problem," she said. "It's such a big world out there and we know so little at this point."

But she added, scientists expect to develop "quite a few leads in a year or so."

The UC Davis researchers have been studying autistic children's exposure to flame retardants and pesticides to see if there is a connection. The results have not yet been published.

"If we're going to stop the rise in autism in California, we need to keep these studies going and expand them to the extent possible," Hertz-Picciotto said.

Funding for studying genetic causes of autism is 10 to 20 times higher than funding for environmental causes, she said. "It's very off-balance," she said.

Weiss agreed, saying that "excessive emphasis has been placed on genetics as a cause. "The advances in molecular genetics have tended to obscure the principle that genes are always acting in and on a particular environment. This article, I think, will restore some balance to our thinking," he said.

Research links soaring incidence of the mysterious neurological disorder to fetal and infant exposure to pesticides, viruses, household chemicals

Some issues related to whether the increase is merely a reporting artifact remain unresolved. There could be other, unknown issues involving diagnosis and reporting, scientists say.

The surge in autism is similar to the rise in childhood asthma, which has reached epidemic proportions for unexplained reasons. Medical officials originally thought that, too, might be due to increased reporting of the disease, but now they acknowledge that many more children are asthmatic than in the past. Experts suspect that environmental pollutants or immune changes could be responsible.

Autism has serious effects, not just on an individual child's health but on education, health care and the economy "Autism incidence in California shows no sign yet of plateauing," Hertz-Picciotto and Delwiche said in their study.

Testosterone linked to autism

“A prenatal screening test for autism comes closer today,” says The Guardian. It reports that scientists have found links between high testosterone levels in the womb and autistic traits in children. It says this could lead to tests that can identify autistic children before birth.

The findings are based on a scientific study of 235 children aged between eight and 10, whose mothers had amniocentesis, a test analysing fluid taken from around a foetus. None of these children were autistic, but those exposed to higher testosterone levels showed higher levels of “autistic traits”, such as poor verbal and social skills.

While this research gives us further insight into the biology behind autistic-like traits, it is important to remember that none of the children in this study were autistic. The researchers must now confirm that their findings apply to children with the condition. Should this prove to be the case, the ethical issues surrounding prenatal screening for risk of autism would need to be debated before any testing could be introduced.

Where did the story come from? This research was conducted by Dr Bonnie Auyeung and colleagues from University of Cambridge, two Cambridge hospitals, and a university in the US. It was funded by the Nancy Lurie-Marks Family Foundation and the Medical Research Council. The study was published in the peer-reviewed British Journal of Psychology.

What kind of scientific study was this?

This was a cohort study looking at the relationship between levels of the male hormone testosterone in the womb and levels of autistic traits in children.

Studies have suggested that exposure to testosterone in the womb may affect some aspects of cognition and behaviour that differ between males and females. Autism is more common among males, and some people have suggested that the condition is an extreme form of typical male traits.

The researchers identified records from 950 women who had routine amniocentesis in the Cambridge region between 1996 and 2001. The children from these pregnancies would have been aged six to 10 years old at the time of the study.

The researchers excluded certain types of pregnancy from the study. These included pregnancies in which a chromosomal abnormality was identified, pregnancies that ended in termination or miscarriage, pregnancies where there were significant medical problems after birth, or the mother was carrying twins. Cases were also excluded where there was incomplete information, or if medical practitioners felt that contacting the family would be inappropriate.

The remaining 452 women were sent two standard questionnaires, which assessed their children’s levels of autistic traits. These were the Childhood Autism Spectrum Quotient (AQ-Child) and the Childhood Autistic Spectrum Test (CAST).

Of the 452 women contacted, 235 completed and returned both questionnaires and were included in this study. The researchers measured IQ using a standard test in a subgroup of 74 children whose mothers agreed to bring them in for cognitive testing.

The researchers then looked at the levels of testosterone found in the amniotic fluid taken during amniocentesis. The researchers used statistical tests to assess whether there was any relationship between testosterone levels in the womb, and the children’s IQ and levels of autistic traits.

The researchers also looked at girls and boys separately to see if gender had any effect. The researchers also took into account various factors that might affect their results, such as the mother's age, duration of the pregnancies when the amniocentesis was carried out (usually between 14 and 22 weeks), parental education, having an older sibling, and the child's age at the time of the questionnaire.

What were the results of the study? The researchers found that, as expected, the amniotic fluid in pregnancies carrying males had higher testosterone levels than in pregnancies carrying girls. At age six to 10 boys, showed higher levels of autistic traits than girls.

Children whose amniotic fluid contained higher levels of testosterone had stronger autistic traits, as indicated by higher scores on the CAST and AQ-Child questionnaires. The researchers found similar results if they looked at boys and girls separately on the AQ-Child measure, but on the CAST measure, foetal testosterone levels were only associated with levels of autistic traits in boys, not girls.

There was no relationship between IQ and testosterone levels or level of autistic traits in the subset of children who were tested for IQ.

What interpretations did the researchers draw from these results? The researchers concluded that their findings fit with the theory that exposure to testosterone in the womb is related to higher levels of autistic traits.

They add that they need to repeat their study in a much larger sample to see if these findings extend to children with autism.

What does the NHS Knowledge Service make of this study? This study indicates an association between higher levels of testosterone in the womb and levels of autistic traits at age six to 10 years.

There are a number of points to consider:

* As the authors acknowledge, the association between testosterone levels and autistic traits does not necessarily mean that high levels of testosterone in the womb directly “cause” an increase in autistic traits. Other factors could have an effect. For example, genetic variations might affect both the levels of testosterone in the womb and levels of autistic traits.
* The samples of amniotic fluid tested were taken at different points in pregnancies, and at different times of day. As testosterone levels are likely to fluctuate over time, it is unclear whether one measurement of testosterone is representative of the foetus’ overall exposure to testosterone.
* Women who undergo routine amniocentesis are often older than the general childbearing population. The average age of women in this study was 35 years old. Although the researchers took maternal age into account, these results may not be representative of younger pregnant women.
* None of the children in this study had autism, therefore the authors note that “caution needs to be taken when extrapolating these results to individuals with a formal diagnosis of [autistic spectrum conditions]”. They report that they are currently working on obtaining a larger sample so that they can determine whether their results apply to children with autistic spectrum conditions.
* The current sample of 235 children was still relatively small. When considering that there was only a 52% response rate among those who were sent the questionnaires, the children may not be representative of the whole group. For example, some parents who had concerns about their child’s development may have felt less inclined to answer a questionnaire about it than those who were happy with their child’s level of development.

Although many newspapers describe the potential for a prenatal test for autism, the authors did not aim to develop such a test. Instead, their aim was to further understand how testosterone may affect development of autistic traits.

Even if such a test were possible, it is important to note that this would be a screening test and not a definitive diagnostic test, i.e. it would identify foetuses more or less likely to develop autism rather than identify those who would definitely go on to develop autism.

Screening tests are rarely 100% accurate, and the many ethical issues surrounding prenatal screening for risk of autism would need to be debated before any test could be offered. Also, there are currently no ways to prevent a child from developing autism. Therefore, it is unclear whether identifying children at greater risk of autism would benefit the child or the parents.