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expert reaction to new research suggesting an association between air pollution and autism

A study in Archives of General Psychiatry suggested exposure to traffic-related air pollution, particulate matter and nitrogen dioxide during pregnancy and during the first year of a child’s life appears to be associated with an increased risk of autism. A before the headlines analysis accompanied this roundup.

 

Prof Emily Simonoff, Professor of Child & Adolescent Psychiatry at the Institute of Psychiatry, King’s College London, said:

“Autism has been recognized for over 40 years now to be a highly heritable disorder, in which the genetic influences are likely to be due to multiple genes acting together. More recently, however, different aetiological factors have been recognized.  These include genetic variants, often called copy number variants or CNVs. In addition, the possible role of gene-environment interplay, whereby the combined effect of genes and environment creates a particular risk for autism, has been highlighted.

“The role of environmental influences has been of particular interest for at least two reasons. First, despite the very high heritability, the genes identified as increasing the risk of autism have each been of small effect. Second, studies over the last two decades consistently show higher rates of autism than previous studies. While it is clear that in part this increase is due to factors such as better case identification and improved diagnostic tools, which do not involve causal factors, there nevertheless remain questions about whether new environmental risk factors could be a cause for a true increase in the prevalence of autism.

“The present study uses a case-control design that compares the early history of 279 children with autism compared to 145 age and case-matched children without autism.  Specifically, potential exposure to a range of air pollutants during pregnancy and the first year of life was compared, using as proxy measures of exposure the mother’s (and child’s) address and a range of reported measures of the level of air pollution. The study found an association between having autism (i.e., being in the ‘case’ group) and residing in the areas in which the highest (top quartile) levels of air pollution were reported. Children with autism were roughly twice as likely to have been resident either before birth or in the first year of life in areas corresponding to the top quartile for air pollutant exposure on a range of measures.

“This is potentially an important finding and it is therefore essential to consider the strengths and limitations of the study.  I cannot comment on the appropriateness of the measures of air pollution nor how such measures of residential exposure to air pollution relate to biological exposure and biological effect. It will be important to gain an expert opinion on this. However, the case-control design is not ideal for demonstrating causation and this is particularly problematic when exposure levels have been measured in a manner that is so distal to the putative biological effect. Most importantly, neither the case nor control group appears to have been ascertained systematically from the population. This makes the possibility of biases in either, or both, groups a considerable cause for concern, as other factors may differ between the groups and could bias the present findings. Second, the range of factors accounted for in the adjusted model was limited and did not include a number of factors that could the findings. These include accounting for paternal age and family history of autism and autistic-like traits. Such case-control differences could lie at the core of the present findings. At present, therefore, the findings need to be considered with caution.

“To add to the credence to the present findings, further research is essential and should consider the following points. An observational study commencing before birth and with more direct measures of air pollution (as well as a range of other potential causal factors) is an important next step. A range of outcomes should be considered. The evidence from both genetic and environmental (such as birth prematurity) studies indicates that these risk factors confer a broader risk for developmental disorders and not just autism. Therefore, a range of outcomes should be studied. Several geographic regions should be included and the sample sizes need to be considerably larger. Replication of the present findings will be an important next step.

“At present, pregnant women should continue to look after their health during pregnancy but should not be unduly concerned.”

 

Prof Uta Frith, Emeritus Professor of Cognitive Development at UCL, said:

“It seems to me very unlikely that the association is causal, rather than correlational. The authors bolster up their previous study suggesting that in California there are more cases of autism if the mother during pregnancy lived near a highway. The recent paper adds detailed measures of air pollution but does not get us any further since it does not present a convincing mechanism by which pollutants could affect the developing brain to result in autism. Rather than taking the results at face value I would like to know what it implies to live near a highway. It could imply all sorts of disadvantages, any of which might be associated with increased risk of autism – and with increased risk of other disorders as well.”

 

On the editorial on autism and research prevalence: Prof Tony Charman, Chair in Autism Education, Institute of Education, said:

“The measured prevalence has risen, but this may or may not be a true increase. Geri Dawson cites the Centers for Disease Control and Prevention (CDC) figures that show an uplift in recent years.

“However, other factors, such as increased awareness amongst professionals, parents, others might underlie this measured increase. The CDC methodology is a care/records review/extraction process (health and education) so the way of measuring prevalence cannot rule out that increase is due to these kind of factors and may not be a ‘true’ increase.

“There are other international studies that have found similar rates (our work in the Lancet from 2006 in the UK: Baird et al, 2006, Lancet) , i.e. 1.16% (1 in 86 children)  for all ASDs (broadly defined). We also did a survey in 2002 where we found a similar rate to the latest CDC publication some 6 to 10 years before – ie. They just caught up. There are other studies where the rate is ~1%.

“The issue of whether this increase is real, and if so whether and what environmental (as opposed to clinical/cultural/awareness) factors might explain this, is still an empirical question.”

 

Sophia Xiang Sun, Autism Research Centre at the University of Cambridge, said:

‘Although traffic-related air pollution might be one of the contributing factors to the development of autism, other factors cannot be ruled out. These factors include second hand smoking during pregnancy, medical conditions related to pregnancy, indoor air pollution, especially if the family has a history of mental disorders as autism is highly genetic.

“Further research is needed to investigate the potential association between traffic-related air pollution and autism, ideally a prospective study that monitors traffic-related air pollution with the control of indoor air pollution and smoking. Until further research is carried out we will not know definitely if the association is there and, if it is there, how direct and to what degree.

“We know that traffic related air pollution can contribute to many other diseases and conditions, and it is biologically plausible it also has a role in pathways of autism. However, whether or not the potential association between autism and traffic-related air pollution exists, reduction of traffic-related air pollution would be good for public health.

“Regarding reports of an increase in prevalence of autism, there has been no clear evidence whether it is a real increase or not. This is because there have been many changes that could make it appear that the prevalence of autism is increasing, including:

  • changes to the way we diagnose autism (broadening of the spectrum, a change in diagnostic criteria and a change to the way we view autism)
  • the development of improved screening, diagnostic instruments and services for autism
  • increased awareness of the condition among professionals and the public
  • changes in study methods such as  variation in demographic characteristics of study populations

We need more robust research before we will know if this is a real increase or whether it is simply due to these changes.”

 

‘Traffic-Related Air Pollution, Particulate Matter, and Autism’ by Heather  Volk et al.  published in Archives of General Psychiatry on Monday 26th November.

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