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Research published in JAMA Paediatrics shows that in a population based birth cohort there was an association between exposure to nitric oxide and autism spectrum disorder.
A Before the Headlines accompanied this Roundup.
Dr Ioannis Bakolis, Lecturer in Biostatistics, Institute of Psychiatry Psychology & Neuroscience, King’s College London, said:
“This is a well-conducted study that benefits from its large sample size, adequate consideration for potential confounders and established clinically verified ASD diagnostic criteria. The link presented between prenatal exposure to air pollution and ASD is strengthened by a series of previous studies from other regions that replicate the findings. We know air pollution particles can get into the placenta and toxic air is already strongly linked with harmful effects in foetuses. However, questions still remain about which specific component of air pollution is the most relevant, which trimester of pregnancy is most important, how inhaled nanoparticles could gain access to the brain and which are the potential mechanisms by which pollutants can affect CNS health. Thus, a causal link cannot yet be established. Metro Vancouver is not an area that suffers from very bad air quality and meets health-based WHO Air Quality Guidelines. This raises an important public health issue, since the majority of world’s population still breathe air more toxic than the current WHO guidelines.”
Dr James Cusack, Director of Science, Autistica, said:
“This research should not concern people thinking about having children.
“Autism is strongly genetic. We know this because it runs in families. Recently, researchers have also been trying to find out if aspects of parents’ environments increase their chances of having an autistic child.
“The study monitored expectant mothers who lived in a neighbourhood with higher levels of nitric oxide in the air during pregnancy. They found a tiny increase in the likelihood of having an autistic child – from 1 percent to 1.07 percent.
“It’s easy to find coincidental changes in the environment at the same time that the number of people receiving autism diagnoses increases. And other differences which were not measured, such as genetic differences, may explain this increase. This study does not provide evidence that air pollution causes autism.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:
“This is a careful study, but its results are a bit hard to interpret. If air pollution really does affect the risk of autism spectrum disorder (ASD), the effects do appear to be pretty small. Imagine 1500 births in the Vancouver area, where the study took place. If they are like the births studied in this research, 15 of the children will be diagnosed with ASD. Imagine now that pollution round Vancouver got worse, so that the average level of nitric oxide (NO) in the atmosphere went up by 10 parts per billion. That’s a fairly substantial increase, for an area like Vancouver where air pollution levels are generally quite low (though it wouldn’t be big in one of Asia’s highly polluted cities). If nitric oxide is really affecting ASD risk to the extent measured in this study, that would lead to about 1 extra ASD diagnosis in the 1500 children. In addition, the uncertainty about the size of the increased risk in this study is fairly large. For nitric oxide, the results are consistent with an increase in risk that’s nearly zero, or is about double what I’ve just described, or anything between. The uncertainty is large because, despite the large number of births involved, what really matters is the number of ASD diagnoses, and that number was pretty small. In fact, in broad terms, the results of the study were much the same for all three pollutants that were considered (fine particles and nitrogen dioxide as well as nitric oxide), though only for nitric oxide did they go over the conventional boundary of statistical significance (and only just over).
“In any case, it’s not really possible in studies like this to truly sort out what causes what. The problem is that people who live in more polluted areas tend to be different from those who live in less polluted areas in many ways not caused by the pollution, and it could be that one or more of these other differences is the real cause of differences in rates of ASD diagnosis. You can make statistical adjustments to try to allow for these other differences, and these researchers did that for several possible factors, but it can only be done for factors that you have data for, and even then it’s not possible to know for sure how well the adjustments worked. In this study, the adjustments that were made did make quite substantial differences to the estimated levels of risk. That shows how important such adjustments are, but it also draws attention to the possible consequences of being unable to adjust for an important factor. Perhaps more comprehensive adjustments would make the apparent risk from air pollution disappear altogether, or perhaps they would make it bigger – we just can’t tell.
“Because of these issues about what causes what, no one study of this kind can, on its own, establish a link between a pollutant and its health consequences. To do that, you have to look across a range of studies of the same potential effects, in different places and times, and possibly using different methods. In this new research report, the researchers summarise previous studies on air pollutants and ASD. The results aren’t by any means consistent across all the studies. As the researchers point out, there are all sorts of possible reasons for this inconsistency, but it’s certainly true that no consistent picture is yet emerging. Perhaps air pollution does really affect ASD risk, or perhaps it doesn’t. This new study adds more evidence, but in my view, we’re a very long way from knowing.”
Dr Rosa Hoekstra, Senior Lecturer in Psychology, Institute of Psychiatry Psychology & Neuroscience, King’s College London, said:
“This study reports findings from a very large population group encompassing nearly all births in the Vancouver metropolitan area of Canada between 2004 and 2009. The study suggests that an increase in exposure during pregnancy to one particular airborne pollutant, nitric oxide, may be associated with a very slight increase in odds of the child developing autism. No increased risk of autism was found for exposure to two other pollutants implicated in autism risk in previous studies, nitrogen dioxide and PM2.5.
“Because this study was conducted in a very large study group, even a very slight increase in risk could be detected. However, it should be borne in mind that the increase in risk was only very slight: around 1% of the overall group of children studies had an autism diagnosis, the odds of autism in children prenatally exposed to higher levels of nitric oxide was still only 1.07%.
“Compared to other cities worldwide, Vancouver has relatively low levels of pollution. We can’t tell from this study whether it is the air pollutant or something else that actually causes any increase in autism risk – if it is causal, it may be that the risk of autism is increased more when exposed to greater levels of air pollution, but we can’t tell that from this research. Previous studies examining an association between air pollution and autism risk reported conflicting results, some suggesting a link, others not finding evidence of an association.”
‘Association of prenatal exposure to air pollution with autism spectrum disorder’ by Lief Pagalan et al. was published in JAMA Pediatrics at 16:00 UK time on Monday 19 November 2018.
Declared interests
Dr Ioannis Bakolis: “I have no conflict of interest to declare.”
Dr James Cusack: “No conflicts.”
Prof Kevin McConway: “Kevin McConway is a trustee of the SMC.”
Dr Rosa Hoekstra: “I have no conflict of interest to report.”