Pollution and autism spectrum disorder

Monday 7 April 2014 5:30PM (view full episode)

Research from Harvard University suggests that autism spectrum disorder, which affects perhaps about 1 in 100 Australian children and, some say, is increasing in prevalence, may be partly caused by air pollutants. This can have enormous implications for housing near roads and industry.


Norman Swan: Hello from me, Norman Swan, and welcome to the Health Report. Today: Unlocking the secrets of the brain, new discoveries of tiny molecular machines in our nervous system which might hold the answers for problems like autism and schizophrenia; and speaking of autism … a link to air pollution. Research is suggesting that children’s brain development is put at risk with increased chances of autism spectrum disorder if their mothers were exposed to excessive air pollution during pregnancy.


The autism spectrum goes from a child with severe behavioural, language and intellectual disabilities, through to quite well functioning people but who nonetheless have trouble relating to others, reading their emotions, and expressing themselves. This isn’t some fringe finding; it comes from Harvard School of Public Health where Marc Weisskopf is Associate Professor of Occupational and Environmental Epidemiology.


Marc Weisskopf: Air pollution has been studied in relation to many things. In particular cardiovascular and respiratory symptoms; obviously brain development and exposure to the mother is a different issue. There has been a literature that’s evolved and has grown around effects of air pollution on birth outcomes such as birth weight, prematurity, things of that sort; but the idea that it might affect autism is relatively new and quite frankly I got into it because of a report out of California, suggesting in a study, in the sort of Bay area of California, that mothers who were in census tracts that had higher estimated pollutant levels, had a higher risk of giving birth to a child with autism.


Norman Swan: Who were living in areas where there are lots of freeways, lots of trucks passing by, diesel fumes and things like that?


Marc Weisskopf: Yes, this was based on an EPA model, or EPA models of different pollutants.


Norman Swan: Environmental Protection Agency.


Marc Weisskopf: Environmental Protection Agency models that takes into account many factors—traffic, other point sources from industry, weather patterns, things of that sort. But they did find something that I was initially sceptical of because I thought there’s too much error in the way they were assessing how a mother was exposed.


Norman Swan: Well precisely, I mean, if you’re living in one of those areas with lots of trucks going by and maybe under a flight path to an airport, then you probably don’t have as much money to live in a fancier neighbourhood which is away from the freeway and the airline routes.


Marc Weisskopf: That’s right. So there are huge opportunities for what, in epidemiology we call confounding, which is basically another variable that is explaining what you’re seeing. They try to address that by adjusting for different factors that are related to socioeconomics or aspects of that sort, and they did it to the best of their ability, and they did it reasonably well, as far as these studies go; that might explain it. But the other issue is just that with an estimate based on these models from the EPA that are not great, they can give you general ideas of who happens to be a little higher, a little lower, but they’re not terribly accurate and so my initial reaction was, when you have that kind of error in how you’re saying who’s exposed and who’s not, you tend not to see things; so the fact that they saw something was sort of surprising.


Norman Swan: What have you done?


Marc Weisskopf: We wanted to build on that and we, at Harvard, have these very large cohorts that are across the United States, the Nurses’ Health Study in particular, the Nurses Health Study II.


Norman Swan: And when you’re saying cohort, what you’re saying is that you’ve gathered a large group of people …


Marc Weisskopf: Yes.


Norman Swan: … in this case they were nurses and all female …


Marc Weisskopf: That’s right.


Norman Swan: … and you’ve been following them now for 20 or 30 years to see what their health …


Marc Weisskopf: Exactly.


Norman Swan: … turns out to be. You know lots about them.


Marc Weisskopf: We know lots about them. This was started in 1989. It was over 100,000 nurses at the time. It’s focussed on the health of the nurse. So we had to, later on … in the course of … they get followed every 2 years. They answer extensive questionnaires and we track where they are and what they’re doing and in 2005 we asked them if they had any children with autism and we went through a process to validate the ones who said they did …


Norman Swan: This is full blown autism, rather than autism spectrum disorder where they might just have a bit of communication difficulty?


Marc Weisskopf: I said ‘autism’, I should have said autism spectrum disorder because we specifically asked whether they had a child with either autism, Asperger’s or pervasive developmental disorder. So we were capturing a broader spectrum and it’s the maternal report. Now they’re all nurses, so would some of them potentially just have behaviours that are a little bit more extreme than normal but don’t meet true definition of autism? It’s possible; and the way we check that is we took a random sample of these mothers and we administered what’s considered a gold standard autism interview—the Autism Diagnostic Interview—and got very excellent agreement. Over 95 per cent met full autism … autism spectrum disorder, criteria.


Norman Swan: So if one of these mothers who had been a nurse told you that her child with autism spectrum disorder, they did indeed have a child with autism spectrum disorder.


Marc Weisskopf: Yes.


Norman Swan: So how did you assess the exposure to air pollution?


Marc Weisskopf: Really we started by using the exact same models that they used in the California study. We had berths over a much wider period. The Environmental Protection Agency puts out a few of these—there are four of them in different years. They average over the year, they’re at the level of the census tract, and we simply compared the mothers who had reported a child with autism compared her where she was at the time of the pregnancy, what the census tract levels of different pollutants were for her compared to the women who said they had no children with autism.


To my mind, somewhat surprisingly actually, we found results that were strikingly similar to what they saw in California. So I, at that point, went from being mildly sceptical to thinking there was something worth pursuing here.


Norman Swan: Now there are other ways of checking whether something’s cause and effect or just some sort of association and it’s something else that you’re observing rather than just the air pollution. So when it’s dosed, if this is cause and effect, the more air pollution they experienced, the higher the risk of a child with autism spectrum disorder. Did you find a dose effect?


Marc Weisskopf: We did. Though that said, one has to be a little careful because doses—there can be threshold effects, they don’t have to always be linear relations with the outcome. We, in general, found as you got higher with those estimates, you had a higher risk of autism spectrum disorders. It wasn’t perfect …


Norman Swan: And were you able to measure, for example, the exposure in pregnancy to the exposure in the first years of life?


Marc Weisskopf: That’s what I’ve been working on now, in fact. That original study used these exposure models that estimated over an entire year; and only in four different years. So for some of our children, we were assigning an estimated exposure from say 1999 to a child who’s mother was pregnant in 1998. So what we really wanted to do was say, well let’s now … it looks like something’s there. Let’s go after this with a much finer resolution tool; something where we have finer spatial and temporal resolution. We don’t have that for all of the pollutants that the EPA has in their models but one that we do have very good data on is particulate matter, which is basically just stuff in the air. We can size fractionate it, that is, we can look at small stuff that’s less than two and a half microns in diameter, we can look at the bigger stuff that’s up to ten microns in diameter; and we have very extensive models that the Nurses’ Health Study researchers, many of them have used, for example, to link air pollution to cardiovascular disease, to respiratory problems, to mortality in general.


It’s based on, again, EPA monitors that are around the entire country, meteorological factors; it’s a model then that takes those monitor data and incorporates meteorological conditions and incorporates land use patterns like traffic or other point sources; and it gets down to a resolution of a month—you could go even finer—but we have it as a month at a time.


So now we can look specifically at the pregnancy or even trimesters of pregnancy. We also have it on the spatial level that now we know it at her address.


Norman Swan: That’s extraordinary. What did you find?


Marc Weisskopf: We initially looked at the nine months. So we averaged over the nine months of the pregnancy, we considered the nine months prior to that, and the nine months after that … so when the child was born. And what we found was a significant association between higher particulate matter that was less than 2.5 microns, so not with the larger stuff, but less than 2.5, for that pregnancy period. Again in a dose response fashion; and we then went further and said, okay, if it’s the pregnancy period, when in the pregnancy period? And we broke it out again by trimester of pregnancy and found results that looked much more dramatic for the third trimester of pregnancy.


Norman Swan: For the third trimester? With brain development, wouldn’t you expect the second trimester?


Marc Weisskopf: It depends on which part of the brain you’re talking about. But certainly the third trimester you have a lot of neural development, you have a lot of synapse formation, you have a lot of growth going on.


Norman Swan: So in summary then, what you’ve found is that, when you really boil this down, these women are getting exposed in the third trimester, the last 3 months of pregnancy, thereabouts …


Marc Weisskopf: Right.


Norman Swan: … and they’re getting exposed to really tiny particles, which are those also that seem to be associated with heart disease and other problems …


Marc Weisskopf: That’s right.


Norman Swan: … tend to come from traffic, don’t they, these small particles?


Marc Weisskopf: That’s an issue. These small particles have many sources and those sources can in fact vary even across different areas in the United States. So between Australia and the United States, they could be vastly different; and even we know on the west coast, for example, they have a very different pattern than on the east coast because of a lot of the winds come over the water.


So we don’t yet know which aspect of—and this is one of the things we’re trying to pursue now is—what element of the particulate matter, if there is a particular one within that, that matters? Or is it just anything that happens to be two and a half?


Norman Swan: What could be—because the next step …cause and effect—so you’ve shown the time element, you’ve shown the exposure, you’ve shown that the story is related—so it’s getting …

pretty close to cause and effect, but the killer one is, what could possibly be the biological reasons? There are plenty associations between pollutants and disease …


Marc Weisskopf: Right.


Norman Swan: … but they fall down when it comes to the biology because you can’t work out …


Marc Weisskopf: How that can …


Norman Swan: … a sensible biological explanation for why this would occur because you’ve got the lungs to filter these particles, you’ve got the placenta. You know the mother is designed to protect the foetus from lots of rubbish, why would these pollutants make a difference?


Marc Weisskopf: That is of course the 64,000 dollar question. We don’t know but we would like to know. What we do know is that exposure to these particles can cause things like immune dysfunction in the mother, inflammatory processes to be set off in the mother and these things can potentially pass through to the foetus and potentially affect the foetus as well.


Norman Swan: So it might be indirect rather than direct?


Marc Weisskopf: We think it’s probably indirect. There’s a lot of interest right now on these very fine particles and the possibility in brain effects in general because in part of the possibility that they may actually go directly to the brain through the olfactory valve, skipping the lungs and circulatory system.


Norman Swan: So you smell them in? They go into your nose and at the top of your nose there’s actually brain tissue at the top of your nose, and so it just might hit your brain tissue and …


Marc Weisskopf: Go right in, yes.


Norman Swan: That’s the mother and not the baby.


Marc Weisskopf: Exactly. So that’s the mother. So I … given that our findings are quite specific to this in utero period, I don’t suspect that’s happening; I suspect that it is an exposure to mother that is a more typical effect that engages some type of biological activity in the circulatory system that then gets passed to the placenta, to the foetus, to affect the development. Or perhaps affect simply oxygenation status, whatever it might be in terms of the placental health.


Norman Swan: Can you give a sense of the increased risk associated with living with exposure, you know, there’s a background risk of having a child with autism spectrum disorder, it is rare, and what’s the increased risk?


Marc Weisskopf: Right. So it is quite rare although of course there’s the whole idea that it’s getting more and more common. Right now in the US it’s, I think, one child in 88 is said to have an autism spectrum disorder. It’s less than that for boys; it’s much more common in boys. What we find, in our data, for what it’s worth is, when you go from the bottom 25 per cent to the top 25 per cent of exposure to this type of particulate matter, you increase the risk for having a child with autism by about 60 per cent, 50-60 per cent, something like that.


Norman Swan: So it’s not huge. It’s 1.6 times the size.


Marc Weisskopf: So it’s not huge, it’s small. That’s right.


Norman Swan: So people don’t need to panic too much about if they’re living in an area with reasonable pollution. You’d expect other effects here. You’d expect perhaps increased risk of premature delivery in pollution because it could affect placenta and things like that. Is there other stuff with the foetus that’s going on here that complicates the story?


Marc Weisskopf: Yes. You would expect other effects and in fact, as I alluded to earlier that there’s in fact a little earlier literature on that in fact with some very elegant studies suggesting indeed that this particular matter exposure or traffic related exposures can decrease birth weight or prematurity as well. That is out there prior to this autism literature. We have to be concerned about that because those things may be also related to autism so one question is, is what we’re seeing the result of changes in birth weight more risk of prematurity and therefore more autism?


One of the beauties of the Nurses’ Health Study is we have lots of data on these women and we have information on that and we’ve adjusted for it and it doesn’t affect our results; we still seem to see this independent of any effect on prematurity or birth weight.


Norman Swan: Now even though the Nurses’ Health Study is 120,000 women followed for many years, it’s still a small sample in population terms.


Marc Weisskopf: What you say is absolutely right. I should point out quite clearly that even though the Nurses’ Health Study is 100,000 people, they don’t all have children and they don’t all have children with autism and they don’t all have children with autism during the period where we have estimates for their exposures to particulate matter.


Norman Swan: So the sample …


Marc Weisskopf: So in the end, the sample was around 300 kids with autism and a couple thousand or three thousand kids without so it’s bigger than things that are out there but yes we would love to do a whole population study. I am exploring this now in Israel, in fact, looking at the entire population and trying to get similar data there.


Norman Swan: So if a woman lives near a freeway or in an industrial zone, what does she do with this information?


Marc Weisskopf: I guess part of this is where it comes in to the point you raised that the risk is raised but it’s still reasonably small so keep that in mind and don’t panic. I would say that if you want to be particularly careful or if you … if you have the means, it would be great to move somewhere else during that period; and I understand not everybody can do that. I mean, what I will say is that as these results get stronger and stronger—and there are other groups looking at this too—it does open up precisely that avenue for either public health interventions on a larger political entity scale like regulation to bring this stuff down, or individual behaviour change where yes you do move during critical periods or get away somehow. Now, obviously not everybody can do that but if we can understand better exactly what components are perhaps we can devise ways that, you know, you can protect yourself more in the home. I don’t think we’re there yet but that’s part of the idea behind this is we would like to have enough information so we can make policy changes, make behaviour change suggestions that would reduce the risk of having a child with autism.


Norman Swan: Marc Weisskopf is Associate Professor of Occupational and Environmental Epidemiology at Harvard School of Public Health in Boston.



Associate Professor Marc Weisskopf
Associate Professor of Environmental and Occupational Epidemiology
Harvard University School of Public Health


Dr Norman Swan
Brigitte Seega