Parental exposures and risk of offspring autism: some curious details

"Overall, our results were consistent with no positive association between parental asthmagen exposure and ASD [autism spectrum disorder] in the children."

So said the findings reported by Alison Singer and colleagues [1] (open-access) continuing a research theme from this group [2] looking at whether "parental workplace exposures to risk factors for asthma (“asthmagens”)" might have relevance to offspring risk for autism.

Based on data derived from some of those oh-so-important Scandinavian research registries (this one based in Denmark), researchers initially looked at some 12,000 cases (where autism was mentioned in medical records) compared with over 48,000 controls (not autism) to ascertain whether parental work exposures might play some role in autism risk. This numbers were eventually boiled down somewhat.

Despite the opening line to the post, there were some curious details to emerge from the collected analyses. So: "We observed an inverse association between any maternal occupational asthmagen exposure and ASD in the children." Researchers reported that maternal occupational exposure actually seemed to be protective against the development of offspring autism according to their findings. They note that this finding was "largely explained by latex exposures" on the basis of linking occupational codes "to an asthma-specific job exposure matrix (JEM)." In other words, they didn't specifically look at latex exposure in every single case but rather relied on the probability that a particular occupation would entail this or other exposure.

A few other curious details also emerged: "Some paternal occupational asthmagen categories were positively associated with ASD, including bioaerosols..., pharmaceutical drugs (manufacturing or extensive handling)..., and metals." The authors tend to talk down these findings as per the suggestion that: "Some of these associations could be chance findings resulting from multiple comparisons or could reflect bias, such as unmeasured confounding" but I would perhaps be a little more cautious about rejecting them outright. Indeed the authors note on one point in relation to maternal exposures: "While adjustment for unmeasured confounding could bring the association to the null, the confounding would need to be implausibly strong to mask a positive association."

I've covered the topic of parental (occupational) exposures and offspring autism risk before on this blog (see here) alongside associated research (see here). The current take-away message from quite a bit of this research is that there may be target classes of compounds to 'look out for' when it comes to offspring autism risk, but as of yet there is no smoking gun. One also needs to read such research in the context of the myriad of 'associations' that have been made with offspring autism risk down the years (see here for example) and how genes and environment might mix in relation to the plural autisms. Cumulative effects are more likely over single factors.

Insofar as the current Singer results, I do feel that the authors might have been a little premature in making the sweeping claims that they have on the basis of their findings: "this large population-based case-control study does not suggest a positive measurable association between parental occupational asthmagen exposure and ASD." I say this in the context that 'asthmagen' exposure could be incurred via several routes (see here). I don't doubt that the correlations/findings reported by Singer could be 'due to chance', but until such claims can be independently verified in direct study (see here for one idea) and perhaps tested in animal models for example, they should really just report what they found without fear, favour or complication...

----------

[1] Singer AB. et al. Parental exposures to occupational asthmagens and risk of autism spectrum disorder in a Danish population-based case-control study. Environmental Health. 2017 16: 31.

[2] Singer AB. et al. Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development. J Autism Dev Disord. 2016 Nov;46(11):3458-3468.

----------

Singer, A., Burstyn, I., Thygesen, M., Mortensen, P., Fallin, M., & Schendel, D. (2017). Parental exposures to occupational asthmagens and risk of autism spectrum disorder in a Danish population-based case-control study Environmental Health, 16 (1) DOI: 10.1186/s12940-017-0230-8

Autism, parental concerns and socioeconomic status

I'd like to think that there are some rather important messages to be taken from the paper by Xiang Sun and colleagues [1] on level of parental concern, socioeconomic status (SES) and risk of autism. Not only did the authors conclude that: "a higher SES was not associated with the risk of having ASC [autism spectrum conditions]" they also found that: "No child met ASC criteria where parents expressed no concerns".

Do you prefer "fashion victim" or "ensembly challenged"?

SES - including variables such as family income, parental educational attainment(s) and parental occupation(s) - has been something of a talking point in autism research down the years and the rather mixed messages which have come out of the research literature on SES and offspring autism risk (see here). The growing appreciation that children of those positioned in a higher SES bracket don't seem to be at any significantly greater risk of autism is something rather important as per other evidence, for example, noted by Fujiwara [2]. Whether this means previous contrary findings were in error or that there has been some shift in the factors linked to the onset of contemporary autism is unknown at this time.

Some of my first thoughts on the Sun SES findings were in relation to all the discussions about offspring autism potentially being associated with certain types of parental occupational choices [3]. Indeed, considering that the Sun study was both carried out in and originated from Cambridge (UK) and included Prof. Simon Baron-Cohen on the authorship team, it is coincidental that the findings could be construed as counter to such occupational links with autism (assuming that Physicists, Engineers and Mathematicians would be described as higher SES jobs).

Of course I'm not saying the research on any relationship between offspring autism and parental occupation choice is all bunk; the paper from Windham and colleagues [4] and other evidence is too strong to negate (including that of occupational exposures potentially being involved). Merely that there may be much more to see than just a spectrum of 'talent' genes overlapping with autism risk genes [5] when it comes to receipt of a diagnosis on the very wide autism spectrum. Oh, and assuming you believe talent is all in the genes...

The other finding from Sun et al discussing parental concern and potential diagnosis of autism in offspring also carries quite a bit of potential importance. Regular readers of this blog might already have picked up my respect for parents and carers as active agents both in terms of picking up the signs and symptoms of autism in their loved ones (see here) and also detecting and reporting other important comorbidity (see here). I see the Sun findings - "No child met ASC criteria where parents expressed no concerns" - as corroborating parents and caregivers as doing what they do best: knowing their own child. I might also suggest that the discussions on increasing autism rates solely being down to better awareness and greater diagnostic vigilance are not seemingly backed up by the Sun findings if we assume parental concerns represent the starting point of the diagnostic journey into autism.

Some music to close. Gershon Kingsley and Popcorn.

----------

[1] Sun X. et al. Parental concerns, socioeconomic status, and the risk of autism spectrum conditions in a population-based study. Res Dev Disabil. 2014 Sep 25;35(12):3678-3688.

[2] Fujiwara T. Socioeconomic status and the risk of suspected autism spectrum disorders among 18-month-old toddlers in Japan: a population-based study. J Autism Dev Disord. 2014 Jun;44(6):1323-31.

[3] Baron-Cohen S. Does Autism Occur More Often in Families of Physicists, Engineers, and Mathematicians? Autism. 1998; 2: 296-301.

[4] Windham GC. et al. Autism spectrum disorders in relation to parental occupation in technical fields. Autism Res. 2009 Aug;2(4):183-91.

[5] Baron-Cohen S. Autism and the technical mind: children of scientists and engineers may inherit genes that not only confer intellectual talents but also predispose them to autism. Sci Am. 2012 Nov;307(5):72-5.

----------

Sun, X., Allison, C., Auyeung, B., Baron-Cohen, S., & Brayne, C. (2014). Parental concerns, socioeconomic status, and the risk of autism spectrum conditions in a population-based study Research in Developmental Disabilities, 35 (12), 3678-3688 DOI: 10.1016/j.ridd.2014.07.037