Pregnancy hypertension and offspring autism reloaded

"There is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD)."

Go on.

"These findings indicate that HDP [hypertensive disorders of pregnancy] exposure may increase the risk of ASD in the offspring."

So said the findings reported by Eileen Curran and colleagues [1] whose results have previously appeared on this blog with hypertension in mind (see here). I'm not altogether sure if this latest publication from this group represents 'new data' or is the same as/similar to that previously published [2]. It doesn't really matter to be honest given that the latest publication also includes a research addition insofar as the examination of "cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this serum could change patterns of neuronal growth."

Drawing on data from some 13,000 children whose details were included in the Millennium Cohort Study (MCS) researchers, after "adjusting for several potential confounders including maternal alcohol consumption, education, depression, age, and poverty status", observed "a significant association between HDP and a twofold increased risk of ASD." They also reported that: "exposure of foetal cortical neurons to 3% serum isolated from women with an established HDP increased neuronal growth and branching in vitro." The authors have reported similar things with attention-deficit/hyperactivity disorder (ADHD) in mind too [3]; something that might be particularly important in the context of autism and ADHD overlapping in quite a few people (see here).

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[1] Curran EA. et al. Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring. Mol Neurobiol. 2017 Oct 3.

[2] Curran EA. et al. Hypertension in pregnancy and autism spectrum disorder in a British cohort: Long term consequences for mother and child. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2016; 6: 153.

[3] Curran EA. et al. The effect of hypertensive disorders of pregnancy on the risk of attention-deficit/hyperactivity disorder in the offspring: Long term consequences for mother and child. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2016; 6: 169–170.

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On the question of a 'real' increase in cases of autism

A quote to begin: "Increased ASD [autism spectrum disorder] diagnosis may partially reflect [an] increase in rates of behaviour associated with ASD and/or greater parent/teacher recognition of associated behaviours."

That was a primary finding reported by Ginny Russell and colleagues [1] (open-access) who set about to "confirm an increase in parent-reported ASD diagnosis at age 7 in the UK between two time points (two population-based cohorts from 1998/1999 and 2007/2008)" among other things. Their findings were based on the examination of 2 UK birth cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Millennium Cohort Study (MCS). As per other entries on ALSPAC (see here) and the MCS (see here) respectively, these two initiatives continue to give as a function of their large participant numbers and longitudinal status.

Russell et al threw their research hat into one of the more important autism debates in recent times on whether the quite extraordinary increase in cases of autism being reported (see here) is representative of a real increase or solely down to variables such as changing diagnostic criteria or diagnostic substitution or just better awareness of autism or some combination of these and other factors. My view, if you want it, is that the increase is likely due to many different factors operating in different parts of the world, but at least some of the rise is probably going to be real (see here). Why else would we have headlines such as this one - see here - and reports that autism spectrum assessment facilities "anticipating 1,500 children coming each year forward to autism services" are faced with double that amount? Did we miss so many children in years gone by? The associated issue of waiting times of up to nearly 2 years to be seen and assessed (even 6 YEARS in some cases) is nothing short of a modern day tragedy given what's coming out on the [peer-reviewed] topic of early diagnosis and the value of early intervention (see here). We might do well to listen more to parents on the topic of their own children I might add (see here).

Anyhow, Russell and colleagues set about looking at "parent-reported ASD diagnosis" in the ALSPAC and MCS groups, using a line of questioning not a million miles away from that used in the latest 1 in 45 [estimated] prevalence on autism in the United States (see here). Further: "To validate parent-reported diagnosis of ASD, parent report of an autism diagnosis was checked against the medical report of clinical ASD diagnosis" in at least one of the cohorts (ALSPAC). And: " The sensitivity of parent report in identifying medical diagnosis was 95% and the specificity was 99%, indicating it was a good but not perfect indicator of clinical diagnosis."

Behavioural traits associated with autism were also assessed by teacher and parent report. Indeed, we are told that derived from the various measures employed across the study, a "composite autism-type trait score (CATS)" was built up that "resulted in 4530 children with CATS scores in ALSPAC (56% of the age 7 sample) and 11 210 in MCS (81% of the age 7 sample)."

Results: almost 1.1% of the 1998 ALSPAC cohort had an ASD diagnosis. This contrasted with approaching 1.7% of the 2008 MCS participants; a not-insignificant step-up. Likewise those CATS scores also seemed to suggest a disparity between the different years covered by the different cohorts: 4.2% of the ALSPAC cohort "fell in the high CATS category" defined as having "poor communication, was less able to sustain peer relationships, and/or was afraid of new situations and/or did not share easily or empathise well." For the later MCS cohort, 6.8% were similarly coded into that high CATS category; again something potentially significant to see.

One might quibble about the use of a composite score (CATS) to describe the behaviours of autism when so many instruments can make claim to this purpose but as the authors comment "no such measures are presently available across UK population cohorts" at the times of sampling. I might add that this is likely to change as new measures are (knowingly or unknowingly) rolled out across parts of the United Kingdom (see here). The authors are also relaxed on CATS "representing autism" instead choosing to suggest that CATS 'characterises' facets of autism but "is not a validated ASD measure." Bear these details in mind by all means.

But still I find these results to be really quite important and crying out for further investgation. As per other discussions on the topic of diagnosis vs. "the autism symptom phenotype" (see here) the peer-reviewed literature in this area is not totally one-way. But for anyone shouting about all the increase in cases of autism purely being down to administrative factors, I'd suggest that you might need to look again at the collected data. And that's not also to say that children presenting with autism/autistic traits are correctly identified all the time [2]...

Now, if one does accept that there is at least a partial 'real' increase in the number of cases of autism, how about edging closer to the idea that genes and environment might [variably] work together [3] to bring someone to a diagnosis of autism?

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[1] Russell G. et al. Changes in diagnosis rates and behavioural traits of autism spectrum disorder over time. BJPysch Open. 2015; 1: 110-115.

[2] Russell G. et al. Identification of children with the same level of impairment as children on the autistic spectrum, and analysis of their service use. J Child Psychol Psychiatry. 2010 Jun;51(6):643-51.

[3] Charman T. & Chakrabarti B. Commentary: Not just genes - reclaiming a role for environmental influences on aetiology and outcome in autism. A commentary on Mandy and Lai (2016). J Child Psychol Psychiatry. 2016 Mar;57(3):293-295.

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Russell, G., Collishaw, S., Golding, J., Kelly, S., & Ford, T. (2015). Changes in diagnosis rates and behavioural traits of autism spectrum disorder over time British Journal of Psychiatry Open, 1 (2), 110-115 DOI: 10.1192/bjpo.bp.115.000976