Maternal vitamin D and autism phenotype

Autism research in the media is currently buzzing with the news that maternal influenza - or at least something that looks like flu - during pregnancy might potentially increase the risk of offspring autism as per the paper by Hjördis Ósk Atladóttir and colleagues*. Not for the first time has maternal infection during those special nine months been the focus of interest similar to some discussions earlier this year (2012) emulating some interesting mouse research from Paul Patterson among others.

Bring me sunshine @ Wikipedia 

I'm not really going to go into the Atladóttir research in any great detail because quite a few others have already said what needs to be said. I will say that some of Dr Atladóttir's other research on autism is actually of more interest to me and this blog (see this post).

Instead then, another paper is the focus, but again with mums, pregnancy and autism in mind.

The paper by Andrew Whitehouse and colleagues** on maternal vitamin D levels and offspring scores on the Autism Spectrum Quotient (AQ)*** caught my eye recently. Not only because it made mention of the sunshine vitamin D and autism, a topic which has graced this blog previously, but also because of the relative simplicity of the study (both a good thing and a not-so good thing) and the fact that this authorship group have made a splash before on this blog with some work looking at the stability of autistic traits in the general population. A blogpost about a potentially bigger splash from another paper by this group**** is under construction and will follow quite soon (hint: perinatal testosterone levels might not necessarily be so related to autistic traits).

The beginning is often a good place to start. The AQ is best described as a self-report screening instrument covering the main areas of behaviour and functioning seen in autism spectrum disorders. Readers can take the on-line AQ test here if they so wish bearing in mind that this is not a replacement for the formal diagnosis of autism or anything else.

Outside of a little pop psychology, the AQ has found a home in quite a bit of autism research and beyond as per example studies like this one from Freeth and colleagues***** on a possible link between social anxiety and autistic traits in a University population (a classic participant group!) and this one from Pertusa and colleagues****** on the question of hoarding disorder and autistic traits. I was also quite interested in the paper by Lau and colleagues******* suggestive of some kind of relationship between agenesis of the corpus callosum and autistic traits based on measurement using the AQ. Indeed the whole 'red flags' arena is rather interesting.

Anyhow, Prof. Whitehouse and colleagues reported some interesting things:

• Serum 25(OH)-vitamin D - the pre-active form of vitamin D - levels were analysed for 929 randomly selected pregnant women at 18 weeks gestation as part of the Raine study (a longitudinal study originally designed to look at ultrasound imaging). The form of vitamin D examined as part of the trial is not to be confused with calcitriol (1,25-dihydroxyvitamin D3) which is often referred to as the active form of vitamin D.
• Four hundred and six offspring (male = 149, female = 257) (44%) completed the AQ in "early adulthood".
• Results: "Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales". So, there was no overall link between 25(OH)-vitamin D levels in pregnant mums at 18 weeks and early adulthood offspring scores on the AQ.
• That being said, lower levels of pregnancy 25(OH)-vitamin D levels (defined as below 49 nmol/L, nanomoles per litre) did seem to correlate with higher offspring scores in the domain of Attention Switching (r = -0.13; p = 0.01) (although this significance waned when season of blood collection was taken into account).
• Mums of three children identified as having an autism spectrum disorder (ASD) presented with 25(OH)-vitamin D levels "above the population mean" (63-78 nmol/L).

This is not the first time that this group has looked at vitamin D with regards to neurodevelopmental outcome. I note for example their earlier paper******** suggesting a link between maternal vitamin D levels and offspring language impairment as being relevant.

In terms of their latest findings, a closer look at what Attention Switching on the AQ actually encompasses reveals that outside of the obvious (attention and er, switching of attention) it also includes questions loosely tied into the presence of repetitive behaviours ("I prefer to do things the same way over and over again"), routines and rituals ("I tend to have very strong interests, which I get upset about if I can't pursue") and indeed [social] anxiety ("New situations make me anxious"). All this bearing in mind that we aren't talking about formal diagnosis of these traits, merely self-report.

I don't think anyone would actually believe that the measurement of one biological value at one time period during pregnancy and reported results based on a single questionnaire conducted some time later constitutes a strong relationship outside of the multitude of other factors which could have influenced the results obtained and can't possibly all be controlled for. Indeed although I grow tired of using it, the term correlation ≠ causation immediately springs to mind. That and the fact that maternal vitamin D levels might not necessarily translate uniformly into offspring vitamin D levels as per this study by Josefson and colleagues********* on mum's weight being a potential confounder.

Having said all that I think back to the potential basis for this kind of study and in particular the work of Cecilia Magnusson and colleagues (discussed in this post) on migrant parents and risk of offspring autism. To reiterate, they reported some interesting trends of an increased risk of offspring autism where parents were migrants and in particular when migrating from countries with a low human development index. If you follow the development index link and look at the countries in question, you might spot one or two trends in terms of things like predominant skin colour (compared with the very high human development countries) as being apparent. The theory continues that skin colour and exposure to vitamin D producing sunlight might affect functional vitamin D levels, which in turn might have consequences for both person and offspring health.

Whilst the Whitehouse results seemingly adds very little to support the argument of vitamin D being linked to autism from a maternal or pregnancy point of view, there are still some unanswered questions about the potential for a link between autism (some autism perhaps) and vitamin D. Not least because vitamin D is a functional vitamin and unlike other vitamins such as folic acid, birth and early infancy might be just part of the story of any effect. That and the functioning of things like vitamin D receptors...

To end, I'm in the mood for some Kiss, and how about those crazy, crazy nights?

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* Atladóttir HO. et al. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. November 2012.

** Whitehouse AJ. et al. Maternal vitamin D levels and the autism phenotype among offspring. JADD. October 2012.

*** Baron-Cohen S. et al. The Autism-Spectrum Quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. JADD. 2001; 31: 5-17.

**** Whitehouse AJ. et al. Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study. J Neurodev Disord. 2012; 4: 25.

***** Freeth M. et al. The distribution of and relationship between autistic traits and social anxiety in a UK student population. Autism. September 2012.

****** Pertusa A. et al. Do patients with hoarding disorder have autistic traits? Depress Anxiety. 2012; 29: 210-218.

******* Lau YC. et al. Autism traits in individuals with agenesis of the corpus callosum. JADD. October 2012.

******** Whitehouse AJ. et al. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics. 2012; 129: 485-493.

********* Josefson JL. et al. Maternal obesity and vitamin D sufficiency are associated with cord blood vitamin D insufficiency. J Clin Endocrinol Metab. November 2012.

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Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, & Kusel MM (2012). Maternal Vitamin D Levels and the Autism Phenotype Among Offspring. Journal of autism and developmental disorders PMID: 23070790