Generation R does gestational vitamin D levels and autistic traits

"Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny."

So said the findings reported by Vinkhuyzen and colleagues [1] (open-access) reporting on data derived from "the Generation R Study, a population-based prospective cohort from fetal life onward, based in Rotterdam, The Netherlands." I've talked about this study initiative before on this blog (see here) but this time around its scientific eyes turned towards the possibility that vitamin D - the sunshine vitamin/hormone - might have some important connections to the presentation of some of the facets of autism or at least autistic traits. Yes, yet again, vitamin D and autism comes into view (see here)...

The Vinkhuyzen paper is open-access for all to see (and has already received some media exposure) but here are a few choice details:

• Hypothesis: explore "the association between gestational 25OHD concentrations and a widely used parent-report continuous measure of autism-related traits—the Social Responsive Scale (SRS)." Said levels of 25-hydroxyvitamin D (25OHD) (the functional unit of vitamin D assessment) were obtained from "maternal mid-gestation sera and from neonatal sera (collected from cord blood)." SRS scores relevant to offspring were provided by parents "when the children were ~6 years of age."
• Results: well, this certainly wasn't an under-powered study as data for "4229 children and their mothers were available with measures of vitamin D concentrations drawn from maternal blood at mid-gestation and/or drawn from cord blood at time of birth as well as data on the SRS, 2489 children and their mothers were available with measures of vitamin D concentrations at both time points." Approximately 16% of mothers were classed as deficient based on that mid-gestation serum sample rising to 36% when looking at cord blood samples. As I've mentioned before, issues with vitamin D generally fall into a few bandings associated with insufficiency and deficiency at the lower end of typical.
• "In all analyses, 25OHD deficiency or lower 25OHD concentrations were associated with higher (more impaired) SRS scores." This was based on the use of an "18-item abridged version of the questionnaire" that specifically looked at "behavioural features related to social cognition, social communication and autistic mannerisms." Remember, this was a study looking at autistic traits not autism diagnoses. Interestingly too, authors were also able to restrict their analysis to "offspring with European ethnicity" and reported similar results associating lower vitamin D levels and higher SRS scores. This subgroup analysis perhaps ties into other research where ethnicity has been suggested to be a factor in relation to vitamin D levels and diagnosed autism (see here).

So, there you have it. Yet more evidence linking vitamin D and autism and/or autistic traits; this on the back of my previous entry not-so-long-ago (see here) talking about supplementation as a potential means to affect presentation of at least some autism, with appropriate caveats (see here). It's getting increasingly difficult to say that there is 'no connection' between the two factors.

Strengths of the Vinkhuyzen study? Well, as I said, it was big in terms of participant numbers. I note also the authors proudly announce: "We used a gold standard assessment of 25OHD concentrations" in light of the application of "isotope dilution liquid chromatography-tandem mass spectrometry." A gold star for the authors indeed in light of some 'chaos' when it comes to the hows and whys of measuring vitamin D status. Limitations: well, as per every study that looks at the association between a small number of variables, there are potentially a million and one other factors that might also account for the results. Another gold star is due for the authors' mention of the fact that vitamin D seems to be 'associated' with various diagnostic labels outside of rickets these days (see here for example) and hence one cannot rule out that traits or diagnoses not specifically covered by the study could have exerted some effect. More so when one considers how much autistic traits might not be just autism-specific traits (see here). I might also add that subsequent work could/should also be looking at the genetics of vitamin D metabolism not just functional levels of the stuff (see here).

A final quote from the authors to close: "Just as prenatal folate supplementation has reduced the incidence of spina bifida, we speculate that prenatal vitamin D supplementation may reduce the incidence of ASD." I know such sentiments might not be welcomed by everyone, and the assumption that autistic traits are 'always a negative thing' needs some continued careful consideration. The ideas however that: (a) nutrition might impact on both psychology and physiology and (b) that where appropriate and/or where wanted, use of vitamin D supplement might impact on risk of autism or the presentation of autism, are ideas that are deserving of a lot more investigation.

And again, minus any charges of clinical or medical advice being given on this blog (they're not), here is what the UK Government (or parts of the UK) are currently saying about vitamin D and the population as a whole...

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[1] Vinkhuyzen AA. et al. Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Mol Psychiatry. 2016 Nov 29.

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Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, & McGrath JJ (2016). Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Molecular psychiatry PMID: 27895322