Thursday, 3 March 2016

Pregnancy vitamin D supplementation and offspring autism risk

Although I'm pretty interested in the idea that the sunshine vitamin/hormone known as vitamin D might have quite a few more biological effects than previously appreciated (see here), I accept that the findings reported by Gene Stubbs and colleagues [1] are probably not going to be everyone's cup of tea.

With the aim of testing the hypothesis of "whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD [autism spectrum disorder] in the offspring" based on some external findings (see here), researchers set about the task. I think I might have mentioned this trial protocol in a post not-so-long-ago (see here). They relied on a prospective study method to follow 20 mothers "who had one or more children who had been diagnosed with autism by a physician or psychologist and who were pregnant in the first, second or early third trimester." The risk of familial recurrence for autism by the way, is estimated at around about 10% (see here) with some important caveats (see here).

Said mothers were initially tested for "25 hydroxy D3 levels (25 OHD) and serum calcium levels" and then prescribed "5000 IU [international units] D3/day during the pregnancy and 7000 IU D3/day while breastfeeding." Various birth outcomes were assessed, and at 18 months and 3 years of age researchers relied on a couple of screening instruments pertinent to the presentation of autism: the Modified Checklist for Autism in Toddlers (M-CHAT) and the Pervasive Developmental Disorder Behavior Inventory (PDDBI).

What happened? Well, one mother and child pair withdrew from the study so the final participant number was 19. In terms of vitamin D deficiency during pregnancy: "Only two [mothers] were in the deficient range of less than 20 ng/ml of 25 OHD when starting vitamin D." At the second time of vitamin D testing (2 months after the first testing occasion), none of the mums where data were available (n=18) were in that deficient range defined as less than 20ng/ml. Interestingly though, I counted at least three mothers whose second vitamin D test scores were lower than the first testing occasion. You could quibble about pregnancy effects on vitamin D levels or the reliability of the vitamin D assay, but on that last point at least, these were all measured "using liquid chromatography/mass spectrometry (LC–MS/MS) methodology" so the 'gold-standard' for assaying assuming accurate measurement [2]. The question about compliance to the prescribing regime is one area however, not commented on in the publication.

In terms of those autism screens at 18 months and 3 years of age: "17 of 19 (89%) pass the MCHAT screening test at 18 months of age, that is, they were negative for autism." Further: "17 of 19 (89%) pass the PDDBI diagnostic questionnaire at 3 years of age. Eighteen of 19 (95%) had a final diagnosis as not having autism." The authors concluded that their findings were evidence of "a reduction in the recurrence rate of autism in newborn siblings compared to the reported recurrence rate in the literature of about 20%." A 20% recurrence rate? Well, as I've previously mentioned, I'd put it closer to 10% but am willing to accept some variation listed in the peer-reviewed literature [3].

There are some other very interesting details included in the Stubbs data; dare I say even more important than the main findings. So: "The two children in our study who developed autism as diagnosed by the PDDBI, both regressed following an infection." Illness including "bilateral ear infections" is mentioned, tapping into another potentially really important area of the autism research landscape (see here) and including the issue of regression (see here). That gastrointestinal (GI) issues are also mentioned - "The symptoms of autism seemed to coincide with the severity of GI problems. As the GI symptoms got more severe, the symptoms of autism got more severe. As the GI symptoms improved, so did the autism symptoms" - is something crying out for much more detailed study beyond the subjective descriptions offered in this paper. As regular readers might know, GI issues accompanying autism are no longer the taboo subject they used to be (see here) but still require lots more study particularly with a view to the hows and whys and what options for management are available. And yes, this is on top of the Buie et al guidance (see here) already available and more recent findings [4] (blog post to follow on these soon).

From a methodological point of view, the small number of participants and the lack of any 'control' group reported on, means the Stubbs study/results are not perfect and easy to pick holes in. I'm sure some people will do just that; even pointing out the publishing journal too (see here). I personally am interested to see how this area progresses further from a scientific point of view. Similar to other suggestions that pregnancy use of folic acid for example, *might* affect offspring risk of autism (see here), I don't envisage a straight-forward relationship appearing but this may not be unexpected in these times of plural autisms (see here). I'm also mindful of the implications of a potential 'screening test for autism' where vitamin D may, at some point, be potentially included (see here) and what this might mean to quite a few people on the autism spectrum and their families.

Research into vitamin D and autism seemingly continues at a pace [5]...

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[1] Stubbs G. et al. Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Medical Hypotheses. 2016; 88: 74-78.

[2] Yang Y. et al. High-throughput measurement of 25-hydroxyvitamin D by LC-MS/MS with separation of the C3-epimer interference for pediatric populations. Clin Chim Acta. 2016 Feb 15;454:102-6.

[3] Wood CL. et al. Evidence for ASD recurrence rates and reproductive stoppage from large UK ASD research family databases. Autism Res. 2015 Feb;8(1):73-81.

[4] Kushak RI. et al. Evaluation of Intestinal Function in Children with Autism and Gastrointestinal Symptoms. J Pediatr Gastroenterol Nutr. 2016 Feb 20.

[5] Shan L. et al. Research advances in the role of vitamin D in autism spectrum disorders. Zhongguo Dang Dai Er Ke Za Zhi. 2016 Feb;18(2):183-8.

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ResearchBlogging.org Stubbs, G., Henley, K., & Green, J. (2016). Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Medical Hypotheses, 88, 74-78 DOI: 10.1016/j.mehy.2016.01.015