Showing posts with label newborn. Show all posts
Showing posts with label newborn. Show all posts

Tuesday, 20 January 2015

Autism and low vitamin D at birth

Discussions about vitamin D (the 'sunshine' vitamin/hormone) and autism are not unfamiliar to this blog. Just last year (2014) I covered research talking about the possibility of a connection between vitamin D and [some] autism at least three times (see here and see here and see here), possibly more.
..but in my game, I'm the bad guy,
and I live in the garbage.

I wouldn't say that I'm an advocate for everything implied by the correlations being made between vitamin D levels and autism given that vitamin D levels have also been linked to everything from depression (see here) to schizophrenia (see here), issues which might also show some passing connection for some people on the autism spectrum (see here for example). But I am interested in how this research area is evolving...

And evolving it is, as yet another study has been published on vitamin D and autism, this time from Elisabeth Fernell and colleagues [1] (open-access) based at the University of Gothenburg in Sweden. Examining 25-hydroxyvitamin D (25(OH)D) levels in dried blood spots "taken in the neonatal period for metabolic screening", researchers concluded that: "low prenatal vitamin D may act as a risk factor for ASD [autism spectrum disorder]."

Aside from some happiness that the fantastic resource which is the neonatal blood spot is being put to good scientific use with autism in mind (see here), I was particularly interested to read about the findings from this research group given their previous foray in this area (see here) based on the paper from Kočovská and colleagues [2] (open-access). On that occasion they concluded that young adults diagnosed with an ASD were, as a group, quite a bit more likely to present with lower vitamin D levels than siblings, parents and an asymptomatic control group.

Back to the Fernell paper, and a few pointers might be in order:

  • "The aim of the present study was to address the emerging hypothesis that low levels of vitamin D at birth increase the risk for ASD." OK.
  • Sibling pairs were used, one child diagnosed with autism, the other "non-ASD affected". Participants were drawn from two samples, a Gothenburg catchment area sample and a "Stockholm Somali group" which have been previously used in a prevalence study of autism in Somali children in Sweden (see here). Those in the know about autism research will perhaps have heard about autism and Somali children a few times before (see here).
  • Participants were coded according to ethnicity into one of three groups: Swedish, Miscellaneous (non-Scandinavian Europe, South America and East Asia) and African/Middle East. This was due to: "well-known ethnic disparity of vitamin D status."
  • Results: "Children to parents of non-Scandinavian ethnicities had lower mean 25(OH)D levels than children to Swedish parents." See the previous point. 
  • "The mean 25(OH)D level was lower in children with ASD... than in their siblings." This trend was significant in "the Swedish and Miscellaneous groups, but not in the African/Middle East group." The authors report that season of birth, a potentially important factor in birth vitamin D levels was likely not the primary variable to account for the ASD - non-ASD sibling differences but there were some disparities noted. I would also draw your attention to another comment from the authors: "Since we studied newborn children before diagnosis, our results are definitely unrelated to lifestyle and diet of the individual, although the mother’s lifestyle and other environmental factors cannot be ruled out."
  • Author conclusion: their findings may support: "the hypothesis that developmental vitamin D deficiency during late pregnancy may carry an increased risk of ASD in the child." Alongside, that is, the requirement for further research with larger numbers of participants.

I would certainly echo the sentiments of the authors for the need for larger-scales studies of any connection between low pregnancy/birth vitamin D levels and risk of autism. This is however not the first time that this issue has been studied as per my commentary on the results from Whitehouse and colleagues [3] (see here) who based on the use of the Autism-Spectrum Quotient (AQ) (itself the topic of some recent inquiry) concluded that: "Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales" bearing in mind their focus on mums not offspring when assaying for vitamin D.

A few further points before I let you go about your business.

"In this study we did not examine other possible causes for ASD, such as for instance infections during pregnancy." A very important point indeed if one looks at some of the research literature in this area (see here).

"Autoimmunity is another possible cause for ASD, which was not investigated. However, as low vitamin D is suggested to contribute to the pathogenesis of autoimmunity... our findings could be relevant in this context as well." Again, another potentially important point raised here on the basis of other research which has brought the issue of autoimmunity into the autism-vitamin D frame (see here). More generally, the issue of autoimmunity and autism is of increasing research interest.

Finally, the authors leave us with a tantalising question: "whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring"? Before anyone get's ahead of themselves, I think we need quite a bit more discussion and study on this question specific to autism given that more generally vitamin D for pregnant women is seemingly being more frequently indicated.

Just one more thing (to coin a phrase)... although no-one really knows the specific hows, whys and wherefores of any vitamin D connection to autism, I'd be minded to suggest that physiological issues such as gut permeability (yes, it is a real thing) might also register on any future research endeavours given data like that from Assa and colleagues [4] adding to an already interesting area (see here). I'm not saying that this is the only potential factor but one among many.

Music: Do you feel lucky punk?

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[1] Fernell E. et al. Autism spectrum disorder and low vitamin D at birth: a sibling control study. Molecular Autism. 2015; 6: 3.

[2] Kočovská E. et al. Vitamin D in the General Population of Young Adults with Autism in the Faroe Islands. J Autism Dev Disord. 2014 Jun 14.

[3] Whitehouse AJ. et al. Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord. 2013 Jul;43(7):1495-504.

[4] Assa A. et al. Vitamin D Deficiency Predisposes to Adherent-invasive Escherichia coli-induced Barrier Dysfunction and Experimental Colonic Injury. Inflamm Bowel Dis. 2015 Jan 14.

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ResearchBlogging.org Elisabeth Fernell, Susanne Bejerot, Joakim Westerlund, Carmela Miniscalco, Henry Simila, Darryl Eyles, Christopher Gillberg, & Mats B Humble (2015). Autism spectrum disorder and low vitamin D at birth: a sibling control study. Molecular Autism : 10.1186/2040-2392-6-3

Tuesday, 5 February 2013

Insulin-like growth factor and autism

I admit to being a tiny bit sceptical/skeptical whenever I read a press release about hypothesis-only papers. Don't get me wrong, I'm all for people airing their ideas and opinions in the peer-reviewed domain, in fact in any domain including the blogosphere, as long as they are backed up by some kind of evidence (which need not just be of the double-blind, placebo-controlled variety). But I still feel a little bit cheated when there are no new findings or data included in a paper which is judged worthy to have the the fanfare of entering my Google News stream.
Hypotheses and speculations @ Wikipedia   

When I therefore came across a press release titled: Researcher uncovers potential cause, biomarker for autism and proposes study to investigate theory you can perhaps imagine my initial thoughts as the study by Steinman & Mankuta* was quite loudly proclaimed, very aptly appearing in the journal Medical Hypotheses.

So let's briefly go through what the hypothesis is and some background, bearing in mind my considerable non-expertise in this area:

  • The focus of the hypothesis is insulin-like growth factor-1 (IGF-1), sorry "sulphation factor", and how "depressed levels of this protein in the blood of newborns could potentially serve as a biomarker for the later development of autism". The focus on the prenatal and neonatal periods seems to be following recent research trends.
  • IGF-1 has lots of potential uses and links to body functions outside of its myelination duties including those related to apoptosis (programmed cell death) and also related to growth. There may even be some more aesthetic links to the protein (see here) highlighting its wide ranging uses and applications.
  • One has to go back quite a few years to see the golden age of IGF-1 - autism research as per papers like this one from Vanhala and colleagues** and this one from Riikonen and colleagues*** who eagle-eyed readers will note are one and the same research group. Both papers noted a decrease in IGF-1 levels in cerebrospinal fluid samples from participants with autism compared to controls.
  • Measuring IGF-1 levels in other biological fluids such as urine have also revealed some interesting findings potentially related to autism as per the paper by Anlar and colleagues****.
  • But don't be under any impression that the research literature is all one way on this issue. I note for example that Mills and colleagues***** reported elevations in IGF-1 and other growth-related compounds in their cohort, bearing in mind their chosen analytical medium and those all important issues of heterogenetity and comorbidity.

OK, like just about every other potential biomarker put forward for autism, things are not entirely cut-and-dried and the old chestnut that is heterogeneity comes into play. The big questions remain as to why IGF-1 might be aberrant in potential cases of autism and whether one could feasibly assume that supplementation with "Prozac®, Copaxone®, Increlex®, and recombinant human IGF" are safe enough to be indicated during the "early postnatal period of newborns" to affect IGF-1 levels. This particularly in light of both IGF-1 administration being linked to things like hypoglycemia (low blood sugar levels) and at least one of those meds being suggested to prop up IGF-1 levels potentially show some connection to autism offspring risk. The breast milk - IGF-1 angle does sound like the better alternative at the moment, bearing in mind what's already been done on 'bitty' and autism and other relationships in other developmental conditions such as ADHD.

A little reading outside of the IGF-1 - autism story also asks some interesting questions. I might be simplifying things here but quite a lot of the IGF-1 deficiency literature seems to circle the issue of growth impediment as per the research body on Laron syndrome. In those cases, and bearing in mind the related issue of growth hormone, "IGF-1 deficiency throughout childhood causes dwarfism". With such a connection in mind, does autism also manifest as growth impediment during childhood? Er, probably not, in fact just the opposite****** if I were to generalise.

But that's not to say that there may be something interesting with regards to IGF-1 and at least some cases of autism. Whilst trawling the literature for example, I stumbled across a paper by a favourite researcher on this blog, Paul Patterson******* and some work on how maternal immune activation might bring into play the pro-inflammatory cytokine, IL-6 (see this post) which could potentially impact on "the growth hormone-insulin-like growth factor (GH-IGF) axis". You can read some more about this proposed link in this paper (open-access).

As per the accompanying press release, the authors have drawn up a sort of routemap as to how they would like to see the IGF-1 - autism possible link looked at in a more scientific fashion. Quite a bit of the discussion focuses on looking at aminotic fluid or umbilical cord blood for measures of IGF-1. Neonatal blood spots are also mentioned (which have already been utilised in autism research circles). Indeed, I'd be tempted to suggest that if this is an area of potential investigation, rather than looking at bloodspots in a prospective study, assuming some stability of IGF-1, could not one begin by looking retrospectively based on a blood spot library for this potential biomarker?

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* Steinman G. & Mankuta D. Insulin-like growth factor and the etiology of autism. Medical Hypotheses. January 2013.

** Vanhala R. et al. Low levels of insulin-like growth factor-I in cerebrospinal fluid in children with autism. Dev Med Child Neurol. 2001; 43: 614-616.

*** Riikonen R. et al. Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism. Dev Med Child Neurol. 2006; 48: 751-755.

**** Anlar B. et al. Urinary epidermal and insulin-like growth factor excretion in autistic children. Neuropediatrics. 2007; 38: 151-153.

***** Mills JL. et al. Elevated levels of growth-related hormones in autism and autism spectrum disorder. Clin Endocrinol (Oxf). 2007; 67: 230-237.

****** Dissanayake C. et al. Growth in stature and head circumference in high-functioning autism and Asperger disorder during the first 3 years of life. Dev Psychopathol. 2006; 18: 381-393.

******* Hsiao EY. & Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun. 2011; 25: 604-615.

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ResearchBlogging.org Steinman, G., & Mankuta, D. (2013). Insulin-like growth factor and the etiology of autism Medical Hypotheses DOI: 10.1016/j.mehy.2013.01.010