Maternal thyroid autoantibody and offspring autism risk

I have, on this blog, previously mentioned the paper by Alan Brown and colleagues [1] suggesting that: "The prevalence of maternal TPO-Ab+ [thyroid peroxidase antibody] was significantly increased in pregnancies giving rise to autism cases (6.15%) compared to controls (3.54%)." It was during some discussion on the suggested diagnosis of Down syndrome disintegrative disorder (see here) and the idea that some signs and symptoms of regressive autism (?) might overlap with TPO antibodies in some cases of Down syndrome.

You've got a playdate with destiny!

I've had a few weeks to further reflect on the Brown paper and decided that their suggestion of: "the first biomarker-based evidence that a class of known maternal autoimmune disorders is related to autism in offspring" is worthy of a post all of its own.

A quick recap first: thyroid peroxidase antibodies translates as the body mounting an immune response against thyroid peroxidase, an important enzyme in the production of the thyroid hormones. As per another mention of TPO based on research suggestive of a tentative link between anti-TPO antibodies and [some] depressive disorder (see here), the more usual clinical occasion regarding detection of such antibodies is in relation to something like Hashimoto's thyroiditis, an autoimmune condition.

Brown and colleagues drew upon collected data from the Finnish Prenatal Study of Autism (FiPS-A) [2], an initiative which had at its disposal "archived maternal serum specimens from virtually the entire pregnant population of Finland beginning in 1983". Alongside quite a bit of other registry based information on things like an ICD-10 diagnosis of autism in offspring, Brown et al set to work analysing those archived serum specimens for some "967 matched case-control pairs" (autism cases matched 1:1 with sex and date of birth linked asymptomatic controls) for the presence of thyroid peroxidase antibody (TPO-Ab).

As per the previous sentence, serum samples from mums who went on to have a child with autism were significantly more likely to present with TPO-Ab; indeed: "The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab+ during pregnancy" compared with those antibody negative. Perhaps just as important, authors also reported that: "Measures of maternal thyroid hormones did not differ between groups" suggesting that the actual antibodies might be the more important factor over and above a thyroid hormone link (see here for discussion on other work in this area).

For those who follow this blog, the idea that [some] autism and [some] autoimmunity / autoimmune conditions might show [some] linkage is not a new one. If one delves deeper into the peer-reviewed research arena one finds other hints that other maternal antibodies might also show a connection to offspring autism risk as per the idea of MAR autism (see here), that is, maternal autoantibody-related autism. Granted, the research road has not run entirely smoothly when it comes to any possible connection (see here) and there are still questions to be answered, not least when it comes to the effects of comorbidity common to autism and how they may likewise have an autoimmune connection too (see here for example). The Brown results however cannot be readily brushed under the scientific carpet given their origin and pretty powerful participant numbers used in the current study alongside some prior research 'form in the inflammatory area (see here). I for one, am keenly awaiting further investigations perhaps including a study or two on offspring autism risk among mothers with autoimmune thyroiditis [3]...?

To close: California Über Alles. Let moshing commence...

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[1] Brown AS. et al. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:86-92.

[2] Lampi KM. et al. Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A): overview and design. J Autism Dev Disord. 2011 Aug;41(8):1090-6.

[3] Molloy CA. et al. Familial autoimmune thyroid disease as a risk factor for regression in children with Autism Spectrum Disorder: a CPEA Study. J Autism Dev Disord. 2006 Apr;36(3):317-24.

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Brown, A., Surcel, H., Hinkka-Yli-Salomäki, S., Cheslack-Postava, K., Bao, Y., & Sourander, A. (2015). Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort Progress in Neuro-Psychopharmacology and Biological Psychiatry, 57, 86-92 DOI: 10.1016/j.pnpbp.2014.10.010