Maternal thyroid dysfunction and autism or ADHD?

The paper by Andersen and colleagues [1] talking about the risk of offspring attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) where mothers presented with "maternal thyroid disease" is the source material for this post.

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Based on data derived from Denmark, and those very useful Danish health registries which seem to be producing all-manner of potentially important information (see here), researchers reported that: "Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05-1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14-1.59)".

Upon reading the suggested correlation between maternal hypothyroidism - where thyroid function is reduced - and something of an increased risk for an autism diagnosis in offspring, my mind headed back to the study by Gustavo Román and colleagues [2] talked about in this post, and their findings of "a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring". Of course, there are some differences between the way the Anderson and Román studies were conducted (registry diagnosis of thyroid dysfunction post-pregnancy vs. laboratory testing of thyroid function during early pregnancy) but the similar direction of the findings with autism in mind is interesting.

Equally interesting was the suggestion that maternal hyperthyroidism - an overactive thyroid - was related to some heightened risk of offspring ADHD in the Anderson cohort. A quick trawl of the limited research carried out in this area reveals some support for this assertion as per the data produced by Päkkilä and colleagues [3] who reported: "Increases in maternal TSH [thyroid stimulating hormone] in early pregnancy showed weak but significant association with girls' ADHD symptoms". That being said, I don't doubt that this is going to be a complicated relationship as per other reports on things like maternal thyroid autoimmunity during pregnancy and offspring outcomes [4] and the issue of iodine and offspring outcome [5] which has previously been talked about on this blog with autism in mind (see here). The fact that autism and ADHD can and do present comorbid in quite a few people adds to the complication.

I'd be hard-pressed to offer anything definitive about how and why thyroid function might impact specifically on the risk of diagnoses such as ADHD and autism outside of what is already known about maternal thyroid function and infants (see here). I assume as part of a larger clinical picture, there may be some direct effects specifically acting on the infant during the nine months that made us as well as other peripheral effects acting on for example, delivery issues as per the correlation between thyroid function and something like preterm birth risk [6] which might play some role [7].

Similarly when talking about the 'hows' of how issues with thyroid function come about in mums-to-be, one is faced with an array of possible factors. I could start going on about some of the genetics of thyroid disease [8] but I have neither the time, space or expertise to provide any thorough overview. Environment can also play a role as per the factors listed on this website so take your pick as to what might be relevant or not to cases. With the continuing interest in environmental effects and conditions like autism and ADHD, I might direct you to some of the work done on endocrine disruptors and thyroid functions [9] but with the realisation that the picture is going to be a complicated one varying from one group to the next, even one person to the next.

Still, the Anderson results further add to the interest looking at maternal thyroid function and offspring outcome and merit some further investigations in this area. Indeed, thyroid function is turning up in all manner of places these days [10] and perhaps point to some interesting associations which might have some important knock-on effects [11] ...

So, New Kids On The Block making a come-back.... You Got It!

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[1] Andersen S. et al. Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study. BJOG. 2014 Mar 10.

[2] Román GC. et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Nov;74(5):733-42.

[3] Päkkilä F. et al. The impact of gestational thyroid hormone concentrations on ADHD symptoms of the child. J Clin Endocrinol Metab. 2014 Jan;99(1):E1-8.

[4] Ghassabian A. et al. Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study. Thyroid. 2012 Feb;22(2):178-86.

[5] Vermiglio F. et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab. 2004 Dec;89(12):6054-60.

[6] Stagnaro-Green A. et al. The thyroid and pregnancy: a novel risk factor for very preterm delivery. Thyroid. 2005 Apr;15(4):351-7.

[7] Silva D. et al. Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder. Pediatrics. 2014 Jan;133(1):e14-22.

[8] Medici M. et al. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease. PLoS Genet. 2014 Feb 27;10(2):e1004123.

[9] Hofmann PJ. et al. Interference of endocrine disrupters with thyroid hormone receptor-dependent transactivation. Toxicol Sci. 2009 Jul;110(1):125-37.

[10] Wysokiński A. & Kłoszewska I. Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia, Unipolar Depression or Bipolar Disorder. Neurochem Res. 2014 Apr 11.

[11] van der Pals M. et al. Prevalence of thyroid autoimmunity in children with celiac disease compared to healthy 12-year olds. Autoimmune Dis. 2014;2014:417356.

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Andersen S, Laurberg P, Wu C, & Olsen J (2014). Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study. BJOG : an international journal of obstetrics and gynaecology PMID: 24605987