Early pregnancy maternal hypothyroxinemia and offspring ADHD symptoms

"Children exposed to maternal hypothyroxinemia in early pregnancy had more ADHD [attention-deficit/hyperactivity disorder] symptoms, independent of confounders. This finding suggests that intrauterine exposure to insufficient thyroid hormone levels influences neurodevelopment in offspring."

That was the bottom line reported by Thiago Modesto and colleagues [1] looking at how "mild thyroid hormone insufficiency" in early pregnancy might link into offspring behavioural outcomes a few years down the line. Based on data collected as part of the Generation R initiative - itself the source of previous research looking at the potential involvement of thyroid hormones and offspring outcome - researchers looked at maternal hypothyroxinemia "characterized by low levels of free thyroxine coexisting with reference thyrotropin levels" during pregnancy and how it correlated (or not) with parental report of offspring ADHD type behaviours based on scores on the Conners' Parent Rating Scale-Revised Short Form. They reported something of a possible association where: "Maternal hypothyroxinemia... in early pregnancy was associated with higher scores for ADHD symptoms in children at 8 years of age after adjustments for child and maternal factors (ie, sex, ethnicity, maternal age, maternal educational level, and income)." Interestingly too, when those presenting with thyroid peroxidase antibodies (a marker of autoimmune-related issues) were excluded from the analyses, the results did not differ to any great extent suggesting that the processes of being exposed to too lower a dose of thyroid hormone during early pregnancy seems to be the important factor outside of the possible reasons for such lower levels such as autoimmunity.

I've been pretty interested in the various [peer-reviewed] research looking at pregnancy thyroid hormones and offspring developmental outcomes down the years. In amongst that collected research, the idea that ADHD (or ADHD type symptoms) and even the presentation of autism might tie into the pregnancy levels of thyroid hormones has been quite a frequent feature (see here for example). Indeed, other research such as that from Libbe Kooistra and colleagues [2] over 10 years ago, had indicated that "maternal hypothyroxinemia constitutes a serious risk factor for neurodevelopmental difficulties" potentially detectable even as young as 3 weeks of age. Insofar as a role for autoimmunity in relation to pregnancy thyroid functions and offspring outcome, I'm also not quite ready to move on from a possible association as per other findings with autism in mind (see here).

Questions remains about the hows and whys of such an association and whether more could be done to extend screening for thyroid hormones particularly during early pregnancy in order to intervene and potentially 'offset' any additional developmental risks to offspring. Without making any clinical recommendations or giving anything like medical advice, I would also be interested to see how such thyroid findings might intersect with the body of work looking at issues with iodine availability (see here) and whether a wider research aim of looking at what happens in cases of pregnancy iodine deficiency in relation to thyroid hormone production and subsequent offspring development and behaviour is merited. It's not as if there isn't already some basis for further research inspection [3] in this area, also potentially extending into [some] autism (see here) too...

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[1] Modesto T. et al. Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention-Deficit/Hyperactivity Disorder Symptoms in Children. JAMA Pediatr. 2015 Jul 6.

[2] Kooistra L. et al. Neonatal Effects of Maternal Hypothyroxinemia During Early Pregnancy. Pediatrics. 2006; 117: 161-167.

[3] 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.

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Modesto T, Tiemeier H, Peeters RP, Jaddoe VW, Hofman A, Verhulst FC, & Ghassabian A (2015). Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention-Deficit/Hyperactivity Disorder Symptoms in Children. JAMA pediatrics PMID: 26146876