Thyroid Fluctuations in Pregnancy Impact ADHD Risk


Hypothyroxinemia is not uncommon during pregnancy and may impact neurocognitive outcomes in children-but to what degree?

Maternal thyroid hormone levels in early pregnancy are known to impact fetal brain development and subsequent neurocognitive outcomes in children, with some studies pointing to an association between maternal hypothyroidism and ADHD or autism spectrum disorders. Transient hypothyroidism (hypothyroxinemia) is not uncommon during pregnancy and may also impact outcomes but to what degree?

Small and retrospective studies, some of which lacked clearly defined outcomes or controls for confounders, have found associations. Now, more robust findings on the matter have emerged from the Generation R study, a population-based birth-cohort of Dutch children born between 2002 and 2006.1

Modesto and colleagues1 accessed Generation R data on mother-child pairs for whom thyroid hormone values were available and conducted an analysis that compared maternal hormone values during early pregnancy with ADHD scores of the children at age 8 years. A total of 3873 children were included in the study. The results point to a modest increased risk for ADHD symptoms in children of mothers who experience hypothyroxinemia during early pregnancy.

In this study, maternal thyrotropin, free thyroxine (FT4), and thyroid peroxidase antibodies were measured at the first prenatal visit, which took place at a mean 13.6 weeks of gestation. Thyroid hormone levels were measured again after childbirth. Maternal hypothyroxinemia was defined as thyrotropin levels of 0.1 to 2.5mIU/L and FT4 levels below 0.85 ng/dL as per guidelines set by the American Thyroid Association.

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A total 127 women, representing 3.4% of mothers participating in the study, were found to be hypothyroxinemic during early pregnancy. Maternal hypothyroxinemia was indeed associated with higher CPRS-R:S ADHD index scores in offspring after adjusting for factors such as sex, ethnicity, maternal age, maternal educational level, and income. The increase was modest, though (P =.04), with ADHD index scores being an average 7% higher for children born to mothers who experienced hypothyroxinemia during early pregnancy. No correlation with oppositional symptoms was seen.

The researchers conjectured that gestational thyroid hormone insufficiency, though having a global impact, may affect some subregions of the fetal brain more than others. In addition, no correlation between subclinical maternal hyothyroxinemia and ADHD risk was detected.

The researchers concluded that intrauterine exposure to insufficient levels of thyroid hormones-even mild insufficiency during early gestation-can impact neurodevelopment. Although their study design was more robust than earlier, related studies, they noted that measuring thyroid hormones only once during pregnancy was a limitation. Repeated testing may have offered insight into the impact of fluctuating hormone levels on ADHD outcomes.


1. Modesto T, Tiemeier H, Peeters RP, et al. Maternal mild thyroid hormone insufficiency in early pregnancy and attention-deficit/hyperactivity disorder symptoms in children. JAMA Pediatr. 2015 Jul 6. [Epub ahead of print]

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