Preliminary Findings Show Maternal Hypothyroidism May Contribute to Abnormal Cortical Morphology in Offspring

Abstract

In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10–12 years born to women treated for preexisting or de novo hypothyroidism in pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses, suggesting that mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency.

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

“…Studies from Canada (7, 9, 10) evaluated MRI scans of 20-30 children aged 9-14 years born to mothers who were treated with L-T4 in the pregnancy for previously or newly diagnosed hypothyroidism and matched controls. In these studies (7,9,10), children born to mothers with hypothyroidism had smaller volume of the hippocampus, abnormal development of the corpus callosum and abnormal cortical morphology. Studies performed within the Generation R birth cohort in the Netherlands (8, 11) investigated MRI scans of 650 children aged 8 years.…”

“…Recent studies including data on brain MRI scans from children born to mothers with thyroid dysfunction have demonstrated structural defects in the brain (7,8,9,10,11). However, most studies in humans include indicators of exposure or outcome and are observational in design, which may challenge the interpretation of the results.…”

Maternal hormonal milieu influence on fetal brain development

“…Brain structural changes were also described for more pronounced levels of maternal thyroid dysfunction. Particularly, small studies from Canada reported reduced hippocampal volumes, abnormal development of corpus callosum, and abnormal cortical morphology in children aged 9–14 years born to women who were treated with levothyroxine during pregnancy for previously or newly detected hypothyroidism (Lischinsky, Skocic, Clairman, & Rovet,; Samadi, Skocic, & Rovet, ; Willoughby, McAndrews, & Rovet, ).…”

Clinical associations of maternal thyroid function with foetal brain development: Epidemiological interpretation and overview of available evidence

“…The first studies on maternal thyroid function and offspring neuroimaging outcomes were performed by the group of Rovet et al They composed a study population consisting of 20‐24 children (~30% of an original birth cohort) born from mothers that were undertreated for overt hypothyroidism (HYPO group) during at least a part of pregnancy, and 20‐30 healthy controls. The group of children in the HYPO group had smaller hippocampi, differently sized sub regions of the corpus callosum and unilateral thinning or thickening of certain (unilateral) cortical regions at the age of 10‐12 years . In addition, interesting hints towards dose‐dependent effects and differences according to thyroid dysfunction severity were identified .…”