Maternal thyroid function during pregnancy and early adolescent regional differences in cerebral gray matter morphology.

Background: Thyroid hormone regulates fetal brain development. Both low and high maternal thyroid function during early pregnancy has been associated with smaller offspring total gray matter and cortex volume. However, it remains unknown whether regional gray matter differences underlie global brain morphology findings.

Aim: To assess the association of gestational thyroid function with regional gray matter morphology through detailed vertex-wise analysis of cortical surface area and thickness, and volumetric analyses of subcortical gray matter.

Methods: We enrolled 2,426 women of the population-based prospective cohort Generation R with TSH and/or FT4 assessment before 18 weeks of gestation and offspring brain MRI scans at age 10 and/or 14 years. We studied the association of gestational TSH, FT4 and (sub)clinical thyroid disease entities with local cortical surface area, thickness and subcortical volumes.

Results: There was an inverse J-shaped association of TSH with cortical surface area in the rostral middle frontal region (β[SE] for quadratic TSH: -0.005[0.001] mm2, linear TSH 0.009[0.004]). FT4 was not associated with cortical measures. Post-hoc analyses revealed an inverse J-shaped association of TSH with gyrification in a similar region and children of hyperthyroid women had less gyrification in three cortical regions, mainly frontal (-0.082[0.022], -0.077[0.020], -0.069[0.020]). Moreover, there was an inverse U-shaped association of FT4 with caudate volume (β[SE] for quadratic FT4: -0.004[0.001] SD, linear FT4 0.010[0.010]). TSH and FT4 were not associated with other subcortical volumes.

Conclusion: Maternal thyroid function during early pregnancy is associated with offspring cerebral gray matter morphology in certain brain regions, specifically the frontal lobe. These findings expand on global brain morphology associations and support previous associations with behavioral outcomes.