Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology

Context: Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear.

Objective: To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF).

Design and setting: The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI).

Participants: A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)).

Main outcome measures: Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores.

Results: There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons.

Conclusions: We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.