Controlled Antenatal Thyroid Screening Study III: Effects of Gestational Thyroid Status on Adolescent Brain Morphology

Abstract

Abstract Context Children born to mothers with gestational hypothyroidism or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. Objective This work aimed to establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). Methods The Controlled Antenatal Thyroid Screening (CATS) study randomly assigned mothers with SGTF to levothyroxine or no supplementation from approximately 12 weeks’ gestation. At age 9, children born to mothers who were overtreated 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). A total of 85 children aged 11 to 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), overtreated (n = 20)]). The primary outcome was to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes were to investigate the association of maternal thyrotropin (TSH) and free thyroxine (FT4) 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 = .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. Conclusion We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no effect of levothyroxine supplementation.