Controlled Antenatal Thyroid Screening Study III: Effects of Gestational Thyroid Status on Brain Microstructure.

Abstract

Children born to mothers with gestational thyroid dysfunction may have an increased risk of adverse neurodevelopmental outcomes, but the effects of maternal thyroid function on brain microstructure are unknown. To establish whether adolescent white matter microstructure is affected by suboptimal gestational thyroid function (SGTF). The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from 12 weeks' gestation. For the current study, CATS children underwent microstructural magnetic resonance imaging (MRI), including diffusion MRI, to explore white matter microstructure and quantitative magnetization transfer (qMT) imaging to investigate myelin. Seventy-five children aged 11-16 years had usable diffusion and/or qMT data: untreated SGTF (n = 19), normal GTF (n = 21), or treated SGTF (optimally treated [n = 18], overtreated [n = 17]). The primary outcome was to examine the effects of SGTF and its treatment on white matter microstructure. Secondary and exploratory outcomes were to investigate the association of (1) maternal thyrotropin and free thyroxine levels with white matter microstructure, and (2) white matter microstructure with attention deficit hyperactivity disorder symptom scores. Untreated SGTF was associated with higher mean diffusivity (indicating reduced axonal integrity) than normal GTF (P = .007) within the inferior longitudinal fasciculus, a major white matter tract connecting the occipital and temporal lobes and involved in several cognitive functions. Secondary and exploratory outcomes did not survive corrections for multiple comparisons. Untreated SGTF is associated with altered tract-specific microstructural morphology in adolescence, which may be reversible with levothyroxine administration in pregnancy.