Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on brain microstructure.

Context: 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.

Objective: To establish whether adolescent white matter microstructure 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. 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.

Participants: 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), over-treated (n=17)).

Main Outcome Measures: Primary outcome: to examine the effects of SGTF and its treatment on white matter microstructure. Secondary and exploratory outcomes: to investigate the association of (a) maternal TSH and free T4 levels with white matter microstructure, and (b) white matter microstructure with attention deficit hyperactivity disorder (ADHD) symptom scores.

Results: Untreated SGTF was associated with higher mean diffusivity (indicating reduced axonal integrity) compared with normal GTF (p=0.007) 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.

Conclusions: Untreated SGTF is associated with altered tract-specific microstructural morphology in adolescence, which may be reversible with levothyroxine administration in pregnancy.