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Controlled Antenatal Thyroid Screening Study III: Effects of Gestational Thyroid Status on Adolescent Brain
Anna Scholz1, Carolyn B McNabb2, Laura Bloomfield2
1Centre for Endocrine and Diabetes Sciences, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Insights
Maternal thyroid function during pregnancy did not impact adolescent brain development. Suboptimal gestational thyroid function (SGTF) and levothyroxine treatment showed no association with brain morphology in children.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- Maternal thyroid dysfunction during pregnancy may affect fetal neurodevelopment.
- The precise impact of suboptimal gestational thyroid function (SGTF) on offspring brain development remains unclear.
Purpose of the Study:
- To investigate the association between SGTF and adolescent brain morphology.
- To evaluate the effect of levothyroxine supplementation for SGTF on brain development.
Main Methods:
- The Controlled Antenatal Thyroid Screening (CATS) III study utilized T1-weighted structural MRI in 85 adolescents (aged 11-16).
- Participants were categorized based on maternal gestational thyroid status: untreated SGTF, normal gestational thyroid function (GTF), and treated SGTF (optimally or overtreated).
- Analyses examined global and subregional brain volumes, correlating them with maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels.
Main Results:
- No significant differences in global brain volumes, including gray matter, were observed between the groups.
- Weak positive correlations between maternal TSH levels and some brain volumes did not withstand correction for multiple comparisons.
- Maternal free thyroxine (FT4) levels showed no significant association with brain volumes.
Conclusions:
- SGTF is not associated with alterations in adolescent brain morphology.
- Levothyroxine supplementation for SGTF did not demonstrate a discernible effect on brain development in this cohort.
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.
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