Impact of Maternal Thyroid Hormones on Adolescent Brain Gray Matter Regions

Overview

Maternal thyroid function during early pregnancy is associated with regional differences in offspring cerebral gray matter morphology, particularly in the frontal lobe. Both low and high maternal TSH levels showed inverse J-shaped relationships with cortical surface area and gyrification, while FT4 levels exhibited an inverse U-shaped association with caudate volume.

Background

Thyroid hormone is crucial for fetal brain development, influencing neuronal proliferation and differentiation. The fetal thyroid gland matures around 18 to 20 weeks gestation, making early fetal brain thyroid hormone availability dependent on maternal T4 supply. Previous studies linked maternal thyroid dysfunction with lower offspring IQ and neurodevelopmental disorders, as well as reduced total gray matter volume. However, the regional brain effects of maternal thyroid function during pregnancy have not been well characterized.

Data Highlights

Key Findings

• Maternal TSH levels during early pregnancy show an inverse J-shaped association with offspring cortical surface area in the rostral middle frontal region.
• Children of hyperthyroid mothers exhibit reduced gyrification in multiple frontal cortical regions.
• FT4 levels have an inverse U-shaped relationship with caudate nucleus volume in offspring.
• No significant associations were found between maternal thyroid hormones and other subcortical gray matter volumes.
• These regional brain morphology differences may underlie previously observed global brain volume changes and behavioral outcomes linked to maternal thyroid function.

Clinical Implications

Monitoring maternal thyroid function during early pregnancy is important as both hypo- and hyperthyroid states can impact offspring brain development, particularly in frontal gray matter regions. These findings support the need for careful thyroid screening and management in pregnancy to potentially mitigate adverse neurodevelopmental outcomes. Further research may guide targeted interventions to optimize fetal brain development.

Conclusion

Maternal thyroid hormone levels in early pregnancy are associated with specific regional alterations in offspring cerebral gray matter, especially in frontal brain areas. This expands understanding of thyroid-related neurodevelopmental risks beyond global brain volume changes.

References

1. Generation R Study Group 2024 -- Thyroid Hormone Levels in Pregnancy and Their Impact on Adolescent Cerebral Gray Matter Structure