Endocrine Abstracts

Background: Maternal thyroid hormones regulate neurodevelopment of the fetus. Maternal thyroid dysfunction has been associated with lower offspring IQ and alterations in brain morphology in early childhood, but it remains unknown if these associations persist as development progresses.

Methods: We performed a prospective cohort study including participants from an ongoing birth cohort in Rotterdam, the Netherlands, with data on gestational thyroid function and offspring IQ (measured by the Wechsler Intelligence Scale for Children) and/or brain MRI data at the follow-up visit at age 13 years. For participants who did not participate at 13 years, MRI data from the follow-up visit at 10 years were included. We excluded those with a pre-existing thyroid disorder, twin pregnancy, IVF pregnancy, and suboptimal-quality MRI data or major incidental finding. Regression analyses were adjusted for gestational age at blood sampling, maternal age, ethnicity, education level, smoking, child sex and age at outcome assessment. We assessed effect modification by TPOAb positivity and age of outcome assessment.

Results: After exclusions, 2464 mother-child pairs were included. Thyroid function tests were measured during pregnancy at a median of 13.2 weeks of gestation (IQR 12.1-14.6) and offspring brain morphology at a median age of 13.3 years (9.9–13.8). There was an inverse U-shaped association of maternal FT4, but not TSH, with cortical grey matter volume (GMV; P = 0.049), with no association found with white matter volume (WMV). In TPOAb positive women, there was an inverted U-shaped association of TSH and FT4 with GMV and between FT4 and WMV, while any association in TPOAb negative women was absent. Overt hypothyroidism was associated with lower total GMV (-92 cm³, CI -144 to -41), cortical GMV (-71 cm³, CI -116 to -27), subcortical GMV (-7.8 cm³, CI -11.8 to -3.7) and total WMV (-69 cm³, -111 to -26). Overt hyperthyroidism was associated with lower total GMV (-24 cm³, CI -45 to -3.3) and cortical GMV (-23 cm³, CI -40 to -5). Sensitivity analyses revealed that the associations of maternal thyroid function with offspring brain morphology persisted between age 5 to 16 years, but that there was no longer an association of maternal thyroid function with offspring IQ at the median age of 15 years.

Conclusion: The association of maternal thyroid function with brain morphology persisted throughout follow-up, while the association with child IQ-scores was no longer present, in contrast to previous follow-up visits. This discrepancy could be attributed to differences in IQ tests used, or neuroplasticity influenced by societal factors impacting child IQ scores. The previously reported inverse U shaped associations seemed to be primarily driven by TPOAb positive women. These results underscore the importance of sufficient thyroid hormone availability during pregnancy.