Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology

Mulder, Tessa A.; Guxens Junyent, Mònica; Rebagliato, Marisa; Dineva, Mariana; Bath, Sarah C.; Hunziker, Sandra; Sunyer Deu, Jordi; Delgado-Saborit, Juana Maria; Irizar, Amaia; Lertxundi, Nerea; Muetzel, Ryan L.; Tiemeier, Henning; Peeters, Robin P.; Korevaar, Tim I. M.

doi:http://dx.doi.org/10.1210/clinem/dgae679

Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology

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Mulder TA, Guxens M, Rebagliato ML, Dineva M, Bath SC, Hunziker S, et al. Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology. J Clin Endocrinol Metab. 2025 Jun 17;110(7):2007-15. DOI: 10.1210/clinem/dgae679

Abstract

Background: Low maternal urinary iodine concentration (UIC) during pregnancy is associated with adverse offspring neurodevelopment. Thyroglobulin (Tg) has been suggested as a more sensitive biomarker than UIC of long-term iodine status, but associations of Tg with neurodevelopment and the possible mediating role of thyroid function remain unknown. Aim: To study whether maternal Tg is associated with (1) maternal and newborn thyroid function and (2) offspring IQ and brain morphology. Methods: Participants were selected from 2 population-based prospective cohorts: Generation R (the Netherlands, iodine-sufficient) and INfancia y Medio Ambiente (Spain, mildly iodine-deficient) with maternal Tg and thyroid function data in the first half of pregnancy or in cord blood, early childhood IQ (age 4.5 and 6 years), late childhood IQ (age 9 and 13), or brain morphology at 10 years. Associations of Tg with TSH, free T4 (FT4), IQ, and brain morphology were studied with multivariable linear regression. Results: (1) Tg was associated with lower TSH (-0.12 [-0.16; -0.08]) and higher FT4 (0.08 [0.05; 0.12]) in pregnancy (n = 4367) but not with cord blood TSH or FT4 (n = 2008). (2) Tg was associated with lower IQ in early childhood (β [95% confidence interval]: -0.06 [-0.10; -0.01], n = 2919) but not with IQ (n = 2503) or brain morphology (n = 1180) in later childhood. None of the associations of Tg with the studied outcomes differed by the iodine-to-creatinine ratio (ie, effect modification) or changed when adjusted for thyroid function. Conclusion: Higher Tg is associated with lower IQ in early childhood and higher thyroid function during pregnancy but not with IQ or brain morphology in later childhood. Further research should determine the value of Tg in addition to UIC for defining iodine status.