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. 2025 Jun 17;110(7):2007-2015.
doi: 10.1210/clinem/dgae679.

Association of Maternal Thyroglobulin With Gestational Thyroid Function and Offspring IQ and Brain Morphology

Tessa A Mulder  1   2   3 , Mònica Guxens  3   4   5   6 , Maria Luisa Rebagliato  4   7   8 , Mariana Dineva  9   10 , Sarah C Bath  11 , Sandra Hunziker  12   13 , Jordi Sunyer  4   5   6 , Juana Maria Delgado-Saborit  7   8 , Amaia Irizar Loibide  4   14   15 , Nerea Lertxundi  4   16   17 , Ryan L Muetzel  3   18 , Henning Tiemeier  3   19 , Robin P Peeters  2 , Tim I M Korevaar  2   20
Affiliations

Association of Maternal Thyroglobulin With Gestational Thyroid Function and Offspring IQ and Brain Morphology

Tessa A Mulder et al. J Clin Endocrinol Metab. .

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.

Keywords: brain development; iodine; thyroglobulin; thyroid function.

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Figures

Figure 1.
Figure 1.
Flowchart of the study population.
Figure 2.
Figure 2.
Associations of thyroglobulin with maternal thyroid function. Associations are adjusted for national origin (cohort-specific categories), gestational age, maternal age, education, BMI, parity and smoking, and child sex. Tg (ng/mL) and TSH (mU/L) are transformed by the natural logarithm. Back-transformed values for Tg are shown on the x-axis for better interpretation. TSH (mU/L) and FT4 (pmol/L) are standardized. Abbreviations: BMI, body mass index; FT4, free T4; Tg, thyroglobulin.
Figure 3.
Figure 3.
Associations of thyroglobulin with IQ. Associations are adjusted for national origin (cohort-specific categories), gestational age, maternal age, education, BMI, parity and smoking, and child sex and age at IQ measurement. Early childhood IQ includes IQ measured at 6.2 years in Generation R and 4.5 years in INMA. Later childhood IQ includes IQ measured at 13.6 years in Generation R and 8.5 years in INMA. Abbreviations: BMI, body mass index; INMA, Infancia y Medio Ambiente.
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