Exploration of thyroglobulin as a biomarker of iodine status in iodine-sufficient and mildly iodine-deficient pregnant women

Mariana Dineva, Margaret P. Rayman, Deborah Levie, Sandra Hunziker, Mònica Guxens, Robin P. Peeters, Mario Murcia, Marisa Rebagliato, Amaia Irizar, Alba Jimeno-Romero, Jordi Sunyer, Tim I.M. Korevaar, Sarah C. Bath*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Purpose: Urinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency. Methods: Stored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg. Results: Median serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated. Conclusion: The association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed.

Original languageEnglish
Pages (from-to)2139-2154
Number of pages16
JournalEuropean Journal of Nutrition
Volume62
Issue number5
Early online date27 Mar 2023
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Funding Information:
This study was part of the EUthyroid project which has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 634453; this funding was used to support Tg measurements, data harmonisation and initial data analysis. The writing of the manuscript and final data analysis were completed as part of a grant from The Academy of Medical Sciences Springboard programme [SBF005\1097].

Funding Information:
1) EUthyroid project: This project has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 634453. We would like to thank Prof Michael Zimmermann (ETH Zurich) for leading the laboratory analyses of thyroglobulin as part of the EUthyroid project. 2) Generation R: The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The Generation R Study is supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport. A grant from the Sophia Children’s Hospital Research Funds supports the neurodevelopmental work on thyroid; Robin P. Peeters is supported by a clinical fellowship from ZonMw, project number 90700412. 3) INMA: This study was funded by grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1) and Spain: Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; FIS-FEDER: PI041436, PI05/1079, PI06/0867, PI081151, FIS-and PS09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051, MS13/00054), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Mònica Guxens is funded by a Miguel Servet II fellowship (CPII18/00018) awarded by the Spanish Institute of Health Carlos III.

Funding Information:
1) EUthyroid project: This project has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 634453. We would like to thank Prof Michael Zimmermann (ETH Zurich) for leading the laboratory analyses of thyroglobulin as part of the EUthyroid project. 2) Generation R: The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The Generation R Study is supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport. A grant from the Sophia Children’s Hospital Research Funds supports the neurodevelopmental work on thyroid; Robin P. Peeters is supported by a clinical fellowship from ZonMw, project number 90700412. 3) INMA: This study was funded by grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1) and Spain: Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; FIS-FEDER: PI041436, PI05/1079, PI06/0867, PI081151, FIS-and PS09/00090, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, and PI16/1288; Miguel Servet-FEDER CP11/00178, CP15/00025, and CPII16/00051, MS13/00054), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, and UGP-15-249), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), Department of Health of the Basque Government (2005111093 and 2009111069), and the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001). We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Mònica Guxens is funded by a Miguel Servet II fellowship (CPII18/00018) awarded by the Spanish Institute of Health Carlos III.

Publisher Copyright:
© 2023, The Author(s).

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