INTRODUCTION: Maternal urinary iodine concentration and blood neonatal thyroid-stimulating hormone (TSH) concentration reflect iodine status in pregnancy and serve as markers of iodine deficiency. As dietary measures in gestational diabetes mellitus (GDM) could affect iodine intake, our study aimed to investigate iodine supply in women with GDM compared to healthy pregnant women and to evaluate its relationship to maternal and neonatal thyroid function. METHODS: Urinary iodine concentration (UIC) and serum TSH, free thyroxine (FT4), and autoantibodies against thyroid peroxidase (TPOAb) were analyzed in 195 women with GDM and 88 healthy pregnant women in the second trimester. Subsequently, neonatal TSH concentrations measured 72 h after delivery in a subgroup of 154 newborns (115 of mothers with GDM and 39 controls) from the national register were analyzed. RESULTS: Median UIC was significantly lower in women with GDM compared to controls (89.50 µg/L vs. 150.05 µg/L; P < 0.001). Optimal iodine intake was found only in nine women with GDM (4.6%) and 33 healthy pregnant women (37.5%) (P < 0.001). Most pregnant women with GDM (88.7%) compared to one half of controls (50%) had iodine deficiency (P < 0.001). Although serum TSH and the prevalence of hypothyroidism (TSH > 4.0 mIU/L) were not different in both groups, hypothyroxinaemia was more prevalent in GDM compared to controls (12.3% vs 3.4%, P = 0.032). Consistently, neonatal TSH > 5.0 mIU/L indicating iodine deficiency, was found in 6 (5.2%) newborns of women with GDM as compared to none in controls. In women with GDM, the prevalence of perinatal complications was significantly lower in those who were taking dietary iodine supplements compared to those who were not (3/39 (7.69%) vs 46/156 (28.85%), P <0.001). In the multiple logistic and linear regression models in women with GDM, hypothyroxinaemia was associated with preterm births, and a negative association of serum FT4 and HbA1c was found. CONCLUSION: Iodine deficiency in pregnancy was more prevalent among women with GDM compared to healthy pregnant controls. Serum FT4 negatively correlated with HbA1c, and hypothyroxinaemia was associated with preterm births in women with GDM. Conversely, women with GDM who used dietary iodine supplements had a lower risk of perinatal complications.

3rd Department of Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Children and Adolescents 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Gynaecology Obstetrics and Neonatology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Institute of Clinical Biochemistry and Laboratory Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Institute of Endocrinology Prague Czech Republic

University Center of Internal Medicine Cantonal Hospital Baselland and University of Basel Switzerland

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Lopez-Munoz E Mateos-Sanchez L Mejia-Terrazas GE & Bedwell-Cordero SE. Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic. Taiwanese Journal of Obstetrics and Gynecology 201958757–763. (10.1016/j.tjog.2019.09.005) PubMed DOI

Andersson M Takkouche B Egli I Allen HE & de Benoist B. Current global iodine status and progress over the last decade towards the elimination of iodine deficiency. Bulletin of the World Health Organization 200583518–525. PubMed PMC

Andersson M Karumbunathan V & Zimmermann MB. Global iodine status in 2011 and trends over the past decade. Journal of Nutrition 2012142744–750. (10.3945/jn.111.149393) PubMed DOI

Zimmermann MB & Andersson M. Global endocrinology: global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020. European Journal of Endocrinology 2021185R13–R21. (10.1530/EJE-21-0171) PubMed DOI PMC

Yang Y Li Q Wang Q & Ma X. Thyroid antibodies and gestational diabetes mellitus: a meta-analysis. Fertility and Sterility 2015104665–71.e3. (10.1016/j.fertnstert.2015.06.003) PubMed DOI

Sitoris G Veltri F Ichiche M Kleynen P Praet JP Rozenberg S & Poppe KG. Association between thyroid autoimmunity and gestational diabetes mellitus in euthyroid women. European Thyroid Journal 202211. (10.1530/ETJ-21-0142) PubMed DOI PMC

Tudela CM Casey BM McIntire DD & Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstetrics and Gynecology 2012119983–988. (10.1097/AOG.0b013e318250aeeb) PubMed DOI

Fernandez Alba JJ Castillo Lara M Jimenez Heras JM Moreno Cortes R Gonzalez Macias C Vilar Sanchez Á San Laureano FC & Moreno Corral LJ. High first trimester levels of TSH as an independent risk factor for gestational diabetes mellitus: a retrospective cohort Study. Journal of Clinical Medicine 202211. (10.3390/jcm11133776) PubMed DOI PMC

Milovanovic Z Filimonovic D Soldatovic I & Karadzov Orlic N. Can thyroid screening in the first trimester improve the prediction of gestational diabetes mellitus? Journal of Clinical Medicine 202211. (10.3390/jcm11133916) PubMed DOI PMC

Oguz A Tuzun D Sahin M Usluogullari AC Usluogullari B Celik A & Gul K. Frequency of isolated maternal hypothyroxinemia in women with gestational diabetes mellitus in a moderately iodine-deficient area. Gynecological Endocrinology 201531792–795. (10.3109/09513590.2015.1054801) PubMed DOI

Buchanan TA Xiang AH & Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nature Reviews. Endocrinology 20128639–649. (10.1038/nrendo.2012.96) PubMed DOI PMC

Nazarpour S Ramezani Tehrani F Simbar M & Azizi F. Thyroid dysfunction and pregnancy outcomes. Iranian Journal of Reproductive Medicine 201513387–396. PubMed PMC

Springer D Bartos V & Zima T. Reference intervals for thyroid markers in early pregnancy determined by 7 different analytical systems. Scandinavian Journal of Clinical and Laboratory Investigation 20147495–101. (10.3109/00365513.2013.860617) PubMed DOI

Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, et al.2017 Guidelines of the American Thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 201727315–389. (10.1089/thy.2016.0457) PubMed DOI

Hnikova O. Význam neonatálního TSH. Česko-Slovenská Pediatrie 20035252–254.

Ryšavá L.Screening TSH novorozenců a prevence jodového deficitu u novorozenců, kojenců, gravidních a kojících žen. Konference ke dni jódu. Státní zdravotní ústav 2012 [epub]. (available at: https://archiv.szu.cz/tema/podpora-zdravi/screening-tsh-novorozencu-a-prevence-jodoveho-deficitu-u-1)

WHO. Urinary iodine concentrations for determining iodine status deficiency in populations. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization, 2013. (available at: http://www.who.int/nutrition/vmnis/indicators/urinaryiodine)

Plows JF Stanley JL Baker PN Reynolds CM & Vickers MH. The pathophysiology of gestational diabetes mellitus. International Journal of Molecular Sciences 201819. (10.3390/ijms19113342) PubMed DOI PMC

Malaguarnera R Vella V Nicolosi ML & Belfiore A. Insulin resistance: any role in the changing epidemiology of thyroid cancer? Frontiers in Endocrinology (Lausanne) 20178314. (10.3389/fendo.2017.00314) PubMed DOI PMC

Al-Attas OS Al-Daghri NM Alkharfy KM Alokail MS Al-Johani NJ Abd-Alrahman SH Yakout SM Draz HM & Sabico S. Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2. Experimental and Clinical Endocrinology and Diabetes 2012120618–622. (10.1055/s-0032-1323816) PubMed DOI

Mansourian AR. A review on the metabolic disorders of iodine deficiency. Pakistan Journal of Biological Sciences 201114412–424. (10.3923/pjbs.2011.412.424) PubMed DOI

Neven KY Cox B Cosemans C Gyselaers W Penders J Plusquin M Roels HA Vrijens K Ruttens A & Nawrot TS. Lower iodine storage in the placenta is associated with gestational diabetes mellitus. BMC Medicine 20211947. (10.1186/s12916-021-01919-4) PubMed DOI PMC

Jin M, Zhang Z, Li Y, Teng D, Shi X, Ba J, Chen B, Du J, He L, Lai X, et al.U-shaped associations between urinary iodine concentration and the prevalence of metabolic disorders: a cross-sectional study. Thyroid 2020301053–1065. (10.1089/thy.2019.0516) PubMed DOI

Lecube A Zafon C Gromaz A Fort JM Caubet E Baena JA & Tortosa F. Iodine deficiency is higher in morbid obesity in comparison with late after bariatric surgery and non-obese women. Obesity Surgery 20152585–89. (10.1007/s11695-014-1313-z) PubMed DOI

Omar AX Karina SAE Rocío CR & Elind AHO. Iodine deficiency is associated with overweight and obesity on adults. Galore International Journal of Applied Sciences and Humanities 2021512–15.

Zimmermann MB Jooste PL & Pandav CS. Iodine-deficiency disorders. Lancet 20083721251–1262. (10.1016/S0140-6736(0861005-3) PubMed DOI

Wong EM Sullivan KM Perrine CG Rogers LM & Pena-Rosas JP. Comparison of median urinary iodine concentration as an indicator of iodine status among pregnant women, school-age children, and nonpregnant women. Food and Nutrition Bulletin 201132206–212. (10.1177/156482651103200304) PubMed DOI

Zimmermann MB Gizak M Abbott K Andersson M & Lazarus JH. Iodine deficiency in pregnant women in Europe. Lancet. Diabetes and Endocrinology 20153672–674. (10.1016/S2213-8587(1500263-6) PubMed DOI

Caldwell KL Pan Y Mortensen ME Makhmudov A Merrill L & Moye J. Iodine status in pregnant women in the National Children’s Study and in U.S. women (15–44 years), National Health and Nutrition Examination survey 2005–2010. Thyroid 201323927–937. (10.1089/thy.2013.0012) PubMed DOI PMC

Bilek R Kanova N Mindzakova V Neumann D Jiskra J Rysava L & Zamrazil V. Iodine supply of pregnant women in the Czech Republic. Vnitrni Lekarstvi 201662(Supplement 3) 10–16. PubMed

Bell GA Mannisto T Liu A Kannan K Yeung EH Kim UJ Suvanto E Surcel HM Gissler M & Mills JL. The joint role of thyroid function and iodine concentration on gestational diabetes risk in a population-based study. Acta Obstetricia et Gynecologica Scandinavica 201998500–506. (10.1111/aogs.13523) PubMed DOI

Purdue-Smithe AC, Mannisto T, Bell GA, Mumford SL, Liu A, Kannan K, Kim UJ, Suvanto E, Surcel HM, Gissler M, et al.The joint role of thyroid function and iodine status on risk of preterm birth and small for gestational age: a population-based nested case-control study of Finnish women. Nutrients 201911. (10.3390/nu11112573) PubMed DOI PMC

Lindorfer H Krebs M Kautzky-Willer A Bancher-Todesca D Sager M & Gessl A. Iodine deficiency in pregnant women in Austria. European Journal of Clinical Nutrition 201569349–354. (10.1038/ejcn.2014.253) PubMed DOI

Jiskra J Fait T Bilek R Kratky J Bartakova J Lukas J Límanová Z Telička Z Zamrazil V & Potluková E. Mild iodine deficiency in women after spontaneous abortions living in an iodine-sufficient area of Czech Republic: prevalence and impact on reproductive health. Clinical Endocrinology 201480452–458. (10.1111/cen.12298) PubMed DOI

Lazarus J Brown RS Daumerie C Hubalewska-Dydejczyk A Negro R & Vaidya B. 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. European Thyroid Journal 2014376–94. (10.1159/000362597) PubMed DOI PMC

Fuse Y Ohashi T Yamaguchi S Yamaguchi M Shishiba Y & Irie M. Iodine status of pregnant and postpartum Japanese women: effect of iodine intake on maternal and neonatal thyroid function in an iodine-sufficient area. Journal of Clinical Endocrinology and Metabolism 2011963846–3854. (10.1210/jc.2011-2180) PubMed DOI

Krylova K Bilek R Kulicka J Dejmek P Bayer M Kacerovsky M & Neumann D. Urinary iodine concentrations in mothers and their term newborns in country with sufficient iodine supply. Journal of Maternal-Fetal and Neonatal Medicine 2017302633–2639. (10.1080/14767058.2016.1260114) PubMed DOI

Stohl HE Ouzounian J Rick AM Hueppchen NA & Bienstock JL. Thyroid disease and gestational diabetes mellitus (GDM): is there a connection? Journal of Maternal-Fetal and Neonatal Medicine 2013261139–1142. (10.3109/14767058.2013.773309) PubMed DOI

Oguz A Tuzun D Ozdemir D Baci Y Ersoy R Avsar AF & Cakir B. Prevalance of gestational diabetes mellitus in patients with gestational transient thyrotoxicosis. Gynecological Endocrinology 201329336–339. (10.3109/09513590.2012.752451) PubMed DOI

Mannisto T Vaarasmaki M Pouta A Hartikainen AL Ruokonen A Surcel HM Bloigu A Järvelin MR & Suvanto E. Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life. Journal of Clinical Endocrinology and Metabolism 2010951084–1094. (10.1210/jc.2009-1904) PubMed DOI

Karakosta P Alegakis D Georgiou V Roumeliotaki T Fthenou E Vassilaki M Boumpas D Castanas E Kogevinas M & Chatzi L. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. Journal of Clinical Endocrinology and Metabolism 2012974464–4472. (10.1210/jc.2012-2540) PubMed DOI

Mannisto T Mendola P Grewal J Xie Y Chen Z & Laughon SK. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. Journal of Clinical Endocrinology and Metabolism 2013982725–2733. (10.1210/jc.2012-4233) PubMed DOI PMC

Nelson DB Casey BM McIntire DD & Cunningham FG. Subsequent pregnancy outcomes in women previously diagnosed with subclinical hypothyroidism. American Journal of Perinatology 20143177–84. (10.1055/s-0033-1334457) PubMed DOI

Cleary-Goldman J Malone FD Lambert-Messerlian G Sullivan L Canick J Porter TF Luthy D Gross S Bianchi DW & D’Alton ME. Maternal thyroid hypofunction and pregnancy outcome. Obstetrics and Gynecology 200811285–92. (10.1097/AOG.0b013e3181788dd7) PubMed DOI PMC

Ong GS Hadlow NC Brown SJ Lim EM & Walsh JP. Does the thyroid-stimulating hormone measured concurrently with first trimester biochemical screening tests predict adverse pregnancy outcomes occurring after 20 weeks gestation? Journal of Clinical Endocrinology and Metabolism 201499E2668–E2672. (10.1210/jc.2014-1918) PubMed DOI

Kumru P Erdogdu E Arisoy R Demirci O Ozkoral A Ardic C Ertekin AA Erdogan S & Ozdemir NN. Effect of thyroid dysfunction and autoimmunity on pregnancy outcomes in low risk population. Archives of Gynecology and Obstetrics 20152911047–1054. (10.1007/s00404-014-3533-9) PubMed DOI

Haddow JE, Craig WY, Neveux LM, Palomaki GE, Lambert-Messerlian G, Malone FD, D’Alton ME. & First and Second Trimester Risk of Aneuploidy (FaSTER) Research Consortium. Free thyroxine during early pregnancy and risk for gestational diabetes. PLoS One 201611e0149065. (10.1371/journal.pone.0149065) PubMed DOI PMC

Yalakanti D & Dolia PB. Association of type II 5’ monodeiodinase Thr92Ala single nucleotide gene polymorphism and circulating thyroid hormones among type 2 diabetes mellitus patients. Indian Journal of Clinical Biochemistry 201631152–161. (10.1007/s12291-015-0518-9) PubMed DOI PMC

Casey BM Dashe JS Spong CY McIntire DD Leveno KJ & Cunningham GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstetrics and Gynecology 20071091129–1135. (10.1097/01.AOG.0000262054.03531.24) PubMed DOI

Hamm MP Cherry NM Martin JW Bamforth F & Burstyn I. The impact of isolated maternal hypothyroxinemia on perinatal morbidity. Journal of Obstetrics and Gynaecology Canada 2009311015–1021. (10.1016/S1701-2163(1634345-6) PubMed DOI

Su PY Huang K Hao JH Xu YQ Yan SQ Li T Xu YH & Tao FB. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. Journal of Clinical Endocrinology and Metabolism 2011963234–3241. (10.1210/jc.2011-0274) PubMed DOI

Delange F. Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. Thyroid 199881185–1192. (10.1089/thy.1998.8.1185) PubMed DOI

Selinger E & Nejedlá. Konference Jód 21 – problematika jódu v 21. roce 21. století. Hygiena 20216664.

Du Y Gao YH Feng ZY Meng FG Fan LJ & Sun DJ. Serum thyroglobulin-A sensitive biomarker of iodine nutrition status and affected by thyroid abnormalities and disease in adult populations. Biomedical and Environmental Sciences 201730508–516. (10.3967/bes2017.067) PubMed DOI

Ma ZF & Skeaff SA. Thyroglobulin as a biomarker of iodine deficiency: a review. Thyroid 2014241195–1209. (10.1089/thy.2014.0052) PubMed DOI PMC