Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Maternal Urinary Iodine Concentration and Pregnancy Outcomes: Tehran Thyroid and Pregnancy Study


Iodine is essential for the production of thyroid hormones, and its deficiency during pregnancy may be associated with poor obstetric outcomes. The aim of this study was to investigate the relationship between maternal iodine statuses with pregnancy outcomes among pregnant Iranian women, considering their baseline thyrotropin (TSH) status. We used data from the Tehran Thyroid and Pregnancy Study (TTPS), a two-phase population-based study carried out among pregnant women receiving prenatal care. By excluding participants with overt thyroid dysfunction and those receiving levothyroxine, the remaining participants (n = 1286) were categorized into four groups, according to their urine iodine status: group 1, urine iodine concentration (UIC) < 100 μg/L; group 2, UIC between 100 and 150 μg/L; group 3, UIC between 150 and 250 μg/L; and group 4, UIC ≥ 250 μg/L. Primary outcome was preterm delivery. Preterm delivery occurred in 29 (9%), 19 (7%), 15 (5%), and 8 (4%) women, and neonatal admission was documented in 22 (7%), 30 (12%), 28 (11%), and 6 (3%) women of groups 1, 2, 3, and 4, respectively. Generalized linear regression model (GLM) demonstrated that the odds ratio of preterm delivery was significantly higher in women with urinary iodine < 100 μg/L and TSH ≥ 4 μIU/mL than those with similar urinary iodine with TSH < 4 μIU/mL (OR 2.5 [95% CI 1.1, 10], p = 0.024). Adverse pregnancy outcomes are increased among women with UIC < 100 μg/L, with serum TSH concentrations ≥ 4 μIU/mL.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Perez-Lopez FR (2007) Iodine and thyroid hormones during pregnancy and postpartum. Gynecol Endocrinol 23(7):414–428

  2. 2.

    Delange F (2007) Iodine requirements during pregnancy, lactation and the neonatal period and indicators of optimal iodine nutrition. Public Health Nutr 10:1571–1580 discussion 1581–1573.

  3. 3.

    Delange F (2001) Iodine deficiency as a cause of brain damage. Postgrad Med J 77:217–220

  4. 4.

    Yarrington CD, Pearce EN (2011) Dietary iodine in pregnancy and postpartum. Clin Obstet Gynecol 54:459–470

  5. 5.

    Crew MD, Spindler SR (1986) Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem 261:5018–5022

  6. 6.

    Samuels MH, Wierman ME, Wang C, Ridgway EC (1989) The effect of altered thyroid status on pituitary hormone messenger ribonucleic acid concentrations in the rat. Endocrinology 124:2277–2282

  7. 7.

    Hochberg Z, Bick T, Harel Z (1990) Alterations of human growth hormone binding by rat liver membranes during hypo- and hyperthyroidism. Endocrinology 126:325–329

  8. 8.

    Pearce EN (2012) Effects of iodine deficiency in pregnancy. J Trace Elem Med Biol 26:131–133

  9. 9.

    Glinoer D (2006) Iodine nutrition requirements during pregnancy. Thyroid 16:947–948

  10. 10.

    Glinoer D (1997) The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 18:404–433

  11. 11.

    Dafnis E, Sabatini S (1992) The effect of pregnancy on renal function: physiology and pathophysiology. Am J Med Sci 303:184–205

  12. 12.

    Glinoer D (2004) The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab 18:133–152

  13. 13.

    Hershman JM (2004) Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. Best Pract Res Clin Endocrinol Metab 18:249–265

  14. 14.

    Dunn JT, Delange F (2001) Damaged reproduction: the most important consequence of iodine deficiency. J Clin Endocrinol Metab 86:2360–2363

  15. 15.

    Elnagar B, Eltom A, Wide L, Gebre-Medhin M, Karlsson FA (1998) Iodine status, thyroid function and pregnancy: study of Swedish and Sudanese women. Eur J Clin Nutr 52:351–355

  16. 16.

    Zimmermann MB (2009) Iodine deficiency. Endocr Rev 30:376–408

  17. 17.

    Hetzel BS (1983) Iodine deficiency disorders (IDD) and their eradication. Lancet 2:1126–1129

  18. 18.

    Zimmermann MB, Jooste PL, Pandav CS (2008) Iodine-deficiency disorders. Lancet 372(9645):1251–1262

  19. 19.

    Pearce EN, Lazarus JH, Moreno-Reyes R, Zimmermann MB (2016) Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr 104(Suppl 3):918S–923S

  20. 20.

    Zimmermann MB (2012) The effects of iodine deficiency in pregnancy and infancy. Paediatr Perinat Epidemiol 26(Suppl 1):108–117

  21. 21.

    Chaouki ML, Benmiloud M (1994) Prevention of iodine deficiency disorders by oral administration of lipiodol during pregnancy. Eur J Endocrinol 130:547–551

  22. 22.

    DeLong GR, Leslie PW, Wang SH, Jiang XM, Zhang ML, Rakeman M, Jiang JY, Ma T, Cao XY (1997) Effect on infant mortality of iodination of irrigation water in a severely iodine-deficient area of China. Lancet 350:771–773

  23. 23.

    International Council for Control of Iodine Deficiency Disorders (2007) Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. World Health Organization, Geneva

  24. 24.

    McMichael A, Potter J, Hetzel B (1980) Iodine deficiency, thyroid function and reproductive failure. In Endemic Goitre and Endemic Cretinism. Wiley Medical, New York

  25. 25.

    Torlinska B, Bath SC, Janjua A, Boelaert K, Chan S-Y (2018) Iodine status during pregnancy in a region of mild-to-moderate iodine deficiency is not associated with adverse obstetric outcomes; results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Nutrients 10:291

  26. 26.

    Azizi F, Sheikholeslam R, Hedayati M, Mirmiran P, Malekafzali H, Kimiagar M, Pajouhi M (2002) Sustainable control of iodine deficiency in Iran: beneficial results of the implementation of the mandatory law on salt iodization. J Endocrinol Investig 25:409–413

  27. 27.

    Amouzegar A, Azizi F (2013) Variations of urinary iodine during the first trimester of pregnancy in an iodine-replete area. Comparison with non-pregnant women. Hormones 12:111–118

  28. 28.

    Mirmiran P, Nazeri P, Amiri P, Mehran L, Shakeri N, Azizi F (2013) Iodine nutrition status and knowledge, attitude, and behavior in Tehranian women following 2 decades without public education. J Nutr Educ Behav 45:412–419

  29. 29.

    Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Azizi F (2016) Thyroid and pregnancy in tehran, Iran: objectives and study protocol. Int J Endocrinol Metab 14:e33477

  30. 30.

    Azizi F, Mehran L, Amouzegar A, Delshad H, Tohidi M, Askari S, Hedayati M (2013) Establishment of the trimester-specific reference range for free thyroxine index. Thyroid 23:354–359

  31. 31.

    Suff N, Story L, Shennan A, editors (2018) The prediction of preterm delivery: what is new? Semin Fetal Neonatal Med Elsevier 28: S1744-165X(18)30111-2.

  32. 32.

    Elsasser DA, Ananth CV, Prasad V, Vintzileos AM, Investigators NJ-PAS (2010) Diagnosis of placental abruption: relationship between clinical and histopathological findings. Eur J Obstet Gynecol Reprod Biol 148:125–130

  33. 33.

    Blencowe H, Cousens S, Jassir FB, Say L, Chou D, Mathers C, Hogan D, Shiekh S, Qureshi ZU, You D, Lawn JE, Lancet Stillbirth Epidemiology Investigator G (2016) National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health 4(2):e98–e108

  34. 34.

    Diggle P, Diggle PJ, Heagerty P, Heagerty PJ, Liang K-Y, Zeger S (2002) Analysis of longitudinal data, 2nd edn. Oxford University Press, UK

  35. 35.

    Sang ZN, Wei W, Zhao N, Zhang GQ, Chen W, Liu H, Shen J, Liu JY, Yan YQ, Zhang WQ (2012) Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women. J Clin Endocrinol Metab 97:E1363–E1369

  36. 36.

    Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, Cunningham FG (2005) Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 105:239–245

  37. 37.

    Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Minooee S, Rahmati M, Azizi F (2018) Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J Clin Endocrinol Metab 103:926–935

  38. 38.

    Charoenratana C, Leelapat P, Traisrisilp K, Tongsong T (2016) Maternal iodine insufficiency and adverse pregnancy outcomes. Matern Child Nutr 12:680–687

  39. 39.

    León G, Murcia M, Rebagliato M, Álvarez-Pedrerol M, Castilla AM, Basterrechea M, Iñiguez C, Fernández-Somoano A, Blarduni E, Foradada CM (2015) Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, S pain. Paediatr Perinat Epidemiol 29:113–122.

  40. 40.

    Breathnach FM, Donnelly J, Cooley SM, Geary M, Malone FD (2013) Subclinical hypothyroidism as a risk factor for placental abruption: evidence from a low-risk primigravid population. Aust N Z J Obstet Gynaecol 53:553–560.

  41. 41.

    Dillon JC, Milliez J (2000) Reproductive failure in women living in iodine deficient areas of West Africa. BJOG 107:631–636

  42. 42.

    Ohara N, Tsujino T, Maruo T (2004) The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. J Obstet Gynaecol Can 26:982–990

  43. 43.

    Zhou SJ, Skeaff SA, Ryan P, Doyle LW, Anderson PJ, Kornman L, McPhee AJ, Yelland LN, Makrides M (2015) The effect of iodine supplementation in pregnancy on early childhood neurodevelopment and clinical outcomes: results of an aborted randomised placebo-controlled trial. Trials 16:563

  44. 44.

    König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB (2011) Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women–4. J Nutr 141:2049–2054

  45. 45.

    Ozdemir H, Akman I, Coskun S, Demirel U, Turan S, Bereket A, Bilgen H, Ozek E (2013) Maternal thyroid dysfunction and neonatal thyroid problems. Int J Endocrinol 2013:987843

  46. 46.

    Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, Thomas S, Thomas T, Winichagoon P, Srinivasan K, Zimmermann MB (2017) Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 5:853–863

  47. 47.

    Soldin OP, Tractenberg RE, Hollowell JG, Jonklaas J, Janicic N, Soldin SJ (2004) Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency. Thyroid 14:1084–1090

  48. 48.

    Khalil AB, Salih BT, Chinengo O, Bardies MRD, Turner A, Wareth LOA (2018) Trimester specific reference ranges for serum TSH and free T4 among United Arab Emirates pregnant women. Pract Lab Med 12.

  49. 49.

    Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S (2017) 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 27:315–389

  50. 50.

    Nazeri P, Zarghani NH, Mirmiran P, Hedayati M, Mehrabi Y, Azizi F (2016) Iodine status in pregnant women, lactating mothers, and newborns in an area with more than two decades of successful iodine nutrition. Biol Trace Elem Res 172:79–85

  51. 51.

    Delshad H, Amouzegar A, Mirmiran P, Mehran L, Azizi F (2012) Eighteen years of continuously sustained elimination of iodine deficiency in the Islamic Republic of Iran: the vitality of periodic monitoring. Thyroid 22:415–421

Download references


The authors wish to acknowledge Ms. Niloofar Shiva for critical editing of English grammar and syntax of the manuscript. The authors would also like to thank the laboratory staff of RIES for their cooperation and assistance.

Author information

Correspondence to Fahimeh Ramezani Tehrani.

Ethics declarations

The study was approved by the ethics committee of the Research Institute of Endocrine Sciences (RIES), approval no: IR.SBMU.ENDOCRINE.REC.1397.273.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nazarpour, S., Ramezani Tehrani, F., Amiri, M. et al. Maternal Urinary Iodine Concentration and Pregnancy Outcomes: Tehran Thyroid and Pregnancy Study. Biol Trace Elem Res 194, 348–359 (2020).

Download citation


  • Iodine deficiency
  • Pregnancy
  • Outcomes
  • Tehran Thyroid and Pregnancy Study
  • Subclinical hypothyroidism