Iodine Deficiency and Human Development


Iodine is а vital microelements that are essential for the normal human development and functions. Iodine deficiency is a global problem: about 2 billion individuals worldwide suffer from a lack of iodine. Despite goiter is the most visually noticeable manifestation of iodine deficiency, the most significant consequence of the iodine deficiency is impaired neurodevelopment, particularly early in life. Moreover, moderate to severe iodine deficiency increases the risk of spontaneous abortion, low birth weight and infant mortality. Babies in utero affected by iodine deficiency are at increased risk of mental developmental disorders, cretinism is their extreme degree. In addition, moderate to severe iodine deficiency in childhood negatively affects somatic growth. Iodine deficiency compensation improves cognitive and motor function in children. Iodine prophylaxis of deficient populations is an extremely effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.

Endocrinology Research Centre, Moscow

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  • Hetzel BS. Iodine deficiency disorders (IDD) and their eradication. Lancet. 1983;2:1126-1129.
  • Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008;372:1251-1262.
  • Andersson M, de Benoist B, Rogers L. Epidemiology of iodine deficiency: salt iodisation and iodine status. Best Pract Res Clin Endocrinol Metab. 2010;24(1):1-11.
  • de Benoist B, McLean E, Andersson M, Rogers L. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. 2008;29:195-202.
  • Дефицит йода - угроза здоровью и развитию детей России. Пути решения проблемы. Национальный доклад. М., 2006.
  • Абдулхабирова ФМ. Профилактика йододефицитных заболеваний у детей. Педиатрия. 2010;4.
  • World Health Organization UNCsF, International Council for Control of Iodine Deficiency Disorders. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. Geneva: World Health Organization; 2007.
  • Alexander W, Harden R, Harrison M, Shimmins J. Some aspects of the absorption and concentration of iodide by the alimentary tract in man. Proc Nutr Soc. 1967;26:62-66.
  • Nath SK, Moinier B, Thuillier F et al. Urinary excretion of iodide and fluoride from supplemented food grade salt. Int J Vitam Nutr Res. 1992;62:66-72.
  • Fisher DA, Oddie TH. Thyroid iodine content and turnover in euthyroid subjects - validity of estimation of thyroid iodine accumulation from short-term clearance studies. J Clin Endocr Metab. 1969;29:721-727.
  • Degroot LJ. Kinetic analysis of iodine metabolism. J Clin Endocr Metab. 1966;26:149-173.
  • Stanbury JB. The adaptation of man to iodine deficiency. Cambridge, MA: Harvard University Press; 1954. p. 1-209.
  • Delange F. Iodine deficiency. In: Braverman L, Utiger R, eds. Werner and Ingbar’s the thyroid: a fundamental and clinical text. Philadelphia: JD Lippincott; 2000. p. 295-316.
  • Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18:404-433.
  • Bernal J. Thyroid hormones and brain development. Vitam Horm. 2005;71:95-122.
  • Flamant F, Samarut J. Thyroid hormone receptors: lessons from knockout and knock-in mutant mice. Trends Endocrin Met. 2003;14:85-90.
  • Davis PJ, Davis FB, Cody V. Membrane receptors mediating thyroid hormone action. Trends Endocrin Met. 2005;16:429-435.
  • Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol. 2004;16:809-818.
  • Benowitz LI, Routtenberg A. GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 1997; 20:84-91.
  • Huang KP, Huang FL, Jager T et al. Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J Neurosci. 2004;24:10660-10669.
  • Silva AJ, Paylor R, Wehner JM, Tonegawa S. Impaired spatial-learning in alpha-calcium-calmodulin kinase-II mutant mice. Science. 1992;257:206-211.
  • Gong J, Dong J, Wang Y et al. Developmental iodine deficiency and hypothyroidism impair neural development, up-regulate caveolin-1 and down-regulate synaptophysin in rat hippocampus. J Neuroendocrinol. 2010;22:129-139.
  • de Escobar GM, Obregon MJ, del Rey FE. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab. 2004;18:225-248.
  • Bernal J, Pekonen F. Ontogenesis of the nuclear 3,5,3-triiodothyronine receptor in the human fetal brain. Endocrinology. 1984;114:677-679.
  • Jensovsky J, Ruzicka E, Spackova N, Hejdukova B. Changes of event related potential and cognitive processes in patients with subclinical hypothyroidism after thyroxine treatment. Endocr Regul. 2002;36:115-122.
  • Desouza LA, Ladiwala U, Daniel SM et al. Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci. 2005;29:414-426.
  • Hetzel BS. Iodine and neuropsychological development. J Nutr. 2000;130(February(2S Suppl.)):493S-495S.
  • Vulsma T, Gons MH, Devijlder JJM. Maternal fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. New Engl J Med. 1989;321:13-16.
  • McCarrison R. Observations on endemic cretinism in the Chitral and Gilgit valleys. Lancet. 1908;2:1275-1280.
  • Chen ZP, Hetzel BS. Cretinism revisited. Best Pract Res Clin Endocrinol Metab. 2010;24:39-50.
  • Pharoah PO, Buttfield IH, Hetzel BS. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet. 1971;1:308-310.
  • Pharoah PO, Connolly KJ. A controlled trial of iodinated oil for the prevention of endemic cretinism: a long-term follow-up. Int J Epidemiol. 1987;16:68-73.
  • Pharoah PO, Connolly KJ. Effects of maternal iodine supplementation during pregnancy. Arch Dis Child. 1991;66:145-147.
  • Pharoah P, Buttfield IH, Hetzel BS. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Int J Epidemiol. 2012 Jun;41(3):589-592.
  • Thilly CH, Delange F, Lagasse R et al. Fetal hypothyroidism and maternal thyroid status in severe endemic goiter. J Clin Endocrinol Metab. 1978;47:354-360.
  • Moreno-Reyes R, Hindlet JY, Bourdoux P, Vanderpas JB. Maternal, fetal and juvenile hypothyroidism, birthweight and infant mortality in the etiopathogenesis of the IDD spectrum in Zaire and Malawi. In: Stanbury JB, editor. The damaged brain of iodine deficiency cognitive, behavioral, neuromotor, educative aspects. New York: Cognizant Communication Corporation; 1994. p. VII,335 S.
  • Cao XY, Jiang XM, Dou ZH et al. Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. N Engl J Med. 1994;331:1739-1744.
  • O’Donnell KJ, Rakeman MA, Zhi-Hong D et al. Effects of iodine supplementation during pregnancy on child growth and development at school age. Dev Med Child Neurol. 2002;44:76-81.
  • Murcia M, Rebagliato M, Iniguez C et al. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age. Am J Epidemiol. 2011 Apr 1;173(7):804-812.
  • Haddow JE, Palomaki GE, Allan WC et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549-555.
  • Pop VJ, Kuijpens JL, van Baar AL et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol. 1999;50:149-155.
  • Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr. 2009;89:668S-672S.
  • Chaouki ML, Benmiloud M. Prevention of iodine deficiency disorders by oral administration of lipiodol during pregnancy. Eur J Endocrinol. 1994;130:547-551.
  • Alvarez-Pedrerol M, Guxens M, Mendez M et al. Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their offspring. Eur J Endocrinol. 2009;160(3):423-429.
  • Das SC, Mohammed AZ, Al-Hassan S et al. Effect of environmental iodine deficiency (EID) on foetal growth in Nigeria. Indian J Med Res. 2006;124(5):535-544.
  • Mason JB, Deitchler M, Gilman A et al. Iodine fortification is related to increased weight-for-age and birthweight in children in Asia. Food Nutr Bull. 2002;23(3):292-308.
  • DeLong GR, Leslie PW, Wang SH et al. Effect on infant mortality of iodination of irrigation water in a severely iodine-deficient area of China. Lancet. 1997;350:771-773.
  • Thilly CH, Delange F, Lagasse R et al. Fetal hypothyroidism and maternal thyroid status in severe endemic goiter. J Clin Endocrinol Metab. 1978;47:354-360.
  • Cobra C, Muhilal, Rusmil K et al. Infant survival is improved by oral iodine supplementation. J Nutr. 1997;127:574-578.
  • Semba RD, de Pee S, Hess SY et al. Child malnutrition and mortality among families not utilizing adequately iodized salt in Indonesia. Am J Clin Nutr. 2008;87:438-444.
  • Azizi F, Kalani H, Kimiagar M et al. Physical, neuromotor and intellectual impairment in non-cretinous schoolchildren with iodine deficiency. Int J Vitam Nutr Res. 1995;65:199-205.
  • Boyages SC, Collins JK, Maberly GF et al. Iodine deficiency impairs intellectual and neuromotor development in apparently normal persons. A study of rural inhabitants of north-central China. Med J Aust. 1989;150:676-682.
  • Choudhury N, Gorman KS. Subclinical prenatal iodine deficiency negatively affects infant development in Northern China. J Nutr. 2003;133:3162-3165.
  • Fenzi GF, Giusti LF, Aghini-Lombardi F et al. Neuropsychological assessment in schoolchildren from an area of moderate iodine deficiency. J Endocrinol Invest. 1990;13:427-431.
  • Gao TS, Teng WP, Shan ZY et al. Effect of different iodine intake on schoolchildren’s thyroid diseases and intelligence in rural areas. Chin Med J (Engl). 2004;117:1518-1522.
  • Huda SN, Grantham-McGregor SM, Rahman KM, Tomkins A. Biochemical hypothyroidism secondary to iodine deficiency is associated with poor school achievement and cognition in Bangladeshi children. J Nutr. 1999;129:980-997.
  • Ojule AC, Osotimehin BO. The influence of iodine deficiency on the cognitive performance of school children in Saki, south-west Nigeria. Afr J Med Sci. 1998;27:95-99.
  • Vermiglio F, Sidoti M, Finocchiaro MD et al. Defective neuromotor and cognitive-ability in iodine-deficient schoolchildren of an endemic goiter region in Sicily. J Clin Endocr Metab. 1990;70:379-384.
  • Santiago-Fernandez P, Torres-Barahona R, Muela-Martinez JA et al. Intelligence quotient and iodine intake: a cross-sectional study in children. J Clin Endocrinol Metab. 2004;89: 3851-3857.
  • Vermiglio F, Lo Presti VP, Moleti M et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab. 2004;89:6054-6060.
  • Sameroff AJ, Seifer R, Baldwin A, Baldwin C. Stability of intelligence from preschool to adolescence - the influence of social and family risk-factors. Child Dev. 1993;64:80-97.
  • Щеплягина ЛА. Препараты йода в укреплении здоровья детей. Consilium Medicum. Педиатрия. 2010;12(1).
  • Bautista A, Barker PA, Dunn JT et al. The effects of oral iodized oil on intelligence, thyroid status, and somatic growth in school-age children from an area of endemic goiter. Am J Clin Nutr. 1982;35:127-134.
  • Huda SN, Grantham-McGregor SM, Tomkins A. Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol). J Nutr. 2001;131:72-77.
  • Isa ZM, Alias IZ, Kadir KA, Ali O. Effect of iodized oil supplementation on thyroid hormone levels and mental performance among Orang Asli schoolchildren and pregnant mothers in an endemic goitre area in Peninsular Malaysia. Asia Pac J Clin Nutr. 2000;9:274-281.
  • Shrestha R. Effect of iodine and iron supplementation on physical, psychomotor and mental development in primary school children in Malawi [doctoral thesis]. Wageningen: Wageningen Agricultural University; 1994.
  • Taylor PN, Okosieme OE, Dayan CM, Lazarus JH. Impact of iodine supplementation in mild-to-moderate iodine deficiency: Systematic review and meta-analysis. Eur J Endocrinol. 2013 Nov 22;170(1):R1-R15.
  • Bougma K, Aboud FE, Harding KB, Marquis GS. Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis. Nutrients. 2013 Apr 22;5(4):1384-1416.
  • Zimmermann MB, Connolly K, Bozo M et al. Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. Am J Clin Nutr. 2006;83:108-114.
  • Gordon RC, Rose MC, Skeaff SA et al. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr. 2009;90:1264-1271.
  • Calza L, Fernandez M, Giardino L. Cellular approaches to central nervous system remyelination stimulation: thyroid hormone to promote myelin repair via endogenous stem and precursor cells. J Mol Endocrinol. 2010;44(1):13-23.
  • Dussault JH, Ruel J. Thyroid hormones and brain development. Annu Rev Physiol. 1987;49:321-324.
  • Isaacs E, Oates J. Nutrition and cognition: assessing cognitive abilities in children and young people. Eur J Nutr. 2008;47:4-24.
  • Bleichrodt N, Born MP. A metaanalysis of research on iodine and its relationship to cognitive development. In: Stanbury FA, editor. The damaged brain of iodine deficiency cognitive, behavioral, neuromotor, educative aspects. New York [etc.]: Cognizant Communication Corporation; 1994. p. VII, 335 S.
  • Qian M, Wang D, Watkins WE et al. The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China. Asia Pac J Clin Nutr. 2005;14:32-42.
  • Koutras DA, Christakis G, Trichopoulos D et al. Endemic goiter in Greece: nutritional status, growth, and skeletal development of goitrous and non goitrous populations. Am J Clin Nutr. 1973;26:1360-1368.
  • Bautista A, Barker PA, Dunn JT, Sanchez M. Lack of correlation between thyroid size and body growth in an area of endemic goiter. Am J Clin Nutr. 1977;30:275-279.
  • Ali O, Tan TT, Sakinah O, Khalid BA et al. Thyroid function and pubertal development in malnutrition. Ann Acad Med Singapore. 1994;23:852-825.
  • Lal RB, Srivastava VK, Chandra R. A study of spectrum of iodine deficiency disorders in rural area of Uttar Pradesh. Indian J Publ Health. 1996;40:10-12.
  • Thurlow RA, Winichagoon P, Pongcharoen T et al. Risk of zinc, iodine and other micronutrient deficiencies among school children in North East Thailand. Eur J Clin Nutr. 2006;60:623-632.
  • Ren Q, Gr D, Cao X et al. Effect of environmental supplementation of iodine on infant mortality and growth in children in Xinjiang, China. Zhonghua Liu Xing Bing Xue Za Zhi. 2002;23:198-202.
  • Moreno-Reyes R, Mathieu F, Boelaert M et al. Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy. Am J Clin Nutr. 2003;78: 137-144.
  • Rivera JA, Gonzalez-Cossio T, Flores M et al. Multiple micronutrient supplementation increases the growth of Mexican infants. Am J Clin Nutr. 2001;74:657-663.
  • van Stuijvenberg ME, Kvalsvig JD, Faber M et al. Effect of iron-, iodine-, and beta-carotene-fortified biscuits on the micronutrient status of primary school children: a randomized controlled trial. Am J Clin Nutr. 1999;69:497-503.
  • Shapiro LE, Samuels HH, Yaffe BM. Thyroid and glucocorticoid hormones synergistically control growth-hormone messenger-Rna in cultured Gh1 cells. Proc Natl Acad Sci USA. 1978;75:45-49.
  • Robson H, Siebler T, Shalet SM, Williams GR. Interactions between GH, IGF-I, glucocorticoids, and thyroid hormones during skeletal growth. Pediatr Res. 2002;52:137-147.
  • Shields BM, Knight BA, Hill A et al. Fetal thyroid hormone level at birth is associated with fetal growth. J Clin Endocrinol Metab. 2011;96(6):E934-938.
  • Ceda GP, Fielder PJ, Donovan SM et al. Regulation of insulin-like growth factor-binding protein expression by thyroid-hormone in rat Gh3 pituitary-tumor cells. Endocrinology. 1992;130:1483- 1489.
  • Ezzat S, Laks D, Oster J, Melmed S. Growth-hormone regulation in primary fetal and neonatal rat pituitary cell-cultures - the role of thyroid-hormone. Endocrinology. 1991;128:937-943.
  • Samuels MH, Wierman ME, Wang C, Ridgway EC. The effect of altered thyroid status on pituitary-hormone messenger ribonucleic-acid concentrations in the rat. Endocrinology. 1989;124: 2277-2282.
  • Crew MD, Spindler SR. Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem. 1986;261:5018- 5022.
  • Hochberg Z, Bick T, Harel Z. Alterations of human growth-hormone binding by rat-liver membranes during hypothyroidism and hyperthyroidism. Endocrinology. 1990;126:325-329.
  • Nilsson A, Ohlsson C, Isaksson OGP et al. Hormonal regulation of longitudinal bone-growth. Eur J Clin Nutr. 1994;48:S150-160.
  • Hernandez-Cassis C, Cure-Cure C, Lopez-Jaramillo P. Effect of thyroid replacement therapy on the stature of Colombian children with minimal thyroid dysfunction. Eur J Clin Invest. 1995;25:454- 456.
  • Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3-34.
  • Sjogren K, Jansson JO, Isaksson OG, Ohlsson C. A model for tissue-specific inducible insulin-like growth factor-I (IGF-I) inactivation to determine the physiological role of liver-derived IGF-I. Endocrine. 2002;19:249-256.
  • Ferry RJ, Cerri RW, Cohen P. Insulin-like growth factor binding proteins: new proteins, new functions. Horm Res. 1999;51:53-67.
  • Miell JP, Taylor AM, Zini M et al. Effects of hypothyroidism and hyperthyroidism on insulin-like growth-factors (IGFs) and growth hormone-binding and IGF-binding proteins. J Clin Endocr Metab. 1993;76:950-955.
  • Iglesias P, Bayon C, Mendez J et al. Serum insulin-like growth factor type 1, insulin-like growth factor-binding protein-1, and insulin-like growth factor-binding protein-3 concentrations in patients with thyroid dysfunction. Thyroid. 2001;11:1043-1048.
  • Wan Nazaimoon WM, Osman A, Wu LL, Khalid BA. Effects of iodine deficiency on insulin-like growth factor-I, insulin-like growth factor-binding protein-3 levels and height attainment in malnourished children. Clin Endocrinol (Oxf). 1996;45:79-83.
  • Aydin K, Bideci A, Kendirci M et al. Insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels of children living in an iodine- and selenium-deficient endemic goiter area. Biol Trace Elem Res. 2002;90:25-30.
  • Alikasifoglu A, Ozon A, Yordam N. Serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels in severe iodine deficiency. Turk J Pediatr. 2002;44:215-218.
  • Zimmermann MB, Jooste PL, Mabapa NS et al. Treatment of iodine deficiency in school-age children increases insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations and improves somatic growth. J Clin Endocrinol Metab. 2007;92:437-442.

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