Associations between thyroid dysfunction and developmental status in children with excessive iodine status

Inger Aakre, Tor A Strand, Khalil Moubarek, Ingrid Barikmo, Sigrun Henjum, Inger Aakre, Tor A Strand, Khalil Moubarek, Ingrid Barikmo, Sigrun Henjum

Abstract

Background and objective: Adequate iodine status and normal thyroid hormone synthesis are important for optimal child development. In this study, we explored whether young children's developmental status is associated with thyroid dysfunction in an area of chronic excessive iodine exposure.

Methods: We included 298 children between 18 and 48 months of age residing in Algerian refugee camps. Early child development was measured using the Ages and Stages Questionnaires, third edition (ASQ-3), consisting of five domains: Communication, Gross Motor, Fine Motor, Problem Solving and Personal-Social. Due to poor discriminatory ability in the Gross Motor domain, the total ASQ-3 scores were calculated both including and excluding this domain. Urinary iodine concentration (UIC), thyroid hormones (TSH, FT3 and FT4), thyroid antibodies and serum thyroglobulin (Tg) were measured.

Results: The median UIC was 451.6 μg/L, and approximately 72% of the children had a UIC above 300 μg/L. Furthermore, 14% had thyroid disturbances, of whom 10% had TSH outside the reference range. Children with thyroid disturbances and TSH outside the reference ranges had lower odds of being among the 66% highest total ASQ scores, with adjusted odds ratios (95% CI) of 0.46 (0.23, 0.93) and 0.42 (0.19, 0.94), respectively.

Conclusion: We found an association between thyroid dysfunction and poorer developmental status among children with excessive iodine intake. The high iodine intake may have caused the thyroid dysfunction and hence the delayed developmental status; however, other influential factors cannot be excluded. Optimal child development is important for a sustainable future. With iodine excess being an increasing problem globally, this subject should be further explored.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart for selection of Saharawi…
Fig 1. Flowchart for selection of Saharawi children from 2010 baseline study and 2013 follow-up study.
*low age, high age, deaf, and mute.

References

    1. WHO. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination. A guide for programme managers. World Health Organisation, International Council for Control of Iodine Deficiency Disorders, United Nations Children’s Fund; 2007.
    1. Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008;372(9645):1251–62. doi:
    1. Zimmermann BM. The role of iodine in human growth and development. Semin Cell Dev Biol. 2011;22:645–52. doi:
    1. Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72(4):267–84. doi:
    1. Zimmermann MB. Iodine deficiency. Endocr Rev. 2009;30(4):376–408. doi:
    1. Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014;10(3):136–42. doi:
    1. Burgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab. 2010;24(1):107–15. doi:
    1. Vanderpas J. Nutritional epidemiology and thyroid hormone metabolism. Annu Rev Nutr. 2006;26:293–322. doi:
    1. IGN. The Iodine Global Network: 2015 Annual Report. Zurich, Switzerland: IGN; 2016.
    1. Zimmermann BM. Iodine Deficiency and Excess in Children: Worldwide status in 2013. Endocr Pract. 2013;11:1–27.
    1. Zimmermann MB, Andersson M. Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev. 2012;70(10):553–70. doi:
    1. Gizak M, Gorstein J, Andersson M. Epidemiology of Iodine Deficiency In: Pearce EN, editor. Iodine Deficiency Disorders and Their Elimination. Cham: Springer International Publishing; 2017. p. 29–43.
    1. Thaker V, Leung A, Braverman L, Brown R, Levine B. Iodine-induced hypothyroidism in full-term infants with congenital heart disease: more common than currently appreciated? J Clin Endocr Metab. 2014;99(10):3521–6. doi:
    1. Connelly KJ, Boston BA, Pearce EN, Sesser D, Snyder D, Braverman LE, et al. Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion. J Pediatr. 2012;161(4):760–2.
    1. Theodoropoulos T, Braverman LE, Vagenakis AG. Iodide-induced hypothyroidism: a potential hazard during perinatal life. Science. 1979;205(4405):502–3.
    1. Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. 2013;382(9889):331–7. doi:
    1. Walker SP, Wachs TD, Grantham-McGregor S, Black MM, Nelson CA, Huffman SL, et al. Inequality in early childhood: risk and protective factors for early child development. Lancet. 2011;378(9799):1325–38. doi:
    1. Liu H-L, Lam LT, Zeng Q, Han S-q, Fu G, Hou C-c. Effects of drinking water with high iodine concentration on the intelligence of children in Tianjin, China. J Public Health. 2009;31(1):32–8.
    1. Gao T-S, Teng W-P, Shan Z-Y, Jin Y, Guan H-X, Teng X-C, et al. Effect of different iodine intake on schoolchildren's thyroid diseases and intelligence in rural areas. Chin Med J. 2004;117(10):1518–22.
    1. Aakre I, Strand TA, Bjøro T, Norheim I, Barikmo I, Ares S, et al. Thyroid Function among Breastfed Children with Chronically Excessive Iodine Intakes. Nutrients. 2016;8(7):398.
    1. Aakre I, Bjøro T, Norheim I, Strand TA, Barikmo I, Henjum S. Excessive iodine intake and thyroid dysfunction among lactating Saharawi women. J Trace Elem Med Biol. 2015;31:279–84. doi:
    1. Barikmo I, Henjum S, Dahl L, Oshaug A, Torheim LE. Environmental implication of iodine in water; milk and other foods used in Saharawi refugees camps in Tindouf; Algeria. J Food Comp Anal. 2011.
    1. Henjum S, Barikmo I, Gjerlaug AK, Mohamed-Lehabib A, Oshaug A, Strand TA, et al. Endemic goitre and excessive iodine in urine and drinking water among Saharawi refugee childrren. Public Health Nutr. 2010;13(9):1472–7. doi:
    1. Squires J, Twombly E, Bricker D, Potter L. ASQ-3 User's guide. Baltimore: Paul H Brookers Publishing Co; 2009.
    1. WHO. Process of translation and adaption of instruments: WHO; [.
    1. WHO. Global Database on Body Mass Index. BMI classification.: WHO; 10.01.2011 [.
    1. WHO. WHO Child Growth Standards. Length/height-for age, weight-for -age, weight-for-length, weight-for-height and body mass index-for-age. Methods and Development. 2006.
    1. WHO. WHO Anthro (version 3.2.2, January 2011) and macros 2011 [.
    1. Hosmer DW, Lemenshow S, Sturdivant RX. Applied Logistic Regression. Third Edition ed. Hoboken, New Jersey: Wiley; 2013.
    1. Aakre I, Bjøro T, Norheim I, Strand TA, Barikmo I, Henjum S. Development of thyroid dysfunction among women with excessive iodine intake–A 3-year follow-up. J Trace Elem Med Biol. 2015;31:61–6. doi:
    1. Walker SP, Wachs TD, Meeks Gardner J, Lozoff B, Wasserman GA, Pollitt E, et al. Child development: risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9556):145–57. doi:
    1. Black MM, Walker SP, Fernald LC, Andersen CT, DiGirolamo AM, Lu C, et al. Early childhood development coming of age: science through the life course. Lancet. 2017;389(10064):77–90. doi:
    1. Lu C, Black MM, Richter LM. Risk of poor development in young children in low-income and middle-income countries: an estimation and analysis at the global, regional, and country level. Lancet Glob Health. 2016;4(12):e916–e22. doi:
    1. Piek JP, Barrett NC, Smith LM, Rigoli D, Gasson N. Do motor skills in infancy and early childhood predict anxious and depressive symptomatology at school age? Hum Mov Sci. 2010;29(5):777–86. doi:
    1. Piek JP, Dawson L, Smith LM, Gasson N. The role of early fine and gross motor development on later motor and cognitive ability. Hum Mov Sci. 2008;27(5):668–81. doi:
    1. Freire C, Ramos R, Amaya E, Fernández MF, Santiago-Fernández P, Lopez-Espinosa M-J, et al. Newborn TSH concentration and its association with cognitive development in healthy boys. Eur J Endocrinol. 2010;163(6):901–9. doi:
    1. Perez-lobato R, Ramos R, Arrebola JP, Calvente I, Ocon-Hernandez O, Dávila-Arias C, et al. Thyroid status and its association with cognitive functioning in healthy boys at 10 years of age. Eur J Endocrinol. 2014;172(2):129–39. doi:
    1. Belcari F, Placidi G, Guzzetta A, Tonacchera M, Ciampi M, Bartoli A, et al. Thyroid-stimulating hormone levels in the first days of life and perinatal factors associated with sub-optimal neuromotor outcome in pre-term infants. J Endocrinol Invest. 2011;34(10):e308–e13. doi:
    1. Zimmermann MB, Connolly K, Bozo M, Bridson J, Rohner F, Grimci L. Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. Am J Clin Nutr. 2006;83(1):108–14.
    1. Calzà 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. doi:
    1. Brown JL, Pollitt E. Malnutrition, poverty and intellectual development. Sci Am. 1996;274(2):38–43.
    1. Strupp BJ, Levitsky DA. Enduring Cognitive Effects of Early Malnutrition: A Theoretical Reappraisal. J Nutr. 1995;125(8):2221S.
    1. 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;5(4):1384–416. doi:
    1. Roze E, Meijer L, Bakker A, Van Braeckel KN, Sauer PJ, Bos AF. Prenatal exposure to organohalogens, including brominated flame retardants, influences motor, cognitive, and behavioral performance at school age. Environ Health Perspect. 2009;117(12):1953–8. doi:
    1. Trumpff C, De Schepper J, Vanderfaeillie J, Vercruysse N, Van Oyen H, Moreno-Reyes R, et al. Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age. Arch Dis Child. 2016;101(12):1100–6. doi:
    1. Pearce EN, Lazarus JH, Moreno-Reyes R, Zimmermann MB. Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr. 2016;104(Supplement 3):918S–23S.
    1. Sun X, Shan Z, Teng W. Effects of increased iodine intake on thyroid disorders. Endocrinol Metab. 2014;29(3):240–7.
    1. Velasco I, Carreira M, Santiago P, Muela JA, García-Fuentes E, Sanchez-Munoz B, et al. Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life. J Clin Endocrinol Metab. 2009;94(9):3234–41. doi:
    1. Berbel P, Mestre JL, Santamaria A, Palazón I, Franco A, Graells M, et al. Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation. Thyroid. 2009;19(5):511–9. doi:
    1. Costeira MJ, Oliveira P, Santos NC, Ares S, Saenz-Rico B, de Escobar GM, et al. Psychomotor development of children from an iodine-deficient region. J Pediatr. 2011;159(3):447–53. doi:
    1. Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian A, Schmidt HG, Visser TJ, et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab. 2010;95(9):4227–34. doi:
    1. Li Y, Shan Z, Teng W, Yu X, Li Y, Fan C, et al. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months. Clin Endocrinol (Oxf). 2010;72(6):825–9.
    1. Päkkilä F, Männistö T, Hartikainen A-L, Ruokonen A, Surcel H-M, Bloigu A, et al. Maternal and child's thyroid function and child's intellect and scholastic performance. Thyroid. 2015;25(12):1363–74. doi:
    1. Kempers M, Van der Sluijs Veer L, Nijhuis-Van der Sanden M, Kooistra L, Wiedijk B, Faber I, et al. Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening. J Clin Endocrinol Metab. 2006;91(2):418–24. doi:
    1. Oerbeck B, Sundet K, Kase BF, Heyerdahl S. Congenital hypothyroidism: influence of disease severity and L-thyroxine treatment on intellectual, motor, and school-associated outcomes in young adults. Pediatrics. 2003;112(4):923–30.
    1. Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493–501. doi:
    1. Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. N Engl J Med. 2017;376(9):815–25. doi:
    1. Zoeller R, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol. 2004;16(10):809–18. doi:
    1. Charafeddine L, Sinno D, Ammous F, Yassin W, Al-Shaar L, Mikati MA. Ages and Stages Questionnaires: Adaptation to an Arabic speaking population and cultural sensitivity. Eur J Paediatr Neurol. 2013;17(5):471–8. doi:
    1. Kvestad I, Taneja S, Kumar T, Bhandari N, Strand TA, Hysing M. The assessment of developmental status using the Ages and Stages questionnaire-3 in nutritional research in north Indian young children. Nutr J. 2013;12(1):50.
    1. Kvestad I, Taneja S, Kumar T, Hysing M, Refsum H, Yajnik CS, et al. Vitamin B12 and folic acid improve gross motor and problem-solving skills in young north Indian children: A randomized placebo-controlled trial. Plos one. 2015;10(6):e0129915 doi:
    1. Kvestad I, Hysing M, Shrestha M, Ulak M, Thorne-Lyman AL, Henjum S, et al. Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children. Am J Clin Nutr. 2017:ajcn144931.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir