Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial

Nicole J E Verhagen, Sueppong Gowachirapant, Pattanee Winichagoon, Maria Andersson, Alida Melse-Boonstra, Michael B Zimmermann, Nicole J E Verhagen, Sueppong Gowachirapant, Pattanee Winichagoon, Maria Andersson, Alida Melse-Boonstra, Michael B Zimmermann

Abstract

Background: Iodine deficiency during pregnancy may be associated with lower offspring IQ, but there are few data on the safety and efficacy of maternal iodine supplementation on child development. In a previously reported multi-center randomized trial conducted in Thailand and India, we assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on offspring development. In this secondary analysis of that trial, we report data only from the Thai pregnant women in the study, who were more iodine deficient at entry. Methods: Pregnant women in Bangkok, Thailand, were randomized to receive daily 200 μg oral iodine or placebo until delivery. We assessed thyroid size and thyroid function during pregnancy and cognitive and motor development at ages 1, 2, and 5.7 years. The trial was registered at www.clinicaltrials.gov/NCT00791466. Findings: Women (n = 514) entered the trial between November 2008 and March 2011 at a mean ± SD gestational age of 11 ± 2.8 weeks; their median (IQR) UIC was 112 (75, 170) μg/L. Mean compliance with supplementation was 88%. We assessed 397 mothers in the 3rd trimester, 231 infants at age 2 y, and 157 children at mean age 5.7 y. During pregnancy, there was a slightly greater decrease in free and total thyroxine concentrations in the iodine group (p < 0.05). At age 2 years, the iodine group had borderline lower scores for combined fine and gross motor function (p = 0.05), but there were no other significant differences in development. At 5.7 years, there were no significant group differences in child development. Conclusion: Daily iodine supplementation in mildly iodine deficient pregnant women was associated with small negative effects on maternal thyroxine concentrations, but did not affect child development. The safety and efficacy of iodine supplementation in mildly-iodine deficient pregnant women needs to be evaluated further in large randomized controlled trials.

Keywords: brain development; children; cognition; infants; iodine deficiency; pregnancy; supplementation; thyroid.

Copyright © 2020 Verhagen, Gowachirapant, Winichagoon, Andersson, Melse-Boonstra and Zimmermann.

Figures

Figure 1
Figure 1
Study overview.

References

    1. Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. (2015) 3:286–95. 10.1016/S2213-8587(14)70225-6
    1. Zimmermann MB. The effects of iodine deficiency in pregnancy and infancy. Paediatr Perinat Epidemiol. (2012) 26(Suppl. 1):108–17. 10.1111/j.1365-3016.2012.01275.x
    1. Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol. (2004) 16:809–18. 10.1111/j.1365-2826.2004.01243.x
    1. World Health Organization United Nations Children's Fund International Council for Control of Iodine Deficiency Disorders Assessment of Iodine Deficiency Disorders and Monitoring their Elimination. A Guide for Programme Managers. Geneva: WHO; (2007).
    1. Dineva M, Fishpool H, Rayman MP, Mendis J, Bath SC. Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women. Am J Clin Nutr. (2020) 11:389–412. 10.1093/ajcn/nqaa071
    1. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. . Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. (2017) 27:315–89. 10.1089/thy.2016.0457
    1. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. (2014) 3:76–94. 10.1159/000362597
    1. Lee SY, Pearce EN. Iodine intake in pregnancy–even a little excess is too much. Nat Rev Endocrinol. (2015) 11:260–1. 10.1038/nrendo.2015.28
    1. Shi X, Han C, Li C, Mao J, Wang W, Xie X, et al. . Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China. J Clin Endocrinol Metab. (2015) 100:1630–8. 10.1210/jc.2014-3704
    1. Murcia M, Rebagliato M, Iniguez C, Lopez-Espinosa MJ, Estarlich M, Plaza B, et al. . Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 year of age. Am J Epidemiol. (2011) 173:804–12. 10.1093/aje/kwq424
    1. Rebagliato M, Murcia M, Alvarez-Pedrerol M, Espada M, Fernandez-Somoano A, Lertxundi N, et al. . Iodine supplementation during pregnancy and infant neuropsychological development: INMA mother and child cohort study. Am J Epidemiol. (2013) 177:944–53. 10.1093/aje/kws333
    1. Markhus M, Dahl L, Moe V, Abel M, Brantsæter A, Øyen J, et al. . Maternal iodine status is associated with offspring language skills in infancy and toddlerhood. Nutrients. (2018) 10:1270. 10.3390/nu10091270
    1. Gowachirapant S, Jaiswal N, Melse-Boonstra A, Galetti V, Stinca S, Mackenzie I, et al. . Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. (2017) 5:853–63. 10.1016/S2213-8587(17)30332-7
    1. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. . Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. (2011) 21:1081–125. 10.1089/thy.2011.0087
    1. Mandel SJ, Spencer CA, Hollowell JG. Are detection and treatment of thyroid insufficiency in pregnancy feasible? Thyroid. (2005) 15:44–53. 10.1089/thy.2005.15.44
    1. R Core Team R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; (2019).
    1. Zimmermann MB, Gizak M, Abbott K, Andersson M, Lazarus JH. Iodine deficiency in pregnant women in Europe. Lancet Diabetes Endocrinol. (2015) 3:672–3. 10.1016/S2213-8587(15)00263-6
    1. Gowachirapant S, Ruencharoen S, Techasaensiri B, Wecharak P, Winichagoon P. Iodine supplementation in mildly iodine-deficient Thai pregnant women had no beneficial effect on offspring development. J Nutr Assoc Thailand. (2018) 53:28–41. Available online at:
    1. Brucker-Davis F, Ganier-Chauliac F, Gal J, Panaïa-Ferrari P, Pacini P, Fénichel P, et al. . Neurotoxicant exposure during pregnancy is a confounder for assessment of iodine supplementation on neurodevelopment outcome. Neurotoxicol Teratol. (2015) 51:45–51. 10.1016/j.ntt.2015.07.009
    1. Romano R, Jannini EA, Pepe M, Grimaldi A, Olivieri M, Spennati P, et al. . The effects of iodoprophylaxis on thyroid size during pregnancy. Am J Obstet Gynecol. (1991) 164:482–5. 10.1016/S0002-9378(11)80004-9
    1. Censi S, Watutantrige-Fernando S, Groccia G, Manso J, Plebani M, Faggian D, et al. The effects of iodine supplementation in pregnancy on iodine status, thyroglobulin levels and thyroid function parameters: results from a randomized controlled clinical trial in a mild-to-moderate iodine deficiency area. Nutrients. (2019) 11:2639 10.3390/nu11112639
    1. Pedersen KM, Laurberg P, Iversen E, Knudsen PR, Gregersen HE, Rasmussen OS, et al. . Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation. J Clin Endocrinol Metab. (1993) 77:1078–83. 10.1210/jcem.77.4.8408456
    1. Nøhr SB, Jørgensen A, Pedersen KM, Laurberg P. Postpartum thyroid dysfunction in pregnant thyroid peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine supplementation safe? J Clin Endocrinol Metab. (2000) 85:3191–8. 10.1210/jcem.85.9.6799
    1. Brucker-Davis F, Panaïa-Ferrari P, Gal J, Fénichel P, Hiéronimus S. Iodine supplementation throughout pregnancy does not prevent the drop in FT4 in the second and third trimesters in women with normal initial thyroid function. Eur Thyroid J. (2013) 2:187–94. 10.1159/000350882
    1. Liesenkötter KP, Göpel W, Bogner U, Stach B, Grüters A. Earliest prevention of endemic goiter by iodine supplementation during pregnancy. Eur J Endocrinol. (1996) 134:443–8. 10.1530/eje.0.1340443
    1. Silva JE, Silva S. Interrelationships among serum thyroxine, triiodothyronine, reverse triiodothyronine, and thyroid-stimulating hormone in iodine-deficient pregnant women and their offspring: effects of iodine supplementation. J Clin Endocrinol Metab. (1981) 52:671–7. 10.1210/jcem-52-4-671
    1. Eriksen KG, Andersson M, Hunziker S, Zimmermann MB, Moore SE. Effects of an iodine-containing prenatal multiple micronutrient on maternal and infant iodine status and thyroid function: a randomised trial in The Gambia. Thyroid. (2020) 30:1355–65. 10.1089/thy.2019.0789
    1. Santiago P, Velasco I, Muela JA, Sánchez B, Martínez J, Rodriguez A, et al. Infant neurocognitive development is independent of the use of iodised salt or iodine supplements given during pregnancy. Br J Nutr. (2013) 110:831–9. 10.1017/S0007114512005880
    1. Antonangeli L, Maccherini D, Cavaliere R, Di Giulio C, Reinhardt B, Pinchera A, et al. . Comparison of two different doses of iodide in the prevention of gestational goiter in marginal iodine deficiency: a longitudinal study. Eur J Endocrinol. (2002) 147:29–34. 10.1530/eje.0.1470029
    1. Velasco I, Carreira M, Santiago P, Muela JA, García-Fuentes E, Sánchez-Muñoz 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) 94:3234–41. 10.1210/jc.2008-2652
    1. Moleti M, Di Bella B, Giorgianni G, Mancuso A, De Vivo A, Alibrandi A, et al. . Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study. Clin Endocrinol. (2011) 74:762–8. 10.1111/j.1365-2265.2011.04007.x
    1. Marco A, Vicente A, Castro E, Eva Perez C, Rodríguez O, Merchan MA, et al. . Patterns of iodine intake and urinary iodine concentrations during pregnancy and blood thyroid-stimulating hormone concentrations in the newborn progeny. Thyroid. (2010) 20:1295–9. 10.1089/thy.2010.0046
    1. Menéndez Torre E, Delgado Alvarez E, Rabal Artal A, Suárez Gutiérrez L, Rodríguez Caballero MG, Ares Blanco J, et al. . Iodine nutrition in pregnant women from Oviedo area. Is iodine supplementation necessary? Endocrinol y Nutr. (2014) 61:404–9. 10.1016/j.endoen.2014.07.004
    1. Katko M, Gazso AA, Hircsu I, Bhattoa HP, Molnar Z, Kovacs B, et al. . Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply. Matern Child Nutr. (2017) 14:e12470. 10.1111/mcn.12470
    1. Manousou S, Andersson M, Eggertsen R, Hunziker S, Hulthén L, Nyström HF. Iodine deficiency in pregnant women in Sweden: a national cross-sectional study. Eur J Nutr. (2019) 59:2535–45. 10.1007/s00394-019-02102-5
    1. Rebagliato M, Murcia M, Espada M, Álvarez-Pedrerol M, Bolúmar F, Vioque J, et al. . Iodine intake and maternal thyroid function during pregnancy. Epidemiology. (2010) 21:62–9. 10.1097/EDE.0b013e3181c1592b
    1. Abel MH, Korevaar TIM, Erlund I, Villanger GD, Caspersen IH, Arohonka P, et al. . Iodine Intake is associated with thyroid function in mild to moderately iodine deficient pregnant women. Thyroid. (2018) 28:1359–71. 10.1089/thy.2018.0305
    1. Murcia M, Espada M, Julvez J, Llop S, Lopez-Espinosa MJ, Vioque J, et al. . Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA mother and child cohort study. J Epidemiol Community Health. (2018) 72:216–22. 10.1136/jech-2017-209830
    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) 161:760–2. 10.1016/j.jpeds.2012.05.057
    1. Theodoropoulos T, Braverman LE, Vagenakis AG. Iodide-induced hypothyroidism: a potential hazard during perinatal life. Science. (1979) 205:502–3. 10.1126/science.451615
    1. de Vasconcellos TJ, Collett-Solberg PF. Perinatal goiter with increased iodine uptake and hypothyroidism due to excess maternal iodine ingestion. Horm Res. (2009) 72:344–7. 10.1159/000249162
    1. WHO Secretariat. Andersson M, de Benoist B, Delange F, Zupan J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the technical consultation. Public Health Nutr. (2007) 10:1606–11. 10.1017/S1368980007361004

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe