IODINE

IODINE   

Iodine (I) is an essential element/component for hormonal production by the thyroid gland.[1], order [2]  Iodine deficiency (ID) can cause brain damage and can be prevented by adequate iodine status in pregnancy, health infancy and childhood.  WHO defines ID as population median urinary iodine excretion less than 100 mcg/L; mild=50-99 mcg/L, visit this site moderate=20-49 mcg/L and severe if <20 mcg/L.[3]

IODINE in Pregnancy

In pregnancy, iodine requirement is increased as T4 production is increased, urinary iodine loss is increased and the fetus needs iodine for thyroid function (after the onset of fetal thyroid function).[4],[5]  Thyroid hormones are required for neuronal migration in the first trimester, dependent on the maternal T4 supply to prevent irreversible brain damage.[6],[7]  In low iodine status, T4:T3 ratio lowers to spare one atom of iodine and hypothyroxinaemia/low T4 can develop.6  TSH is not increased because T3 levels remain normal but the amount of T4, available to the fetus, will be reduced.  Evidence reveals a relationship between maternal ID in pregnancy and impaired cognitive function in children.[8],9],[10],[11]  Less is known about the effects of mild-to-moderate ID during early pregnancy, though some evidence reveals increased risk on impaired cognitive development in the offspring.[12],[13],[14]

IODINE and Cognition in the Offspring

Evidence reveals an association between lower levels of free T4 (FT4) and lower intake of iodine affecting cognitive or psychomotor development in children.[15],[16],[17],[18]   However, great variation in methods, criteria, design, psychometric evaluation procedures, and exposure period affects the results of these studies which are therefore not conclusive.  Children of women who received iodine during pregnancy had higher psychomotor scores (p<0.02) in a region of mild ID in Spain.  There were differences between treated and comparison group, e.g. age of IQ testing.[19]  Iodized salt (IS), versus iodine supplements, was assessed during pregnancy in women with insufficient iodine intake (median UIC=145 mcg/L).[20]  No significant association with children’s neurological development (mental/psychomotor) and maternal consumption of IS (for at least one year prior to pregnancy) was found in any of the groups.

Bath et al[21] analyzed mother-child pairs from the ALSPAC cohort by measuring stored urine samples from 1040 pregnant women.  The samples were selected from the first trimester and iodine concentration was measured and offspring IQ was then measured at the age of eight years.  Assessment was made on the association between maternal iodine status and child IQ (8 years) and reading ability (9 years).  The group was classified as mildly-to-moderately deficient (median 91.1 mcg/L [IQR 53.8-143; iodine-to-creatine ratio 110 mcg/g, IQR 74-170]).  Findings revealed children born to women with an iodine-to-creatinine ratio <150 mcg/g (classified as “deficient”) were more likely to score in the lowest quartile for reading comprehension (OR 1.54 95% CI 1.06, 2.23), reading accuracy (OR 1.69 95% CI 1.15, 2.49), and verbal IQ (OR 1.58 95% CI 1.09, 2.30), than were those of mothers with ratios ?150 mcg/g (classified as “sufficient”).21

Scores for spelling and grammar as well as English literacy were poorer with children (9 years) born to mothers with low iodine status (<150 mcg/L) in Tasmania, Australia. [22]  According to Costeira et al[23] lower mental and psychomotor scores at 18 months and lower mental score at 24 months was associated with low iodine status (<50 mcg/L) in the first and third trimester.  According to Brucker-Davis et al[24] 2/3 of women showed mild first-trimerster ID.  Impact of bHCG (the main driver of maternal thyroid function in early pregnancy) contrasts the absence of correlation between UIE and thyroid tests at that stage of pregnancy and might be overriding the ID.

According to Bougma et al[25] ID is associated with mental development; “We believe that the best estimate to date of the effect size of iodine supplementation on mental development in children 5 years old and under is 0.49, which translates into 7.4 IQ points lost due to iodine deficiency”.  Gordon et al[26] suggests that mild ID could prevent children from attaining their full intellectual potential.  Iodine supplementation (150 mcg/d) improved perceptual reasoning in mildly iodine-deficient (median UIC=63 mcg/L) children when compared to placebo after 28 weeks, but no difference in number search or letter sequencing was observed.26

Visual problem solving, fine motor skills and information processing are improved by iodine supplementation according to Zimmermann et al[27].  Moderately iodine deficient (median UI 48 mcg/L) children in Albania (10-12 years old) received 400 mg iodized oil or placebo.  Iodine improved scores for rapid object naming, symbol search, rapid target marking and Raven´s Colored Progressive Matrices.  There was no difference observed in digit span, coding or bead threading.

THE IODINE Situation in the UK

UK is now classified as “mildly iodine deficient” [28] despite increased iodine intake (three-fold) between the 1950s and 1980s.[29]  Median iodine status of UK schoolgirls (14-15 years) was 80.1 mcg/L in a cross-section survey in 2009.[30]  NDNS Rolling-Programme results (years 1-3) reveal falling intake of iodine; mean intake for females (19-64 years) is 140 mcg/d vs. 161 mcg/d in the 2000/01 survey.[31]  Iodine intake in pregnancy in the UK and Ireland seems to be below recommended levels in about 40% cases (23%-55%).[32],[33],[34],[35]

HOW to improve Iodine Status in the UK?

Bath et al[36] suggest that pregnant women and women of childbearing age should be given advice on how to improve their iodine status as ID is common amongst pregnant women (median UIC=85.3 mcg/L) according to a cross-sectional study carried out at the Royal Surrey County Hospital in Guildford.  Only 16% of mothers are aware of the role of iodine in pregnancy and 66% had not received information on iodine.[37]  Midwives could inform pregnant women more on the importance of iodine, as 67% of them do not mention iodine.

In Australia[38], New Zealand38, United States[39] and Canada39, iodine (150 mcg/d) is recommended periconceptionally and in pregnancy/lactation.  Zimmermann et al[40] advocate a policy on iodine supplementation (»150 mcg/d), periconceptionally and in pregnancy/lactation.  Voluntary or mandatory salt iodisation has never been introduced in the UK[41], but could be worth considering (e.g. in bread) like in Australia and New Zealand[42], as dietary sources in UK are haphazard.

CONCLUSION

Negative effects on infant/child development and behavior caused by iodine deficiency could be prevented trough preemptive action.  Implementing active measures and balanced policy response of iodine supplementation periconceptionally and during pregnancy/lactation is needed.

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REFERENCES

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2 UNICEF. Sustaninable elimination of iodine deficiency. UNICEF, Now York 2008.

3 WHOUNICEF International Council for the Control of Iodine Deficiency Disorders. Assessment of iodine deficiency disorders and monitoring their elimination, 3rd edn. World Health Organization, Geveva, Switzerland 2007.

4 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.

5 Morreale de Escobar G, Obregón MJ, Escobar del Ray F. Iodine deficiency and brain development in the first half of pregnancy. Pub Health Nutr 2007;10(12A):1554-1570.

6 Morreale de Escobar G, Obregón MJ, Escobar del Rey F. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Cl En 2004;18(2):225-248.

7 Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18(3):404-433.8 Zimmermann MB. Iodine deficiency. Endocr Rev 2009;30(4):376-408.

9 Pharoah PO, Buttfield IH, Hetzel BS. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 1971;1(7694):308-10.

10 Pharoah POD, Connolly KJ.  A controlled trial of iodinated oil for the prevention of endemic cretinism: a long-term follow-up. Int J Epidemiol 1987;16(1):68-73.

11 Bleichrodt N, Born M. A metaanalysis of research on iodine and its relationshpip to cognitive development. The damaged brain of iodine deficiency. Stanbury JB ed. New York, Cognizant Communication; 1994.

12 Leung AM, Brent GA. Children of mothers with iodine deficiency during pregnancy are more likely to have lower verbal IQ and reading scores at 8-9 years of age. Evid Based Nurs Month 2013;0:0.

13 Delange F. Iodine deficiency as a cause of brain damage. Postrad Med J 2001,77:217-220.

14 Berbel P, Mestre JL, Santamaría 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.

15 Reuss ML, Paneth N, Pinto-Martin JA, Lorenz JM, Susser M. The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age. N Engl Med 1996;334:821-827.

16 Van den Briel T, West CE, Bleichrodt N, van de Vijver FJ, Ategbo EA, Haustvast JG. Improved iodine status is associated with improved mental performance of schoolchildren in Benin. Am J Clin Nutr 2000;72:1179-1185.

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19 Velasco I, Carreira M, Santiago P, Muela JA, García-Fuentes E, Sánchez-Munoz B, et al. Effect of Iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life. J Clin Endocriol Metab 2009;94(9):3234-3241.

20 Santiago P, Velasco I, Muela JA, Sánchez B, Martínes J, Rodriguez A, et al. Infant neurocognitive development is independent of the use of iodined salt or iodine supplements given during pregnancy. Brit J Nutr 2013;110(5):831-839.

21 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);331-337.

22 Hynes KL, Otahal P, Hay I, Burgess JR. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort. J Clin Endocrin Metab 2013;98(5):1954-1962.

23 Costeira MJ, Olivera P, Santos NS, Ares S, Sanez-Rico B, de Escobar GM, et al. Psychomotor development of children from an iodine-deficient region. J Pediatr 2011;159(3):447-453.

24 Brucker-Davis F, Ferrari P, Gal J, Berthier F, Fenichel P, Hieronimus S. Iodine status has no impact on thyroid function in early healthy pregnancy. J Thyroid Res 2012;ID 168764;1-6.

25 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;5:1384-1416.

26 Gordon RC, Rose MC, Skeaff SA, Gray AR, Morgan KM; Ruffman T. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr 2009;90(5):1264-71.

27 Zimmermann MB, Connolly K, Bozo M, Bridson J, Rohner F, Grimci L. Iodine supplementation improves cognition in iodine-decient schoolchildren in Albania: a randomized, controlled, double-blind study. Am J Clin Nutr 2006,83(1):108-14.

28 Anderson M, Karumbuathan V, Zimmermann MB. Global iodine status in 2011 and trends over the past decade1-3. J Nutr 2012;142.4:744-50.

29 Phillips DI. Iodine, milk, and the elimination of endemic goitre in Britain: the story of an accidental public health triumph. J Epidemiol Community Health 1997;51(4):391-393.

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32 Kibirige MS, Hutchison S, Owen CJ, Delves HT. Prevalence of maternal dietary iodine insufficiency in the north east of England: implications for the fetus. Arch Dis Child Fetal Neonatal 2004;89:F436-F439.

33 Barnett C, Visser T, Williams F, et al. Inadequate iodine intake of 40% of pregnant women from a region in Scotland. J Endocrionl Invest 2002;25(7):90-110.

34 Pearce EN; Sazarus JH, Smyth PP, et al. Perchlorate and thiocyanate exposure and thyriod function in first-trimester pregnant women J Clin Endocrinol Metab 2010;95:3207-3215.

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37 Williamson et al. Proc Nutr Soc 2012

38 NHMRC. Iodine Supplementation: public statement: iodine supplementation for pregnant and breastfeeding women. NHMRC;2010.

39 Becker DV, Braverman LE, Delange F, Dunn JT, Franklyn JA, Gollowell JG, et al. Iodine supplementation for pregnancy and lactation – United States and Canada: recommendations of the American Thyroid Association 2006;16(10):949-951.

40 Zimmermann M, Delange F. Iodine supplementation of pregnant women in Europe: a review and recommendations. Eur J Clin Nutr 2004;58:979-984.

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