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H. Delshad M.D Endocrinologist Research Institute For Endocrine Sciences What is Iodine ? ● Iodine is a chemical element (as are Oxygen,Hydrogen,Iron) ● Iodine is an essential trace element for the human ● Iodine is an essential part of the chemical structure of thyroid hormones Total quantity present in body is (15-20 mg) Mostly in thyroid gland Discovery of Iodine ● Bernard Courtois discovered Iodine in 1811 ● Like most other discoveries, the discovery of Iodine was a fortuitous accident. ● While most scientists discovered something when trying to help people to save their lives, Courtois discovered Iodine when 4 he was trying to kill people. TSH T3 T4 Iodine Thyroid Hormone Synthesis Iodine nutrition and thyroid function • Iodine is an essential component of thyroid hormone. • In turn, thyroid hormone is critical for neurological development both in utero and in early life. Thyroid hormone • Brain Maturation Stimulate: – Genes for myelin – Neurotrophins and their receptors – Cytoskletone components – Transcription factors – Matrix proteins – Adhesion molecules – Intracellular signaling molecules – Mitocondrail gens – Cerebellar gens Thyroid hormone • Mediates growth • • • • Body growth Cell differentiation Bone maturation Chondrocyte differentiation • Brown Fat Thermogenesis • Non shivering thermogenesis to keep desired body temperature Importance of iodine in brain development • 50,000 brain cells produced/second in developing fetal brain • 100 billion brain cells in adult • One million billion connections between these brain cells: Determine IQ Importance of iodine in brain development ● 90 % of human brain development occurs between 3rd month of pregnancy & 3rd year of life ● Maternal T4 essential for first 24 weeks ● Foetal T4 starts at 24 weeks Recommended daily intake of iodine Preschool children 90 g Schoolchildren (6-12 y) 120 g Adult (>12 y) 150 g Pregnant women & Lactating 250 g 12 Iodine Requirement (g/day) During pregnancy Basal 150 40-50 % increased T4 requirements 50-100 Transfer of T4 and I from mother to fetus 50 Increased renal clearance of I ? 250-300 During lactation Basal 150 0.5-1.1 L milk/day x 150-180 gI/L 225-350 Delange: Int.J. Endocrinol. Metab. 2: 1, 2004 75-200 Physiologic Changes in Thyroid Function During Pregnancy • Thyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesis • The test results that change in pregnancy are influenced by changes in TBG concentration • Plasma iodide levels decrease due to fetal iodide use and increased maternal clearance > leads to notable increase in gland size in 15% of women (without abnormal TFTs) The spectrum of IDD Fetus Abortions Stillbirths Congenital anomalies Increased perinatal mortality Neurologic creatinism Psychomotor defects Neonate Neonatal goiter Neonatal hypothyroidims Child & adolescent Goitrous juvenile hypothyroidism Impaired mental function Retarded physical development Adult Goiter with its complications Hypothyroidism Impaired mental function 16 • The adverse effects of iodine deficiency in populations (decreased IQ, goiter, hypothyroidism, and hyper-thyroidism) are easily corrected with salt iodisation. • Adequate iodine nutrition in the general population is shown by a median urinary iodine concentration for school-age children (aged 6–12 years) of 100–299 μg/L • Adequate iodine nutrition in pregnant women is shown by a median urinary iodine concentration between 150 and 499 μg/L Iodine nutrition and thyroid function • Mild –moderate iodine deficiency has reemerged in countries previously believed to be iodine sufficient. • Lately, there has been increasing concern that even mild-to-moderate iodine deficiency has adverse clinical outcomes. • Iodine nutrition during pregnancy has become an important public health concern Author Country pregnant women ( n) Median UIC µg/L % UIC < 150 µg/L ( IQR ) Katz PM 2013 Canada Toronto 142 221 ( 142 – 397 ) 29.6 Lindorfer H 2015 Austria Viena 246 87 86.2 Granfors M 2015 Sweden 459 98 ( 57 – 148) 100 Fuse Y 2011 Japan 934 219 16.1 Bath SC 2015 UK 230 56.8 98 Bath SC 2014 South East UK 100 85.3 86 Knight BA 2016 South West UK 308 88 ( 54.3 – 157.5) 73 Kirkegeard 2016 Denmark 240 Iodine user : 118 ( 79 – 196 ) Non-users: 82 ( 41 – 122) Author Country pregnant women ( n) Median UIC µg/L % UIC < 150 µg/L ( IQR ) Kasap B 2016 Turkey 135 222 ( 141 – 397 ) 28.1 Ferreiya SM 2014 Brazil 191 137.7 (132.9 – 155.9 ) 92 Bilek R 2016 Czech Republic 532 82 71.2 De Zoysa E 2016 Sri Lanka 425 105 (67 – 153) 98 Konrad I 2015 Latvia 696 69.4 (53.9 – 92.6 ) 100 Raverot V 2012 French Lyon 228 81 ( 8 – 832 ) 77 Choyy 2016 Korea 344 427.3 - • هدف :بر رس ی وضعيت دريافت يد و عملکرد غده تيروئيد زنان باردار کشور • روش کار :در طی يک بر رس ی مقطعی ملی تعداد 1200زن باردار در تريمستر های مختلف بارداری از 12استان کشور از آبان ماه تا بهمن ماه سال 1392وارد مطالعه شدند • شاخص ها :ميانه يد ادرار T4, T3RU, FT4I, TSH, تيروگلوبولين و آنتی تيروئيد پر اکسيداز سرم مورد اندازه گيری قرار گرفتند. Mean ±SD age of the cohort : 27 ± 7.2 years. Mean ±SD gestational age:20.7 ± 10.0 weeks. Min. نتايج کلی UIE (µg /L) ) ( میانه ید ادرار T4 (µg/dl) TSH mIU/L 20 4.92 0.01 : Max. Preliminary 400 Results 23.92 Mean Median 114 87.3 14.05 11.19 2.20 10.88 1.95 میانه ید ادرار کمتر از 100 میانه ید ادرار بين 100و 150 نتیجه گیری نتایج این مطالعه نشان داد که عليرغم دریافت ید کافی جامعه ایرانی جمعیت قابل توجه ای از زنان باردار ایرانی دچار کمبود متوسط ید بوده که نیاز به مکمل ید رسانی در این زمان دارند. Conclusion • Pregnant women living in mild-moderate iodine deficient areas are at particularly high risk of being iodine deficient. Clinical question Iodine supplementation in pregnancy- is it time? How big is the problem? • 32 countries ( 1/3 of the global population) still have inadequate iodine intake. • In Europe: ►21 countries are iodine deficient in pregnancy ►10 countries are iodine sufficient ►In 23 countries no data are available What is the evidence for benefit from iodine supplementation in pregnancy in mild-moderate iodine deficiency? • Avon Longitudinal Study of Parents and Children ( ALSPAC) study in UK • 1040 mother-child pairs • mild-to-moderate iodine deficiency (UIC < 150 µg/l ) in the first trimester of pregnancy : odds of offspring IQ being in the lowest quartile OR = 1.43; 95%CI 1.04-1.98; P=0.03 • Hynes et al. from Australia Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort. JCEM 2013 • Taylor et al. Impact of iodine supplementation in mild-tomoderate iodine deficiency: systematic review and meta-analysis. Eur J Endo. 2014 • These studies imply there are potentially substantial benefits from correcting/ preventing even mild iodine deficiency in pregnancy. Summary of relevant national and societal guidelines Guideline Guidance ATA Australian Department of Health ETA US Teratology Society Endocrine Society All women who are planning to be pregnant or are pregnant or breastfeeding should supplement their diet with a daily oral American Academy of Pediatrics Spanish Endocrine Society World Health Organization UK Department of Health British Thyroid Association supplement of 150 µg of iodine (Endocrine Society : 150 - 200µg ) Pregnant and lactating women should take a supplement containing adequate iodine to achieve a total of 250 µg iodine / day. No specific guidance on iodine intake Key message • It is probable that, in mild-moderate iodine deficient countries, iodine supplementation during pregnancy and lactation may have substantial obstetric and offspring benefits and is economically advantageous.