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Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
Iodine lecture jan2014
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Iodine lecture jan2014

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  • The “inside-out” gradient of the cortex is established by newly formed neurons migrating farther as development proceeds: later-born neurons migrate past early-born neurons to form six layers – a process known as lamination. After formation at the basal lamina (BL), newly formed neurons migrate along scaffolds established by radial glia (RG), which extend through the successive layers through to layer I on top. Specialized neurons in layer I produce and secrete reelin, a protein involved in terminating the migration of new neurons as they climb the scaffold and reach their normal destination.In the developing cortex, thyroid hormone is also needed for normal neuronal migration. In rats born to dams with moderately low thyroid hormone, many neurons do not migrate to their normal destination, providing an explanation for the reduced cognition observed in individuals living in iodine deficient areas. Moreover, the action of thyroid hormone in this migration occurs during early fetal development. This type of “damage of iodine deficiency” is structural and cannot be reversed by correcting iodine deficiency later in life.
  • Time gap between enactment of legislation and achievement of universal coverage/optimum iodine nutrition is approx. 4-5 years.
  • Transcript

    • 1. Global Elimination of Iodine Deficiency Progress, Experience & Evidence Frits van der Haar Hubert Department of Global Health January 2014
    • 2. Goiter… Present in 130 out of 198 countries (WHO reports)
    • 3. And Cretinism Bolivia Pakistan Tanzania
    • 4. 1990: A Starting Point World Summit for Children sets the Goal
    • 5. Scientific Underpinning Nico Bleichrodt et al, in: The Damaged Brain of Iodine Deficiency, 1994
    • 6. Effect Size of Iodine Interventions on IQ performance, 37 Studies in China, 1984 - 1993: Case-control studies with 12,291 children 0 St Dev IQ Points A B C -0.5 -1 Group A: ID areas, no iodine intervention Group B: ID areas, uncontrolled iodized salt Group C: ID areas, iodine supplements @ pregnancy or birth Ming Qian et al, Asia-Pacific J Clin Nutr 2005
    • 7. From Goiter & Cretinism, focus shifted to the brain Science discovered the real issue
    • 8. Thyroid Gland Physiology Iodine Thyroid Hormone
    • 9. In the thyroid gland, iodide uptake and thyroid hormone production is regulated by TSH (thyrotropin) from the pituitary gland Iodide is an essential ingredient for the thyroid gland to make thyroid hormone The thyroid gland secretes two types of thyroid hormone into the blood: T4 and T3 In the blood stream, T4 and T3 are carried by binding proteins T4 is converted to T3 by deiodinase enzymes active in the blood circulation and in the tissue cells The active thyroid hormone at the nuclear receptor is T3
    • 10. T4 T4 is the precursor hormone The blood and the tissues have inner and outer ring deiodinase enzymes T3 rT3 The activity of the deiodinase enzymes vary from tissue to tissue rT3 is inactive T3 is the active thyroid hormone at the nuclear receptor Inner ring deiodinase Outer ring deiodinase
    • 11. Developing Brain needs normal levels of circulating T4 T4 from child from mother cochlea Myelination Cerebral cortex Subarachnoid pathways Corpus callosum Cerebellum Eye Dentate of hippocampus Face 0 1 2 3 4 5 6 7 8 Birth
    • 12. Experimental Findings Without sufficient maternal T4 many newly formed neurons do not migrate to their normal destination Lavado-Autric et al, J Clin Invest 2003
    • 13. The Developing Brain Critical phases of brain development are affected The networks of interconnection less dense
    • 14. Problem Statement  There is widespread iodine deficiency of the common diet • One-half to two-thirds of the world population at risk  In affected populations, goiter and cretinism in a few co-exist with cognitive deficits in all • In populations where >5% of schoolchildren have goiter, cognitive performance in apparently healthy individuals is diminished by approx. 10-15 IQ points
    • 15. The Available Solution Universal Salt Iodization recommended
    • 16. Households Consuming Iodized Salt Bangladesh Percent 100 Bolivia Central African Rep. 90 Chad Chile 80 China Congo Dem. Rep. 70 Ecuador Ghana Guatemala 60 Indonesia Iran 50 Jordan Kazakhstan 40 Lao PDR Madagascar 30 Mexico Myanmar Nicaragua 20 Oman Paraguay 10 Syria Togo 0 1991 Unicef data 1992 1993 1994 1995 1996 1997 1998 1999 Year 2000 Uzbekistan Viet Nam Yemen
    • 17. Year 2000: Household Salt Iodized Percent 0 10 20 E/S Africa W/C Africa M East/N Africa S Asia E Asia/Pacific C/S America E Europe/CIS/B Unicef data Other unknown 30 40 50 60 70 80 90 100
    • 18. Changes in HH use of iodized salt, 2001-2006 0 20 40 60 80 100 E/S Africa W/C Africa M East/N Africa 2001 S Asia 2006 E Asia/Pacific C/S America E Europe/CIS/B Source: ChildInfo.org
    • 19. Global monitoring of household salt iodization shows continuous progress in USI Source: ChildInfo.org
    • 20. 2010: ±38 million newborns not yet protected Source: ChildInfo.org
    • 21. Keys to Success • Salt is not produced or Realizing the distributed by roles and governments, agencies or responsibilities health experts of major • A regulation and standard are helpful in providing the participating legal framework actors • Agencies and academic groups must be supportive
    • 22. Studies of Iodine and Intellectual performance Pertinent examples
    • 23. Cognitive Achievement Albania • • • • Moderate iodine deficiency, 87% goiter 310 school children, 10-12y, 24 weeks, random allocation One oral dose containing 400mg iodine (iodized oil) or placebo Cognitive tests at baseline and follow-up Urinary iodine concentrations 200 Serum thyroxine concentrations 120 P<0.0001 P<0.01 150 100 n.s. 50 nmol/Liter µg iodine/Liter 100 n.s. 80 Baseline 60 Follow-up 40 20 0 0 iodine Zimmermann et al, AJCN 2006 placebo iodine placebo
    • 24. Cognitive Achievement Albania Effect Size (Mean, 95% CI) -2 0 2 4 6 8 Raven's Matrices Bead threading Rapid target marking Digit span forward Digit span backward Symbol search Coding Rapid object naming Correction of iodine deficiency in moderately deficient Albanian children was followed by improvements in 50% of cognitive and motor scores
    • 25. Cognitive Achievement N Zealand • • • • Mild iodine deficiency 184 school children, 10-13y, 28 weeks, random allocation Daily tablets containing either 150µg iodine (KIO3) or placebo Cognitive tests at baseline and follow-up Urinary iodine concentrations Serum thyroglobulin concentrations 200 20 P<0.001 P<0.001 P<0.001 15 100 P<0.001 µg Tg/Liter µg iodine/Liter 150 Baseline 10 50 5 0 Follow-up 0 iodine Gordon et al, AJCN 2009 placebo P<0.001 iodine placebo P<0.001
    • 26. Cognitive Achievement N Zealand Effect Size (SD Units) -0.25 0 0.25 0.5 0.75 Picture Concepts Matrix Reasoning Symbol Search Letter-number Sequencing Overall Cognitive Score Correction of iodine deficiency in mildly deficient NZ children was followed by improvements in overall cognitive performance based on four tests applied
    • 27. School Attainment Tanzania Severely affected districts in Tanzania that benefitted of mass oral iodized oil capsule distributions during 1986 - 1992 Assey et al, Public Health Nutrition 2007
    • 28. School Attainment Tanzania • Tanzania Household Budget Survey, 2000 • Schooling accomplishments of 10-13y old children • 22,178 households, 25.1% in beneficiary districts • Analysis adjusted for household wealth, age of school enrolment, distance to school, etc • Separate analyses by gender The children born to mothers who were supplemented had accomplished 0.36-0.51 more years of education than their siblings from other districts and than younger and older children from their own districts Field at al, Am Econ J Appl Econ 2009
    • 29. Child Cognition, United Kingdom • A longitudinal observational study in Avon, UK • Enrolled 14,541 Pregnant Women in their 1st trimester during 04/1991 to 12/1992 • Selection of 1,040 singleton women who had volunteered a urine sample • Offspring had cognitive tests at age 8 and 9 • Classified the maternal iodine status by urinary iodine measurement Bath et al. Lancet 2013
    • 30. Sub-optimum cognitive outcomes by maternal iodine status (unadjusted) Urinary iodine-to-creatinine ratio <150µg/g ≥150µg/g IQ at age 8y Verbal Performance Total Reading at age 9y Words read per minute Accuracy Comprehension Reading score p-value 186/646 (29%) 184/646 (28%) 177/646 (27%) 61/312 (20%) 70/312 (22%) 65/312 (21%) 0.002 0.05 0.03 170/161 (28%) 178/612 (29%) 182/612 (30%) 164/618 (27%) 62/293 (21%) 55/283 (19%) 62/293 (21%) 54/293 (18%) 0.03 0.001 0.007 0.007 Suboptimum = Scores in the bottom quartile Bath et al. Lancet 2013
    • 31. Risks of sub-optimum outcomes in the offspring according to maternal iodine status Unadjusted OR (95% CI) p-value Adjusted OR (95% CI) p-value 1.66 (1.20-2.31) 0.002 1.38 (1.00-1.89) 0.05 1.43 (1.04-1.98) 0.03 1.58 (1.09-2.30) 0.02 1.22 (0.86-1.72) 0.27 1.35 (0.93-1.94) 0.11 1.44 (1.03-2.00) 1.78 (1.26-2.50) 1.58 (1.13-2.19) 1.60 (1.13-2.26) 1.20 (0.83-1.74) 1.69 (1.15-2.49) 1.54 (1.06-2.23) 1.47 (1.00-2.16) IQ at age 8y Verbal Performance Total Reading at age 9y Words read per minute Accuracy Comprehension Reading score Suboptimum = Scores in the bottom quartile Bath et al. Lancet 2013 0.03 0.001 0.007 0.008 0.33 0.007 0.02 0.05
    • 32. Elimination of IDD through Salt Iodization Progress made in CEE/CIS 2000 - 2009 Food Nutr Bull Supplement Dec 2011
    • 33. Sample of 20 Post-Soviet Countries Balkan Area CIS Area 1. 2. 3. 4. 5. 6. 7. 8. 9. Armenia 10. Azerbaijan 11. Belarus 12. Georgia 13. Kazakhstan 14. Kyrgyz Republic 15. Moldova 16. Russian Federation 17. Tajikistan 18. Turkmenistan 19. Ukraine 20. Uzbekistan Albania Bosnia & Herzegovina Bulgaria Kosovo Macedonia Montenegro Romania Serbia
    • 34. Uzbekistan Ukraine Turkmenistan Turkey Tajikistan Serbia Russian Federation Romania Montenegro Moldova Kyrgyzstan Kosovo Kazakhstan Georgia FRY Macedonia Bulgaria Bosnia and Herzegovina Belarus Azerbaijan Armenia Albania Percent Households Year 2000: Household use of adequately iodized salt (≥15ppm) 100 90% 80 60 40 20 0
    • 35. Key National Benchmarks 100% 90% 80% Percent Countries 70% 60% 50% 40% 30% 20% 10% 0% 2000 2001 2002 Legislation/regulations enacted 2003 2004 2005 Household coverage ≥ 90% 2006 2007 2008 2009 Population iodine nutrition optimal
    • 36. Armenia FRY Macedonia Bulgaria Kazakhstan Georgia Turkmenistan Bosnia and Herzegovina Romania Kosovo Turkey Albania Moldova Tajikistan Uzbekistan Azerbaijan Kyrgyz Republic Belarus Russian Federation Serbia Ukraine Montenegro Percent of households 2009: CEE/CIS Household use of iodized salt 100 90 90% 80 70 60 50 1-14 mg/kg 40 ≥ 15mg/kg 30 20 10 0
    • 37. USI Attainment in South-East Europe and the Commonwealth of Independent States, 2000-2009 100% 4 more countries attained USI 90% Proportion of countries 80% 2 more are close to the goal 70% Coverage >90 70-89 50-69 20-49 <20 4 more have coverage of 50-69% 60% 50% 40% The number of countries with coverage <50% fell by 8 30% 20% 10% 0% ± 2000 ± 2010
    • 38. 350 Urinary Iodine Concentrations in School-age Children Balkan Area CIS Area 300 250 200 150 100 50 0 BUL 300 MAC ROM BiH ALB MON SER KOS TUR ARM GEO BEL MOL AZE and in Pregnant Women Balkan Area KYR TAJ CIS Area 250 200 150 100 50 0 BUL MAC ROM ALB MON SER BiH KOS UKR* KAZ* * Reproductive-age women AZE KYR TAJ
    • 39. Importance of Proper Strategy Focus Regulation Attainment by the end of the decade N Successful countries All food-grade salt Household salt only 9 9 0 Countries nearly successful 6 3 3 With continued deficiency 5* 0 3 * No mandatory legislation in Russian Federation and Ukraine
    • 40. Importance of Proper Regulation: Fortificant type and Standards Details of Regulations Date enacted Focus Fortificant Standard Outcome Romania 1993 HH salt only KI and KIO3 15 to 25 Near success Serbia 1993 True USI KI and KIO3 12 to 18 Near success Montenegro 2002 True USI KI and KIO3 12 to 18 Near success Bulgaria 2001 True USI Only KIO3 17 to 33 Successful Kosovo 2007 True USI Only KIO3 18 to 23 Successful 2001, 2005 True USI KI and KIO3 20 to 30 Successful Macedonia 1999 True USI Only KIO3 20 to 30 Successful Albania 2008 True USI Only KIO3 25 Too early to say Bosnia & Herz
    • 41. Lessons for Policy & Program Management • • • • • • • • • Joint, positive advocacy by stakeholders is essential Legislation/regulation alone is not sufficient Address all edible (food grade) salt supplies, and Set proper, adequate iodization standards Participate in oversight for managing of progress Develop systemic capacity in small salt factories Promote public acceptance of the strategy Prepare for opposing opinions or negative publicity Monitor both iodine exposures & iodine outcomes
    • 42. Protect Developing Brains Ensure optimum iodine nutrition before, during and after pregnancy Use iodized household salt + use iodized salt in food products

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