7. 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
10. 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
11. 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
12.
13. 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
16. 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
18. 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
19. 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
20. 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
21. Global monitoring of household salt iodization
shows continuous progress in USI
Source: ChildInfo.org
23. 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
26. 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
27. 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
28. 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
29. 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
30. 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
31. 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
32. 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
33. 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
34. Elimination of IDD through Salt
Iodization
Progress made in CEE/CIS
2000 - 2009
Food Nutr Bull Supplement Dec 2011
35. 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
40. 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
41. 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
42. 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
43. 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
44. 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
45. 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
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.
