Iodine lecture jan2014
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Transcript of Iodine lecture jan2014
Global Elimination of Iodine Deficiency
Progress, Experience & Evidence
Frits van der Haar Hubert Department of Global Health
January 2014
Goiter…
Goiter
1990
Present in 130 out of 198 countries (WHO reports)
And Cretinism
Bolivia TanzaniaPakistan
World Summit for Children sets the Goal
1990: A Starting Point
Scientific Underpinning
Nico Bleichrodt et al, in: The Damaged Brain of Iodine Deficiency, 1994
A B C
-1
-0.5
0
Effect Size of Iodine Interventions on IQ performance, 37 Studies in China, 1984 - 1993:
Case-control studies with 12,291 children
St
Dev
IQ
Po
ints
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
From Goiter & Cretinism, focus
shifted tothe brain
Science discovered the real issue
Iodine ThyroidHormone
Thyroid Gland Physiology
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
The active thyroid hormone at the nuclear receptor is T3
T4 is converted to T3 by deiodinase enzymes active in the blood circulation and in the tissue cells
In the blood stream, T4 and T3 are carried by binding proteins
In the thyroid gland, iodide uptake and thyroid hormone production is regulated by TSH (thyrotropin) from the pituitary gland
T4 is the precursor hormone
The blood and the tissues have inner and outer ring deiodinase enzymes
The activity of the deiodinase enzymes vary from tissue to tissue
rT3 is inactive
T3 is the active thyroid hormone at the nuclear receptor
T4
T3 rT3
Inner ring deiodinaseOuter ring deiodinase
0 1 2 3 4 5 6 7 8 Birth
Face
Eye
Corpus callosum
Subarachnoid pathways
Cerebral cortex
cochlea
Cerebellum
Dentate of hippocampus
Myelination
from motherfrom child
T4
Developing Brain needs normal levels of circulating T4
Experimental Findings
Lavado-Autric et al, J Clin Invest 2003
Without sufficient maternal T4 many newly formed neurons do not migrate to their normal destination
The DevelopingBrain
Critical phasesof brain
developmentare
affected
The networks of interconnection less dense
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
The Available Solution
Universal Salt Iodizationrecommended
1991 1992 1993 1994 1995 1996 1997 1998 1999 20000
10
20
30
40
50
60
70
80
90
100
Households Consuming Iodized Salt
Bangladesh Bolivia
Central African Rep. Chad
Chile China
Congo Dem. Rep. Ecuador
Ghana Guatemala
Indonesia Iran
Jordan Kazakhstan
Lao PDR Madagascar
Mexico Myanmar
Nicaragua Oman
Paraguay Syria
Togo Uzbekistan
Viet Nam Yemen
Year
Per
cen
t
Unicef data
E/S Africa
W/C Africa
M East/N Africa
S Asia
E Asia/Pacific
C/S America
E Europe/CIS/B
Other
0 10 20 30 40 50 60 70 80 90 100Percent
unknown
Year 2000: Household Salt Iodized
Unicef data
Changes in HH use of iodized salt, 2001-2006
Source: ChildInfo.org
E/S Africa
W/C Africa
M East/N Africa
S Asia
E Asia/Pacific
C/S America
E Europe/CIS/B
0 10 20 30 40 50 60 70 80 90
2006
2001
Global monitoring of household salt iodization shows continuous progress
in USI
Source: ChildInfo.org
2010:
±38 million newborns not yet protected
Source: ChildInfo.org
Keys to Success
Realizing the roles and
responsibilities of major participating
actors
• Salt is not produced or distributed by governments, agencies or health experts
• A regulation and standard are helpful in providing the legal framework
• Agencies and academic groups must be supportive
Studies of Iodine andIntellectual performance
Pertinent examples
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
Zimmermann et al, AJCN 2006
iodine placebo0
50
100
150
200Urinary iodine concentrations
µg
iod
ine
/Lit
er
iodine placebo0
20
40
60
80
100
120Serum thyroxine concentrations
Baseline
Follow-up
nm
ol/L
ite
rn.s.
P<0.0001
n.s.
P<0.01
Cognitive Achievement Albania
Raven's Matrices
Bead threading
Rapid target marking
Digit span forward
Digit span backward
Symbol search
Coding
Rapid object naming
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5Effect Size (Mean, 95% CI)
Correction of iodine deficiency in moderately deficient Albanian children was followed by improvements in 50% of cognitive and motor scores
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
Gordon et al, AJCN 2009
iodine placebo0
50
100
150
200
Urinary iodine concentrations
µg
iod
ine
/Lit
er
iodine placebo0
5
10
15
20
Serum thyroglobulin concentrations
Baseline
Follow-up
µg
Tg
/Lit
er
P<0.001P<0.001
P<0.001
P<0.001
P<0.001 P<0.001
Cognitive Achievement N Zealand
Picture Concepts
Matrix Reasoning
Symbol Search
Letter-number Sequencing
Overall Cognitive Score
-0.25 -0.15 -0.05 0.05 0.15 0.25 0.35Effect Size (SD Units)
Correction of iodine deficiency in mildly deficient NZ children was followed by improvements in overall cognitive performance based on four tests applied
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
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
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
Sub-optimum cognitive outcomes by maternal iodine status
(unadjusted)Urinary iodine-to-creatinine ratio p-value
<150µg/g ≥150µg/g IQ at age 8yVerbal 186/646 (29%) 61/312 (20%) 0.002Performance 184/646 (28%) 70/312 (22%) 0.05Total 177/646 (27%) 65/312 (21%) 0.03
Reading at age 9yWords read per minute 170/161 (28%) 62/293 (21%) 0.03Accuracy 178/612 (29%) 55/283 (19%) 0.001Comprehension 182/612 (30%) 62/293 (21%) 0.007Reading score 164/618 (27%) 54/293 (18%) 0.007Suboptimum = Scores in the bottom quartile
Bath et al. Lancet 2013
Risks of sub-optimum outcomes in the offspring according to maternal iodine
status
Bath et al. Lancet 2013
Unadjusted Adjusted OR (95% CI) p-value OR (95% CI) p-value
IQ at age 8yVerbal 1.66 (1.20-2.31) 0.002 1.58 (1.09-2.30) 0.02Performance 1.38 (1.00-1.89) 0.05 1.22 (0.86-1.72) 0.27Total 1.43 (1.04-1.98) 0.03 1.35 (0.93-1.94) 0.11
Reading at age 9yWords read per minute 1.44 (1.03-2.00) 0.03 1.20 (0.83-1.74) 0.33Accuracy 1.78 (1.26-2.50) 0.001 1.69 (1.15-2.49) 0.007Comprehension 1.58 (1.13-2.19) 0.007 1.54 (1.06-2.23) 0.02Reading score 1.60 (1.13-2.26) 0.008 1.47 (1.00-2.16) 0.05Suboptimum = Scores in the bottom quartile
Elimination of IDD through Salt Iodization
Progress made in CEE/CIS2000 - 2009
Food Nutr Bull Supplement Dec 2011
Sample of 20 Post-Soviet Countries
Balkan Area1. Albania2. Bosnia & Herzegovina3. Bulgaria4. Kosovo5. Macedonia6. Montenegro7. Romania8. Serbia
CIS Area9. Armenia10. Azerbaijan11. Belarus12. Georgia13. Kazakhstan14. Kyrgyz Republic15. Moldova16. Russian Federation17. Tajikistan18. Turkmenistan19. Ukraine20. Uzbekistan
Alb
ania
Arm
enia
Aze
rbai
jan
Bela
rus
Bosn
ia a
nd H
erze
govi
na
Bulg
aria
FRY
Mac
edon
ia
Geo
rgia
Kaza
khst
an
Koso
vo
Kyrg
yzst
an
Mol
dova
Mon
tene
gro
Rom
ania
Russ
ian
Fede
ratio
n
Serb
ia
Tajik
ista
n
Turk
ey
Turk
men
ista
n
Ukr
aine
Uzb
ekis
tan
0
20
40
60
80
100
Year 2000: Household use of adequately iodized salt (≥15ppm)
Perc
ent
Hou
seho
lds
90%
2000 2001 2002 2003 2004 2005 2006 2007 2008 20090%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Key National Benchmarks
Legislation/regulations enacted Household coverage ≥ 90% Population iodine nutrition optimal
Perc
ent C
ount
ries
Mon
tene
gro
Ukr
aine
Serb
ia
Russ
ian
Fede
rati
on
Bela
rus
Kyrg
yz R
epub
lic
Aze
rbai
jan
Uzb
ekis
tan
Tajik
ista
n
Mol
dova
Alb
ania
Turk
ey
Koso
vo
Rom
ania
Bosn
ia a
nd H
erze
govi
na
Turk
men
ista
n
Geo
rgia
Kaza
khst
an
Bulg
aria
FRY
Mac
edon
ia
Arm
enia
0
10
20
30
40
50
60
70
80
90
100
2009: CEE/CIS Household use of iodized salt
1-14 mg/kg≥ 15mg/kg
Perc
ent o
f hou
seho
lds
90%
± 2000 ± 20100%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
USI Attainment in South-East Europe and the Commonwealth of Independent States, 2000-2009
>9070-8950-6920-49<20
Prop
ortio
n of
cou
ntrie
s
Coverage
4 more countries attained USI
2 more are close to the goal
4 more have coverage of 50-69%
The number of countries with cover-age <50% fell by 8
BUL MAC ROM BiH ALB MON SER KOS2003 2004 2005 2006 2007 2009
0
50
100
150
200
250
300
350
TUR ARM GEO BEL MOL AZE KYR TAJ2004 2005 2006 2007
BUL MAC ROM ALB MON SER BiH KOS2001 2003 2004 2006 2007 2008 2009
0
50
100
150
200
250
300
UKR* KAZ* AZE KYR TAJ2002 2006 2007 2007
and in Pregnant Women
Urinary Iodine Concentrations in School-age Children
Balkan Area
Balkan Area
CIS Area
CIS Area
* Reproductive-age women
* No mandatory legislation in Russian Federation and Ukraine
Attainment by the end of the decade N
Regulation
All food-grade salt
Household salt only
Successful countries 9 9 0
Countries nearly successful 6 3 3
With continued deficiency 5* 0 3
Importance of Proper Strategy Focus
Importance of Proper Regulation: Fortificant type and Standards
Details of Regulations Date enacted Focus Fortificant Standard OutcomeRomania 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
Bosnia & Herz 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
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
Protect DevelopingBrains
Ensure optimumiodine nutrition before, during and after pregnancy
Use iodized household salt + use iodized salt in food products