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