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International Council for Control of Iodine Deficiency Disorders, Women’s and Children’s Hospital, North Adelaide 5006, Australia
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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KEY WORDS: • iodine deficiency • cretinism • goiter • fetus • human brain development
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). |
Iodine deficiency as a cause of fetal brain damage |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). In general, cretinism is associated with
higher rates of goiter (~30%) in a population (Pharoah et al. 1980
). A decline in the prevalence of goiter and cretinism was
noted by the Sardinia Commission in 1848. A further decline was
apparent in the first half of the twentieth century in Switzerland in
Cantons in which iodized salt had not been introduced and in Northern
Italy. These observations raised doubt as to whether iodine deficiency
was a significant causative factor in cretinism.
The demonstration of the prevention of cretinism in a double-blind
controlled trail with iodized oil in Papua New Guinea established the
causal role of iodine deficiency in cretinism by an effect on the
developing fetus (Pharoah et al. 1971
). Cretinism could
not be prevented unless the iodized oil was given before pregnancy,
i.e., an injection during pregnancy was ineffective. The apparent
spontaneous disappearance of cretinism in Europe was attributed to an
increase in iodine intake (in the absence of iodized salt) arising from
dietary diversification with increasing use of iodine supplements as
noted in Switzerland in the 1920s (Bürgi et al. 1990
).
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Mechanism of the effect of iodine deficiency on fetal brain development |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). At that time, maternal hypothyroidism seemed an unlikely cause because no such syndrome as cretinism had been noted in children born to hypothyroid mothers; infants suffering from congenital hypothyroidism do not show the features of deaf mutism or neuromuscular defect seen in the common form of cretinism. This made elemental iodine deficiency an attractive hypothesis.
To investigate these various possibilities, an animal model was
developed in sheep because of the access provided for both maternal and
fetal thyroidectomy and previous experience with trace element
deficiencies. Subsequently, a similar model was developed in the
primate marmoset monkey (Callithrix jacchus jacchus) and in
rats (Hetzel and Mano 1989
).
Significant effects of iodine deficiency in slowing fetal brain
development have been shown in all three species. In sheep and
marmosets, there was reduction of brain weight and brain DNA, with
histologic changes characterized by delayed maturation of the
cerebellum and greater neurone density in the cerebral hemispheres
(motor and visual areas). The effect was significant in the sheep from
70 d gestation, which suggests an effect on neuroblast
multiplication that is known to occur at 40–80 d gestation
(Hetzel and Mano 1989
). These findings indicated an
effect that could be significant in the pathogenesis of cretinism in
humans.
Analysis of the mechanism involved in the sheep has shown a significant
effect of maternal thyroidectomy (carried out 6 wk before pregnancy) on
the brain at midgestation. There was also an effect at the end of
gestation after fetal thyroidectomy at both 60 and 98 d, with a
more severe effect after the earlier fetal thyroidectomy. The most
striking effect has occurred after the double procedure. It was
similar, but more severe than that observed in iodine deficiency
associated with a greater reduction in maternal and fetal thyroid
hormone levels than in iodine deficiency (Hetzel and Mano 1989
).
It was concluded that both maternal and fetal thyroid hormones were
involved in the effect of iodine deficiency on the fetal brain. This is
now supported by evidence of placental transfer of maternal T4 in rats
followed more recently by evidence in humans (Hetzel and Mano 1989
).
There has been no support for the role of elemental iodine deficiency from the animal models. The effect of iodine deficiency in early gestation now appears to be due to maternal hypothyroidism with reduced T4 transfer across the placental barrier. However, an additional direct effect of iodine itself cannot be excluded from the existing data.
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Quantitative estimates of the effect of iodine deficiency on brain function at the population level |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). At
all ages, the most common IDD is goiter, but the most important effect
is on neuropsychological development. The adoption of the term IDD
effectively reconceptualized the problem of iodine deficiency from
goiter to one of impaired brain development and brain damage.
The major features of the IDD at the different stages of life are
varying effects on brain function, which are characteristic of the
effect of any environmental stimulus on a population. These states of
altered brain function arise from fetal damage or hypothyroidism at
various stages of life, i.e., fetus, neonate, juvenile and adult
(Delange 1994
).
There is much anecdotal evidence coming from long-standing
observations in Europe supported by recent reports from China and
India, indicating that iodine-deficient village populations suffer
from general lethargy, poor work performance and defective school
performance in children. These effects are due to hypothyroidism,
particularly cerebral hypothyroidism. Beneficial effects of iodization
programs on this general lethargy (even the village dogs) have also
been described (Hetzel 1989
).
More quantitative data that indicate the effect of iodine deficiency on
the brain function of a population are required. Various approaches
have already been made which could be developed further (Hetzel et al. 1990
, Hetzel 1994
).
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Cognitive development in iodine-deficient populations |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). These studies revealed that
the mean scores for the iodine and noniodine deficient groups were 13.5
IQ points apart. These data further indicate the major population
dimension of the effect of iodine deficiency on neuropsychological
development. |
Bridging the knowledge application gap: development of a global program for the elimination of brain damage due to iodine deficiency |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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). In 1985, a report on the prevention and control of IDD
was made at the request of the United Nations system. The occurrence of
a broad spectrum of IDD with >400 million people at risk in Asia as
well as millions in Africa and South America was noted. Evidence was
available from controlled trials and successful iodization programs
that these disorders could be prevented successfully. But there was
also evidence of a breakdown of the iodization program.
Although the basic requirement for a national iodization program is the
availability of suitable technology in the form of iodized salt and
iodized oil, it is only one element of an IDD control program. Analysis
of the reasons for success and lack of success indicated the need for a
multidisciplinary approach, including assessment, communication,
planning, political support, monitoring and evaluation. The effect of
IDD had to be expressed in social terms, i.e., in terms of economic
effect, impaired learning of school children and reduced quality of
life. A multidisciplinary model for a national program was developed
and has been subsequently adopted in many countries (Hetzel 1989
).
In 1985, the establishment of an International Consultative Group (NGO) was recommended as a necessary step to provide multidisciplinary expertise for the international agencies and national governments with major IDD problems for the development of a more active IDD control program. The UN Nutrition Group approved this step at the Nairobi meeting in February 1985 and the following month the International Council for Control of Iodine Deficiency Disorders (ICCIDD) was established.
The ICCIDD was formally inaugurated in Kathmandu, Nepal in March 1986 with the support of the Director General of WHO and the Executive Director of UNICEF. The ICCIDD now comprises an international network of 450 multidisciplinary professionals from 82 countries.
Since 1986, the ICCIDD has worked closely with WHO and UNICEF in the establishment of a global program for the elimination of IDD by the year 2000. An Action Plan was prepared for the ICCIDD and approved by the UN System and WHO in 1990. Subsequently, in 1990, the goal of elimination was accepted by the World Summit for Children at the UN. Since that time, the policy of Universal Salt Iodization (USI) was adopted and has proved remarkably successful throughout all regions of the world.
At the global level, WHO reported in 1996 that 56% of the
population of 83 developing countries now has adequate access to
iodized salt. This represents an increase of 750 million since 1990
with protection of 12 million children (WHO Fact Sheet 1996
).
Achievement of the goal would eliminate an ancient scourge of mankind;
the descriptions of goiter date back to 2500 BC in the ancient
literature of India and China and cretinism to the Middle Ages
(Hetzel and Pandav 1996
).
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FOOTNOTES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONIodine deficiency as a...Mechanism of the effect...Quantitative estimates of the...Cognitive development in iodine...Bridging the knowledge...REFERENCES |
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1. Bleichrodt N., Born M. P. A metaanalysis of research on iodine and its relationship to cognitive development. Stanbury J. B. eds. The Damaged Brain of Iodine Deficiency 1994:195-200 Cognizant Communication Corporation New York, NY.
2. Bürgi H., Supersaxo Z., Selz B. Iodine deficiency diseases in Switzerland one hundred years after Kocher’ s survey: a historical review with some new prevalence data. Acta Endocrinol 1990;123:577-590
3. Delange F. The disorders induced by iodine deficiency. Thyroid 1994;4:107-128[Medline]
4. Hetzel B. S. The iodine deficiency disorders (IDD) and their eradication. Lancet 1983;2:1126-1129[Medline]
5. Hetzel B. S. The Story of Iodine Deficiency: An International Challenge in Nutrition 1989 Oxford University Press Oxford , UK.
6. Hetzel B.S. Historical development of the concepts of brain thyroid relationships. Stanbury J. B. eds. The Damaged Brain of Iodine Deficiency 1994:1-7 Cognizant Communication Corporation New York, NY.
7. Hetzel B. S., Mano M. A review of experimental studies of iodine deficiency during fetal development. J. Nutr. 1989;119:145-181
8. Hetzel B. S., Pandav C. S. SOS for a Billion: The Conquest of Iodine Deficiency Disorders 1996 Oxford University Press New Delhi, India.
9. Hetzel B. S., Potter B. J., Dulberg E. M. The iodine deficiency disorders; nature, pathogenesis and epidemiology. World Rev. Nutr. Diet. 1990;62:59-119[Medline]
10. Pharoah P.O.D., Buttfield I. H., Hetzel B. S. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 1971;1:308-310[Medline]
11. Pharoah P.O.D., Delange F., Fierro-Benitez R., Stanbury J. B. Endemic cretinism. Stanbury J.B. Hetzel B.S. eds. Endemic Goitre and Endemic Cretinism 1980:395-421 Wiley New York, NY.
12. World Health Organization Report to 43rd World Health Assembly 1990 Geneva Switzerland.
13. World Health Organization (1993) Global Prevalence of Iodine Deficiency Disorders. WHO/UNICEF/ICCIDD Micronutrient Deficiency Information System (MDIS Working Paper #1). WHO, Geneva, Switzerland.
14. World Health Organization (1996) Iodine Deficiency Disorders. WHO Fact Sheet No. 121. WHO, Geneva, Switzerland.
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