Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy.

Endemic cretinism is characterised by multiple neurological defects including deaf-mutism, diplegia, squint, and mental deficiency. The condition is widely prevalent in the Highlands of New Guinea in association with severe iodine deficiency. Previous studies have shown that iodised oil provides a very satisfactory correction of severe iodine deficiency in New Guinea. A controlled trial on the use of intramuscular iodised oil in the prevention of endemic cretinism was carried out in the Western Highlands of New Guinea and involved a population of approximately 8000. Subsequent follow-up over four years revealed 26 endemic cretins out of a total of 534 children born to mothers who had not received iodised oil; the mothers of 5 of these cretins were pregnant at the start of the trial. In comparison, 7 cases of endemic cretinism occurred among 498 children born to mothers who had been treated with iodised oil; in 6 of these 7 cases, the mother was pregnant when the trial commenced. It is concluded that intramuscular iodised oil is effective in the prevention of endemic cretinism and that, for it to be effective, it should be given prior to conception. This suggests that severe iodine deficiency in the mother produces neurological damage during fetal development.

Iodine and neuropsychological development.

The establishment of the essential link among iodine deficiency, thyroid function and brain development has emerged from a fascinating combination of clinical, epidemiologic and experimental studies. The central human phenomenon that focuses this relationship is the condition of endemic cretinism, described from the Middle Ages and characterized in its fully developed form by severe brain damage, deaf mutism and a spastic state of the hands and feet. The demonstration of the prevention of cretinism in a double-blind controlled trial with injections of iodized oil in Papua New Guinea (1966-1970) established the causal role of iodine deficiency in cretinism by an effect on the developing fetal brain. Cretinism could not be prevented unless the iodized oil was given before pregnancy. Iodine deficiency is now regarded by the WHO as the most common preventable cause of brain damage in the world today, with at least 30 million suffering from this preventable condition. Since 1986 the international NGO, the International Council for Control of Iodine Deficiency Disorders, has worked closely as an expert group with WHO and UNICEF in assisting countries with a program of universal salt iodization for the elimination of iodine deficiency as a cause of brain damage by the year 2000. In 1996, WHO reported that 56% of the population of 83 developing countries now had adequate access to iodized salt. This represents an increase of 750 million since 1990 with protection of 12 million children.

Historical perspectives on indigenous health in Australia.

In spite of much effort over the past 25 years, the life expectancy of the indigenous people remains nearly 20 years behind the non-Aboriginal white population of Australia. These figures compare unfavourably with the improved life expectancy over the past 25 years of other indigenous peoples, such as the New Zealand Maori and the American Indian populations. By 1990-94, the average Australian indigenous all-cause mortality rate was 1.9 times the Maori rate, 2.4 times the US indigenous rate and 3.15 times the all-Australian rate. The persistence of this discrepancy in Australia is obviously a matter of great concern. There is clearly a gap between available knowledge and its application. Some indication of the possibility of reversal of the current situation is given by a recent report of the beneficial impact of the Homelands Movement on Health Outcomes in Central Australian Aborigines. The study compared the prevalence of obesity, hypertension and diabetes in two groups of Aboriginal adults: those living in homelands versus those living in centralized communities in Central Australia. Baseline studies revealed a lower prevalence of diabetes, hypertension and obesity in the homelands group, compared with those living in centralized communities. They were also less likely to die and less likely to be hospitalized for any cause, particularly infections, injury involving alcohol and other injury. Mean age at death was 58 and 48 years for the residents of homelands and centralized communities, respectively. The benefits were most marked in young adults. It is suggested that the homelands communities have a greater degree of control of their own lives than those living in the centralized communities and this may be an important factor in their improved health status. Improvement in indigenous health should be one of the key issues of reconciliation. Priorities include community control of Aboriginal Health Services under the National Aboriginal Community Controlled Health Organisation (NACCHO), throughout Australia, a greater priority for prevention and public health services (housing, water supply and environmental services) education and economic issues, improved training of indigenous health professionals and increased funding. A national professional organization including NACCHO needs to be established to bridge the big gap between available knowledge and its application for the benefit of the indigenous people of Australia.

Iodine Deficiency and the Brain.

The effects of iodine deficiency on growth and development are known as the iodine deficiency disorders (IDDs). Most common is goitre at all ages, but most significant are the effects on brain development during pregnancy. The major effect of iodine deficiency is the clinical syndrome of endemic cretinism characterised in its fully developed form by mental defect, deaf mutism and spastic diplegia. This condition can be totally prevented by correction of the iodine deficiency before pregnancy. There is considerable variation in the degree of brain damage that occurs due to iodine deficiency in a given population. A meta-analysis of studies comparing iodine deficient populations with appropriate control groups reveals a mean loss of 13.5 IQ points. Experimental studies in the sheep, rat and marmoset confirm the effect of iodine deficiency on foetal brain development. They show that the effect is due to a slowing of neuroblast multiplication and differentiation and a consequent effect on neuroglial development. Iodine deficiency is now recognised as the most common cause of preventable brain damage in the world today. In 1990, the elimination of iodine deficiency as a cause of brain damage by the year 2000 was accepted by the UN system and substantial progress has been made since 1990 with the mass correction of iodine deficiency through Universal Salt Iodisation (USI).

Iodine deficiency: a global problem.

The United Nations and other international organisations, in cooperation with national governments, aim to eliminate this major cause of fetal brain damage by the year 2000.

Communication and health--health as an ecosystem.

The importance of communication in public health is described with reference to recent experiences in Australia where good progress has been made with certain major public health problems. There has been a 30% fall in road accident deaths and a 40% fall in deaths from coronary heart disease, and a smoke free environment has been established in public places and in the work place. These successes depended on effective communication based on appropriate data. Evaluation data have also been used to keep the public informed and to reinforce the message. The cooperation of the media has been most important in stimulating a new awareness of health and the opportunities for self help and community initiatives. In central Australia, new initiatives involving the Central Australian Aboriginal Congress have led to an improvement in the health of Aborigines, the training of Aborigines as health workers and the development of a Centre for Appropriate Technology at the Alice Springs College of Technical and Further Education. At the international level, Australia sponsored a World Health Assembly resolution in 1986 calling for the elimination of iodine deficiency disorders. With the support of the Australian International Development Assistance Bureau and the United Nations Children's Fund (UNICEF), an international expert group of scientists and public health professionals, the International Council for Control of Iodine Deficiency Disorders (ICCIDD), based in Adelaide, has been able to work with the World Health Organization (WHO) and UNICEF in the development of an international public health programme aimed at eliminating iodine deficiency disorders by the year 2000. The ICCIDD is a new model for communication and action in international health which is now being advocated for other areas.

The effect of thyroxine, 3, 5-dimethyl-3'isopropyl-L-thyronine and iodized oil on fetal brain development in the iodine-deficient sheep.

Studies have been carried out to investigate the role of maternal and fetal thyroid function in the effects of iodine deficiency on fetal brain development in sheep. Iodine deficiency was established with an especially prepared low-iodine diet of maize and pea pollard. The iodine-deficient sheep were mated and the end of the second trimester of pregnancy (100 days gestation) were divided into groups which received either a sc injection of T4 or 3,5-dimethyl-3-isopropyl-L-thyromine or an injection of iodized oil. AT 140 days gestation (10 days prior to parturition) comparison of the fetuses delivered by hysterotomy revealed that the retarded fetal brain development observed in iodine deficiency was greatly improved by T4 and by iodized oil. However, T4 and iodized oil failed to correct the reduction in the number and the increase in the length of synaptic appositions which were observed in the fetal cerebral cortex after iodine deficiency. In addition, the histological appearance of the fetal thyroid gland and the levels of plasma thyroid hormones were restored to normal. The administration of 3,5-dimethyl-3'-isopropyl-L-thyronine had no effect on the retarded fetal brain and body development of the iodine-deficient fetuses. The lack of response may be due to the ability of 3,5-dimethyl-3'-isopropyl-L-thyronine to cross the ovine placenta as no reduction in the abnormally elevated fetal plasma TSH observed in spite of a fall in maternal plasma TSH and apparent restoration of maternal thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of experimental studies of iodine deficiency during fetal development.

Iodine deficiency is now recognized as a major international public health problem. It is estimated that 800 million people may be at risk of the effects of iodine deficiency. In humans, the effects occur at all stages of development: the fetus, the neonate, the child and adult. The effects are now denoted by the term iodine deficiency disorders (IDD). They include miscarriages, stillbirths, congenital anomalies, as well as the more familiar goiter, cretinism, impaired brain function, and hypothyroidism in children and adults. In domestic animals, reproductive failure has been reported with the production of aborted, stillborn and weak calves. Experimental studies in animal models have been reviewed to provide evidence of the mechanisms involved, particularly in relation to brain development. The findings in three different species (rat, sheep, monkey) indicate that the effects are mediated by a combination of maternal and fetal hypothyroidism, the effect of maternal hypothyroidism being earlier than the onset of fetal thyroid secretion. The findings suggest that iodine deficiency has an early effect on neuroblast multiplication and, if so, this could be important in the pathogenesis of the neurological form of endemic cretinism. The assessment of the full effects of iodine deficiency on the brain requires further studies in the postnatal period to determine the duration of these effects.

Fall in coronary heart disease mortality in U.S.A. and Australia due to sudden death: evidence for the role of polyunsaturated fat.

Epidemiological studies have been reviewed which provide suggestive evidence of an association between the fall in coronary heart disease mortality in the U.S.A and Australia since 1967, characterized by a fall in sudden deaths, to the increase in polyunsaturate fat consumption that has occurred in both countries since 1960. This association led directly in the same institution to carefully designed experimental studies undertaken in the rat, and a non-human primate, the marmoset (Callithrix jacchus jacchus) with a heart and lipid metabolism more closely resembling that of man. In both animal species, a vegetable fat diet had a protective effect against the increase in contractility of isolated papillary muscles induced by age, the addition of animal fat, or by isoprenaline in vitro. Similar effects were observed following coronary artery ligation, where the extent of dysrhythmia was greatly reduced by supplementing the diet with a linoleic acid rich vegetable oil. It is concluded that the combination of epidemiological and experimental evidence indicates a protective effect of dietary polyunsaturates against sudden cardiac death. This work illustrates the value of the integration of epidemiological and experimental approaches to the aetiology of disease.

The brain in iodine deficiency.

Global descriptive, epidemiological studies have established the relation of iodine deficiency to endemic cretinism which, in its fully developed form, is characterized by mental deficiency, deaf mutism and spastic diplegia. However, a second less common variant--myxedematous or hypothyroid cretinism--is characterized by severe hypothyroidism with dwarfism. Mixed forms occur. It has been shown that both conditions can be prevented by correction of the iodine deficiency before pregnancy. Cretinism and development--now termed iodine deficiency disorders (IDD). A number of recently developed animal models establish the effect of severe iodine deficiency on brain development. These include the rat, the marmoset monkey and the sheep. These models are all characterized by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. Studies of the mechanisms involved have been carried out in the sheep. The findings reveal significant, though less severe, effects of fetal thyroidectomy (late gestation) and a significant effect of maternal thyroidectomy on brain development in mid-gestation. A combination of maternal and fetal thyroidectomy has similar but more severe effects than iodine deficiency. In the light of current knowledge of the embryology of the brain it is suggested that the critical time for the effect of iodine deficiency is the mid-trimester (14-18 weeks) when the neurons of the cerebral cortex and basal ganglia are formed and could be damaged by the effect of iodine deficiency on maternal thyroid function. There is now recent evidence indicating transfer of maternal thyroxine across the placental barrier early in pregnancy. In this way, neurological cretinism might be produced. Impaired fetal thyroid function would follow in the third trimester and augment the effect of reduced maternal thyroid function. Impaired fetal thyroid function alone could produce the hypothyroid form of cretinism. Further experimental studies, particularly into the postnatal period, are required to substantiate these suggestions. Apart from this, further study of the effects of iodine deficiency on brain development at the subcellular and cellular levels are likely to be most productive.

Fetal brain development in response to iodine deficiency in a primate model (Callithrix jacchus jacchus).

The common cotton-eared marmoset (Callithrix jacchus jacchus) has been used for the first time as a primate model to study the effects of dietary iodine deficiency on fetal brain development. Paired male and female marmosets were fed a low-iodine diet of maize, peas, meat meal, Torula yeast, maize oil and added vitamins, minerals and amino acids for 6 months before mating. Offspring from first and second pregnancies were compared with offspring from control marmosets fed the same diet but supplemented with iodine. Severe iodine deficiency in the fetus at birth was evident by reduced plasma thyroxine levels, increased plasma thyroid stimulating hormone levels, increased thyroid weight and reduced thyroid iodine content. Thyroid histology revealed hyperplasia, hypertrophy and absence of colloid material in the follicles. Iodine deficiency caused a reduction in the weight of the fetal brain and in particular the cerebellum. Brain cell number was reduced in the cerebellum and brainstem but cell size was reduced in the cerebral hemispheres. Histology of the brain revealed morphological changes in the cerebellum and cerebral hemispheres. In the-cerebellum there was: an increase in the thickness of the external germinal layer indicative of impaired cell acquisition; a decrease in total area; a decrease in molecular layer area; and an increase in Purkinje cell (Pc) linear density due to a reduction in the length of the Pc line. The decrease in molecular layer area and increase in Pc linear density imply diminished ascending and lateral extension of Pc dendrites. Changes in the cerebral hemispheres consisted of an increase in the density of neuronal cell bodies in the granular band and a decrease in synaptic counts in the layer between the pia mater and supragranular band of the visual cortex. Offspring from second pregnancies compared to those from first pregnancies were more severely affected and associated with lower plasma levels of maternal and fetal thyroxine. These findings indicate the importance of maternal and fetal thyroid function in relation to fetal brain development in the primate.