Teratology public affairs committee position paper: iodine deficiency in pregnancy.

Iodine deficiency is an important nutritional deficiency, with more than 2 billion people worldwide estimated to be at risk. The developing fetus and young children are particularly at risk. During pregnancy and lactation, iodine requirements increase, whether in iodine-poor or iodine-sufficient countries, making the mother and the developing fetus vulnerable. The American Thyroid Association (ATA) recommends 250 micrograms per day of iodine intake for pregnant and lactating women. The thyroid gland is able to adapt to the changes associated with pregnancy as long as sufficient iodine is present. Dietary intake is the sole source of iodine, which is essential to the synthesis of thyroid hormones. Iodine is found in multiple dietary sources including iodized salt, dairy products, seaweed, and fish. Prenatal vitamins containing iodine are a good source of iodine, but iodine content in multivitamin supplements is highly variable. Congenital hypothyroidism is associated with cretinism. Clinical hypothyroidism has been associated with increased risk of poor perinatal outcome including prematurity, low birth weight, miscarriage, preeclampsia, fetal death, and impaired fetal neurocognitive development. Subclinical hypothyroidism is also associated with poor pregnancy outcomes and potential fetal neurocognitive deficits, but the data are more variable than those for clinical hypothyroidism. We concur with the ATA recommendation that all pregnant and lactating women should ingest (through diet and supplements) 250 micrograms of iodine daily. To achieve this goal, we recommend that all pregnant and lactating women take daily iodine supplementation of 150 micrograms.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

Iodine status and supplementation before, during, and after pregnancy.

Iodine intake is essential for the production of thyroid hormone. Iodine deficiency remains a public health problem in many regions around the world. Iodine deficiency can present as a spectrum of disorders depending on the degree of severity. Pregnant and lactating women are particularly vulnerable to iodine deficiency disorders because of their increased iodine requirements. Severe maternal iodine deficiency has been associated with cretinism or impaired neurodevelopment in children as well as obstetric complications. Universal salt iodization has been shown to prevent these disorders in severely iodine deficient areas. Recently, observational studies have demonstrated an association between mild-to-moderate iodine deficiency and poorer cognitive outcomes in children. In this review, we describe the iodine requirements for pregnant and lactating women, how population iodine status can be assessed, the effects of maternal iodine deficiency and excess, and current data regarding efficacy of iodine supplementation for women who are pregnant or lactating.

WITHDRAWN: Maternal iodine supplements in areas of deficiency.

BACKGROUND: Iodine deficiency is the leading preventable cause of intellectual impairment in the world. Although iodine supplementation is generally considered to be safe, there is a possibility of high doses of iodine suppressing maternal thyroid function. OBJECTIVES: The objective of this review was to assess the effects of iodine supplementation before or during pregnancy in areas of iodine deficiency. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: All acceptably controlled trials of maternal iodine supplementation during pregnancy with clinical outcomes. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by two reviewers. MAIN RESULTS: Three trials involving 1551 women were included. In two trials, iodine supplementation was associated with a statistically significant reduction in deaths during infancy and early childhood (relative risk 0.71, 95% confidence interval 0.56 to 0.90). Iodine supplementation was associated with decreased prevalence of endemic cretinism at the age of four years (relative risk 0.27, 95% confidence interval 0.12 to 0.60) and better psychomotor development scores between four to 25 months of age. AUTHORS' CONCLUSIONS: Iodine supplementation in a population with high levels of endemic cretinism results in an important reduction in the incidence of the condition with no apparent adverse effects.

The way forward in Italy for iodine.

Italy is dealing with iodine deficiency since ancient times. In 1848 an ad hoc committee appointed by the king of Sardinia, identified extensive areas afflicted by endemic goiter and endemic cretinism in Piedmont, Liguria and Sardinia. Since then many epidemiological studies have been conducted in our country. These showed that iodine deficiency was present not only in mountain areas but also in coastal areas. In 1972 the iodization of salt at 15 mg/kg was allowed by law and iodized salt was distributed on request to selected endemic areas. Five years later the distribution was extended to the whole country. However the sale of iodized salt was not mandatory at that time and only a small fraction of the Italian population started using iodized salt. In 1991 the content of iodine in the salt was raised to 30 mg/kg and in 2005 a nationwide salt iodization program was finally implemented. Some years later a nationwide monitoring program of iodine prophylaxis was also implemented. Since 2005 the sale of iodized salt in Italian supermarkets has increased (34% in 2006, 55% in 2012), although it has been observed that the use of iodized salt is still low in the communal eating areas and in the food industry. These data are coherent with recent epidemiological studies showing that some regions in our country are still characterized by mild iodine deficiency and a high frequency of goiter and other iodine deficiency disorders. This implies that further efforts should be made to successfully correct iodine deficiency in Italy.

Iodine-supplementation trials.

Iodine deficiency as a major determinant of endemic goiter has been recognized for several decades. The evidence is also strong that iodine supplementation is effective in preventing both varieties of endemic cretinism, provided it is given before conception; early fetal and infant death may also be prevented. However, the reason for the variation in prevalence of the different types of cretinism is still a matter of conjecture. Iodine supplementation may improve motor and cognitive performance, but the evidence needs to be evaluated in light of the difficulty in transposing tests of intellectual and motor ability developed in one culture to another very different one.

Mitigation of cretinism by breast-feeding.

An athyrotic infant had hypothyroidism at 1 year of age. He had grown at an above-average velocity until age 10 months when breast-feeding was discontinued, yet his bone age remained that of a newborn. These observations suggested that breast-feeding had attenuated hypothyroidism by providing significant quantities of thyroid hormones in the milk. To test this hypothesis, thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3,5'-triodothyronine (reverse T3) were measured in breast milk samples collected serially from three months before to four months after delivery. Mean breast milk T4 content fell from 1.4 to 0.7 microgram/dl within 48 hours after delivery, while T3 content rose from 136 to 286 ng/dl. Reverse T3 content remained unchanged. The shift in the T4/T3 ratio after delivery was observed in samples of all five donors; the highest postpartum T4 level was 1.1 microgram/dl and the highest postpartum T3 level was 405 ng/dl. It is concluded that breast-feeding may deliver sufficient thyroid hormones to the athyrotic infant to mitigate severe hypothyroidism and to prevent impaired neurological development.

On goiters and the stupidity which in some countries accompanies them. Endeavours of Vincenzo Malacarne, from Saluzzo.

Two hundred years ago, V. Malacarne, pathologist and surgeon, published a booklet entitled "Su i gozzi e sulla stupidità che in alcuni paesi gli accompagna". Malacarne was born at Saluzzo, a town at the foot of the Cottian Alps, in Western Piedmont. Goiter and endemic cretinism were prevalent at the time (1789) in the countryside. In 1940-45 goiter epidemics spread through these still endemic regions. On the basis of his own observations on autoptic material, he suggested that the main cause of cretinism was brain damage due to impeding of the blood circulation by the neck swelling, and invited the pathologists of the Po and Aosta valleys to send him the head and the neck of these goitrous idiots for his researches. Today, too, we believe the thyroid and the brain to contain crucial factors of cretinism and assume that iodine deficiency is the main cause of the disease. Yet we do not know either the factor which damages and prevents in the myxoedematous cretin postnatal thyroid growth, or the pathogenesis of deaf-mutism, spastic paraplegia and severe mental deficiency of the neurological, non-hypothyroid cretin. While these questions remain unanswered, ample evidence has been gathered during the last two centuries regarding the practical importance of iodine prophylaxis to prevent these scourges, today referred to as "iodine deficiency disorders".

Metabolic maladaptation: individual and social consequences of medical intervention in correcting endemic hypothyroidism.

Endemic hypothyroidism has been studied in a Central African population in remote Congo (ex-Zaire) to investigate the prevalence, severity, causes, and potential control of this disorder, with questions as to why this disease is conserved, and whether it confers any adaptive advantage in this resource-constrained environment. Iodine deficiency, cassava goiterogens, and selenium deficiency were found to be the factors implicated in the severe hypothyroidism expressed in congenital cretinism and high goiter incidence in this isolated population, which continues to be under observation following medical intervention. Profound hypothyroidism was encountered in whole village populations as measured by serum thyrotropin determinations ranging from very high to over 1000 IU, and thyroxin levels ranging from low to undetectable; cretinism rates were as high as 11% and goiter incidence approached 100%. Assessment of endocrinologic status, caloric requirement, energy output, fertility, and ecologic factors was carried out before and during iodine repletion by depot injection. Hypothyroidism was corrected and cretinism eliminated in the treatment group, with goiters reduced in most instances (with regrowth exhibited in some who escaped control) and some symptomatic goiter patients were offered surgical treatment for respiratory obstruction. Individual patient benefits, including improved strength and increased energy output, were remarkable. The social and developmental consequences observed within the collective groups of treated patients were remarkable for an increase in caloric requirement and a dramatic increase in fertility that led to quantitative as well as qualitative increases in resource consumption. Micronutrient iodine repletion was not accompanied by any concomitant increase in macronutrient supply, and hunger and environmental degradation resulted. The highly prevalent disease of hypothyroidism is found in highest incidence in areas of greatest resource constraint. It may be that hypothyroidism is conserved in such areas because it may confer adaptive advantage in such marginal environments as an effect, as well as a cause, of underdevelopment. Hypothyroidism may limit energy requirements, fertility, and consumer population pressure in closed ecosystems that could otherwise be outstripped. Single factor intervention in a vertical health care program not sensitive to the fragile biologic balance and not part of a culture-sensitive development program might result in medical maladaptation.

Maternal iodine supplements in areas of deficiency.

BACKGROUND: Iodine deficiency is the leading preventable cause of intellectual impairment in the world. Although iodine supplementation is generally considered to be safe, there is a possibility of high doses of iodine suppressing maternal thyroid function. OBJECTIVES: The objective of this review was to assess the effects of iodine supplementation before or during pregnancy in areas of iodine deficiency. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: All acceptably controlled trials of maternal iodine supplementation during pregnancy with clinical outcomes. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by two reviewers. MAIN RESULTS: Three trials involving 1551 women were included. In two trials, iodine supplementation was associated with a statistically significant reduction in deaths during infancy and early childhood (relative risk 0.71, 95% confidence interval 0. 56 to 0.90). Iodine supplementation was associated with decreased prevalence of endemic cretinism at the age of four years (relative risk 0.27, 95% confidence interval 0.12 to 0.60) and better psychomotor development scores between four to 25 months of age. REVIEWER'S CONCLUSIONS: Iodine supplementation in a population with high levels of endemic cretinism results in an important reduction in the incidence of the condition with no apparent adverse effects.

["Goiters and the associated idiocy in several countries. Attempts of Vincenzo Malacarne from Saluzzo". Current interpretation of endemic cretinism]. / "Su i gozzi e sulla stupidità che in alcuni paesi gli accompagna. Tentativi di Vincenzo Malacarne saluzzese". L'odierna interpretazione del cretinismo endemico.

Two hundred years ago V. Malacarne pathologist and surgeon, born in Saluzzo, a town on the foot of the Cottian Alps, published a booklet about goiter and endemic cretinism being diseases prevalent at that time in the countryside. In 1940-45 goiter epidemics spread through these still endemic regions. On the basis of his own observations on autoptic specimens he suggested that the main cause of cretinism was brain damage due to impeded blood circulation by the neck swelling, and invited the pathologists of the Po and Aosta Valleys to send him "il capo ed il collo (the head and the neck)" of these goitrous idiots for a control. Also today we believe the thyroid and the brain to contain crucial factors of cretinism, both sporadic and endemic, and we assume that iodine deficiency is the causal link between the two diseases. Yet we do not know either the factors which damage and prevent, in the myxedematous cretin, postnatal thyroid growth, or the aetiopathogenesis of the deaf-mutism, spastic paraplegia and severe mental deficiency of the neurological non hypothyroid cretin. While these questions remain unanswered, ample evidence has matured during the last two centuries regarding the practical importance of iodine prophylaxis to prevent these scourges, today referred to as "iodine deficiency disorders". Some recent findings on diencephalon inflammation in human and canine goitre are quoted.

Role of goitrogens in iodine deficiency disorders & brain development.

Although iodine deficiency has primarily been implicated in the causation of goitre, the significant role played by food goitrogens in the etiology of iodine deficiency disorder (IDD) is being increasingly recognized. Impaired brain development is the major cause of concern in IDD. Detailed experimental studies were undertaken to ascertain various biochemical changes associated with developing brain in response to treatment with a goitrogens--thiocyanate. Addition of thiocyanate to food deprived of KI brought down significantly the circulating levels of thyroxine (T4) in rats. Nucleic acids and protein content in different regions of brain were significantly lowered in rat pups exposed to thiocyanate. The rate of microtubule assembly, which is detrimental for neurite growth was considerably lowered, thereby influencing both myelin deposition and synaptogenesis in developing brain. Goitrogen intake not only caused an adaptive increase in the activity of type II 5'-deiodinase, which governs availability of triiodothyronine (T3) in brain, it also increased the latter's binding to brain nuclear receptors under conditions of thiocyanate induced hypothyroid state. Addition of adequate quantities of KI mitigated thiocyanate induced alterations by restoring circulating level of thyroxine. These investigations suggest that goitrogens play a significant role in influencing biochemical events unique to developing brain.

Endemic goiter and cretinism: an update on iodine status.

Iodine deficiency is the most prevalent correctable cause of brain damage in the world. Over the past 15 years, great progress has been made towards the elimination of iodine deficiency, principally through universal salt iodization. Much more needs to be done for countries that are lagging in the effort or that have weak systems for sustaining it. The key to maintaining optimal iodine intake is regular monitoring, usually by the measurement of urinary iodine concentration, linked to a prompt response in the event of abnormal results. If the present momentum continues then global iodine sufficiency is possible and, in a landmark achievement, iodine deficiency will be the first major non-infectious disorder to be eliminated.

Iodine deficiency: consequences and progress toward elimination.

While traditionally associated with cretinism and goiter, iodine deficiency has broad effects on central nervous system development that can occur in the absence of either condition. Any maternal iodine deficiency results in a range of intellectual, motor, and hearing deficits in offspring. This loss in intellectual capacity limits educational achievement of populations and the economic prowess of nations. Progress made since the historic World Summit for Children in 1990 has been outstanding. Approximately 70% of households in the world used iodized salt by 2000, compared with less than 20% in 1990. It is estimated that at least 85 million newborns out of 130 million annual births are protected from a loss in learning ability that would otherwise have occurred. The elimination of iodine deficiency, by expedient production, marketing, and universal consumption of iodized salt, represents a significant development effort in public nutrition. Although globally iodine nutrition has greatly improved, 20% to 30% of pregnancies and thus newborns still do not fully benefit from the use of iodized salt. Countries where success is in evidence could rapidly revert back to deficiency if vigilance is not maintained. Just as success came through concerted public-private-civic actions, making sure that this is expanded and will steadily go on requires continuous collaboration.

Iodine deficiency disorders in Zimbabwe. No change in prevalence of endemic goitre in Wedza District, as shown by school surveys carried out 18 years apart.

Goitre prevalence surveys were carried out in 1986 in five primary schools in Wedza District and the results compared with those obtained from the same schools in 1968. Overall, goitre prevalence was 73 percent and there had been no significant change since 1968. In 1986 the visible goitre rate was 14 percent. Goitre was more common in girls on both occasions. Evidence (though not conclusive) of milder forms of endemic cretinism was found. The need for a nationwide iodination programme is emphasised.

[Efficacy and safety of iodine prophylaxis]. / Efficacia e sicurezza della iodoprofilassi.

Iodine deficiency and iodine deficiency disorders (IDD) are still present in developing countries as well as in some European areas. It is well known that iodine deficiency correction prevents endemic goiter and other IDD. Iodized oil has been shown to reduce goiter prevalence and cretinism in African countries. In countries where iodine prophylaxis is performed since many years (USA, Switzerland, Scandinavian countries) IDD are dramatically reduced. One example of the efficacy of iodine prophylaxis through iodized salt was reported in a Tuscan village were urinary iodine excretion increased from 47 micrograms/l in 1981 to 130 micrograms/l in 1991. Goiter prevalence in schoolchildren dropped from 60% in 1981 to 8.1% in 1991. In the same children neuropsychological performances were evaluated showing a reduction of motor response to perceptive stimuli assessed by measurement of reaction times in children born before the beginning of iodine prophylaxis. Iodine prophylaxis has no side effects, although a transitory increase of hyperthyroidism has been reported in the past and recently in African countries. A reevaluation by the experts of the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) has pointed out that this phenomenon is not relevant with respect to the efficacy of iodine prophylaxis. In conclusion, universal iodine prophylaxis prevents endemic goiter and other IDD, without side effects.

Towards the elimination of iodine deficiency disorders in India.

Iodine deficiency disorders (IDD) are an important public health problem in India with an estimated 270 million people at risk of IDD. India has adopted the strategy of salt iodization for control of IDD and has the goal of "Universal iodization of salt by 1995 and elimination of IDD by 2000". There is a high degree of political commitment which need to continue if the goal is to be achieved. Currently the ban on ale of un-iodized salt is only applicable to salt on human consumption. There is a need for extending the ban to include salt for animal consumption as IDD affects livestock as well. India has the installed capacity to produce its requirement of 5 million tonnes iodised salt. Communication strategies have to be strengthened especially to educate people who have concerns about of iodine toxicity. The success to a large extent depends on the quality control and monitoring of iodine content of salt at all stages from production to consumption. NGO's and the community have to be encouraged to participate in this process. To sustain the elimination of IDD, a partnership of various stakeholders IDD elimination is essential.

[The influence of iodine deficiency during pregnancy of fetal and neonatal development]. / Wplyw niedoboru jodu w ciazy na rozwój plodu i noworodka.

The iodine is fundamental substrate for thyroid hormones synthesis. Thyroxine and triiodothyronine play a crucial role in human brain development and maturation. It is well known, that not only fetal, but also maternal thyroid hormones are essential for normal prenatal central nervous system development. During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. With decreasing iodine intake, maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. The severity of iodine deficiency and hypothyroidism in the mother during early and midgestation is related to the severity of the neural damage in the fetus. In severe iodine deficiency, central nervous system damage is already irreversible at birth and can only be prevented by correction of the maternal iodine deficiency early in pregnancy. Therefore iodine supplementation during pregnancy is now strongly recommended.

The implications of iodine and its supplementation during pregnancy in fetal brain development.

Iodine is an essential trace element for life. Its biological effects are a consequence of its incorporation to the thyroid hormones, which play a crucial role in fetal organogenesis, and in particular in brain development. This takes place during early gestation and involves delicate targeting throughout the central nervous system, including adequate neuronal growth, migration and myelinization at different sites, such as the cerebral cortex and neocortex, visual and auditory cortex, hippocampus and cerebellum. Pregnancy is characterized by an increased demand of thyroid hormones by the feto-placental unit in order to fulfill the necessary requirements of thyroid hormone action for normal fetal development. Up until week 20, the fetal thyroid is not fully active and therefore is completely dependent on the maternal thyroxine supply. Thus, the maternal thyroid has to adapt to this situation by producing about 1.5 fold more thyroxine. This requires that enzymatic gland machinery works normally as well as an adequate iodine intake, the principal substrate for thyroid hormone synthesis. Biological consequences of iodine related maternal hypothyroxinemia are currently very well known, by both experimental models and by clinical and epidemiological evidences. The associated disturbances parallel the degree of maternal thyroxine deficiency, ranging from increased neonatal morbi-mortality and severe mental dysfunction, to hyperactivity, attention disorders and a substantial decrease of IQ of an irreversible nature in the progeny of mothers suffering a deprivation of iodine during pregnancy. As a consequence, iodine deficiency is the leading preventable cause of mental impaired function in the world, affecting as many as 2 billion people (35.2% of the entire population). Prevention of fetal iodine deficiency - a problem of pandemic proportions- is feasible, provided that an iodine supply of 200-300 µg/day to the mother is ensured, before and throughout gestation as well as during the lactating period.