Iodine supplementation of pregnant women in Europe: a review and recommendations.

OBJECTIVE: Nearly two-thirds of the population of Western and Central Europe live in countries that are iodine deficient. Damage to reproductive function and to the development of the fetus and newborn is the most important consequence of iodine deficiency. The objective of this review was to examine the iodine status of pregnant women in Europe and the potential need for iodine supplementation. DESIGN: A MEDLINE/PubMed search and compilation of all published studies since 1990 of iodine nutrition and iodine supplementation of pregnant women in Europe, as well as an Internet-based search and review on availability and legislation of iodine supplements in the European Union. RESULTS: Although the data suggest most women in Europe are iodine deficient during pregnancy, less than 50% receive supplementation with iodine. Mild-to-moderate iodine deficiency during pregnancy adversely affects thyroid function of the mother and newborn and mental development of the offspring and these adverse effects can be prevented or minimized by supplementation. There are no published data on the effect of iodine supplementation on long-term maternal and child outcomes. The iodine content of prenatal supplements in Europe varies widely; many commonly used products contain no iodine. The European Union is developing legislation to establish permissible levels for iodine in food supplements. CONCLUSIONS: In most European countries, pregnant women and women planning a pregnancy should receive an iodine-containing supplement ( approximately 150 microg/day). Kelp and seaweed-based products, because of unacceptable variability in their iodine content, should be avoided. Prenatal supplement manufacturers should be encouraged to include adequate iodine in their products. Professional organizations should influence evolving EU legislation to ensure optimal doses for iodine in prenatal vitamin-mineral supplements. SPONSORSHIP: International Council for Control of Iodine Deficiency Disorders.

The elimination of iodine deficiency in the Czech Republic: the steps toward success.

The Czech Republic has a long history of iodine deficiency. Salt iodization was introduced in 1947, followed by a progressive correction of iodine deficiency. The present study reports the changes in the status of iodine nutrition and of thyroid function in the country from 1994 to 2002. The study included 29612 individuals, aged 0 to 98 years, including 5263 individuals randomly selected from the general population and 24349 individuals who attended the Institute of Endocrinology of Prague (hospital population). Urinary iodine was determined in all individuals. Measurements of serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroglobulin (Tg), were taken in 8544 to 19060 individuals. The iodine content of table salt was measured in 1130 samples. The median urinary iodine in the general and hospital populations were not significantly different. They progressively increased with time, starting from values indicating mild iodine deficiency (88-95 microg/L) prior to 1997, reaching the critical threshold of 100 microg/L in 1998, and optimal values between 120-140 microg/L since 2000. There was only a low and not significant positive correlation between the iodine content of salt and the urinary iodine. In contrast, urinary iodine showed marked seasonal changes, with the highest values during winter, when livestock were supplemented by mineral tablets containing iodine. Variables exploring thyroid function were all situated within the normal range in adults but another study (results not reported) has shown the persistence of slightly elevated TSH in neonates. The correction of iodine deficiency was not accompanied by unfavorable side effects. In conclusion, the Czech Republic has achieved sustainable elimination of iodine deficiency. Salt iodization has been a determining, but not the only, factor responsible for the success. Iodine supplementation of livestock and increased consumption of milk rich in iodine have probably played a determining role. Neonatal thyroid screening could constitute the major monitoring tool in order to insure sustainable elimination of iodine deficiency in the Czech Republic.

Control of iodine deficiency in Western and Central Europe.

The paper summarizes the updated information published in peer review journals on the status of iodine deficiency in Western and Central Europe. Nationwide evaluations of the prevalence of goiter and of the concentrations of urinary iodine were conducted during recent years in 17 of the 31 countries of Western and Central Europe, mostly in school-aged children. Fourteen of the 31 countries had reached a normal status of iodine nutrition, three countries were close to iodine sufficiency, iodine deficiency persisted in 13 other countries and data are missing for Albania. The most important alterations of thyroid function due to iodine deficiency in Europe occur in neonates and very young infants. The major measure for the prevention of iodine deficiency is the fortification of all salt for human and animal consumption and for the food industry. The recommended daily intake of iodine for all ages in all inhabitants in Europe are as follows: 90 microg/day from 0 to 59 month, 120 microg/day between 6 and 12 years, 100 microg/day in adolescents and adults and 200 microg/day in pregnant and lactating women. The main guidelines for the correction of iodine deficiency in Europe are included.

Iodized oil as a complement to iodized salt in schoolchildren in endemic goiter in Romania.

OBJECTIVE: To evaluate the long-term efficacy and possible side effects of low doses of iodized oil on iodine nutrition and thyroid function in endemic goiter in Romania. METHODS: Random selection of 214 schoolchildren aged 6-14 years. Serial measurements of urinary iodine, thyroid volume with ultrasound, serum concentrations of thyrotropin, free thyroxine, thyroglobulin and thyroid autoantibodies before and up to 2 years after the oral administration of 200 mg iodine in iodized oil. RESULTS: Urinary iodine concentrations indicated a moderate iodine deficiency before therapy, sharply increased soon after therapy and slowly decreased thereafter but remained within the normal range up to more than 1 year after therapy. The prevalence of goiter was 29% before the administration of iodized oil and 9% 1 year later. Thyroid function tests and autoantibodies were normal before and up to 2 years after therapy. CONCLUSION: A single dose of 200 mg iodine from oral Lipiodol appears adequate and safe for correcting moderate iodine deficiency in children.

Iodine in human milk: perspectives for infant health.

Iodine is essential for normal growth, mental development, and survival of infants. The main source of iodine for breastfeeding infants is the iodine found in human milk. Despite the importance of iodine for infant health, there have been limited studies addressing human milk iodine concentrations. The newly recommended Adequate Intake of iodine for infants is 110 microg/day for infants 0-6 months and 130 microg/day for infants 7-12 months. Further studies of human milk iodine are needed to ensure that iodine prophylaxis is providing sufficient iodine for mothers and infants worldwide.

Iodine prophylaxis following nuclear accidents. Concern for the neonate?

The Professor F. Delange has a substantial experience, since the last decade, in implementing universal salt iodization in a lot of countries, and assessing its impact on iodine deficiency disorders. He comments here the published results of D.E. Hindié et al. concerning the side effects of stable iodine overload on thyroid structure in the young rat (N. Colas-Linhart).

Iodine deficiency in the world: where do we stand at the turn of the century?

Iodine deficiency is the leading cause of preventable mental retardation. Universal salt iodization (USI), calling for all salt used in agriculture, food processing, catering and household to be iodized, is the agreed strategy for achieving iodine sufficiency. This article reviews published information on programs for the sustainable elimination of the iodine deficiency disorders and reports new data on monitoring and impact of salt iodization programs at the population level. Currently, 68% of households from areas of the world with previous iodine deficiency have access to iodized salt, compared to less than 10% a decade ago. This great achievement, a public health success unprecedented in the field of noncommunicable diseases, must be better recognized by the health sector, including thyroidologists. On the other hand, the managers and sponsors of programs of iodized salt must appreciate the continuing need for greatly improved monitoring and quality control. For example, partnership evaluation of iodine nutrition using the ThyroMobil model in 35,223 schoolchildren at 378 sites of 28 countries has shown that many previously iodine deficient parts of the world now have median urinary iodine concentrations well above 300 microg/L, which is excessive and carries the risk of adverse health consequences. The elimination of iodine deficiency is within reach but major additional efforts are required to cover the whole population at risk and to ensure quality control and sustainability.

The ThyroMobil model for standardized evaluation of iodine deficiency disorder control in Indonesia.

Indonesia used to be affected by varying degrees of iodine deficiency. Salt iodization has been the adopted strategy on a national basis since 1979. The prevalence of goiter in school-age children (SAC) determined by palpation subsequently markedly decreased within the next 15 years. The objective of the present work was to perform an updated evaluation of the status of iodine nutrition in Indonesia by using standardized methods for the measurement of thyroid volume by ultrasounds and the concentration of urinary iodine in SAC. The survey included 7,447 SAC ages 6 to 12 years from 129 sites selected by multistage and stratified sampling in five provinces (4 in Java plus Sumatra and the Province of Bali). A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites. In Java plus Sumatra, the median urinary iodine was 195 microg/L. Thirty-four percent of the values were within normal limits (between 100 and 200 microg/L); 17.2% were below 100 microg/L and 48.8% were above 200 microg/L, including 18.2% above 300 microg/L and 0.7% above 1000 microg/L. In Bali, the median was 81 microg/L with 58.3% of the values below 100 microg/L and only 14.7% of the values above 200 microg/L. The prevalence of goiter determined by ultrasounds and using the World Health Organization/International Council for Control of Iodine Deficiency Disorders (WHO/ICCIDD) normative values for gender and age was 3.0% in Java plus Sumatra and 1.9% in Bali. The values were 8.0% and 12.5%, respectively, when using reference values for Indonesia established during the present survey in an iodine replete area in central Java. In conclusion, (1) iodine deficiency has been eliminated in large parts of Indonesia; (2) Bali is still affected by mild iodine deficiency; (3) in many places, iodine deficiency has been replaced by iodine excess, occasionally potentially toxic; (4) the WHO/ICCIDD normative values for thyroid volume measured by ultrasound in SAC are not valid for Indonesia; (5) in Indonesia, the level of salt iodization could be decreased and the biological monitoring of urinary iodine at the population level should be reinforced and maintained; (6) the ThyroMobil model has, as in other parts of the world, demonstrated its efficiency in the organization of partnership evaluation and monitoring of iodine nutrition, as well as in social mobilization.

Iodine deficiency during infancy and early childhood in Belgium: does it pose a risk to brain development?

Iodine deficiency is well documented in Belgium in adults including pregnant women, adolescents, schoolchildren, and neonates, but no data are available in the age group 6 months-3 years. We investigated the status of iodine nutrition in 111 healthy subjects in this age group in an attempt to evaluate the risk of brain damage due to iodine deficiency in Belgium. In 244 causal urine samples collected in these subjects, the median concentration of iodine was 101 micrograms/l vs 180-220 micrograms/l under normal conditions. The daily supplementation of the subjects with a physiological dose of 90 micrograms iodine was followed by a slow and progressive increase of urinary iodine, which reached a normal level only after a delay of about 30 weeks of therapy. This observation suggests that part of the supplement of iodine offered to the children was stored in their thyroid glands until the iodine content of the gland had reverted to normal, reflecting the state of hyperavidity of the thyroid for iodide characteristic of iodine deficiency. In conclusion, infants and young children in Belgium are as iodine deficient as all other age groups of the population and, consequently, are at risk of brain damage. This works further illustrates the need for systematic iodine supplementation of the population in Belgium.

Iodine deficiency as a cause of brain damage.

This editorial reviews the impact of iodine deficiency (1) on thyroid function in pregnant women and neonates and (2) on the neurointellectual development of infants and children. All degrees of iodine deficiency (mild: iodine intake of 50-99 microg/day, moderate: 20-49 microg/day, and severe: <20 microg/day) affect thyroid function of the mother and the neonate as well as the mental development of the child. The damage increases with the degree of the deficiency, with overt endemic cretinism as the severest consequence. Maternal hypothyroxinaemia during early pregnancy is a key factor in the development of the neurological damage in the cretin. Selenium deficiency combined with iodine deficiency partly prevents the neurological damage but precipitates severe hypothyroidism in cretins. Iodine deficiency results in a global loss of 10-15 IQ points at a population level and constitutes the world's greatest single cause of preventable brain damage and mental retardation.

A programme of iodine supplementation using only iodised household salt is efficient--the case of Poland.

BACKGROUND: Iodine prophylaxis in Poland started in 1935 and has been interrupted twice: by World War II and in 1980 for economic reasons. Epidemiological surveys carried out after the Chernobyl accident in 1989 as well as in 1992/1993 and in 1994 as a 'ThyroMobil' study, revealed increased prevalence of goitre in children and adults. Ninety per cent of Poland was classified as an area of moderate iodine deficiency, and 10%, in the seaside area, as mild iodine deficiency territory. Iodine prophylaxis based on iodisation of household salt was introduced again in 1986 as a voluntary model and in 1997 as a mandatory model with 30+/-10 mg KI/kg salt. OBJECTIVE: The evaluation of the obligatory model of iodine prophylaxis in schoolchildren from the same schools in 1994 and 1999. METHODS: Thyroid volume was determined by ultrasonography. Ioduria in casual morning urine samples was measured using Sandell-Kolthoff's method, within the framework of the ThyroMobil study. RESULTS: Goitre prevalence decreased from 38.4 to 7% and urinary iodine concentration increased from 60.4 to 96.2 microg/l mean values between 1994 and 1999. In four schools the prevalence of goitre diminished below 5%. In 1999, 70% of children excreted over 60 microg I/l, and 36% over 100 microg I/l, whereas in 1994 the values were 44 and 13% respectively. CONCLUSION: The present findings indicate that iodine prophylaxis based only on iodised household salt is highly effective.

Toward a consensus on reference values for thyroid volume in iodine-replete schoolchildren: results of a workshop on inter-observer and inter-equipment variation in sonographic measurement of thyroid volume.

OBJECTIVE: Interpretation of thyroid ultrasonography for assessing goiter prevalence requires valid reference criteria from iodine-sufficient populations. Reports have suggested the current reference criteria for thyroid volume (T(vol)) of WHO/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) may be too high. Our objective was to determine if inter-observer and/or inter-equipment variability contributes to the disagreement in sonographic T(vol) in children reported from iodine-sufficient areas. DESIGN: A 2-day workshop in which four experienced ultrasound examiners from around Europe measured T(vol) in 45 6--12-year-old Swiss schoolchildren using four different portable ultrasound machines. One of the participating examiners (observer A) had generated the T(vol) data in European children that are the basis for the WHO/ICCIDD reference criteria. METHODS: Sonographic T(vol) was measured in each child by all four examiners on all four machines. Six hundred and eighty-four examinations were completed, with examiners having no knowledge of one another's results. Inter-observer and inter-equipment variation was calculated. RESULTS: Mean inter-equipment variation in T(vol) was 15.2% (95% CI: 14.1, 16.3%). There were no significant differences in T(vol) between equipment (P=0.51). For all observers, the mean inter-observer variation in T(vol) was 25.6% (95% CI: 23.9, 27.2%). At all ages and all body surface areas, there was a large systematic measurement bias (+30% volume) between the mean T(vol) of observer A and the mean Tvol of observers B, C and D. Reanalysis using data from observers B, C and D reduced the mean inter-observer variation in T(vol) to 13.3% (95% CI: 11.9, 14.7%). A correction factor for the systematic difference of operator A for the P50 and P97 of T(vol) was estimated using analysis of covariance. When applied to the WHO/ICCIDD reference data, it sharply reduced the discrepancy between the WHO/ICCIDD criteria and those from other iodine-sufficient children around the world. CONCLUSIONS: Inter-equipment error contributes minimally to reported differences in sonographic T(vol). Even among experienced examiners, inter-observer variation in sonographic T(vol) in children can be high, and probably contributes to the current disagreement on normative values in iodine-sufficient children. A systematic bias at least partially explains why the WHO/ICCIDD reference data differ from those reported from other iodine-sufficient children around the world. The findings argue strongly for the standardization of methods used for sonographic measurement of T(vol) in children.

The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny.

The adequate functioning of both the maternal and fetal thyroid glands play an important role to ensure that the fetal neuropsycho-intellectual development progresses normally. Three sets of clinical disorders are considered, that may eventually lead to impaired brain development. Firstly, in infants with a defect of glandular ontogenesis (congenital hypothyroidism), the participation of maternal thyroid hormones to the fetal circulating thyroxine environment is normal and, therefore, risk of brain damage results exclusively from the insufficient hormone production by the abnormal fetal thyroid gland. Secondly, when it is only the maternal thyroid gland that is functionally deficient (autoimmune hypothyroidism), the severity and temporal occurrence of maternal underfunction will both drive the resulting consequences for impaired fetal neuronal development. Clinical situations of this type may obviously take place already during early gestation (in women with known but untreated hypothyroidism) or appear only during later gestational stages (in women who have AITD and remain euthyroid during the first half of gestation). Lastly, in conditions with iodine deficiency, both maternal and fetal thyroid functions are affected and, therefore, it is primarily the degree and precocity of the maternal hypothyroxinemia due to iodine deficiency during pregnancy that will drive the potential repercussions for fetal neurological development. In the present review, we summarize available data and develop our present concepts concerning the complex feto-maternal thyroid relationships and the potential impacts of thyroid function abnormalities on the ideal development of the offspring.

Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene.

We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect.

Silent iodine prophylaxis in Western Europe only partly corrects iodine deficiency; the case of Belgium.

OBJECTIVE: Belgium is one of the Western European countries in which no program of iodine-deficiency correction using iodized salt has been implemented, in spite of well-documented mild iodine deficiency. In 1995, the median urinary iodine concentration was 55 microg/l (normal: 100-200) and the prevalence of goiter was 11% (normal: below 5%) in representative samples of schoolchildren aged 6-12 years. Based on these results, the authors of the present study and others had emphasized to health professionals and to the public the necessity for iodine supplementation. The objective of this study was to evaluate as to whether these efforts had resulted in an improvement in the status of iodine nutrition. DESIGN: We performed a national survey of the status of iodine nutrition in Belgium based on the determination of thyroid volume, obtained by ultrasonography, and urinary iodine concentrations in schoolchildren. METHODS: A mobile van equipped with an ultrasound instrument, a computer and a deep-freeze visited 23 schools selected from across the country. The sample included 2855 schoolchildren (1365 boys and 1490 girls) aged 6-12 years. RESULTS: The results show a homogeneous situation in the whole country, with a median urinary iodine concentration of 80 microg/l and a goiter prevalence of 5.7%. Urinary iodine slightly decreases with age in girls and reaches a critical value of 59 microg/l at the age of 12 years, together with a goiter prevalence of 18.4%. CONCLUSION: Iodine nutrition has improved slightly in Belgium but mild iodine deficiency continues, with public-health consequences. The improvement indicates silent iodine prophylaxis, as no official salt-iodization measures have been taken. Silent iodine prophylaxis only partly corrects iodine deficiency in Western Europe. Active measures, including the implementation of a program of salt iodization, are urgently required.