[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.

Effects of iodine supplementation during pregnancy on pregnant women and their offspring: a systematic review and meta-analysis of trials over the past 3 decades.

OBJECTIVE: The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant growth parameters and neurocognitive development using meta-analysis. METHODS: A systematic review was conducted on trials published from January 1989 to December 2019 by searching MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar. For most maternal and neonatal outcomes, a narrative synthesis of the data was performed. For birth anthropometric measurements and infant neurocognitive outcomes, the pooled standardized mean differences (SMDs) with 95% CIs were estimated using fixed/random effect models. RESULTS: Fourteen trials were eligible for inclusion in the systematic review, of which five trials were included in the meta-analysis. Although the findings of different thyroid parameters are inconclusive, more consistent evidence showed that iodine supplementation could prevent the increase in thyroglobulin concentration during pregnancy. In the meta-analysis, no differences were found in weight (-0.11 (95% CI: -0.23 to 0.01)), length (-0.06 (95% CI: -0.21 to 0.09)), and head circumference (0.26 (95% CI: -0.35 to 0.88)) at birth, or in cognitive (0.07 (95% CI: -0.07 to 0.20)), language (0.06 (95% CI: -0.22 to 0.35)), and motor (0.07 (95% CI: -0.06 to 0.21)) development during the first 2 years of life in infants between the iodine-supplemented and control groups. CONCLUSION: Iodine supplementation during pregnancy can improve the iodine status in pregnant women and their offspring; however, according to our meta-analysis, there was no evidence of improved growth or neurodevelopmental outcomes in infants of iodine-supplemented mothers.

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: Iodine supplementation for preventing iodine deficiency disorders in children.

BACKGROUND: Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched. SELECTION CRITERIA: We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency. DATA COLLECTION AND ANALYSIS: Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation.There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation.Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient. AUTHORS' CONCLUSIONS: Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.

Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.

In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used. In the first two groups, the mothers were treated with 0.025% MMI during the critical period of the pregnancy. In the third group, as the control group, the mothers and pups were not treated. Euthanasia was applied to the pups in Group I on Day 10, and to the pups in Groups II and III on Day 21. In the biochemical analyses, total T4 levels of both mothers and pups in Group I and II were found to be lower than those of the control group. Histopathologically, karyopyknosis in migrating neurons and demyelinization were observed in both groups. Caspase-3 and -9 expressions and TUNEL reactions showed parallelism to these findings. eNOS and iNOS activities were also increased in Groups I and II. CB2 receptor activity was observed in the fore and mid brain in Group I, and in the whole brain in Group II. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1334-1347, 2017.

Ação odontológica na triagem neonatal direcionada ao hipotireoidismo congênito / Dental action in the neonatal screening directed to congenital hypothyroidism

O hipotireoidismo congênito é um distúrbio endócrino caracterizado pela diminuição dos níveis séricos dos hormônio da glândula tireóide. Este afeta o metabolismo do cálcio, e, portanto, a formação dos ossos e dentes. É comum nestes pacientes anomalias de formação dentária, atraso na erupção dentária, hipodesenvolvimento do côndilo mandibular e macroglossia. Somados, estes fatores podem ainda levar a uma má-oclusão e ao desenvolvimento inadequado das funções orais. Diante do exposto, Avaliou-se através deste estudo as condições clínicas orais e promoveu-se o atendimento odontológico dos pacientes com esta disfunção endócrina vinculados ao serviço de triagem neonatal do Hospital Universitário da Universidade Federal de Sergipe. Trata-se de um projeto de extensão em que foram atendidos 205 pacientes com idade entre 01 mês e 14 anos, no período de fevereiro à novembro de 2016, os quais passaram por uma avaliação clínica e receberam orientações preventivas. A partir do exame clínico, observou-se que 20% dos pacientes apresentavam alguma necessidade de tratamento odontológico, sendo esses, agendados e encaminhados para a realização do procedimento clínico odontológico. Com os dados obtidos foi possível concluir que é essencial dar aos responsáveis e pacientes as informações necessárias para a prevenção de doenças bucais, estando elas correlacionadas ou não com o Hipotireoidismo Congênito. Além disto, a realização de tratamento clínico, preventivo e curativo nesses pacientes, agregou a Odontologia ao plano multiprofissional já existente representado pelo programa de triagem neonatal do HU ­ UFS.(AU)

Congenital hypothyroidism is an endocrine disorder characterized by a decrease in the serum levels of thyroid gland hormones. This affects the metabolism of calcium, and therefore the formation of bones and teeth. It is common on those patients dental formation anomalies, delayed dental eruption, hypo development of the mandibular condyle and macroglossia. In addition, these factors may also lead to malocclusion and inadequate development of oral functions.In view of the above, this study was chosen as oral clinical conditions and it was promoted in the dental care of patients with this endocrine dysfunction linked to the neonatal screening service of the University Hospital of the Federal University of Sergipe. It is an extension project in which 205 patients aged between 1 month and 14 years were attended, in the period of February to November of 2016, who underwent a clinical evaluation and received preventive guidance. From the clinical examination, it was observed that 20% of the patients had a need for dental treatment, and they were scheduled and sent to perform a dental procedure. With the obtained data, it was possible to conclude that it is essential to give the responsible ones and patients the necessary information for the prevention of oral diseases, being they correlated or not with Congenital Hypothyroidism. In addition, performing clinical, preventive and curative treatment in these patients, added the Dentistry to the existing multiprofessional plan represented by the neonatal screening program of the HU ­ UFS.(AU)

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.

The Importance of Adequate Iodine during Pregnancy and Infancy.

Iodine requirements are increased ≥50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birth weight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10-20%. Mild-to-moderate maternal iodine deficiency can cause thyroid dysfunction, but whether it impairs cognitive and/or neurological function in the offspring remains uncertain. In nearly all regions affected by iodine deficiency, salt iodization is the most cost-effective way of delivering iodine and improving maternal and infant health.

Protective effects of GM-CSF in experimental neonatal hypothyroidism.

Hypothyroidism induced by methimazole (MMI), has a negative impact on the postnatal development. Neonatal Granulocyte Macrophage-Colony Stimulating Factor [GM-CSF; 50µg/kg, intramuscular injection at postnatal day (PND) 17] had been tested to ameliorate the effects of MMI [0.05%, (weight per volume; w/v), intraperitoneal injection at PND 15]-induced hypothyroidism in Wistar rats. The hypothyroid conditions due to the administration of MMI produced inhibitory effects on neonatal serum thyroxine (T4), 3,5,3'-triiodothyronine (T3), neutrophil count in bone marrow and blood, cerebellar glutathione (GSH) and acetylcholinesterase (AchE), although it induced stimulatory actions on serum thyrotropin (TSH), growth hormone (GH), insulin growth factor-II (IGF-II), tumor necrosis factor alpha (TNF-α), and cerebellar malondialdehyde (MDA) at PND 19. The treatment with GM-CSF could reverse the depressing and stimulating effects of MMI on these markers except for cerebellar AchE where its enhancement was non-significant (P>0.05) at tested PND. Thus, neonatal GM-CSF may be responsible for suppressing autoimmune responses and preventing hypothyroidism.

NEW BORN SCREENING IN PREVENTING CONGENITAL HYPOTHYROIDISM.

Congenital Hypothyroidism is one of the most common preventable causes of mental retardation which is highly prevalent in our society due to lack of a national neonatal screening program, lack of education of the parents, increased consanguinity, and lack of suspicion from doctor's leads to delayed diagnosis and an increased incidence of congenital hypothyroidism in our society. This Menace can be easily tackled with a mass neonatal screening program and effective legislation which would make sure that serious efforts are being made to eradicate this preventable disease from Pakistan.

Effect of iodine supplementation in pregnancy on child development and other clinical outcomes: a systematic review of randomized controlled trials.

BACKGROUND: Routine iodine supplementation during pregnancy is recommended by leading health authorities worldwide, even in countries where the iodine status of the population is sufficient. OBJECTIVES: We evaluated the efficacy and safety of iodine supplementation during pregnancy or the periconceptional period on the development and growth of children. Secondary outcomes included pregnancy outcome and thyroid function. DESIGN: A systematic review of randomized controlled trials (RCTs) was conducted. PUBMED, MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials databases were searched to identify relevant RCTs. RESULTS: Fourteen publications that involved 8 trials met the inclusion criteria. Only 2 included trials reported the growth and development of children and clinical outcomes. Iodine supplementation during pregnancy or the periconceptional period in regions of severe iodine deficiency reduced risk of cretinism, but there were no improvements in childhood intelligence, gross development, growth, or pregnancy outcomes, although there was an improvement in some motor functions. None of the remaining 6 RCTs conducted in regions of mild to moderate iodine deficiency reported childhood development or growth or pregnancy outcomes. Effects of iodine supplementation on the thyroid function of mothers and their children were inconsistent. CONCLUSIONS: In this review, we highlight a lack of quality evidence of the effect of prenatal or periconceptional iodine supplementation on growth and cognitive function of children. Although contemporary RCTs of iodine supplementation with outcomes addressing childhood development are indicated, conduct of such RCTs may not be feasible in populations where iodine supplementation in pregnancy is widely practiced.

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.

[Thyroid dysfunction in pregnant women: clinical dilemmas]. / Schildklierdisfunctie bij zwangeren: klinische dilemma's.

Hypothyroidism and hyperthyroidism are associated with maternal and neonatal pregnancy complications. Hypothyroidism should be treated with levothyroxine. Hyperthyroidism requires treatment with propylthiouracil or thiamazole. Subclinical hypothyroidism and thyroid auto-immunity are also associated with maternal and neonatal pregnancy complications. For both subclinical hypothyroidism and thyroid auto-immunity, treatment with levothyroxine has not yet been proven to be effective in preventing complications during pregnancy. For the Dutch population the following reference values for TSH levels during pregnancy may be used: 0.01-4.00 mU/l in the first and second trimesters. Reference values for the third trimester have not reported for this population, but are probably comparable with those of the second trimester.

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.

Combating iodine deficiency disorders to achieve millennium development goal 4 in India: reduction in infant mortality rate.

In severe iodine deficient areas, iodine deficiency has been documented to be an important etiological factor leading to poor fetal growth and development. Iodine is essential for physical growth and development of the central nervous system of the fetus. Iodine deficiency in pregnant mothers leads to increased incidence of infertility and abortions, perinatal mortality and infant child mortality. The clinical iodine supplementation trials have documented adverse health consequences due to iodine deficiency. Evidence from observational studies concludes that prevention of iodine deficiency can lead to reduction in infant mortality rate and facilitate to achieve millennium development goal-4.

Economic evaluation of iodine deficiency disorder control program in Sikkim: a cost effectiveness study.

BACKGROUND: Edible salt iodization and iodized oil injections are the two most commonly used vehicles for iodine supplementation. In year 1989, the state government of Sikkim was planning to implement Iodine Deficiency Disorder control program in state and had following two options to choose from, based on existing knowledge; a) a salt iodization program, b) an iodized oil injection program. No information was available at that point of time on comparative advantages of the above stated two approaches. OBJECTIVES: To identify the most cost-effective alternative for IDD elimination in Sikkim, amongst the following 3 alternatives: a) Iodized salt program (ISP), b) Iodized oil injection program (IOP) to high risk group, c) no preventive program. MATERIALS AND METHODS: Study population was the general population of state of Sikkim, India in year 1990. Cost- effective analysis was undertaken comparing 3 alternative programs, targeted towards IDD elimination in state of Sikkim. Identification, measurement and valuation of the costs of ISP and IOP and identification and measurement of the consequences of IDD were done to carry out the cost-effective analysis. Visible goiter person years (VGPY), endemic cretinism, IDD attributable death were used to assess the health consequences/disease burden of IDD. RESULTS: The cost per VGPY, endemic cretinism and IDD attributable death were Rs 76.67, Rs 24,469 and Rs 9,720, respectively for ISP. The cost per VGPY, endemic cretinism and IDD attributable death were Rs 75.82, Rs 19,106 and Rs 7,709, respectively for IOP. CONCLUSION: The results of the analysis showed that iodized oil program is more cost-effective for prevention of irreversible IDDs than the iodated salt program in state of Sikkim, India.

Thyroid disorders during pregnancy.

Thyroid physiology is altered during pregnancy as a result of an increase in thyroid-binding globulin, the stimulatory effect of hCG on TSH receptors, and increased peripheral thyroid hormone requirements. In addition, hyper and hypothyroid disorders are prevalent among women of reproductive age, and most of them have a significant impact on the gravida, fetus and neonate. Aberrant thyroid function can be readily recognized and treated during pregnancy, avoiding such complications. Here, we will review the thyroid function changes occurring during pregnancy, the different disorders, their maternal and fetal implications, and the ways to screen, prevent and treat these conditions.

Bocio congénito. A propósito de un caso / Congenital goiter

Introducción. La incidencia del hipotiroidismo congénito es de 1:3.000 a 1:4.000 recién nacidos. El bocio congénito no es una forma de presentación común. Caso clínico. Se presenta el caso de una recién nacida con consanguinidad de primer grado entre los padres, que nace mediante cesárea electiva a las 38 semanas. La somatometría es congruente con la edad gestacional. Es hija de una madre diabética pregestacional con buen control metabólico y función tiroidea previa normal. Se presenta con hipotonía, soplo cardíaco y masa cervical anterior en el tercer día de vida. Se sospecha un hipotiroidismo congénito, diagnóstico que se confirma mediante los datos analíticos (tirotropina elevada con tiroxina indetectable) y la ecografía tiroidea. Se inicia tratamiento sustitutivo con tiroxina de forma inmediata con una notable mejoría clínica y analítica. Comentarios. Se revisan las entidades etiológicas del hipotiroidismo congénito, y se discuten las correlaciones clínicas entre diferentes entidades. Además, se enfatiza la necesidad del tratamiento sustitutivo precoz para asegurar un desarrollo neurocognitivo óptimo(AU)

Introduction. Congenital hypothyroidism occurs in approximately 1:3,000 to 1:4,000 newborns. Congenital goiter is not a common presentation of this disease. Case report. We report the case of a female infant born from first-degree consanguineous parents at 38 weeks of gestational age via elective cesarean section. Somatometry was according to her gestational age. The mother had pre-gestational diabetes mellitus with good metabolic control, and normal thyroid function. The newborn was found to have mild hypotonia, a cardiac murmur, and an anterior cervical mass on the third day of life. Congenital hypothyroidism was suspected; the diagnosis was confirmed by elevated thyrotropin and low free thyroxin, and thyroid sonography. Levothyroxin was started immediately, resulting in a significant clinical improvement. Comments. The causes of congenital hypothyroidism are reviewed, and clinical correlations between the different etiologies are discussed. The need for immediate treatment with levothyroixine to ensure an optimal neurocognitive outcome is emphasized(AU)