Modelling the contribution of iodised salt in industrially processed foods to iodine intake in Macedonia.

Evidence from the 1950s showed that Macedonia was iodine deficient. After the introduction of mandatory universal salt iodisation, the country saw a steady increase in iodine intake and decline in goitre prevalence, earning iodine-deficiency free status in 2003. Iodine status assessments in 2007 and 2016 showed adequate iodine intake among school age children (median urinary iodine concentration of 241 µg/L and 236 µg/L respectively). Macedonia participated in piloting the Iodine Global Network Programme Guidance on the use of iodised salt in industrially processed foods to better understand potential iodised salt intake from processed foods. One objective of implementation was to identify the need, opportunities, and required actions to strengthen the processed food component of the national salt iodisation policy. Data from the 2017 Household Consumption and Expenditure Survey (HCES) was used to determine household salt consumption, to identify widely-consumed, salt-containing industrially processed foods, and estimate typical daily intake of these foods. Their estimated contribution to iodine intake was estimated based on their salt content and the percentage of food industry salt that is iodised. Although the study has limitations, including a relatively small selection of foods, the results indicate potential iodine intake from iodised household salt and iodised salt in the selected foods of nearly 300% of the Estimated Average Requirement and over 220% of the Recommended Nutrient Intake for adults. This was approximately 50% of the tolerable safe Upper Level for iodine intake. The study confirmed high daily salt intake (11.2 grams from household salt only). Successful salt reduction would be expected to reduce iodine intake, however, modelling with 10% and 30% reduction implied this is unlikely to put any population group at risk of deficiency. It is recommended that implementation of salt iodisation and salt reduction policies are harmonized, alongside continued regular iodine status monitoring for different population groups.

ISOLATED MATERNAL HYPOTHYROXINEMIA AND ITS PERINATAL OUTCOME IN NORTH MACEDONIA.

Isolated maternal hypothyroxinemia (IMH) is defined as the presence of low maternal total thyroxine (TT4) level in conjunction with normal maternal thyroid-stimulating hormone (TSH) level. The aim was to investigate whether IMH is associated with adverse pregnancy outcome in North Macedonia. Dried blood spot samples were obtained from 359 pregnant women meeting the inclusion criteria and analyzed for TT4 and TSH. Postpartum data were entered from their medical histories. Out of 359 women, 131 (37.42%) belonged to IMH group. There were statistically significant differences in birth weight (p=0.043), intrauterine growth restriction (IUGR) (p=0.028), Apgar score at 1 min <7 (p=0.018) and cesarean section for dystocia/disproportion (p=0.024) between the IMH and normal thyroid function (NTF) groups. In regression analysis, TSH was a significant variable predicting Apgar score (ßst=0.05597, p=0.047), body mass index predicting birth weight (ßst=0.02338, p=0.045) and TT4 predicting small for gestational age/IUGR (ßst=-0.089834, p=0.029) in IMH group. TT4 was a strong predictor of birth weight (ßst=-0.004778, p=0.003) and premature delivery (ßst=0.028112, p=0.004) in NTF group. The impact of IMH in pregnancy remains controversial. IMH was associated with an increased maternal BMI and higher birth weight of neonates. Overweight could be a potential risk factor for thyroid dysfunction in pregnant women, and specifically IMH. The worst fetal outcome was seen in IMH mothers examined in second trimester. We found TSH, TT4 and BMI to be strong predictors of perinatal outcomes.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia.

OBJECTIVE: Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). METHODS: Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). RESULTS: Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypothyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). CONCLUSION: Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

OBJETIVO: As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). MéTODOS: Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). RESULTADOS: Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). CONCLUSãO: Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Centenary of the Birth of Academician Prof. Dr. Isak Tadzer, Founder of the Pathophysiology and Nuclear Medicine in Macedonia.

Academician Prof. Dr. Isak Tadzer was born a hundred years ago on December 24, 1916 in Sofia. He completed the primary and secondary education at the German College in Sofia. In 1935 he began his studies at the Medical Faculty in Vienna, which he had to stop because of the annexation of Austria to Germany in 1938. He returned to Bulgaria where he continued his studies and graduated from the Medical Faculty in Sofia in 1941. During the War, 1941-1944, he was forcedly mobilized and he worked as a doctor in several villages. He was twice interned in camps in Bulgaria. In 1944 he joined the National Liberation Army and the Partisan Groups of Yugoslavia. After the liberation in 1945 he started specialization in internal medicine at the famous clinic of Prof. Chilov in Sofia. In 1946 he applied to the call by the Yugoslav government to the doctors in Bulgaria to come in aid of temporary work in our country. On the advice of the current Federal Minister of Public Health Dr. Dimitar Nestorov, Dr. Tadzer came to Skopje and was assigned to work in the Country hospital. He started specialization in internal medicine at the famous professor Ignjatovski, he established a family and decided to stay in Skopje. In 1949 Prof. Tadzer ended his specialization and he was elected an Assistant at the Department of Internal Medicine. In 1951 he left the Internal Clinic and he was elected an Assistant, and in 1952 he was elected a Docent in the subject of Pathological Physiology. In 1959 he was elected, and in 1964 he was re-elected as an Associate Professor, and in 1967 he was elected a Professor of pathophysiology at the Medical Faculty in Skopje. In the period from 1952 to 1978 he was Head of the Department and Director of the Institute of Pathophysiology. He was elected a Corresponding Member of the Macedonian Academy of Sciences and Arts in 1969, and a Full Member in 1974. In the period from 1984 to 1988 he was a Secretary of the Department of Medicine and Biology of the Academy. Prof. Tadzer has published over 300 scientific papers in the field of clinical medicine and pathological physiology, of which about 200 in journals in English, French, German and Serbo-Croatian, as well as 15 books, which include him among the most prolific pathophysiologists on the territory of former Yugoslavia and beyond. In the period from 1950 to 1966 several times he was on a vocational training in similar institutions and centers in Europe, and in 1972 he was on a study stay at many nuclear and medical laboratories in the USA. In addition to his great research activities his contribution as a teacher was of substantial influence and importance to the faculty. He was one of the greatest lectures at the Medical Faculty, the Faculty of Stomatology and the Pharmaceutical Faculty. Prof. Tadzer co-authored in most of the textbooks on pathophysiology for students of medicine, stomatology and pharmacy. He was an extraordinary physician, one of the pillars of the Macedonian medicine, he possessed universal, encyclopedic knowledge and is one of the most renowned medical workers in the second half of the 20th century in Macedonia. In addition to the scientific, medical and educational work Prof. Tadzer has especially rich social activity. He was President of the Faculty Council in 1975-76, he was Vice Dean of the Medical Faculty in 1958-60, Dean of the Faculty from 1963 to 1965, Dean of the Pharmaceutical Faculty and Vice Rector of the University from 1965 to 1967. Especially it should be noted his long-lasting activity at the Macedonian Medical Association of more than 50 years. Also, significant is his creative work within the Editorial board of the journal "Macedonian Medical Review", where for more than 15 years he was Editor in Chief or member of the Editorial board. For his complete activity Prof. Tadzer has won numerous diplomas, plaques and awards, and among them the following are emphasized: National Award of October 11, Order of Labor of Second Degree, the Award of the City of Skopje - November 13, the Charter of Dr. Trifun Panovski and the Certificate of Acknowledgement awarded by the Macedonian Medical Association for the outstanding results in advancing the medical science, practice and development of the health care and the long-term contribution and promotion of the MMA.

Ensuring Effective Prevention of Iodine Deficiency Disorders.

BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. SUMMARY: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.