Urinary iodine excretion and optimal time point for sampling when estimating 24-h urinary iodine.

Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 µg/24 h and the median UIC (all spot samples) was 104 µg/l. UIC (P < 0·001), 24UIE (P = 0·001) and e24UIE (P < 0·001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0·001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7·4 v. 5·3 µg/h, P < 0·001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

A randomized, double-blind study of iodine supplementation during pregnancy in Sweden: pilot evaluation of maternal iodine status and thyroid function.

PURPOSE: Pregnant women in Sweden are mildly iodine deficient. We investigated the effect of daily iodine supplementation on the iodine and thyroid status of pregnant women. METHODS: In this pilot, randomized, double-blind trial, 200 thyroid-healthy pregnant women were recruited at mean (standard deviation) pregnancy week 8.85 (1.62) and assigned (1:1) to daily intake of a multivitamin tablet with or without 150 µg of iodine. Urine and serum samples were collected at baseline and once during the second and third trimesters. Urinary iodine concentration (UIC), serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOabs) were analyzed. Neonatal TSH data were collected. UIC and Tg were also analyzed in a group of 89 thyroid-healthy non-pregnant women of reproductive age (WRA). RESULTS: At baseline, the intervention and the control groups had similar median UIC (interquartile range (IQR)): 110 µg/L (74-119) and 111 µg/L (66-168), respectively. The intervention group reached iodine sufficiency with median UIC (IQR) 139 µg/L (89-234) and 136 µg/L (91-211) in the second and third trimester, respectively, without significant difference from the lower limit of the recommended range, i.e. 150-250 µg/L (p = 0.42 and p = 0.87, respectively). The intervention group had higher median UIC and lower median Tg compared to the control group during the second (p < 0.001 and p = 0.019, respectively) and third trimester (p < 0.001 and p = 0.003, respectively), whereas thyroid hormones, serum TPOabs, and neonatal TSH were similar. The WRA group presented median UIC (IQR) 65 µg/L (30-98) and median Tg (IQR) 18 µg/L (13-27). CONCLUSION: A daily supplement containing 150 µg of iodine to a group of pregnant women with mild iodine deficiency improved the iodine status from mild ID to iodine sufficiency. This improvement seems to have had a positive impact on maternal thyroglobulin. This study is now under extension to investigate the children's neuropsychological development. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02378246, May 3, 2015, retrospectively registered.

Inadequate iodine intake in lactating women in Sweden: A pilot 1-year, prospective, observational study.

INTRODUCTION: Breastfed infants depend on breast-milk iodine for growth and brain development, as iodine is a trace element important for thyroid hormone production. Iodine need is higher during lactation; hence, mothers and children are at risk of iodine deficiency. We aimed to explore maternal iodine and thyroidal status during lactation. MATERIAL AND METHODS: Pregnant women were recruited in Gothenburg, southwest Sweden. Maternal urine and serum were collected at pregnancy week 35-37 (n = 84) and 0.5, 4, and 12 months postpartum. Seventy mothers provided breast milk at 0.5 months. RESULTS: Median (interquartile range) breast-milk iodine concentration was 90 (66-116) µg/L. About 58% had breast-milk iodine concentration <100 µg/L. Iodine supplement users (n = 13) had higher breast-milk iodine concentration than non-users (n = 49) (140 µg/L vs 71 µg/L, P = .001). Exclusively breastfeeding women at 4 months postpartum (n = 57) had lower median urinary iodine concentration (85 µg/L vs 133 µg/L, P = .004) and higher thyroglobulin serum concentration (22.3 µg/L vs 11.8 µg/L, P = .032) than non-exclusively breastfeeding women (n = 25). Concentrations of thyroid hormones were unaffected. CONCLUSIONS: This pilot study suggests that lactating women in southwest Sweden present mildly inadequate iodine intake, mainly among non-iodine supplement users and exclusively breastfeeding mothers. Studies on the coverage of the iodine fortification program in breastfeeding women are warranted.

Iodine deficiency in pregnant women in Sweden: a national cross-sectional study.

PURPOSE: Voluntary salt iodization at 50 mg/kg salt ensures adequate iodine nutrition in Swedish school-aged children, but iodine status in pregnant women is uncertain. METHODS: We conducted a cross-sectional national study of 743 pregnant women, at median gestational age of 23 weeks (IQR 9, 38), recruited from maternal health care centers. We measured: urinary iodine concentration (UIC) and urinary creatinine concentration in spot urine samples; thyroglobulin (Tg), thyroid-stimulating hormone (TSH), and total thyroxine (tT4) on dried blood spots (DBS); and thyreoperoxidase antibodies in serum samples. Data on dietary supplement use were obtained, and women were classified as supplement users (consuming multivitamins containing ≥ 150 µg iodine/day) and non-supplement users (no supplements or < 150 µg iodine/day from supplements). RESULTS: Overall median UIC [bootstrapped 95% confidence interval (CI)] was 101 µg/L (95, 108; n = 737): 149 µg/L (132, 164) in supplement users (n = 253) and 85 µg/L (79, 92) in non-supplement users (n = 440) (p < 0.001). Overall geometric mean DBS-Tg (95% CI) was 22.1 µg/L (20.8, 23.5; n = 675) and the prevalence of elevated DBS-Tg was 19%. DBS-Tg was lower in supplement users (n = 229) than in non-supplement users (n = 405) (19.1 vs 24.4 µg/L, p < 0.001). DBS-TSH, DBS-tT4, and S-TPOab positivity did not differ between the two groups. CONCLUSIONS: Pregnant women in Sweden have inadequate iodine nutrition. Women not taking iodine supplements containing ≥ 150 µg iodine/day are affected by mild iodine deficiency and are at higher risk for increased thyroid activity, while maintaining euthyroidism. Iodine intake should be improved in women both before and after conception by promotion of iodized salt instead of non-iodized salt. We urge regular monitoring of iodine status in the general Swedish population, as well as in risk groups.

Correlations of water iodine concentration to earlier goitre frequency in Sweden-an iodine sufficient country with long-term iodination of table salt.

BACKGROUND: Before iodination of Swedish table salt in 1936, iodine deficiency resulting in goitre and hypothyroidism was common. Sweden has become iodine sufficient, as shown in a national survey in 2007, proving its iodination fortification programme effective for the general population. The objective of this study was to collect drinking water from water treatment plants nationally and test if water iodine concentration (WIC) correlated to urinary iodine concentration (UIC) of school-aged children in a national survey 2007 to former goitre frequency in 1929 and to thyroid volume data in 2007. METHODS: In 2012, 166 treatment plants, located in 57% (166 of 290) of all Swedish municipalities, were asked to collect drinking water samples of approximately 10 ml. In 2007, tap water samples of the same volume were collected from 30 randomly selected schools for the national survey. Analysis of WIC was done in both treatment plants in 2012 (n = 166) and tap water in 2007 (n = 30). The correlation of WIC to the children's UIC and thyroid volume after iodination was tested based on data from the national survey in 2007. The association of WIC to former goitre frequency was tested based on pre-iodination data, derived from a map of goitre frequency drawn in 1929. RESULTS: The median WIC from water treatment plants was 4.0 µg/L (range 0-27 µg/L). WIC was similar in coastal and inland areas, for both ground and surface water. WIC correlated with historical goitre areas and was lower in the goitre areas than in non-goitre areas (p < 0.001). WIC in the same municipalities as the schools correlated with the UIC of children (p < 0.01), but not with their thyroid volume. CONCLUSIONS: WIC still contributes to iodine nutrition in Sweden, but iodination overrides the goitre effect.

Role of iodine-containing multivitamins during pregnancy for children's brain function: protocol of an ongoing randomised controlled trial: the SWIDDICH study.

INTRODUCTION: Iodine is essential for normal brain development. Moderate and severe fetal iodine deficiency results in substantial to serious developmental delay in children. Mild iodine deficiency in pregnancy is associated with neurodevelopmental deficits in the offspring, but evidence from randomised trials is lacking. The aim of the Swedish Iodine in Pregnancy and Development in Children study is to determine the effect of daily supplementation with 150 µg iodine during pregnancy on the offspring's neuropsychological development up to 14 years of age. METHODS AND ANALYSIS: Thyroid healthy pregnant women (n=1275: age range 18-40 years) at ≤12 weeks gestation will be randomly assigned to receive multivitamin supplements containing 150 µg iodine or non-iodine-containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children-V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years. Iodine status (urinary iodine concentration) will be measured during pregnancy and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones, thyroglobulin), and deiodinase type 2 polymorphisms will be measured during pregnancy and in the offspring at 7 and 14 years. Structural MRI or other relevant structural or functional brain imaging procedures will be performed in a subgroup of children at 7 and 14 years. Background and socioeconomic information will be collected at all follow-up times. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee in Göteborg, Sweden (Diary numbers: 431-12 approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017 (children follow-up)). According to Swedish regulations, dietary supplements are governed by the National Food Agency and not by the Medical Product Agency. Therefore, there is no requirement for a monitoring committee and the National Food Agency does not perform any audits of trial conduct. The trial will be conducted in accordance with the Declaration of Helsinki. The participating sites will be contacted regarding important protocol changes, both orally and in writing, and the trial registry database will be updated accordingly. Study results will be presented at relevant conferences, and submitted to peer-reviewed journals with open access in the fields of endocrinology, paediatrics and nutrition. After the appropriate embargo period, the results will be communicated to participants, healthcare professionals at the maternal healthcare centres, the public and other relevant groups, such as the national guideline group for thyroid and pregnancy and the National Food Agency. TRIAL REGISTRATION NUMBER: NCT02378246; Pre-results.

Iodine Status After Bariatric Surgery-a Prospective 10-Year Report from the Swedish Obese Subjects (SOS) Study.

CONTEXT: Bariatric surgery can lead to nutrient deficiencies. Gastric by-pass (GBP) entails restriction and malabsorption, whereas, vertical banded gastroplasty (VBG) is only restrictive. OBJECTIVE: The objective of this study is to study whether GBP-patients develop iodine deficiency from malabsorption, and if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE) than obese non-operated controls (OB-controls) due to lower iodine intake. DESIGN: The Swedish Obese Subjects (SOS) study is a prospective, non-randomized study of 4047 obese patients included 1987-2001, who chose bariatric surgery or non-surgical treatment. SOS-groups were compared at baseline, after 2 and 10 years and with population-based subsamples (MONICA-controls). PATIENTS: One hundred eighty-eight GBP-patients were matched with 188 VBG-patients and 188 OB-controls and with three subgroups from 412 MONICA-controls. MAIN OUTCOME MEASUREMENTS: Primary outcome was 24-UIE. Secondary outcomes were iodine intake, iodine supplementation, TSH, FT4, and thyroid morbidity. RESULTS: At baseline, median 24-UIE was higher in GBP-patients, VBG-patients and OB-controls than in MONICA-controls (214, 201, 203 and 137 µg/day, p < 0.001). At 10 years, 24-UIE in GBP-patients (161 µg/day) and VBG-patients (149 µg/day) was lower compared with baseline (p < 0.01) and OB-controls (189 µg/day, p < 0.01), but similar to 24-UIE in MONICA-controls (137 µg/day). The 10-year-dietary iodine intake was similar in GPB-patients and OB-controls, but higher in VBG-patients. Iodine supplementation was taken by 0-9% in SOS-groups. CONCLUSION: After surgery, GBP- and VBG-patients did not suffer from iodine deficiency, but both groups had lower iodine status than OB-controls. Dietary supplements recommended after bariatric surgery do not need to include iodine, in iodine sufficient countries. TRIAL REGISTRATION: clinicaltrials.gov : NCT01479452.

Iodine deficiency and nutrition in Scandinavia.

Iodine nutrition is a result of geological conditions, iodine fortification and monitoring strategies within a country together with the dietary habits of the population. This review summarizes the basis for the current iodine situation in the Scandinavian countries in order to identify gaps in knowledge, determine necessary future steps, highlight landmarks in Scandinavian iodine research and consider ongoing studies in Scandinavian countries with high international impact. Historically, iodine deficiency disorders such as goiter were common in Norway and Sweden, but not in Denmark. Different strategies have been used in Scandinavia to improve iodine nutrition. The major source of iodine is iodized salt in Sweden and from milk and dairy products in Norway. In Denmark, drinking water, milk, dairy products and iodized salt used in commercial production of bread are the important sources of iodine. The current iodine status in Scandinavia is not optimal and action is ongoing to increase iodination in Denmark, where there is mild iodine deficiency in the general population. Data from all three countries indicate insufficient iodine nutrition during pregnancy and there is a need for data from children, adolescents and young women. Monitoring a population's iodine status and dietary iodine sources is necessary to secure iodine nutrition in Scandinavia. Ongoing studies in Scandinavia will contribute significantly to the knowledge about the effects of mild to moderate iodine deficiency.