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.

More cost-effective management of patients with musculoskeletal disorders in primary care after direct triaging to physiotherapists for initial assessment compared to initial general practitioner assessment.

BACKGROUND: A model for triaging patients in primary care to provide immediate contact with the most appropriate profession to treat the condition in question has been developed and implemented in parts of Sweden. Direct triaging of patients with musculoskeletal disorders (MSD) to physiotherapists at primary healthcare centres has been proposed as an alternative to initial assessment by general practitioners (GPs) and has been shown to have many positive effects. The aim of this study was to evaluate the cost-effectiveness from the societal perspective of this new care-pathway through primary care regarding triaging patients with MSD to initial assessment by physiotherapists compared to standard practice with initial GP assessment. METHODS: Nurse-assessed patients with MSD (N = 55) were randomised to initial assessment and treatment with either physiotherapists or GPs and were followed for 1 year regarding health-related quality of life, utilization of healthcare resources and absence from work for MSD. Quality-adjusted life-years (QALYs) were calculated based on EQ5D measured at 5 time-points. Costs for healthcare resources and production loss were compiled. Incremental cost-effectiveness ratios (ICERS) were calculated. Multiple imputation was used to compensate for missing values and bootstrapping to handle uncertainty. A cost-effectiveness plane and a cost-effectiveness acceptability curve were construed to describe the results. RESULTS: The group who were allocated to initial assessment by physiotherapists had slightly larger gains in QALYs at lower total costs. At a willingness-to-pay threshold of 20,000 €, the likelihood that the intervention was cost-effective from a societal perspective including production loss due to MSD was 85% increasing to 93% at higher thresholds. When only healthcare costs were considered, triaging to physiotherapists was still less costly in relation to health improvements than standard praxis. CONCLUSION: From the societal perspective, this small study indicated that triaging directly to physiotherapists in primary care has a high likelihood of being cost-effective. However, further larger randomised trials will be necessary to corroborate these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02218749 . Registered August 18, 2014.

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.

Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin.

OBJECTIVE: To assess the effect of treatment with a St John's Wort product (Movina) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. DESIGN: Controlled, randomized, open, crossover pharmacodynamic study. SETTING: Two primary healthcare centres. Intervention. Patients were treated with Movina one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). SUBJECTS: Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10-40 mg daily) for at least three months. MAIN OUTCOME MEASURES: Assessments of total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. RESULTS: All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks' active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total-cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). CONCLUSION: Products containing St John's Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin.

Ser49Gly of beta1-adrenergic receptor is associated with effective beta-blocker dose in dilated cardiomyopathy.

OBJECTIVE: Our objective was to evaluate the influence of polymorphisms at codons 49 and 389 of the beta1-adrenergic receptor (beta1-AR) on the response to beta-blockers and outcome in patients with dilated cardiomyopathy. METHODS: We genotyped both codons of the beta1-AR in 375 patients with dilated cardiomyopathy and 492 control subjects. RESULTS: Neither of the polymorphisms was associated with susceptibility for dilated cardiomyopathy. In a retrospective analysis of patients receiving beta-blockers, there was a significant association between long-term survival rate and codon 49 (P = .014) but not codon 389 (P = .08). Despite a similar mean heart rate (69 beats/min), patients with the Ser49 genotype tended to have higher doses of beta-blockade compared with Gly49 carriers (P = .065). In patients receiving a low dose of beta-blockade (< or = 50% of targeted full dose), the 5-year mortality rate was lower among Gly49 carriers than Ser49 patients (risk ratio [RR], 0.24; 95% confidence interval [CI], 0.07-0.80; P = .020). In patients receiving high doses of beta-blockers, there was no significant difference in outcome between genotypes (P = .20), which was attributable to a better outcome for Ser49 patients treated with a high dose of beta-blockade as compared with a low dose. Gly49 carriers had a similar survival rate with different doses of beta-blockers. With low-dose beta-blockers, both codon 49 (RR, 0.26; 95% CI, 0.08-0.89; P = .029) and codon 389 (RR, 2.42; 95% CI, 1.04-5.63, P = .039) were related to 5-year mortality rate. CONCLUSION: In patients with heart failure, the influence of codon 49 on the outcome and effect of beta-blockers appeared to be more pronounced than that of codon 389. The more common Ser49Ser genotype responded less beneficially to beta-blockade and would motivate genotyping to promote higher doses for the best outcome effect.