Universal Salt Iodization Provides Sufficient Dietary Iodine to Achieve Adequate Iodine Nutrition during the First 1000 Days: A Cross-Sectional Multicenter Study.

Background: Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d. Objective: We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups. Methods: We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk. Results: The salt iodine concentration was low (<15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (>40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia. Conclusions: Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

The application of serum iodine in assessing individual iodine status.

CONTEXT: The prevalence of thyroid disease in China is on the rise, and this could be partly associated with excessive iodine intake in some individuals; therefore, increased attention is being paid to individual iodine status. However, current indices are not appropriate for evaluating individual iodine status. OBJECTIVE: To evaluate the association between serum iodine and urinary iodine (UI), as well as thyroid diseases, and provide an excellent base for future individual iodine status assessment. DESIGN, SUBJECTS AND MEASUREMENTS: A total of 902 adults were enrolled in this study including 325, 286 and 291 subjects from regions in China where iodine is adequate, sufficient and in excess, respectively. Serum iodine, UI and thyroid function were assessed, and ultrasonography performed in all subjects. RESULTS: The median serum iodine values of adults with subclinical hypothyroidism, high serum autoantibody and thyroid nodules were significantly higher than those of euthyroid adults (P<0.05). A serum iodine level higher than 100 µg/L was considered as a risk factor for thyroid diseases. Serum iodine had strong nonlinear correlations with UI and thyroid function. When thyroid function was taken as a gold standard, the area under the receiver operating characteristic (ROC) curve for serum iodine was 0.752 and UI was 0.507 for subjects with lower serum iodine and UI levels. The area for serum iodine was 0.773 and UI was 0.638 for subjects with higher serum iodine and UI levels. The areas under these curves were significantly different (P<0.001). CONCLUSION: In adults, serum iodine had a strong nonlinear correlation with UI and a high level of serum iodine was a risk factor for thyroid diseases.

Breast Milk Iodine Concentration Is a More Accurate Biomarker of Iodine Status Than Urinary Iodine Concentration in Exclusively Breastfeeding Women.

Background: Iodine status in populations is usually assessed by the median urinary iodine concentration (UIC). However, iodine is also excreted in breast milk during lactation; thus, breast milk iodine concentration (BMIC) may be a promising biomarker of iodine nutrition in lactating women. Whether the mammary gland can vary fractional uptake of circulating iodine in response to changes in dietary intake is unclear.Objective: We evaluated UIC and BMIC as biomarkers for iodine status in lactating women with a wide range of iodine intakes.Methods: We recruited 866 pairs of lactating mothers and exclusively breastfed infants from 3 iodine-sufficient study sites: Linfen, China (n = 386); Tuguegarao, Philippines (n = 371); and Zagreb, Croatia (n = 109). We also recruited iodine-deficient lactating women from Amizmiz, Morocco (n = 117). We collected urine and breast milk samples and measured UIC and BMIC.Results: In the 3 iodine-sufficient sites, a pooled regression analysis of the estimated iodine excretion revealed higher fractional iodine excretion in breast milk than in urine at borderline low iodine intakes. In contrast, in the iodine-deficient site in Morocco, a constant proportion (∼33%) of total iodine was excreted into breast milk.Conclusions: In iodine-sufficient populations, when iodine intake in lactating women is low, there is increased partitioning of iodine into breast milk. For this reason, maternal UIC alone may not reflect iodine status, and BMIC should also be measured to assess iodine status in lactating women. Our data suggest a BMIC reference range (2.5th and 97.5th percentiles) of 60-465 µg/kg in exclusively breastfeeding women. This trial was registered at clinicaltrials.gov as NCT02196337.

The relationship between iodine nutrition and thyroid disease in lactating women with different iodine intakes.

Areas with low, adequate and excessive I content in water co-exist in China. Limited data are currently available on I nutrition and thyroid disease in lactating women and their breast-fed infants with different I intakes. This study aimed to evaluate I nutrition in both lactating women and their infants and the prevalence of thyroid disease in areas with different levels of I in water. From January to June 2014, a total of 343 healthy lactating women (excluding those taking anti-thyroid drugs or I supplements within a year of the study, consuming seafood at the time of the study or those diagnosed with congenital thyroid disease) from Beihai in Guangxi province and Jiajiazhuang, Yangcheng, Jicun and Pingyao townships in Shanxi province were selected. Compared with the I-sufficient group, median urinary I concentrations in both lactating women and infants as well as breast milk I levels were significantly lower in the I-deficient group (P<0·001). The prevalence of thyroid disease in lactating women, particularly subclinical hypothyroidism, was higher in the I-excess group than in the I-sufficient group (P<0·05). In areas with excessive water I content, high thyroid peroxidase antibody and high thyroglobulin levels were risk factors for abnormal thyroid-stimulating hormone levels. Our data collectively suggest that excessive I intake potentially causes subclinical hypothyroidism in lactating women. Moreover, enhanced monitoring of I status is important to avoid adverse effects of I deficiency or excess, particularly in susceptible populations such as pregnant or lactating women and infants.

What Iodine Intervention Measures Should Be Taken in Different Water Iodine Areas? Evidence from a Cross-sectional Chinese Survey.

The aim of this study was to assess the population's iodine nutrition and thyroid diseases in different water iodine areas and to offer suggestions to the governments of different countries to adjust the present policy in different water iodine areas. A cross-sectional survey was conducted in different water iodine areas in China. Urinary iodine, water iodine, salt iodine and thyroid function were determined. The thyroid volumes and nodules were measured by ultrasound. Upon categorization by water iodine level for the 10.0 ~ 39.9 µg/L, 40.0 ~ 100.0 µg/L and 100.1 ~ 150.0 µg/L areas, in adults, the prevalence of subclinical hypothyroidism was 9.28%, 5.35% and 11.07%, and the median urinary iodine (MUI) was 153.7 µg/L, 189.8 µg/L and 317.0 µg/L; in children of the three areas, the prevalence of goitre was 3.83%, 4.47% and 16.02%, and the MUI was 164.1 µg/L, 221.0 µg/L and 323.3 µg/L; in pregnant women of those areas, the MUI was 148.6 µg/L, 176.9 µg/L and 324.9 µg/L. Logistic regression results indicated that low iodine intake was a risk factor for developing hypothyroxinaemia in pregnant women. The iodine status of pregnant women is insufficient in areas with a median water iodine level of 10.0 ~ 39.9 µg/L. Low iodine intake increases the risk of developing hypothyroxinaemia in pregnant women. The iodine status of adults and children is excessive, and the iodine status of pregnant women is above the requirements in areas with a median water iodine concentration of 100.1 ~ 150.0 µg/L. Iodized salt, especially for pregnant women, should be supplied in areas with a median water iodine concentration of 10.0 ~ 39.9 µg/L to improve the iodine status of pregnant women. Supplying non-iodized salt is not enough to protect local residents from the harm from excess iodine in areas with a median water iodine concentration above 100.0 µg/L.

Effect of Urinary Iodine Concentration in Pregnant and Lactating Women, and in Their Infants Residing in Areas with Excessive Iodine in Drinking Water in Shanxi Province, China.

It is uncertain how many factors affect urinary iodine concentration. The aim of this study was to determine the effect of consumption of drinking water with high iodine concentration on urinary iodine concentration in pregnant and lactating women, and infants. We included 218 lactating women and their infants and 142 pregnant women in areas with suitable and high water iodine content. Urine, serum, and water iodine concentration were assessed. Breastfeeding women living in areas with high water iodine content had a greater likelihood of iodine sufficiency or iodine excess [odds ratio (P = 0.044, P < 0.001)] compared with women living in areas with suitable water iodine content. Older women were less likely to have higher urinary iodine concentration (P = 0.041). Pregnant women who consumed milk > 4 times weekly during pregnancy were more likely to be iodine sufficient (P = 0.028). Living in areas with high water iodine content for > 5 years is a risk factor for iodine excess (P < 0.001, P = 0.007). There is a probability of higher urinary iodine concentration in pregnant and lactating women and their infants living in areas with high water iodine content. Age had an effect on iodine excess in lactating women. Consumption of milk > 4 times a week during pregnancy and living in an area with high iodine water content for > 5 years were associated with iodine sufficiency and iodine excess in pregnant women.

The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease.

Autoimmune thyroid disease (AITD) is a recurrent and refractory clinical endocrine disease. Some studies have shown that the incidence of AITD is not only related to iodine, a kind of environmental factor, but that susceptibility genes also play a crucial role in its pathogenesis. Since research on susceptibility genes is still underway, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related to susceptibility to AITD, and to explore the risk factors in the occurrence of AITD. Blood samples from five AITD patients and five controls from each area were assessed by chromosome microarray to identify candidate genes. The copy number (CN) of the candidate genes and urinary iodine levels were determined in adults, including 158 AITD patients and 181 controls, from areas having different iodine statuses. The cell growth-related genes, glypican 5 (GPC5), B9 domain containing 2 (B9D2), and ankyrin repeat and suppressor of cytokine signaling [SOCS] box-containing protein family 11 (ASB11), were selected as the candidate genes. The distribution of GPC5, B9D2, and ASB11 CNVs in AITD patients and controls was significantly different, and high urinary iodine levels and GPC5 CNVs are risk factors for AITD. There was no significant association between urinary iodine level and CNVs of the candidate genes. High urinary iodine levels and GPC5 CNVs are risk factors for AITD, but an association with the occurrence of AITD was not found.

Effects of Excessive Iodine Intake on Blood Glucose, Blood Pressure, and Blood Lipids in Adults.

To understand the effects of excess iodine intake on blood glucose, blood pressure, and blood lipids in adults. We selected three villages from Shanxi Province to conduct cross-sectional survey: Maxi [median water iodine concentration (MWIC) 6.3 µg/L, median urinary iodine concentration (MUIC) 126.6 µg/L, 320 adults]; Xiwenzhuang (MWIC 79.8 µg/L, MUIC 221.2 µg/L, 264 adults); and Gaoche (MWIC 506.0 µg/L, MUIC 421.3 µg/L, 241 adults). According to the urinary iodine levels in adults, the three villages were defined as iodine-adequate, iodine-sufficient, and iodine-excess. Urinary iodine, water iodine, thyroid function, blood glucose, blood pressure, and blood lipids were measured. Compared with the iodine-adequate area, blood glucose and systolic and diastolic pressure of adults in iodine-sufficient and iodine-excess areas increased and high-density lipoprotein-cholesterol decreased (all P < 0.001). Urinary iodine, thyroid-stimulating hormone, and free thyroxine have a nonlinear correlation with blood glucose (R2 = 0.8174, 0.8264, and 0.8520, respectively). Excessive iodine intake may result in elevated blood glucose and blood pressure and has some influence on blood lipids, and may increase the risk of hypertension and diabetes.

Thyroglobulin Is Markedly Elevated in 6- to 24-Month-Old Infants at Both Low and High Iodine Intakes and Suggests a Narrow Optimal Iodine Intake Range.

BACKGROUND: In areas with incomplete salt iodization coverage, infants and children aged 6-24 months weaning from breast milk and receiving complementary foods are at risk of iodine deficiency. However, few data exist on the risk of excessive iodine intake in this age group. Thyroglobulin (Tg) is a sensitive marker of iodine intake in school-age children and adults and may be used to estimate the optimal iodine intake range in infancy. The aim of this study was to assess the association of low and high iodine intakes with Tg and thyroid function in weaning infants. METHODS: This multicenter cross-sectional study recruited infants aged 6-24 months (n = 1543; Mage = 12.2 ± 4.6 months) receiving breast milk with complementary foods, from seven countries in areas with previously documented deficient, sufficient, or excessive iodine intake in schoolchildren or pregnant women. Urinary iodine concentration (UIC) and Tg, total thyroxine, and thyrotropin were measured using dried blood spot testing. RESULTS: Median UIC ranged from 48 µg/L (interquartile range 31-79 µg/L) to 552 µg/L (interquartile range 272-987 µg/L) across the study sites. Median Tg using dried blood spot testing was high (>50 µg/L) at estimated habitual iodine intakes <50 µg/day and >230 µg/day. Prevalence of overt thyroid disorders was low (<3%). Yet, subclinical hyperthyroidism was observed in the countries with the lowest iodine intake. CONCLUSIONS: Tg is a sensitive biomarker of iodine intake in 6- to 24-month-old infants and follows a U-shaped relationship with iodine intake, suggesting a relatively narrow optimal intake range. Infants with low iodine intake may be at increased risk of subclinical thyroid dysfunction. In population monitoring of iodine deficiency or excess, assessment of iodine status using UIC and Tg may be valuable in this young age group.

[Investigation and analysis of neonate deformity in water arsenic exposure areas].

OBJECTIVE: To explore the level and feature of neonate deformity in water arsenic exposure areas, as to finding out an evidence for the study and prevention of the arsenic exposure. METHODS: The birth situation of neonate was surveyed from 1998 to 2004 in water arsenic exposure areas according to cross-sectional survey. The results were classified in accordance with ICD-10 and common surveillance of china. The population of Shanyin County served as the common people and the data were analyzed by SPSS 11.5 for windows. RESULTS: The neonates surveyed were 2467 cases. There were 49 neonates deformity found in this investigation, giving a neonate deformity rate of 198.62 per 10,000 cases, which was shown significantly higher in water arsenic exposure areas than in the normal (U = 3.23, P < 0.01), with types of nervous system deformity, limbs deformity and congenital heart disease as in system classification. There was no significant difference of deformity rate in different sex neonates (chi2 = 0.32, P > 0.05). CONCLUSION: The drinking high-arsenic water over a long period of time should be a risk factor of neonate deformity. Prevention and treatment of endemic arsenic exposure should be urgently needed.

Association of TSHR Gene Copy Number Variation with TSH Abnormalities.

Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As3+-Ce4+ catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p = 0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC > 200 µg/l (OR = 1.49, 95% CI = 1.01-2.22) and the TSHR gene (OR = 6.01, 95% CI = 1.96-18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.

Copy Number Variation of Immune-Related Genes and Their Association with Iodine in Adults with Autoimmune Thyroid Diseases.

BACKGROUND: Autoimmune thyroid diseases (AITD) are complex conditions that are caused by an interaction between genetic susceptibility and environmental triggers. Iodine is already known to be an environmental trigger for AITD, but genes associated with susceptibility need to be further assessed. Therefore, the aims of this study were to assess the association between copy number variations (CNVs) and AITD, to identify genes related with susceptibility to AITD, and to investigate the interaction between iodine status and CNVs in the occurrence of AITD. METHODS: Blood samples from 15 patients with AITD and 15 controls were assessed by chromosome microarray to identify candidate genes. The copy number of candidate genes and urinary iodine level was determined in adults from areas of different iodine statuses including 158 patients and 181 controls. RESULTS: The immune-related genes, SIRPB1 and TMEM91, were selected as candidate genes. The distribution of SIRPB1 CNV in AITD patients and controls was significantly different and was considered a risk factor for AITD. There was no significant association between urinary iodine level and candidate gene CNVs. CONCLUSION: SIRPB1 CNV and an excess of iodine were risk factors for AITD, but an association with the occurrence of AITD was not found.

[Epidemiological investigation on thyroid disease among fertile women in different iodine intake areas of Shanxi province].

OBJECTIVE: To understand the prevalence of thyroid diseases and its influencing factors of iodine on thyroid gland function and autoimmune among fertile women in different iodine intake areas. METHODS: Cross-sectional method was used for descriptive epidemiology. 236 women aged 19 to 45 years were sampled in 2011, in Shanxi province. Questionnaire was used to include general data on place, name, age etc. Sample of water from home, one time random urine sample and venous blood were collected to test the iodine contents using arsenic and cerium catalysis spectrophotometric methods. Finally, in blood, free triiodothyronine (FT3), free thyroxine (FT4), thyrotrophin (TSH) in blood were tested under auto-CLIA and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) through radio-immunological methods. RESULTS: 1)The urine iodine's medians were 486.9 µg/L for fertile women in high iodine areas, and 192.6 µg/L in low iodine areas, with difference on urine iodine level statistically significant (Z = -10.676, P = 0.000). 2) Levels of blood FT3 and FT4 in women from high iodine areas were obviously lower than those from proper iodine areas(t = -2.884, P = 0.004; t = -2.862, P = 0.005), but the level of TSH in high iodine areas was higher than that of proper iodine areas(t = 2.332, P = 0.021). 3) In both areas, the rate of the thyroid dysfunction with positive antibodies was obviously higher than those with negative antibodies (χ² = 20.941, P = 0.000;χ² = 5.596, P = 0.018), while the rate of the thyroid dysfunction with positive antibodies and the level of TSH in the blood for high iodine women higher than those in women with proper iodine level(χ² = 5.708, P = 0.37;t = -2.177, P = 0.031). 4)The morbidity rate of inferior clinical hyperthyroidism for women in high iodine areas was obviously higher than those in proper iodine areas(χ² = 9.542, P = 0.003), while the morbidity rate of inferior clinical hypothyroidism for women with positive antibodies in two areas obviously higher than those with negative antibodies (χ² = 17.264, P = 0.000; χ² = 6.002, P = 0.044). CONCLUSION: Morbidity rate of inferior clinical hypothyroidism for women in high iodine areas was obviously higher than those in proper iodine areas, suggesting that there were potential risks of hypothyroidism for overdose iodine intake which causing the existence of positive thyroid antibodies. Monitoring programs on iodine nutrition and thyroid function among women living in high iodine areas should be strengthened.

The standard, intervention measures and health risk for high water iodine areas.

Our study aims to clarify the population nutrient status in locations with different levels of iodine in the water in China; to choose effective measurements of water improvement(finding other drinking water source of iodine not excess) or non-iodised salt supply or combinations thereof; to classify the areas of elevated water iodine levels and the areas with endemic goiter; and to evaluate the risk factors of water iodine excess on pregnant women, lactating women and the overall population of women. From Henan, Hebei, Shandong and Shanxi province of China, for each of 50 ∼ 99 µg/L, 100 ∼ 149 µg/L, 150 ∼ 299 µg/L, and ≥ 300 µg/L water iodine level, three villages were selected respectively. Students of 6-12 years old and pregnant were sampled from villages of each water-iodine level of each province, excluded iodized salt consumer. Then the children's goiter volume, the children and pregnant's urinary iodine and water iodine were tested. In addition, blood samples were collected from pregnant women, lactating women and other women of reproductive age for each water iodine level in the Shanxi Province for thyroid function tests. These indicators should be matched for each person. When the water iodine exceeds 100 µg/L; the iodine nutrient of children are iodine excessive, and are adequate or more than adequate for the pregnant women. It is reasonable to define elevated water iodine areas as locations where the water iodine levels exceed 100 µg/L. The supply of non-iodised salt alone cannot ensure adequate iodine nutrition of the residents, and water improvement must be adopted, as well. Iodine excess increases the risk of certain thyroid diseases in women from one- to eightfold.