Optimal Assessment and Quantification of Iodine Nutrition in Pregnancy and Lactation: Laboratory and Clinical Methods, Controversies and Future Directions.

Iodine intake must be boosted during pregnancy to meet the demands for increased production and placental transfer of thyroid hormone essential for optimal foetal development. Failure to meet this challenge results in irreversible brain damage, manifested in severity from neurological cretinism to minor or subtle deficits of intelligence and behavioural disorders. Attention is now being focused on explaining observational studies of an association between insufficient iodine intake during pregnancy and mild degrees of intellectual impairment in the offspring and confirming a cause and effect relationship with impaired maternal thyroid function. The current qualitative categorisation of iodine deficiency into mild, moderate and severe by the measurement of the median urinary iodine concentration (MUIC) in a population of school-age children, as a proxy measure of dietary iodine intake, is inappropriate for defining the degree or severity of gestational iodine deficiency and needs to be replaced. This review examines progress in analytical techniques for the measurement of urinary iodine concentration and the application of this technology to epidemiological studies of iodine deficiency with a focus on gestational iodine deficiency. We recommend that more precise definitions and measurements of gestational iodine deficiency, beyond a spot UIC, need to be developed. We review the evidence for hypothyroxinaemia as the cause of intrauterine foetal brain damage in gestational iodine deficiency and discuss the many unanswered questions, from which we propose that further clinical studies need to be designed to address the pathogenesis of neurodevelopmental impairments in the foetus and infant. Agreement on the testing instruments and standardization of processes and procedures for Intelligence Quotient (IQ) and psychomotor tests needs to be reached by investigators, so that valid comparisons can be made among studies of gestational iodine deficiency and neurocognitive outcomes. Finally, the timing, safety and the efficacy of prophylactic iodine supplementation for pregnant and lactating women needs to be established and confirmation that excess intake of iodine during pregnancy is to be avoided.

Pre-analytical Factors Influence Accuracy of Urine Spot Iodine Assessment in Epidemiological Surveys.

Urinary iodine concentration (UIC) is commonly used to assess iodine status of subjects in epidemiological surveys. As pre-analytical factors are an important source of measurement error and studies about this phase are scarce, our objective was to assess the influence of urine sampling conditions on UIC, i.e., whether the child ate breakfast or not, urine void rank of the day, and time span between last meal and urine collection. A nationwide, two-stage, stratified, cross-sectional study including 1560 children (6-12 years) was performed in 2012. UIC was determined by the Sandell-Kolthoff method. Pre-analytical factors were assessed from children's mothers by using a questionnaire. Association between iodine status and pre-analytical factors were adjusted for one another and socio-economic characteristics by multivariate linear and multinomial regression models (RPR: relative prevalence ratios). Skipping breakfast prior to morning urine sampling decreased UIC by 40 to 50 µg/L and the proportion of UIC < 100 µg/L was higher among children having those skipped breakfast (RPR = 3.2[1.0-10.4]). In unadjusted analyses, UIC was less among children sampled more than 5 h from their last meal. UIC decreased with rank of urine void (e.g., first vs. second, P < 0.001); also, the proportion of UIC < 100 µg/L was greater among 4th rank samples (vs. second RPR = 2.1[1.1-4.0]). Subjects' breakfast status and urine void rank should be accounted for when assessing iodine status. Providing recommendations to standardize pre-analytical factors is a key step toward improving accuracy and comparability of survey results for assessing iodine status from spot urine samples. These recommendations have to be evaluated by future research.

Lebanese children are iodine deficient and urinary sodium and fluoride excretion are weak positive predictors of urinary iodine.

PURPOSE: To assess iodine and fluoride status among Lebanese children. METHODS: A nationally representative cross-sectional study of 6- to 10-year-old schoolchildren was conducted using multistage cluster sampling. Spot urine samples were collected from 1403 children, and urinary iodine, fluoride, creatinine and sodium levels were measured. Salt samples from markets (n = 30) were tested for iodine concentration by titration. RESULTS: Median urinary iodine concentration was 66.0 µg/l, indicating mild deficiency, and almost 75 % of Lebanese children had a urinary iodine concentration (UIC) <100 µg/l. UIC was higher among children from private schools and in areas of higher socioeconomic status. Most salt samples were fortified at levels far below the legislated requirement, and 56 % of samples contained less than 15 ppm iodine. Fluoride-to-creatinine ratio (F/Cr) was 0.250 (0.159-0.448) mg/g. There were weak positive correlations between UIC and urinary sodium (r 2 = 0.039, P value <0.001) and UIC and urinary fluoride (r 2 = 0.009, P value <0.001). CONCLUSIONS: Lebanese elementary school children are iodine deficient due to inadequately iodized salt. The weak correlation between UIC and urinary sodium suggests most dietary iodine does not come from iodized salt. The poor correlation between UIC and urinary fluoride suggests that fluoride intake is not affecting iodine metabolism. Efforts are needed in Lebanon to improve industry compliance with salt fortification through improved monitoring and enforcement of legislation.

Assessment of Nutritional Status of Iodine Through Urinary Iodine Screening Among Local Children and Adolescents After the Fukushima Daiichi Nuclear Power Plant Accident.

BACKGROUND: Iodine deficiency is an important modifier of the risk of thyroid cancer following irradiation. However, little information is available on the prevalence of iodine deficiency in Fukushima and its surroundings after the Fukushima Daiichi nuclear power plant accident that occurred in March 2011. METHODS: In order to assess urinary iodine concentrations (UIC) and the prevalence of iodine deficiency and to elucidate any associations between demographic characteristics and UIC levels among children and adolescents aged ≤18 years at the time of the accident in Fukushima Prefecture and its surroundings, the data on voluntary UIC testing conducted by Hirata Central Hospital, Fukushima, were evaluated. RESULTS: A total of 4410 children and adolescents with a median age of 10 years at examination underwent UIC testing between October 2012 and October 2015. Calculated for all the participants, the median UIC level was 204 µg/L (range 25-21,100 µg/L). There were 133 (3.0%), 732 (16.6%), and 1472 (33.4%) participants with UIC levels of <50, <100, or ≥300 µg/L, respectively. Based on the World Health Organization criteria for nutritional iodine status, no participants were severely iodine deficient (<20 µg/L), but 16.6% of the population were mildly (50-100 µg/L) or moderately (20-50 µg/L) iodine deficient. While no significant difference in UIC was noted between those who did and did not increase dietary iodine intake after the accident (p = 0.93), there were significant differences by year (p < 0.01), school level (p < 0.001), and residential area at the time of the accident (p < 0.001). CONCLUSIONS: This study demonstrates that the children and adolescents examined had a sufficient amount of iodine during the period 1.5-4.5 years after the nuclear accident. In addition to the differences in the scale and the countermeasures undertaken between the Fukushima and Chernobyl accidents, differences in dietary iodine intake might have played an additional role in resulting in the reportedly different radiation doses to the thyroid between the two nuclear accidents.

Iodine Nutritional Status in Schoolchildren from Public Schools in Brazil: A Cross-Sectional Study Exposes Association with Socioeconomic Factors and Food Insecurity.

INTRODUCTION: National programs of salt iodization were implemented in Brazil to combat iodine deficiency (ID) in children of school age. Currently, there are limited data in Brazil on those still vulnerable to this deficiency and the state of nutritional iodine status in the northeast region of Brazil, where children are vulnerable to malnutrition. OBJECTIVE: The aim of this study was to analyze the iodine nutritional status, household food insecurity, socioeconomic and demographic characteristics among schoolchildren from the public school system living in state the state of Bahia, Brazil. METHODS: A cross-sectional study was conducted on 1419 schoolchildren in Bahia between the ages of 6 and 14 years old. Anthropometric parameters, urinary iodine concentrations (UIC), and thyrotropin (TSH) measurements were evaluated from blood spots on filter paper. RESULTS: The mean UIC was 206.4 ± 80.5 µg/L, with a median of 221.6 µg/L, indicating sufficient iodine intake in the region. Low urinary iodide concentration (<100 µg/L) was detected in 12.3% of the schoolchildren (n = 174), with 6.2% with mild (<100 µg/L), 3.0% with moderate (20-49 µg/L), and 3.1% with severe ID (<20 µg/L). Moreover, 9.4% (n = 134) had a urinary iodide concentration of >300 µg/L, indicating the coexistence of excessive iodine intake (EII). The mean TSH was 1.0 ± 0.6 mIU/L. The body mass index category "overweight/obesity" was a protective factor against EII (odds ratio [OR] = 0.64 [confidence interval (CI) 0.4-1.0]; p = 0.07). Urban areas (73%) had a mean UIC of 213.1 ± 80 µg/L compared with 176.8 ± 76.1 µg/L in rural areas. The risk for EII increased in children living in a house with more than six people (OR = 1.62 [CI 0.9-2.6]; p < 0.05) and water consumption from shallow wells (OR = 1.70 [CI 0.9-3.1]; p = 0.09). The risk of ID was increased by 70% in schoolchildren who had moderate or severe food insecurity (OR = 1.70 [CI 0.9-3.0]; p > 0.05). CONCLUSION: A significant proportion of schoolchildren still have ID or EII in the northeast region of Brazil, emphasizing the importance of committed public policies to address this problem. Socioeconomic factors and the lack of education about nutritional importance of iodine were important influencing factors in the presence of ID in schoolchildren.

Iodine status assessment in children: spot urine iodine concentration reasonably reflects true twenty-four-hour iodine excretion only when scaled to creatinine.

BACKGROUND: Currently, the measurement of urinary iodine concentration (UIC, µg/L) is the recommended parameter to assess iodine status, however, the dependency of UIC on urine volume may limit its use as an accurate parameter for monitoring iodine status in populations. Therefore, our objective was to compare two approaches for the assessment of urinary iodine excretion in spot urine samples: UIC (µg/L) and a creatinine-scaled estimate of 24-hour iodine excretion (est24h-UIEcrea [µg/d]) against actually measured 24-hour urinary iodine excretion rates (24h-UIE, µg/d). METHODS: Urinary iodine and creatinine were measured both in 24-hour urine samples and parallel collected spot urine samples from 180 healthy participants of the DONALD Study, aged 6-18 years. 24h-UIE was used as quasi-reference for actual iodine status. Published 24-hour creatinine reference values served to calculate est24h-UIEcrea. Correlation analysis, cross-classifications, and Bland-Altman plots were used to evaluate agreement between the different assessment approaches. RESULTS: Correlation coefficients of 24h-UIE with UIC (r=0.12, r=0.22; p=n.s.) were substantially weaker than with est24h-UIEcrea (r=0.41, r=0.47; p<0.001) in the 6-12 year old and 13-18 year old groups, respectively. Cross-classification into opposite quartiles by UIC was 7% (6-12 year old group) and 15% (13-18 year old group) versus 5% and 3% by est24h-UIEcrea, respectively. Bland-Altman plots indicated greater deviation from 24h-UIE for the UIC versus the est24h-UIEcrea approach. CONCLUSION: Our findings in children and adolescents clearly show a better comparability of real 24h-UIE with est24h-UIEcrea than with UIC. Whenever highest possible validity is required for iodine status assessment from spot urine sampling, the determination of est24h-UIEcrea appears to be the more accurate monitoring approach.

Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design.

To date, marginal, asymptomatic biotin deficiency has been successfully induced experimentally by the use of labor-intensive inpatient designs requiring rigorous dietary control. We sought to determine if marginal biotin deficiency could be induced in humans in a less expensive outpatient design incorporating a self-selected, mixed general diet. We sought to examine the efficacy of three outpatient study designs: two based on oral avidin dosing and one based on a diet high in undenatured egg white for a period of 28 d. In study design 1, participants (n = 4; 3 women) received avidin in capsules with a biotin binding capacity of 7 times the estimated dietary biotin intake of a typical self-selected diet. In study design 2, participants (n = 2; 2 women) received double the amount of avidin capsules (14 times the estimated dietary biotin intake). In study design 3, participants (n = 5; 3 women) consumed egg-white beverages containing avidin with a biotin binding capacity of 7 times the estimated dietary biotin intake. Established indices of biotin status [lymphocyte propionyl-CoA carboxylase activity; urinary excretion of 3-hydroxyisovaleric acid, 3-hydroxyisovaleryl carnitine (3HIA-carnitine), and biotin; and plasma concentration of 3HIA-carnitine] indicated that study designs 1 and 2 were not effective in inducing marginal biotin deficiency, but study design 3 was as effective as previous inpatient study designs that induced deficiency by egg-white beverage. Marginal biotin deficiency can be induced experimentally by using a cost-effective outpatient design by avidin delivery in egg-white beverages. This design should be useful to the broader nutritional research community.

The prevalence of iodine deficiency disorder in two different populations in northern province of Iran: a comparison using different indicators recommended by WHO.

Comparison of the prevalence of iodine deficiency disorder (IDD) in neonates and school children using two different WHO indicators. From 2006 to 2010, 119701 newborns were screened by measurement of serum TSH level by heel prick. Neonates who had blood TSH ≥ 5 mIU/l were recalled for more evaluation. In the same period of time, urine iodine was measured in 1200 school-aged children. The severity of IDD was classified using WHO, UNICEF, ICCIDD criteria. Between 2006 and 2010 a total of 138832 neonates were screened in Guilan province and the total recall rate (neonates with TSH level ≥ 5 mIU/l) was 1.8 %. The incidence rate of Congenital Hypothyroidism (CH) was 1/625. The median urine iodine level in school-aged children was 200-299 µg/l. Considering the WHO, UNICEF, ICCIDD criteria, Guilan province would be classified as a none-IDD endemic area. However, health care systems should pay attention to the iodine excess and the risk of iodine induced hyperthyroidism in this population.

Consuming iodine enriched eggs to solve the iodine deficiency endemic for remote areas in Thailand.

BACKGROUND: Evidence showed that the occurrence of iodine deficiency endemic areas has been found in every provinces of Thailand. Thus, a new pilot programme for elimination of iodine deficiency endemic areas at the community level was designed in 2008 by integrating the concept of Sufficient Economic life style with the iodine biofortification of nutrients for community consumption. METHODS: A model of community hen egg farm was selected at an iodine deficiency endemic area in North Eastern part of Thailand. The process for the preparation of high content iodine enriched hen food was demonstrated to the farm owner with technical transfer in order to ensure the sustainability in the long term for the community. The iodine content of the produced iodine enriched hen eggs were determined and the iodine status of volunteers who consumed the iodine enriched hen eggs were monitored by using urine iodine excretion before and after the implement of iodine enrichment in the model farm. RESULTS: The content of iodine in eggs from the model farm were 93.57 µg per egg for the weight of 55 - 60 g egg and 97.76 µg for the weight of 60 - 65 g egg. The biological active iodo-organic compounds in eggs were tested by determination of the base-line urine iodine of the volunteer villagers before and after consuming a hard boiled iodine enriched egg per volunteer at breakfast for five days continuous period in 59 volunteers of Ban Kew village, and 65 volunteers of Ban Nong Nok Kean village. The median base-line urine iodine level of the volunteers in these two villages before consuming eggs were 7.00 and 7.04 µg/dL respectively. After consuming iodine enriched eggs, the median urine iodine were raised to the optimal level at 20.76 µg/dL for Ban Kew and 13.95 µg/dL for Ban Nong Nok Kean. CONCLUSIONS: The strategic programme for iodine enrichment in the food chain with biological iodo-organic compound from animal origins can be an alternative method to fortify iodine in the diet for Iodine Deficiency Endemic Areas at the community level in Thailand.

A case for universal salt iodisation to correct iodine deficiency in pregnancy: another salutary lesson from Tasmania.

OBJECTIVE: To assess the impact of iodine fortification of bread on the iodine status of pregnant women, and to determine if studies of iodine levels in school-age children were indicative of women's gestational iodine status. DESIGN: Urinary iodine surveys of pregnant Tasmanian women before and after bread was fortified with iodine in October 2001. PARTICIPANTS AND SETTING: 285 women attending the Royal Hobart Hospital (RHH) antenatal clinic from 1 October 2000 to 30 September 2001 and 517 women attending the RHH antenatal clinic or primary health care centres in 2003-2006. MAIN OUTCOME MEASURES: Median urinary iodine concentration (UIC) for comparison against the World Health Organization recommendation of of 150-249 microg/L for pregnant women. RESULTS: Before supplementation, the median UIC of the 285 women attending the RHH antenatal clinic was 76 microg/L. After supplementation, median UICs were 81 microg/L for 288 women attending primary health care centres and 86 microg/L for 229 women attending the RHH antenatal clinic. Differences in mean UIC were not significant for either the antenatal clinic group (P=0.237) or the primary health care group (P=0.809) compared with the pre-supplementation group. CONCLUSIONS: Iodine deficiency in pregnancy persists despite being corrected in Tasmanian children. Successful iodine supplementation must target reproductive-age and pregnant women and be substantiated by ongoing monitoring during pregnancy and lactation. A robust national program for correcting iodine deficiency is urgently needed. Mandatory universal salt iodisation has international endorsement, and should be considered the preferred strategy for eliminating iodine deficiency in Australia.

Persistent iodine deficiency in a cohort of Tasmanian school children: associations with socio-economic status, geographical location and dietary factors.

OBJECTIVE: To determine the adequacy of iodine nutrition of Tasmanian primary school-aged children and to examine possible associations with socio-economic status (SES), location and dietary factors. METHODS: Urinary iodine levels and measures of SES, geographical information and dietary habits were surveyed in a population-based sample of 170 children (4 to 12 years) at baseline (1998/99) and at follow-up (2000/01). RESULTS: Median urinary iodine concentration in 1989--99 and 2000--01 were 75 microg/L (range 15 microg/L to 240 microg/L) and 76 microg/L (range 18 microg/L to 480 microg/L) respectively. No significant associations with SES or geographical location were found. More frequent or recent intake of foods that are likely to be dietary sources of iodine tended to be associated with greater prevalence of adequate urinary iodine, particularly consumption of yoghurt and 'fruche' (p=0.04). CONCLUSIONS: After several decades of iodine sufficiency, Tasmanian primary school-aged children are again mildly iodine-deficient by WHO criteria. Despite reduction in iodophor use by the dairy industry in the past decade, consumption of dairy products continues to be associated with higher levels of iodine nutrition. IMPLICATIONS: The lack of association of iodine levels with SES and geographical location within Tasmania found in our study, and the results of studies of iodine levels in Melbourne and Sydney, suggest that inadequate iodine nutrition is a widespread problem in south-eastern Australia. Our study suggests that milk-containing products continue to be an important source of iodine for children.

Assessment of some biochemical parameters related to protein-calorie nutrition in children.

A cross-sectional nutrition survey was conducted in five different rural areas of Kenya. Plasma protein and plasma albumin levels, plasma amino acid ratio, urinary nitrogen: creatinine ratio, urinary inorganic sulfate sulfur: creatinine ratio, and the urinary hydroxy-proline index were determined in children aged 1-15 years. The biochemical results were compared with those from a dietary and anthropometric survey. It was concluded that the amino acid ratio, the urea nitrogen: creatinine ratio and the inorganic sulfate sulfur: creatinine ratio were the most useful biochemical tests to establish differences between communities associated with varying adequacy of protein-calorie intake.