Estimating habitual iodine intake and prevalence of inadequacy from spot urine in cross-sectional studies: a modeling analysis to determine the required sample size.

BACKGROUND: The habitual/usual iodine intake and the prevalence of iodine inadequacy may be estimated from spot urinary iodine concentrations in cross-sectional studies by collecting a repeat spot urine in a subgroup of the study population and accounting for within-person variability in iodine intake. However, guidance on the required overall sample size (N) and the replicate rate (n) is lacking. OBJECTIVES: To determine the sample size (N) and replicate rate (n) needed to estimate the prevalence of iodine inadequacy in cross-sectional studies. METHODS: We used data from local observational studies conducted in women 17-49 y old in Switzerland (N = 308), South Africa (N = 154), and Tanzania (N = 190). All participants collected 2 spot urine samples. We calculated the iodine intake using urinary iodine concentrations and accounted for urine volume using urinary creatinine concentration. For each study population, we estimated the habitual iodine intake distribution and determined the prevalence of iodine intake below the average requirement using the Statistical Program to Assess habitual Dietary Exposure (SPADE). We used the obtained model parameters in power analyzes and estimated the prevalence of iodine inadequacy for different sample sizes (N = 400, 600, and 900) and replicate rates (n = 50, 100, 200, 400, 600, and 900). RESULTS: The estimated prevalence (95% CI) of inadequate iodine intake was 21% (15, 28%), 5.1% (1.3, 8.7%), and 8.2% (3.4, 13%) for Swiss, South African, and Tanzanian women, respectively. An N of 400 women, with a repeated measure (n) in 100 women, achieved a satisfactory precision of the prevalence estimate in all study populations. Increasing the replicate rate (n) improved the precision more effectively than increasing the N of the study. CONCLUSIONS: The sample size for cross-sectional studies aiming to assess the prevalence of inadequate iodine intake depend on the expected prevalence, the overall variance in intake, and the study design. However, an N of 400 participants with a repeated measure of 25% may be used as guidance when planning observational studies applying simple random sampling. This trial was registered at clinicaltrials.gov as NCT03731312.

Coverage, Apparent Consumption, and Monthly Use of Packaged Maize Flour in Morogoro Region, Tanzania.

INTRODUCTION: Tanzania aimed to reduce micronutrient deficiencies and neural tube defects by introducing mandatory fortification of large-scale packaged wheat and maize flour but not for small- and medium-scale mills. OBJECTIVES: Ascertain the proportion of the population in Morogoro region, Tanzania, that consumes packaged maize flour from small-, medium- and large-mills; and understand the impact of monthly apparent purchase and consumption of packaged flour. METHODS: In 2018, a regional, multistage cluster probability study was conducted among residents in Morogoro region living in households that reported consuming maize flour. Interviews collected information on sociodemographic factors and patterns of household flour consumption. Weighted medians estimated daily apparent flour consumption and the estimated average requirement (EAR), according to age. RESULTS: Information was collected on 711 households. Packaged maize flour was purchased 10-12 months of the year by 22.9% of households, 6-9 months by 17.6% of households, 1-5 months by 25.1% of households, and 34.4% did not purchased maize flour. Median apparent daily consumption of maize flour was 209.7 g/d/adult male equivalent (AME). Apparent median daily consumption of maize flour was 230.1 g/d/AME in rural areas and 176.2 g/d/AME in urban areas; 228.7 g/d/AME among males and 196.4 g/d/AME among females. If all packaged maize flour were fortified according to standards, those consuming packaged maize flour 10-12 months of the year would apparently consume 199.9 µg folic acid/d representing 49.7% of daily EAR requirements. CONCLUSIONS: Fortifying packaged maize flour at small-, medium- and large-mills is a promising strategy for increasing access to micronutrients, including folic acid.

Multiple micronutrients fortified salt: consumers' acceptability survey, Tanzania.

BACKGROUND: Food fortification with micronutrients is an insufficiently used technology in developing countries. Salt is consumed in small, constant daily amounts by most people globally. Salt has been instrumental in delivering iodine to a wide population globally through fortification. There is a proven effective technology for fortifying iodinated salt with iron, folate, and Vitamin B12. Findings have shown that both Double (Iodine and iron) fortified salt (DFS) and quadruple (iron, iodine, folate, and vitamin B12) fortified salt (QFS) are effective in raising hemoglobin levels. AIM: To assess the acceptability and gauge consumers' willingness to use double-fortified and quadruple-fortified salt formulations. METHODS: We conducted an observational study involving 300 households at Haydom Lutheran Hospital catchment area in Northern rural Tanzania between October 2021 and April 2022. Each household was supplied with one type of salt (iodized salt (IS), DFS or QFS) for cooking common family dishes for one week. Thereafter, at least two adult members of the family who used the dishes cooked with study salt were interviewed using the adopted 5-point Hedonic scale. RESULTS: A total of 899 individuals were interviewed after using study salt for one week: 286 IS, 305 DFS, and 308 QFS. The overall acceptability for the salts was QFS (82%), DFS (78%), and IS (79%). The mean sensory (taste, color and appearance) scores of the QFS (1.7) and DFS (1.7) were comparable to standard iodized salt (1.6). CONCLUSION: Quadruple-fortified salt and double-fortified salt are equally acceptable and have similar sensory scores as standard iodized salt when used to cook commonly eaten dishes in the study population.

Seasonal effects on urinary iodine concentrations in women of reproductive age: An observational study in Tanzania and South Africa.

BACKGROUND: Iodine intake in populations is usually assessed by measuring urinary iodine concentrations (UICs) in spot samples. Hot climate conditions may reduce urine volume, thus leading to overestimations of UIC and thereby masking inadequate iodine intake. OBJECTIVES: We investigated the effects of season on UICs in 2 populations exposed to high-temperature climates. METHODS: In this observational study, we examined women (18-49 years) in Tanzania (ncold = 206; nhot = 179) and South Africa (ncold = 157; nhot = 126) during cold and hot seasons. From each woman in both seasons, we obtained two 24-hour urine collections and 2 spot urine samples, as well as salt, water, and cow's milk samples. We measured the urine volume, UIC, and urinary creatinine concentration (UCC). The 24-hour urinary iodine excretion (UIE) was calculated and used to estimate the iodine intake. We used linear mixed-effects models to test for differences between seasons. RESULTS: In Tanzanian women, we observed no seasonal effect on the urine volume, 24-hour UIE, 24-hour UIC, spot UIC, spot UIC:UCC ratio, or salt iodine concentration. In South African women, the median 24-hour urine volume was 1.40 L (IQR, 0.96-2.05 L) in the winter and 15% lower in the summer (P < 0.001). The median 24-hour UIE was 184 µg/day (IQR, 109-267 µg/day) in the winter and 34% lower in the summer (P < 0.001), indicating a lower iodine intake. As a result, UICs did not significantly differ between seasons in 24-hour collections and spot samples, whereas the spot UIC:UCC ratio differed by 21% (P < 0.001) and reflected the lower iodine intake. In both study populations, the within- and between-person variabilities in urine volume, 24-hour UICs, and spot UICs were higher than the variability between seasons. CONCLUSIONS: Spot UIC may slightly overestimate the iodine intake in hot temperatures due to concentrated urine, and methods to correct for urine volume may be considered. Local seasonal differences in iodine intakes may also occur in some populations. This trial was registered at http://www.clinicaltrials.gov as NCT03215680.

Regional Disparities in the Decline of Anemia and Remaining Challenges among Children in Tanzania: Analyses of the Tanzania Demographic and Health Survey 2004-2015.

The burden of child anemia is on the decline globally but remains prevalent in low- and middle-income countries, including Tanzania. Evidence suggests regional variation and a slow pace of decline even in areas with high food production. The factors behind such decline and remaining challenges behind child anemia remain understudied in Tanzania. This secondary data analysis utilized data including 7361 and 7828 children from the Tanzania Demographic and Health Surveys (TDHS) conducted in 2004-2005 and 2015-2016 separately to examine the decline of child anemia and regional variation thereof. We used a geographic information system (GIS) to visualize the changes and differences between regions and the two study periods, and used regression analyses to examine the recent determinants of child anemia. Anemia has declined among children under five in Tanzania by 42% over a one-decade period, but remained high in relatively high food-producing regions. The risk of anemia is still higher among boys compared to girls (AOR = 1.39, p = 0.005), 41% higher among children lived in households with more than three under-five children compared to those households with only one child (p = 0.002); lower among children whose mothers were educated (p < 0.001) or had first given birth when aged over 25 (p = 0.033); and 34% less among children in the wealthiest households (p < 0.001). Efforts are needed to address social determinants of health, especially targeting women's empowerment through decreasing the number of children and encouraging child spacing, and poverty reduction, particularly in high food producing regions.

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.

Effect of Excess Iodine Intake from Iodized Salt and/or Groundwater Iodine on Thyroid Function in Nonpregnant and Pregnant Women, Infants, and Children: A Multicenter Study in East Africa.

BACKGROUND: Acute excess iodine intake can damage the thyroid, but the effects of chronic excess iodine intake are uncertain. Few data exist for pregnant and lactating women and infants exposed to excessive iodine intake. METHODS: This was a multicenter cross-sectional study. At study sites in rural Kenya and urban Tanzania previously reporting iodine excess in children, urinary iodine concentration (UIC), thyrotropin, total thyroxine, and thyroglobulin (Tg) were measured in school-age children (SAC), women of reproductive age, pregnant (PW) and lactating women, and breast-feeding and weaning infants. In a national study in Djibouti, UIC was measured in SAC and PW. At all sites, daily iodine intake was estimated based on UIC, and iodine concentration was measured in household salt and drinking water. RESULTS: The total sample size was 4636: 1390, 2048, and 1198 subjects from Kenya, Tanzania, and Djibouti, respectively. In Kenya and Tanzania: (i) median UIC was well above thresholds for adequate iodine nutrition in all groups and exceeded the threshold for excess iodine intake in SAC; (ii) iodine concentrations >40 mg of iodine/kg were found in approximately 55% of household salt samples; (iii) iodine concentrations ≥10 µg/L were detected in 9% of drinking water samples; (iv) Tg was elevated in all population groups, but the prevalence of thyroid disorders was negligible, except that 5-12% of women of reproductive age had subclinical hyperthyroidism and 10-15% of PW were hypothyroxinemic. In Djibouti: (i) the median UIC was 335 µg/L (interquartile range [IQR] = 216-493 µg/L) in SAC and 265 µg/L (IQR = 168-449 µg/L) in PW; (ii) only 1.6% of Djibouti salt samples (n = 1200) were adequately iodized (>15 mg/kg); (iii) the median iodine concentration in drinking water was 92 µg/L (IQR = 37-158 µg/L; n = 77). In all countries, UIC was not significantly correlated with salt or water iodine concentrations. CONCLUSIONS: Although iodine intake was excessive and Tg concentrations were elevated, there was little impact on thyroid function. Chronic excess iodine intake thus appears to be well tolerated by women, infants, and children. However, such high iodine intake is unnecessary and should be avoided. Careful evaluation of contributions from both iodized salt and groundwater iodine is recommended before any review of iodization policy is considered.

Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 µg/L: a UNICEF/ICCIDD study group report.

CONTEXT: The median urinary iodine concentration (UIC) is a biomarker of iodine intake. According to the World Health Organization, a median UIC in the range 100-199 µg/L indicates adequate and 200-299 µg/L more than adequate intake. Thyroglobulin (Tg) may be a promising functional biomarker of both iodine deficiency and excess. OBJECTIVES: Using a standardized dried blood spots-Tg assay in children, we evaluated the Tg response to both low- and high-iodine intake and estimated the population cutoff point for iodine deficiency or excess. Also, we compared thyroid functions within the UIC ranges of 100-199 vs 200-299 µg/L. DESIGN AND SETTING: We conducted a cross-sectional study in primary schools in 12 countries. SUBJECTS: SUBJECTS were 6 to 12 years old (n = 2512). MAIN OUTCOME MEASURES: We measured UIC, TSH, total T4, Tg, and thyroid antibodies. RESULTS: Over a range of iodine intakes from severely deficient to excessive, Tg concentrations showed a clear U-shaped curve. Compared with iodine-sufficient children, there was a significantly higher prevalence of elevated Tg values in children with iodine deficiency (UIC <100 µg/L) and iodine excess (UIC >300 µg/L). There was no significant change in the prevalence of elevated Tg, TSH, T4, or thyroid antibodies comparing children within the UIC ranges of 100-199 vs 200-299 µg/L. CONCLUSIONS: In school-aged children, 1) Tg is a sensitive indicator of both low and excess iodine intake; 2) a median Tg of <13 µg/L and/or <3% of Tg values >40 µg/L indicates iodine sufficiency in the population; 3) the acceptable range of median UIC in monitoring iodized salt programs could be widened to a single category of sufficient iodine intake from 100 to 299 µg/L.

Tanzania national survey on iodine deficiency: impact after twelve years of salt iodation.

BACKGROUND: In many low-income countries, children are at high risk of iodine deficiency disorders, including brain damage. In the early 1990s, Tanzania, a country that previously suffered from moderate to severe iodine deficiency, adopted universal salt iodation (USI) as an intervention strategy, but its impact remained unknown. METHODS: We report on the first national survey in mainland Tanzania, conducted in 2004 to assess the extent to which iodated salt was used and its apparent impact on the total goitre prevalence (TGP) and urinary iodine concentrations (UIC) among the schoolchildren after USI was initiated. In 2004, a cross-sectional goitre survey was conducted; covering 140,758 schoolchildren aged 6 - 18 years were graded for goitre according to new WHO goitre classification system. Comparisons were made with district surveys conducted throughout most of the country during the 1980s and 90s. 131,941 salt samples from households were tested for iodine using rapid field test kits. UIC was determined spectrophotometrically using the ammonium persulfate digestion method in 4523 sub-sampled children. RESULTS: 83.6% (95% CI: 83.4 - 83.8) of salt samples tested positive for iodine. Whereas the TGP was about 25% on average in the earlier surveys, it was 6.9% (95%CI: 6.8-7.0) in 2004. The TGP for the younger children, 6-9 years old, was 4.2% (95%CI: 4.0-4.4), n = 41,965. In the 27 goitre-endemic districts, TGP decreased from 61% (1980s) to 12.3% (2004). The median UIC was 204 (95% CF: 192-215) microg/L. Only 25% of children had UIC <100 microg/L and 35% were > or = 300 microg/L, indicating low and excess iodine intake, respectively. CONCLUSION: Our study demonstrates a marked improvement in iodine nutrition in Tanzania, twelve years after the initiation of salt iodation programme. The challenge in sustaining IDD elimination in Tanzania is now two-fold: to better reach the areas with low coverage of iodated salt, and to reduce iodine intake in areas where it is excessive. Particular attention is needed in improving quality control at production level and perhaps the national salt iodation regulations may need to be reviewed.

Improved salt iodation methods for small-scale salt producers in low-resource settings in Tanzania.

BACKGROUND: Universal salt iodation will prevent iodine deficiency disorders (IDD). Globally, salt-iodation technologies mostly target large and medium-scale salt-producers. Since most producers in low-income countries are small-scale, we examined and improved the performance of hand and knapsack-sprayers used locally in Tanzania. METHODS: We studied three salt facilities on the Bagamoyo coast, investigating procedures for preparing potassium-iodate solution, salt spraying and mixing. Different concentrations of solution were prepared and tested using different iodation methods, with the aim of attaining correct and homogeneous iodine levels under real-life conditions. Levels achieved by manual mixing were compared to those achieved by machine mixing. RESULTS: The overall median iodation level in samples of salt iodated using previously existing methods was 10.6 ppm (range 1.1 - 110.0 ppm), with much higher levels in the top than the bottom layers of the salt bags, p < 0.0001. Experimentation using knapsack-sprayers and manual mixing led to the reliable achievement of levels (60.9 ppm +/- 7.4) that fell within the recommended range of 40 - 80 ppm. The improved methods yielded homogenous iodine concentrations in all layers of salt-bags (p = 0.58) with 96% of the samples (n = 45) falling within 40 - 80 ppm compared to only 9% (n = 45) before the experiment and training (p < 0.0001). For knapsack-spraying, a machine mixer improved the iodine levels and homogeneity slightly compared to manual mixing (p = 0.05). CONCLUSION: Supervised, standardized salt iodation procedures adapted to local circumstances can yield homogeneous iodine levels within the required range, overcoming a major obstacle to universal salt iodation.

Remaining challenges in Tanzania's efforts to eliminate iodine deficiency.

OBJECTIVE: To determine iodine levels in salt and iodine deficiency prevalence in school-aged children in 16 districts in Tanzania with previous severe iodine deficiency. DESIGN: A cross-sectional study in schoolchildren. Systematic probability sampling was used to select schools and subjects for goitre assessment and urinary iodine determination. SETTING: Sixteen districts randomly selected from the 27 categorised as severely iodine-deficient in Tanzania. SUBJECTS: The study population was primary-school children aged 6-18 years who were examined for goitre prevalence and urinary iodine concentration (UIC). Salt samples from schoolchildren's homes and from shops were tested for iodine content. RESULTS: The study revealed that 83.3% of households (n=21,160) in the surveyed districts used iodised salt. Also, 94% of sampled shops (n=397) sold iodised salt, with a median iodine level of 37.0 ppm (range 4.2-240 ppm). Median UIC in 2089 schoolchildren was 235.0 microg l(-1) and 9.3% had UIC values below 50 microg l(-1). The overall unweighted mean visible and total goitre prevalence was 6.7% and 24.3%, respectively (n=16,222). The age group 6-12 years had the lowest goitre prevalence (3.6% visible and 18.0% total goitre, n=7147). The total goitre prevalence had decreased significantly in all districts from an unweighted mean of 65.4% in the 1980s to 24.3% in 1999 (P<0.05). We believe this difference was also biologically significant. ConclusionThese findings indicate that iodine deficiency is largely eliminated in the 16 districts categorised as severely iodine-deficient in Tanzania, and that the iodine content of salt purchased from shops is highly variable.