Randomized clinical trial comparing different iodine interventions in school children. Effect of voluntary intake of iodinated salt on prevalence of goitre in children. Intermittent oral administration of potassium iodide solution for the correction of iodine deficiency. The effects of oral iodized oil on intelligence, thyroid status, and somatic growth in school-age children from an area of endemic goiter. Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection. Infant survival is improved by oral iodine supplementation. Salt: an ineffective vehicle for iodine delivery to young children in rural Sarawak. Treatment of iron deficiency in goitrous children improves the efficacy of iodized salt in Côte d'Ivoire. Biochemical hypothyroidism secondary to iodine deficiency is associated with poor school achievement and cognition in Bangladeshi children.
The purpose of this trial was to compare three different iodine interventions.
                School children aged 8-10 years were randomized into one of three groups: group A was provided with iodized salt by researchers with an iodine concentration of 25 ppm; group B purchased iodized salt from the market; and group C was similar to group B with the exception that they were given iodized oil capsules containing 400 mg iodine at the beginning of the study. Salt iodine content was measured bimonthly for 18 months and indicators of iodine deficiency were measured at baseline and 6, 9, 12 and 18 months after randomization.
                The prevalence of abnormal thyroid volumes, based on the World Health Organization (WHO) body surface area reference >97th percentile, was 18% at baseline and declined to less than 5% by 12 months in groups A and C, and to 9% after 18 months in group B. Results for goitre by palpation were similar. The median urinary iodine was 94 microg l(-1) at baseline and increased in all groups to > 200 microg l(-1) at the 6-month follow-up.
                In this population of school children with initially a low to moderate level of iodine deficiency, the group receiving salt with 25 ppm (group A) was not iodine deficient on all indicators after 18 months of study. When the iodine content of the salt varied, such as in group B, by 18 months thyroid sizes had not yet achieved normal status. The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 micrograms of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 +/- 1.4 vs 29.4 +/- 1.4 cm; P less than 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 +/- 16.7 micrograms/g creatinine vs 46.1 +/- 24.9 micrograms/g creatinine; x +/- SD; P less than 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A.(ABSTRACT TRUNCATED AT 250 WORDS) Iodized salt and iodized oil are the main methods used to prevent iodine deficiency, but sometimes alternative approaches are needed. We tested the efficacy of various regimens for the intermittent administration of potassium iodide in Hwedza, Zimbabwe, an area of known severe iodine deficiency. We divided 304 schoolchildren aged 7-13 y into five equal groups that received iodine as a 10% solution of potassium iodide as follows: 8.7 mg every 2 wk (group A), 29.7 mg every month (group B), 148.2 mg every 3 mo (group C), 382 mg every 6 mo (group D), or 993 mg once (group E). The follow-up period was 13 mo. No adverse effects were encountered with any of these doses. After 6 mo, the median blood spot thyroglobulin concentration had decreased in all groups and had normalized in groups A and B to values found in iodine-sufficient populations. The number of children with elevated thyroid-stimulating hormone concentrations decreased in groups A-C, but the changes were not significant. Urine iodine concentration generally remained low in all groups but increased in group A. After 13 mo, mean thyroid volume measured by ultrasound had decreased in groups A and B to values comparable with those in iodine-sufficient areas, and was unchanged in the other groups. We conclude that oral potassium iodide is effective for the prophylaxis of iodine deficiency if given as a dose of 30 mg I monthly or 8 mg biweekly. One hundred goitrous school children received 475 mg iodized oil by mouth, while 100 controls received mineral oil, on a double-blind basis. On follow-up 22 months later the urinary iodine had increased and goiter size had decreased in both groups, more strikingly in the iodine-treated children. There were no consistent differences between the two treatment groups in rate of somatic growth or performance on the Stanford-Binet and Bender tests. Because of the complexities introduced by increases in urinary iodine in the controls, we compared goiter reduction with improvement in IQ score in all children, regardless of group, and found a significant relationship (p = 0.014), particularly in girls (p = 0.029). We conclude that oral iodized oil is an attractive alternative to its injection but we recommend an approximate doubling of the dose used here for more effective control. Also, while our data are not conclusive, they support the possibility that correction of iodine deficiency may improve mental performance in school age children, particularly girls. Oral iodized oil is the major alternative to iodized salt for correcting endemic iodine deficiency. This study responds to a need for better guidelines in its use. Schoolchildren, aged 6-11 yr, from a severely iodine-deficient area of Algeria received iodized poppy seed oil (Lipiodol) in a single oral dose containing 120, 240, 480, or 960 mg iodine (groups A-D) or in an im injection of 480 mg iodine (group E). Thyroid volume by ultrasonography had not changed 395 days after treatment in groups A, B, and C, had decreased in groups D and E. Urinary iodine concentration rose rapidly from an initial median of 0.21 mumol/L, but fell below 0.79 mumol/L (the currently accepted level for indicating iodine deficiency) by 150 days for groups A and B, and by 395 days for groups C and D. Median serum TSH and T4 levels were normal before and after treatment, whereas high initial serum thyroglobulin values decreased in all groups after iodized oil treatment. For correcting iodine deficiency in children, we recommend single oral doses of Lipiodol containing 240 mg iodine for 6-month coverage or 480 mg for 12 months. These doses may not completely sustain iodine sufficiency, but will prevent the worst of the iodine deficiency disorders. Additionally, we conclude that the urinary iodine concentration is the most useful epidemiological indicator for assessing current iodine status, and thyroid volume and serum thyroglobulin levels are the best markers for assessing chronic effects. Although reports suggest that infant mortality is increased during iodine deficiency, the effect of iodine supplementation on infant mortality is unknown. A double-masked, randomized, placebo-controlled, clinical trial of oral iodized oil was conducted in Subang, West Java, Indonesia to evaluate the effect of iodine supplementation on infant mortality. Infants were allocated to receive placebo or oral iodized oil (100 mg) at about 6 wk of age and were followed to 6 mo of age. Six hundred seventeen infants were enrolled in the study. Infant survival was apparently improved, as indicated by a 72% reduction in the risk of death during the first 2 mo of follow-up (P < 0.05) and a delay in the mean time to death among infants who died in the iodized oil group compared with infants who died in the placebo group (48 days vs. 17.5 d, P = 0.06). Other infant characteristics associated with reduced risk of death included weight-for-age at base line, consumption of solid foods, female gender and recent history of maternal iodine supplementation. Oral iodized oil supplementation had a stronger effect on the mortality of males compared with females. This study suggests that oral iodized oil supplementation of infants may reduce infant mortality in populations at risk for iodine deficiency. The urinary iodine excretions of women (15-40 y) and young children (< or = 6 y) from two longhouse villages in the iodine-deficient district of Lubok Antu, Sarawak, were compared. One longhouse (Mengkak) was provided with freshly produced iodized salt every two months (one kg per family) while the other (Menjiling) was provided with iodized water via fortification of the village piped-water supply. Spot urines were collected for iodine determination at baseline and at 6 and 12 months after the start of the study. Salt and water samples were collected at monthly intervals. Goiter assessment was performed on the women at the start and end of the one-year study. The mean iodine concentrations in the salt samples from Mengkak and Menjiling were, respectively, 47.1 +/- 9.7 mg/kg (n = 60) and 0.8 +/- 3.4 mg/kg (n = 60) while the mean iodine concentration in the water samples from Menjiling was 138.6 +/- 43.2 micrograms/L (n = 24); iodine could not be detected in the water samples from Mengkak. There were significant and sustained increases in median urinary iodine excretions of both women and young children in Menjiling; in Mengkak, however, significant and sustained increases in median urinary iodine excretions were observed only in women while the median urinary iodine excretions of children remained essentially unchanged throughout the study period. Goiter prevalences in the women were reduced in both longhouses. The above observations reveal the inadequacy of iodized salt as a vehicle for iodine delivery to young rural Sarawakian children and indicate the need for other means of delivering supplemental iodine to this age group in areas where salt iodization is the only strategy for IDD control. In contrast, iodization of village water supply by itself is adequate in delivering iodine uniformly to the whole community. In many developing countries, children are at high risk of both goiter and iron deficiency anemia. Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter.
                The aim of this study was to determine whether iron supplementation in goitrous, iron-deficient children would improve their response to iodized salt.
                We conducted a randomized, double-blind, placebo-controlled trial in 5-14-y-old children in Côte d'Ivoire. Goitrous, iron-deficient children (n = 166) consuming iodized salt (10-30 mg I/kg salt at the household level) were supplemented with either iron (60 mg Fe/d, 4 d/wk for 16 wk) or placebo. At 0, 1, 6, 12, and 20 wk, we measured hemoglobin, serum ferritin, serum transferrin receptor, whole-blood zinc protoporphyrin, thyrotropin, thyroxine, urinary iodine, and thyroid gland volume (by ultrasonography).
                Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo (P < 0.05). At 20 wk, the mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group (x +/- SD percentage change in thyroid volume from baseline: -22.8 +/- 10.7% compared with -12.7 +/- 10.1%; P < 0.01). At 20 wk, goiter prevalence was 43% in the iron-treated group compared with 62% in the placebo group (P < 0.02). There were no significant differences between groups in whole-blood thyrotropin or serum thyroxine at baseline or during the intervention.
                Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency. A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis. Iodine deficiency in pregnancy leads to poor cognitive function in the offspring; however, the effect of concurrent iodine deficiency on school-aged children is not clear. Several studies have shown that school children in iodine-deficient villages have poorer cognitive function than children in iodine-sufficient villages. However, villages differ in many factors that may also detrimentally affect children's development. In addition, the children's nutritional and health status has not usually been taken into account. In this study, we compared the cognitive function and school achievement levels of 170 children who had recently had low thyroxine (T4) levels [T4 </= 45 nmol/L (hypothyroid)] with children who had not had low T4 levels [T4 >/=70 nmol/L (euthyroid)]. The children were matched for school and grade level and came from the same iodine-deficient regions in rural Bangladesh. They were given a battery of cognitive, motor and school achievement tests. We also measured their nutritional status, examined their stools for geohelminths and assessed their home environments. A factor analysis of cognitive and motor function tests yielded two factors, a general cognitive factor and a fine motor factor. The children's height and arm circumference, experience of hunger, parental characteristics and stimulation in the home made independent contributions to their test scores. Controlling for these variables, the hypothyroid children performed worse than the euthyroid children on reading and spelling and the general cognitive factor. These findings indicate that a large number of disadvantages including hypothyroidism are related to the poor development of these children.
The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.