The objective of this paper is to review the global effort to eliminate iodine deficiency and its impact on public health. Iodine is an essential component of hormones produced by the thyroid gland. Iodine deficiency has multiple adverse effects in humans due to inadequate thyroid hormone production that are termed the iodine deficiency disorders. The major adverse effect is impaired cognition in children. The WHO's first estimate of the global prevalence of goitre in 1960 suggested that 20-60 % of the world's population was affected, with most of the burden in low- and middle-income countries. Iodine deficiency was identified as a key global risk factor for impaired child development where the need for intervention was urgent. This spurred a worldwide effort to eliminate iodine deficiency led by a coalition of international organisations working closely with national governments and the salt industry. In most countries, the best strategy to control iodine deficiency is carefully monitored iodisation of salt. The reach of current iodised salt programmes is remarkable: in 2018, 88 % of the global population used iodised salt. The number of countries with adequate iodine intake has nearly doubled over the past 20 years from 67 in 2003 to 118 in 2020. The resulting improvement in cognitive development and future earnings suggests a potential global economic benefit of nearly $33 billion. Iodine programmes are appealing for national governments because the health and economic consequences are high and can be easily averted by salt iodisation, a low-cost and sustainable intervention. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

BACKGROUND: Iodine deficiency during pregnancy might be associated with reduced intelligence quotient (IQ) score in offspring. We assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on neurodevelopment of their offspring in areas where schoolchildren were iodine sufficient. METHODS: In this randomised, placebo-controlled trial, pregnant women in Bangalore, India, and Bangkok, Thailand, were randomly assigned (1:1) to receive 200 μg iodine orally once a day or placebo until delivery. Randomisation was done with a computer-generated sequence and stratified by site. Co-primary outcomes were verbal and performance IQ scores on the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) and the global executive composite score from the Behaviour Rating Inventory of Executive Function-Preschool Version (BRIEF-P) in the children at age 5-6 years. The trial was double-blinded; some unmasking took place at age 2 years for an interim analysis, but participants and nearly all investigators remained masked to group assignment until age 5-6 years. Analysis was by intention to treat using mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT00791466. FINDINGS: Between Nov 18, 2008, and March 12, 2011, 832 women entered the trial at a mean gestational age of 10·7 weeks (SD 2·7); median urinary iodine concentration was 131 μg/L (IQR 81-213). Mean compliance with supplementation was 87%, assessed by monthly tablet counts. 313 children (iodine group, n=159; placebo group, n=154) were analysed for verbal and performance IQ with WPPSI-III and 315 (iodine group, n=159; placebo group, n=156) for overall executive function with BRIEF-P. Mean WPPSI-III scores for verbal IQ were 89·5 (SD 9·8) in the iodine group and 90·2 (9·8) in the placebo group (difference -0·7, 95% CI -2·9 to 1·5; p=0·77), and for performance IQ were 97·5 (12·5) in the iodine group and 99·1 (13·4) in the placebo group (difference -1·6, -4·5 to 1·3; p=0·44). The mean BRIEF-P global executive composite score was 90·6 (26·2) in the iodine group and 91·5 (27·0) in the placebo group (difference -0·9, -6·8 to 5·0; p=0·74). The frequency of adverse events did not differ between groups during gestation or at delivery: 24 women in the iodine group and 28 in the placebo group reported adverse events (iodine group: abortion, n=20; blighted ovum, and n=2; intrauterine death, n=2; placebo group: abortion, n=22; blighted ovum, n=1; intrauterine death, n=2; early neonatal death, n=1; and neonatal death, n=2). INTERPRETATION: Daily iodine supplementation in mildly iodine-deficient pregnant women had no effect on child neurodevelopment at age 5-6 years. FUNDING: Swiss National Science Foundation, Nestlé Foundation, Wageningen University and Research, and ETH Zurich. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

BACKGROUND: Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. OBJECTIVES: To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. MAIN RESULTS: We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. AUTHORS' CONCLUSIONS: There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

BACKGROUND: Iodine is an essential component of thyroid hormones; either low or high intake may lead to thyroid disease. We observed an increase in the prevalence of overt hypothyroidism, subclinical hypothyroidism, and autoimmune thyroiditis with increasing iodine intake in China in cohorts from three regions with different levels of iodine intake: mildly deficient (median urinary iodine excretion, 84 microg per liter), more than adequate (median, 243 microg per liter), and excessive (median, 651 microg per liter). Participants enrolled in a baseline study in 1999, and during the five-year follow-up through 2004, we examined the effect of regional differences in iodine intake on the incidence of thyroid disease. METHODS: Of the 3761 unselected subjects who were enrolled at baseline, 3018 (80.2 percent) participated in this follow-up study. Levels of thyroid hormones and thyroid autoantibodies in serum, and iodine in urine, were measured and B-mode ultrasonography of the thyroid was performed at baseline and follow-up. RESULTS: Among subjects with mildly deficient iodine intake, those with more than adequate intake, and those with excessive intake, the cumulative incidence of overt hypothyroidism was 0.2 percent, 0.5 percent, and 0.3 percent, respectively; that of subclinical hypothyroidism, 0.2 percent, 2.6 percent, and 2.9 percent, respectively; and that of autoimmune thyroiditis, 0.2 percent, 1.0 percent, and 1.3 percent, respectively. Among subjects with euthyroidism and antithyroid antibodies at baseline, the five-year incidence of elevated serum thyrotropin levels was greater among those with more than adequate or excessive iodine intake than among those with mildly deficient iodine intake. A baseline serum thyrotropin level of 1.0 to 1.9 mIU per liter was associated with the lowest subsequent incidence of abnormal thyroid function. CONCLUSIONS: More than adequate or excessive iodine intake may lead to hypothyroidism and autoimmune thyroiditis. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

Perinatal exposure to excess iodine can lead to transient hypothyroidism in the newborn. In Japan, large quantities of iodine-rich seaweed such as kombu (Laminaria japonica) are consumed. However, effects of iodine from food consumed during the perinatal period are unknown. The concentration of iodine in serum, urine, and breast milk in addition to thyrotropin (TSH), free thyroxine (FT(4)), and thyroglobulin was measured in 34 infants who were positive at congenital hypothyroidism screening. Based on the concentration of iodine in the urine, 15 infants were diagnosed with hyperthyrotropinemia caused by the excess ingestion of iodine by their mothers during their pregnancy. According to serum iodine concentrations, these infants were classified into group A (over 17 microg/dL) and group B (under 17 microg/dL) of serum iodine. During their pregnancies these mothers consumed kombu, other seaweeds, and instant kombu soups containing a high level of iodine. It was calculated that the mothers of group A infants ingested approximately 2300-3200 microg of iodine, and the mothers of group B infants approximately 820-1400 microg of iodine per day during their pregnancies. Twelve of 15 infants have required levo-thyroxine (LT(4)) because hypothyroxinemia or persistent hyperthyrotropinemia was present. In addition, consumption of iodine by the postnatal child and susceptibility to the inhibitory effect of iodine may contribute in part to the persistent hyperthyrotropinemia. We propose that hyperthyrotropinemia related to excessive iodine ingestion by the mother during pregnancy in some cases may not be transient. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

BACKGROUND/OBJECTIVES: Although iodine is essential for thyroid hormone production and controls many metabolic processes, there are few reports on the iodine intake of the population because of the scarcity of information on the iodine content in food. This study estimated the iodine intake of Koreans from brown seaweed, the major source of iodine in nature. SUBJECTS/METHODS: The dietary intake data from the recent Korea National Health and Nutrition Examination Survey (2016-2021) and the iodine content in brown seaweed were used for the estimation. Nationwide brown seaweed samples were collected and prepared using the representative preparation/cooking methods in the Koreans' diet before iodine analysis by alkaline digestion followed by inductively coupled plasma mass spectrometry. RESULTS: The mean (± SE) iodine intake from sea mustard was 96.01 ± 2.36 µg/day in the Korean population. Although the iodine content in kelp was approximately seven times higher than that in sea mustard, the mean iodine intake from kelp (except broth) was similar to that of sea mustard, 115.58 ± 7.71 µg/day, whereas that from kelp broth was 347.57 ± 10.03 µg/day. The overall mean iodine intake from brown seaweed was 559.16 ± 13.15 µg/day, well over the Recommended Nutrient Intake of iodine for Koreans. Nevertheless, the median intake was zero because only 37.6% of the population consumed brown seaweed on the survey date, suggesting that Koreans do not consume brown seaweed daily. CONCLUSION: The distribution of the usual intake of iodine from brown seaweed in Koreans would be much tighter, resulting in a lower proportion of people exceeding the tolerable upper intake levels and possibly a lower mean intake than this study presented. Further study evaluating the iodine nutriture of Koreans based on the usual intake is warranted. Nevertheless, this study adds to the few reports on the iodine nutriture of Koreans. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.