Iodine supplementation for preventing iodine deficiency disorders in children and adolescents.

rationaleIodine is a micronutrient crucial in the early stages of human development, as it is essential for synthesising thyroid hormones involved in somatic growth and neurodevelopment. It is far better to prevent iodine deficiency than to treat it, since children are particularly vulnerable to iodine deficiency disorders, which involve a broad spectrum of consequences including endemic goitre, delayed growth and development of the central nervous system, intellectual impairment, and infant mortality. The primary dietary sources of iodine are iodised salt, seafood (animals and plants concentrate iodine from seawater), and grains from iodine-rich soils. Reliable evidence is needed on the benefits and harms of direct iodine supplementation in children and adolescents before considering its use to prevent the health consequences of iodine deficiency.

objectivesTo assess the benefits and harms of iodine supplementation for preventing iodine deficiency in children and adolescents. SEARCH

methodsWe searched CENTRAL, MEDLINE, eight other databases, and two trials registries to 8 May 2025. We also searched the reference lists of retrieved studies. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) evaluating the benefits and harms of iodine supplementation alone (orally or by injection) or in combination with vitamins and minerals (orally or by injection) compared with placebo. OUTCOMES: Our critical outcomes were cognitive function assessed by validated scales, growth, hypothyroidism, and adverse events. Important outcomes included health-related quality of life, all-cause mortality, and goitre. RISK OF BIAS: We used the Cochrane RoB 2 tool to assess the risk of bias in the included studies. SYNTHESIS

methodsTwo review authors independently selected trials, extracted data, and assessed risk of bias. We used random-effects meta-analysis to combine data. We assessed the certainty of the evidence using GRADE. INCLUDED STUDIES: We included eight RCTs with a total of 2528 participants. The trials were conducted in seven countries between 1982 and 2009. The trials compared iodine supplementation (alone or with iron in one study) versus placebo. In one study, iodine supplementation was 150 μg daily for 28 weeks, while in the remaining studies, iodine supplementation was done in a single dose: 100 mg in a study on infants younger than 1 year, and a dose between 400 mg and 490 mg for children 6 to 17 years. Follow-up ranged from 3 to 22 months. SYNTHESIS OF

resultsIodine supplementation versus placebo Iodine supplementation results in a slight increase in cognitive function compared to placebo (standardised mean difference 0.19, 95% confidence interval (CI) 0.04 to 0.34; 1 study, 166 participants; high-certainty evidence). Iodine supplementation may result in little to no difference in children's weight (kg) compared to placebo (mean difference (MD) -0.20, 95% CI -1.92 to 1.52; I² = 44%; 3 studies, 658 participants; low-certainty evidence). We downgraded the certainty of evidence by one level for imprecision and one level for heterogeneity. Iodine supplementation likely results in a large reduction in hypothyroidism compared to placebo (risk ratio (RR) 0.03, 95% CI 0.00 to 0.23; 1 study, 264 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for risk of bias. No study reported adverse events related to iodine or quality of life. Iodine supplementation likely reduces all-cause mortality in infants compared to placebo (RR 0.32, 95% CI 0.14 to 0.73; 1 study, 617 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for risk of bias. The evidence is very uncertain about the effect of iodine supplementation on the reduction of goitre (RR 0.68, 95% CI 0.15 to 3.07; I² = 97%; 2 studies, 432 participants; very low-certainty evidence). We downgraded the certainty of evidence by one level for imprecision, one level for heterogeneity, and one level for risk of bias. However, a sensitivity analysis removing the study with high risk of bias showed that iodine likely results in a large reduction in goitre (RR 0.31, 95% CI 0.22 to 0.45; 1 study, 230 participants; moderate-certainty evidence). Iodine plus iron supplementation versus placebo Iodine plus iron supplementation was compared to placebo in a single study. The evidence is very uncertain about the effect of iodine plus iron on weight (MD -0.40, 95% CI -1.44 to 0.64; 1 study, 146 participants; very low-certainty evidence). We downgraded the certainty of evidence by two levels for imprecision and one level for risk of bias. No other outcomes were assessed for this comparison. AUTHORS'

conclusionsIodine supplementation, in the doses and follow-up periods evaluated in published RCTs, results in a slight increase in cognitive function and may result in little to no difference in growth. It likely reduces hypothyroidism and the risk of death in infants, but the evidence is very uncertain about its effect on the reduction of goitre. Future studies should focus on areas or populations in which iodine deficiency could be a problem, and include children of lower socioeconomic levels. They should evaluate higher doses of iodine administered during longer periods of treatment and follow-up times.

fundingThis Cochrane review had no dedicated funding. REGISTRATION: Protocol (2023). DOI: 10.1002/14651858.CD014475.