Iodine supplementation: a small cognitive gain, fewer hypothyroid children, and trials that stopped in 2009

Design

Cochrane systematic review and meta-analysis of 8 randomised trials with GRADE assessment

Population

2,528 children and adolescents across seven countries, trials conducted 1982-2009

Primary outcome

cognitive function, growth, hypothyroidism and adverse events

Effect

cognition standardised mean difference 0.19 (95% CI 0.04-0.34); hypothyroidism risk ratio 0.03 (0.00-0.23); infant mortality 0.32 (0.14-0.73); goitre very uncertain

A Cochrane review searched to May 2025 and found eight randomised trials of iodine supplementation against placebo in children and adolescents, 2,528 participants across seven countries, conducted between 1982 and 2009. One trial used 150 micrograms daily for 28 weeks; the rest used a single large dose - 100 mg in infants, 400 to 490 mg in children aged 6 to 17. Follow-up ran from 3 to 22 months.

Iodine supplementation produced a slight increase in cognitive function (standardised mean difference 0.19, 95% CI 0.04 to 0.34), graded high certainty although resting on a single 166-child trial. It likely produced a large reduction in hypothyroidism (risk ratio 0.03, 0.00 to 0.23, one trial, 264 children) and likely reduced all-cause mortality in infants (0.32, 0.14 to 0.73, one trial, 617 infants). Effects on weight were negligible. Goitre was very uncertain overall (0.68, 0.15 to 3.07, I squared 97%), though removing the high risk-of-bias trial left a large reduction (0.31, 0.22 to 0.45).

The finding matters most where salt iodisation is incomplete. India's universal salt iodisation programme has moved most of the country out of severe deficiency, but coverage is not uniform and the sub-Himalayan belt has historically been the concern. This review is an argument for identifying deficient populations rather than for supplementing individual children in clinic: the doses tested are not the doses anyone would prescribe, and none of these trials was conducted in a population like the one most Indian paediatricians see.

• Ask about salt source in a child with goitre or unexplained developmental delay - non-iodised rock or crystal salt is still used
• Do not extrapolate to individual supplementation: the trials used single doses of 100 to 490 mg, not a daily paediatric supplement
• Check thyroid function rather than assuming deficiency in a child with a goitre
• Consider the population question - deficiency is geographic, and the answer is programmatic
• Note that adequate maternal iodine in pregnancy is a separate and better-established issue

Why it matters

It separates a population-level nutrition question from a prescribing decision, which is where iodine advice most often goes wrong in clinic.

Don't overread it

The trials tested single large doses in deficient populations decades ago - they do not support routine supplementation of an individual child today.

The statistics, in plain English

Several of these results are single-trial estimates dressed as meta-analysis, which is why the certainty gradings differ so much between outcomes. A risk ratio of 0.03 for hypothyroidism from one 264-child trial with an interval reaching 0.23 is a huge effect measured imprecisely. The goitre result is the instructive one: pooled across two trials it was uninterpretable at I squared of 97%, and it only became a clear benefit after the poorer trial was removed - which is a sensitivity analysis, not the primary result. And the trials all predate 2009, so they describe populations with deficiency levels that many countries no longer have.

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