Abstract: Eleven studies met the criteria, providing 14 comparisons, and capturing data on 4317 participants. Seven studies were RCTs, three were cluster non-RCTs, and one was a randomised cross-over design. Seven studies were carried out among school children (N = 3636), three among women of reproductive age (N = 648), and one among infants (N = 33). The studies used diverse types of food as vehicle for iodine delivery: biscuits, milk, fish sauce, drinking water, yoghourt, fruit beverage, seasoning powder, and infant formula milk. Daily amounts of iodine provided ranged from 35 µg/day to 220 µg/day; trial duration ranged from 11 days to 48 weeks. Five studies examined the effect of iodine fortification alone, two against the same unfortified food, and three against no intervention. Six studies evaluated the effect of cofortification of iodine with other micronutrients versus the same food without iodine but with different levels of other micronutrients. We assessed one study to be at low risk of bias for all bias domains, three at low risk of bias for all domains apart from selective reporting, and seven at an overall rating of high risk of bias. No study assessed the primary outcomes of death, mental development, cognitive function, cretinism, or hypothyroidism, or secondary outcomes of TSH or serum thyroglobulin concentration. Two studies reported the effects on goitre, one on physical development measures, and one on adverse effects. All studies assessed urinary iodine concentration. The effects of iodine fortification compared to control on goitre prevalence (OR 1.60, 95% CI 0.60 to 4.31; 1 non-RCT, 83 participants; very low-quality evidence), and five physical development measures were uncertain (1 non-RCT, 83 participants; very low-quality evidence): weight (MD 0.23 kg, 95% CI -6.30 to 6.77); height (MD -0.66 cm, 95% CI -4.64 to 3.33); weight-for-age (MD 0.05, 95% CI -0.59 to 0.69); height-for-age (MD -0.30, 95% CI -0.75 to 0.15); and weight-for-height (MD -0.21, 95% CI -0.51 to 0.10). One study reported that there were no adverse events observed during the cross-over trial (low-quality evidence). Pooled results from RCTs showed that urinary iodine concentration significantly increased following iodine fortification (SMD 0.59, 95% CI 0.37 to 0.81; 6 RCTs, 2032 participants; moderate-quality evidence). This is equivalent to an increase of 38.32 µg/L (95% CI 24.03 to 52.61 µg/L). This effect was not observed in the meta-analysis of non-RCTs (SMD 0.25, 95% CI -0.16 to 0.66; 3 non-RCTs, 262 participants; very low-quality evidence). Sensitivity analyses did not change the effect observed in the primary analyses. The evidence on the effect of iodine fortification of foods, beverages, condiments, or seasonings other than salt on reducing goitre, improving physical development measures, and any adverse effects is uncertain. However, our findings suggest that the intervention likely increases urinary iodine concentration. Additional, adequately powered, high-quality studies on the effects of iodine fortification of foods on these, and other important outcomes, as well as its efficacy and safety, are required.

Plain-language summary: We searched for articles from different sources including published research papers, unpublished reports, and through direct communication with experts and organisations working to address iodine and micronutrient deficiency. We last searched the databases in January 2018. Eleven studies, which captured data on 4317 participants (3636 children, 648 women of reproductive age, and 33 infants), met our inclusion criteria. The type of foods used as vehicle to deliver iodine differed between the studies, and included biscuits, milk, fish sauce, drinking water, yoghourt, fruit beverage, seasoning powder, and infant formula milk. The amount of iodine provided to participants ranged from 35 µg/day to 220 µg/day, and study duration ranged from 11 days to 48 weeks. Of the 11 studies included, five examined the effect of adding iodine alone to foods compared to either no intervention or the same foods without iodine; while six evaluated the effect of adding iodine plus other micronutrients to foods compared to the same foods without iodine, but with different levels of other micronutrients. No study evaluated the effect of adding iodine to foods on death, mental development, cognitive function, cretinism (a condition characterized by impaired control of physical movement and intellectual disability), hypothyroidism (underactive thyroid), thyroid-stimulating hormone concentration, or serum thyroglobulin concentration (these are biological markers that indicate the presence of iodine deficiency when concentration in the blood is high). Two studies reported on the effect of the intervention on goitre, one study assessed five physical development measures (weight, height, weight-for-age, height-for-age, and weight-for-height scores), and one examined adverse effects. All studies assessed urinary iodine concentration (the concentration of iodine secreted in the urine, which indicates the presence of iodine deficiency when concentration is low in a population group, rather than in an individual). We combined the data that met our requirements in these studies in a meta-analysis. We are uncertain of the effects of iodine fortification on the proportion of participants with goitre, or on any of the five physical development measures. One study reported narratively that no adverse effects were observed during the trial. We found a significant increase of 38.32 µg/L in urinary iodine concentration after adding iodine to foods, compared to the groups that did not have iodine added, from studies of higher quality. Using GRADE, we rated the quality of the evidence as very low for goitre and physical development measures, due to study limitations (risk of bias) and imprecise results, and low for adverse events due to indirectness and imprecise results. We rated the quality of the evidence for urinary iodine concentration, from studies in which participants were allocated to treatment groups at random (gold standard design for clinical research), as moderate. On the other hand, quality of the evidence for urinary iodine concentration from studies without this random element was rated as very low, due to study limitations and imprecise results. Overall, there is no clear evidence on the effect of the intervention on reducing the proportion of people with goitre, improving physical growth, or adverse events. However, our results show that adding iodine to foods likely increases urinary iodine concentration. Additional studies to better quantify the effect of the intervention on these outcomes, as well as other outcomes, are needed.