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Meta-Analysis
. 2019 Feb 12;2(2):CD010734.
doi: 10.1002/14651858.CD010734.pub2.

Iodine fortification of foods and condiments, other than salt, for preventing iodine deficiency disorders

Joseph Alvin R Santos  1 , Anthea Christoforou, Kathy Trieu, Briar L McKenzie, Shauna Downs, Laurent Billot, Jacqui Webster, Mu Li
Affiliations
Meta-Analysis

Iodine fortification of foods and condiments, other than salt, for preventing iodine deficiency disorders

Joseph Alvin R Santos et al. Cochrane Database Syst Rev. .

Abstract

Background: Iodine deficiency disorders (IDD) affect close to 1.9 billion people worldwide, and are a major public health concern in many countries. Among children, iodine deficiency is the main cause of potentially preventable deficits of central nervous system development and impairment of cognitive function, as well as goitre and hypothyroidism in people of all ages. Salt iodisation is the preferred strategy for IDD prevention and control, however, in some instances where salt is not the major condiment, alternate vehicles for iodine fortification have been considered.

Objectives: To assess the effects of fortifying foods, beverages, condiments, or seasonings other than salt with iodine alone or in conjunction with other micronutrients, on iodine status and health-related outcomes in all populations.

Search methods: Studies were identified through systematic searches of the following databases from their start date to January 2018: Cochrane Public Health Group Specialised Register; CENTRAL; MEDLINE; MEDLINE in Process; Embase; Web of Science; CINAHL; POPLINE; AGRICOLA; BIOSIS; Food Science and Technology Abstracts; OpenGrey; Bibliomap and TRoPHI; AGRIS; IBECS; Scielo; Global Index Medicus-AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched reference list of relevant articles, conference proceedings, and databases of ongoing trials, and contacted experts and relevant organisations to identify any unpublished work. We applied no language or date restrictions.

Selection criteria: Studies were eligible if they were randomised or quasi-randomised controlled trials (RCT) with randomisation at either the individual or cluster level (including cross-over trials), non-randomised RCTs, or prospective observational studies with a control group, such as cohort studies, controlled before-and-after studies, and interrupted time series. We included studies that examined the effects of fortification of food, beverage, condiment, or seasoning with iodine alone, or in combination with other micronutrients versus the same unfortified food, or no intervention. We considered the following measures: death (all-cause), goitre, physical development, mental development, cognitive function and motor skill development, cretinism, hypothyroidism, adverse effects (any reported by trialists), urinary iodine concentration, thyroid-stimulating hormone (TSH) concentration, and serum thyroglobulin concentration. We included all populations, including pregnant women, from any country.

Data collection and analysis: Two review authors independently assessed study eligibility, extracted data, and assessed risk of bias of included studies.We used random-effects meta-analyses to combine data and generate an overall estimate of treatment effect, when more than one study examined the same outcome measure. The overall effect estimate was calculated as the mean difference (MD) or standardised mean difference (SMD) between the intervention group and the comparison group for continuous outcomes, and as odds ratio (OR) for dichotomous outcomes. We assessed the level of heterogeneity through the I² statistic. We conducted post-hoc subgroup analyses to explore possible sources of heterogeneity, and sensitivity analyses to check the robustness of the findings from the primary analyses. We assessed the quality of the evidence for each outcome using the GRADE framework.Where it was not possible to pool the results in a meta-analysis, we provided a narrative summary of the outcomes.

Main results: 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.

Authors' conclusions: 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.

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Conflict of interest statement

JW is the Director of the World Health Organization Collaborating Centre on Population Salt Reduction, and receives funding for her work from the National Health and Medical Research Council, the Victorian Health Promotion Foundation, and headquarters and various regional offices of the World Health Organization. From 2003 to 2006, she managed the UK government's Salt Reduction program while working for the Food Standards Agency. She is currently supported by a four‐year National Health and Medical Research Council Fellowship/National Heart Foundation fellowship for her work on salt reduction.

KT receives support from a National Health and Medical Research Council postgraduate scholarship, the Victorian Health Promotion Foundation (VicHealth), and the World Health Organization. She received financial support from the World Health Organization during the conduct of the study.

ML ‐ none known.

JS ‐ none known.

AC ‐ none known.

BM ‐ none known.

SD ‐ none known.

LB ‐ none known.

Figures

1
1
WHO/CDC logic model for micronutrients interventions in public health (with permission from WHO)
2
2
Study flow diagram
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Forest plot of comparison 1. Iodine fortified versus non‐iodine fortified product; outcome: 1.1 Goitre prevalence
5
5
Forest plot of comparison 1. Iodine fortified versus non‐iodine fortified product; outcome: 1.2 Physical development measures
6
6
Forest plot of comparison 1. Iodine fortified versus non‐iodine fortified food; outcome: 1.3 Urinary iodine concentration (RCT)
7
7
Forest plot of comparison 1. Iodine fortified versus non‐iodine fortified food; outcome: 1.4 Urinary iodine concentration (non‐RCT)
1.1
1.1. Analysis
Comparison 1 Iodine fortified versus non‐iodine fortified food, Outcome 1 Goitre prevalence (non‐RCT).
1.2
1.2. Analysis
Comparison 1 Iodine fortified versus non‐iodine fortified food, Outcome 2 Physical development measures (non‐RCT).
1.3
1.3. Analysis
Comparison 1 Iodine fortified versus non‐iodine fortified food, Outcome 3 Urinary iodine concentration (RCT).
1.4
1.4. Analysis
Comparison 1 Iodine fortified versus non‐iodine fortified food, Outcome 4 Urinary iodine concentration (non‐RCT).
2.1
2.1. Analysis
Comparison 2 Subgroup analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 1 Urinary iodine concentration by age group (RCT).
2.2
2.2. Analysis
Comparison 2 Subgroup analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 2 Urinary iodine concentration by trial duration (RCT).
2.3
2.3. Analysis
Comparison 2 Subgroup analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 3 Urinary iodine concentration by daily iodine dose (RCT).
2.4
2.4. Analysis
Comparison 2 Subgroup analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 4 Urinary iodine concentration by percent with iodine deficiency at baseline (RCT).
2.5
2.5. Analysis
Comparison 2 Subgroup analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 5 Urinary iodine concentration by type of fortification (RCT).
3.1
3.1. Analysis
Comparison 3 Sensitivity analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 1 Analysis using alternative post‐intervention points (RCT).
3.2
3.2. Analysis
Comparison 3 Sensitivity analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 2 Analysis using alternative post‐intervention points (non‐RCT).
3.3
3.3. Analysis
Comparison 3 Sensitivity analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 3 Analysis using different ICC for clustered studies (non‐RCT).
3.4
3.4. Analysis
Comparison 3 Sensitivity analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 4 Analysis including parallel and cross‐over RCTs.
3.5
3.5. Analysis
Comparison 3 Sensitivity analysis: iodine‐fortified versus non‐iodine fortified food, Outcome 5 Analysis excluding studies at high risk of bias (RCT).
See this image and copyright information in PMC

Update of

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