Table 1 Characteristics of included studies
| Â | Author & year | Aim of study | Participants; Study designs considered | Treatment / Exposure; Setting | Control, if applicable | Pre-defined outcomes | No. studies; Study designs included; Locations | Gaps relevant to our research question | AMSTAR score |
|---|---|---|---|---|---|---|---|---|---|
Last search date | |||||||||
Quantitative studies (including meta-analyses) | |||||||||
1 | Taylor et al. (2014) | To evaluate the impact of iodine supplementation in pregnancy and childhood on thyroid function and child | School-age children from populations of mild-to-moderate iodine deficiency (determined from the median population urinary iodine) | Maternal iodine supplementation in pregnancy; Childhood iodine supplementation | No supplementation or significantly lower dose of supplements | Thyroid function; thyroid volume; cognitive performance | 17 studies included in the review, of which 9 RCTs and 8 observational studies | Review only covers maternal and infant thyroid function, and child neurodevelopment. | 8 |
Last search date – April 2013 Ref.: [32] | |||||||||
Setting: Mild to moderate iodine deficiency | Relevant studies: 4 RCTs reporting on neonatal thyroid function | There are no growth outcomes considered. | |||||||
Neurodevelopment in populations with mild-to moderate Iodine deficiency. | RCTs, quasi-randomised trials, prospective cohort or case–control studies considered | ||||||||
Locations: Belgium, Denmark, Germany and Spain | Not all relevant age groups are included (only neonates and school age children) | ||||||||
2 | Bougma et al. (2013) | To examine whether iodine status of mothers or infants affects the mental development of young children | Children 5 years and under RCT, non-randomised trial, prospective cohort trials considered | Exposure to different iodine levels before pregnancy, during pregnancy, or shortly after birth; or Examination of iodine exposure related to mental development outcome | Placebo, historical control, iodine sufficient siblings or children of similar age used as control group | Mental development score | 24 studies included in the review, of which 2 RCT, 8 non-randomized intervention trials, 10 prospective cohort (women), and 9 prospective cohort (infants) | Review only investigates mental development. | 8 |
Last search date – November 2011 Ref.: [8] | |||||||||
There are no growth outcomes considered. | |||||||||
Not all relevant age groups are included (only under 5 years). | |||||||||
Relevant studies: None. No studies report on growth (total of 24 studies included in review) | |||||||||
Setting: Not defined | |||||||||
Locations: China, DR Congo, Ecuador, Peru, Spain, Portugal, USA, Netherlands, Italy, UK, Canada. | |||||||||
3 | Ristić-Medić et al. (2014) | To identify and examine studies investigating iodine intake and biomarkers of iodine status and to combine these studies in a meta-analysis to estimate the dose–response relationships between iodine intake and iodine status. | No criteria specified | For RCTs: Iodine intervention (iodised salt, iodised oil, iodised water, iodine tablets, iodine-enriched food or milk formula) | For RCTs: Placebo or low-dose iodine supplement (<100μg iodine per day) | For RCTs: Mean concentrations of UI, serum Tg, serum TSH, analytical methods to assess iodine status | 58 studies included in the review, of which 33 RCTs 30 observational studies (5 being part of the included RCTs) | Review looked at iodine biomarkers. Does not consider iodine-related outcomes i.e., growth. | 8 |
RCTs, prospective cohort studies, nested case–control studies, cross sectional studies considered | |||||||||
Last search date – December 2011 Ref.: [33] | |||||||||
For observational studies: Concentration of UI, serum Tg, serum TSH, analytical methods to assess iodine status | Relevant studies: None | ||||||||
Observational studies: Evaluation of iodine intake (food frequency questionnaire, dietary history method, 24h recall, adherence to WHO criteria for assessing iodine intake) | |||||||||
Locations: Africa, Americas, Asia, Australasia, Europe | |||||||||
Setting: Not defined | |||||||||
Qualitative studies (not including meta-analyses) | |||||||||
1 | Khor & Misra (2012) Last searched Ref.: [36] | To provide an update on the effects of micronutrient interventions (by supplementation or food fortification) on cognitive performance of children of 5-15 years in developing countries | Children 5-15 years RCTs only considered | Micronutrient (vitamins and/or minerals) supplementation for a period of >4 months | Not specified | Cognitive development indicators including: psychomotor development, cognitive performance, mental development, IQ, school performance. | 13 RCTs included in the review, of which 6 that considered micronutrient-fortified foods including iodine. | Did not consider growth outcomes. Not all relevant age groups are included; 5 – 15 years only. | 4 |
Developing countries (UN classification) | |||||||||
(Studies that used other dietary components such as essential fatty acids, functional foods were excluded.) | Relevant studies: none | Only included RCTs. | |||||||
Locations: Asia, Kenya, Morocco | |||||||||
Setting: Developing countries | |||||||||
Only UN-classification developing countries included | |||||||||
2 | Best et al. (2011) Last search date – not specified Ref.: [35] | To examine the impact of multi-micronutrient (MMN) food fortification on the micronutrient status, growth, health, and cognitive development of school-age children. | School age children. (defined by 75 % of study population being between 6 and 18 years) | MMN-fortified food (defined as food to which > 3 micronutrients were added) | Unfortified food or food fortified with only one or two micronutrients | Biochemical measurements of micronutrient status, prevalence of micronutrient deficiencies, indicators of growth or body composition, stunting, wasting, underweight, morbidities, absence from school, cognitive outcomes, academic performance. | 12 studies included, of which: 6 controlled clinical trials (CCT), 1 controlled before-after (CBA) trial, and 5 RCTs | Looks at multiple MN rather than just supplementation with iodine alone. | 6 |
Experimental controlled efficacy or effectiveness studies including quasi-experimental controlled clinical trials, and controlled before-after studies only considered | |||||||||
Setting: Not defined | Relevant studies: 1 CCT compared effects of MMN fortification to single fortification with iodine (Morocco);4 studies reported on growth outcomes (height/stunting and weight/BMI/ underweight) | Fortified food only, and not supplementation. | |||||||
Restricted to English language publications. | |||||||||
School age children only; review does not consider all relevant population groups. | |||||||||
Locations: Asia, Australasia, India, North Africa, Southern Africa | |||||||||
3 | Gunnars-dottir & Dahl (2012) Last search date – September 2010 Ref.: [34] | To assess the influence of different intakes of iodine at different life stages (infants, children, adolescents, adults, elderly, and during pregnancy and lactation), in order to estimate the requirement for adequate growth, development, and maintenance of health. | Not specified, except that publications must be either in English or a Nordic language; have >50 subjects; consider representative samples of the population or specific sub-samples of the population; have an indicator of iodine status and/or thyroid function, e.g.,: UIC, thyroid volume, TSH, T3 and T4 | Not specified | Not specified | Pregnancy outcome, childhood development (including cognitive function and growth), thyroid function (thyroid hormones, thyroid gland size, hyper- and hypothyroidism), metabolism, health, and weight | 40 studies of mixed design included, of which 2 studies (1 clinical trial, 1 cohort) reported on iodine status in pregnancy, pregnancy outcome and thyroid function of mother and infant 1 cross-sectional study reported on excess iodine intake and UIC | Included adults and elderly as well as children and pregnant women. | 7 |
Setting: Not defined | |||||||||
Some papers were excluded on the basis that they were not relevant to Nordic countries. | |||||||||
Does not only cover intervention studies- also included are observational studies. | |||||||||
Locations: Europe, Nordic countries, Americas, Eastern Mediterranean, Africa, Western Pacific | |||||||||
No specified intervention or control. | |||||||||
All study types considered | |||||||||
4 | Zhou et al. (2013) Last search date – December 2012 Ref.: [9] | To evaluate the efficacy and safety of iodine supplementation during pregnancy or the periconceptual period on the development and growth of children. | Pregnant or women of childbearing age, regardless of iodine status or gestation at trial entry | Any form of iodine supplementation, with or without other nutrients. | Absence of iodine between exposure groups. | Primary outcome: cognitive development of children | 8 RCTs included in the review, of which 2 quasi-randomised | Only included RCTs. | 8 |
Not all relevant age groups are included – children of pregnant women are followed after pregnancy. Does not consider iodine supplementation in children themselves. | |||||||||
RCTs (including quasi-random design) only considered | Setting: Not defined | Secondary outcomes: pregnancy and birth outcomes, childhood growth and mortality, iodine status, thyroid function of mothers and infants. | Relevant studies: 2 quasi-RCT, reporting on growth outcomes (children at 5 years follow-up following intervention: skinfold thickness, MUAC, postnatal bone maturation growth rate; height of children at 15 years follow up; and pregnancy outcomes including birth anthropometrics and APGAR score) | ||||||
Locations: Peru, Papua New Guinea (Q-RCTs); Belgium, Germany, Denmark, Italy, Chile. | |||||||||
5 | Ibrahim et al. (2006) Last search date – November 2005 Ref.: [31] | To determine whether dietary supplementation with iodine affects mortality and morbidity in preterm infants. | Preterm infants (less than 37 weeks completed gestation) | Iodine supplementation (> 30 μg/kg/day) | Placebo or no supplementation | Primary outcomes: Neonatal mortality and mortality prior to hospital discharge; neuro-developmental outcomes at ≥ 12-months; severe neurodevelopmental disability; cognitive and educational outcomes at age > 5 years | 1 study included, which was an RCT. | Only preterm infants considered. | 9 |
Relevance of study: Primary outcome was thyroid hormones | Does not include pregnancy, nor older infants or children. | ||||||||
Controlled trials using random or quasi-random patient allocation considered | Setting: Not defined | ||||||||
Location: UK | Not focussed on growth, rather the prevention of mortality and adverse neurodevelopmental outcomes following preterm births. | ||||||||
Secondary outcomes: Severe respiratory distress syndrome; biochemical measures of thyroid function and iodine status | |||||||||
6 | Angermeyr & Clar (2004) Last search date - October 2003 Ref.: [30] | To assess the effects of iodine supplementation (e.g., iodised oil, salt, water, bread, supplements, tablets) in comparison with placebo or with each other on outcomes relating to iodine deficiency disorders in children | Children ≤ 18 years living in areas with low iodine intake (iodine deficiency) | Any population-based iodine supplementation (e.g., iodised salt, iodised oil (given orally or by injection), iodised water, iodine tablets iodine added to food etc.) | Placebo or other iodine supplementation | Primary outcomes: Goitre rate and thyroid size | Total 26 studies included, of which 15 RCTs, 5 non-randomised controlled trials, 3 prospective controlled studies, 2 quasi-randomised trials, 1 prospective comparative study. | Review does not cover pregnancy. | 9 |
Physical development (height, weight, strength); mental development (measurement of cognitive function) | |||||||||
Relevant studies:22 studies measured one or more thyroid outcomes (goitre rate, thyroid size, urinary iodine excretion, THS, T3, T4, thyroglobulin). | |||||||||
Setting: Low iodine intake | Secondary outcomes: Mortality related to iodine deficiency disorders; symptoms and signs of hypothyroidism; urinary iodine concentration; blood TSH concentration; serum thyroglobulin concentration; adverse effects (e.g., iodine-induced hyperthyroidism, thyroid auto-antibodies); health-related quality of life; acceptability of supplement; compliance, costs; socioeconomic effects (e.g., school performance) | ||||||||
6 studies measured one or more growth outcome measures (height, weight, mortality) | |||||||||
Locations: North Africa, Asia Europe, India, Africa, Americas | |||||||||
RCT, quasi-randomised trials and prospective non-randomised experimental studies considered | |||||||||
7 | Wu et al. (2002) (updated 2004) Last search date – August 2004 Ref.: [21] | To assess the effects of iodised salt in comparison with placebo and other forms of iodine supplementation on the incidence of iodine deficiency disorders | Adults and children living in areas of low iodine intake | Iodised salt | Placebo, other forms of iodine supplementation (iodised oil, iodised water, etc.) | Primary outcomes: Mortality related to iodine deficiency disorders, goitre, physical and mental development in children, symptoms of hypothyroidism. | 6 studies included, of which 1 RCT, 3 RCT (not blinded, blinding unknown, participants unblinded outcome assessment blinded), 2 prospective controlled study | Only covers iodised salt. | 9 |
Setting: Low iodine intake | |||||||||
Any prospective study with a control group considered | All study types (with control group) considered | ||||||||
Secondary outcomes: UIC, TSH in blood and neonatal cord blood, serum thyroglobulin, adverse effects (e.g., iodine induced hyperthyroidism), health related quality of life, costs, compliance, socioeconomic effects | Also considers adults | ||||||||
Relevant studies: 1 RCT reported on UIC | |||||||||
Locations: Germany, China, South Africa, Italy, Malaysia, India | |||||||||