Several reviews and meta-analyses have examined the effects of iodine on mental development. None focused on young children, so they were incomplete in summarizing the effects on this important age group. The current systematic review therefore examined the relationship between iodine and mental development of children 5 years old and under. A systematic review of articles using Medline (1980–November 2011) was carried out. We organized studies according to four designs: (1) randomized controlled trial with iodine supplementation of mothers; (2) non-randomized trial with iodine supplementation of mothers and/or infants; (3) prospective cohort study stratified by pregnant women’s iodine status; (4) prospective cohort study stratified by newborn iodine status. Average effect sizes for these four designs were 0.68 (2 RCT studies), 0.46 (8 non-RCT studies), 0.52 (9 cohort stratified by mothers’ iodine status), and 0.54 (4 cohort stratified by infants’ iodine status). This translates into 6.9 to 10.2 IQ points lower in iodine deficient children compared with iodine replete children. Thus, regardless of study design, iodine deficiency had a substantial impact on mental development. Methodological concerns included weak study designs, the omission of important confounders, small sample sizes, the lack of cluster analyses, and the lack of separate analyses of verbal and non-verbal subtests. Quantifying more precisely the contribution of iodine deficiency to delayed mental development in young children requires more well-designed randomized controlled trials, including ones on the role of iodized salt.

Anthropometric characteristics and iron status affect cognitive performance in children. In addition, selenium can influence cognitive outcomes; protection of the brain from oxidative stress and its role in thyroid hormone metabolism are putative mechanisms. To investigate their association with cognitive performance, anthropometric indicators, iron biomarkers, and serum selenium of children (n = 541) of 54-60mo of age from rural Ethiopia were assessed. Cognitive assessment was conducted with the administration of two reasoning subtests of the Wechsler Preschool and Primary Scale of Intelligence and the school readiness test. Stunting was found in 41.4 % of children, 28.7 % were underweight, and 6.3 % were wasted. The mean score of stunted children was lower than that of non-stunted children on non-verbal reasoning (7.0 ± 3.2vs7.9 ± 3.1; p = 0.01) and the school readiness tests (4.3 ± 2.2 vs 3.3 ± 2.1; p < 0.001). Compared to non-anemic children, anemic children had lower score for the verbal reasoning test (9.5 ± 1.7 vs 8.9 ± 2.2; p = 0.02). However, except for hemoglobin, none of the iron biomarkers had significant associations with the cognitive score of the study children (p > 0.05). Selenium deficient children had lower scores on all cognitive tests than normal children (p < 0.05). The present study finding linking chronic undernutrition and micronutrient deficiency to cognitive deficits suggests the need for designing effective intervention programmes to control for protein energy malnutrition and micronutrient deficiency and address cognitive development in children.

The effectiveness of salt iodisation in improving the mental development of young children has not been assessed. We implemented a community-based cluster-randomised effectiveness trial in sixty randomly selected districts in the Amhara region of Ethiopia. We randomly allocated each district to treatment and randomly selected one of its villages. In parallel to national salt iodisation efforts, iodised salt was brought early into the markets of the thirty intervention villages before it became widely available in the thirty control villages 4–6 months later. The primary outcome was children’s mental development scores on the Bayley Scales. This was an intention-to-treat analysis using mixed linear models adjusted for covariates and clusters. The trial was registered at ClinicalTrials.gov, NCT013496. We assessed 1835 infants aged 5–11 months at baseline. The same children (85 % of the sample) were re-assessed at 20–29 months when all villages had iodised salt. At endline, urinary iodine concentration was higher in children in the intervention group compared with those in the control group (median 228·0v. 155·1 µg/l,P=0·001). The intervention group had higher scores compared with the control group on the Bayley composite score (raw scores:130·60v. 128·51; standardised scores: 27·8v. 26·9;d=0·13; 95 % CI 0·02, 0·23) and three of the four subscales: cognitive (53·27v. 52·54,d=0·13; 95 % CI 0·03, 0·23), receptive language (20·71v. 20·18,d=0·13; 95 % CI 0·03, 0·24) and fine motor (35·45v. 34·94,d=0·15; 95 % CI 0·04, 0·25). The introduction of iodised salt contributes to children’s higher urinary iodine concentration and mental development.

We have found an inadvertent error in our paper published in Nutrients [1]. One standard error was not converted into standard deviation and this affected the following effect sizes and intelligence quotient (IQ):

Objectives: The objective was to examine nutritional, health, and social predictors of early child mental development in the Amhara region of Ethiopia Methods: Using a cluster randomized design, iodized salt was forced early into the markets of 30 villages (intervention group) before it became available in the 30 control villages following national salt iodization legislation. A total of 1880 infants 6 to 10 mo old in the 60 villages were administered Bayley Scales of Infant and Toddler Development (BSID-III) at baseline and when they were 20-29 mo of age (86% of sample) Results: The two groups had similar socioeconomic, nutrition, and mental development scores at baseline. These variables were significant predictors of endline cognitive and language development scores: length-for-age z-score (p<0.001), weight-for-age z-score (p<0.001), psychosocial stimulation (p<0.001), water/sanitation (p<0.001), mother's education (p<0.01), family assets (p<0.001), recent deworming (p<0.05), and maternal depression (p<0.05). The intervention group had significantly higher mental development scores, and a multiple regression analysis revealed that the intervention effect was positively partially mediated by length-for-age z-score (std β= 0.16 to 0.21, p<0.01) and water/sanitation score (std β= 0.09 to 0.10, p<0.01). Conclusions: In conclusion, iodized salt improved children's mental development both directly and indirectly by its effect on growth. The indirect effect through water/sanitation may be because water and sanitation improve health.

Objectives: The study examined nutritional and other predictors of mental development of preschool-aged children in northern Ethiopia. The current analysis of older children from the iodized salt project (see Infant study) included the effects of iodized salt, along with other determinants. Methods: Using a cluster randomized design, 1550 children in 60 villages in Amhara, Ethiopia were given tests of School Readiness and Wechsler verbal and nonverbal reasoning, twice at 54-60 months and again at 69-78 months. Between these assessments, iodized salt was distributed early in the markets of 30 randomly assigned villages (intervention group) before it became available in 30 control villages. Results: The two groups were largely comparable at baseline. In addition to the effects of iodized salt on School Readiness (p=0.01) and nonverbal reasoning (p<0.10) seen at the endline, the following predictors were positively and significantly associated with cognitive outcomes: height-for-age z-score (HAZ; p<0.0001), weight-for-age z-score (p<0.0001), family assets (p<0.0001), recent deworming (p=0.01), improved water/sanitation (p<0.01), and mother's education (p<0.05). Although over two-thirds had palpable goiter, hemoglobin status was good (M=134 g/L). Children overall performed relatively better on the School Readiness test (M=6.66 Intervention and 6.25 Control) than nonverbal reasoning (M= 4.15 Intervention and 3.95 Control)(theoretic ranges 0-19). A multiple regression, following the Baron and Kenny mediation analysis, on School Readiness scores revealed that the intervention effect was partially mediated by HAZ (std β= 0.37 , p<0.0001). Conclusions: In conclusion, iodized salt improved children's School Readiness skills and nonverbal reasoning, both directly, and indirectly by way of its effect on growth.