Deficiency. In contrast to studies reported here and other meta-analyses, the

Deficiency. In contrast to studies reported here and other meta-analyses, the meta-analysis of 37 studies from China mainly compared samples that differed in their access to iodized salt [26]. Universal salt iodization is recommended by WHO and UNICEF for the sustainable elimination of iodine deficiency in all countries where iodine deficiency disorders are of public health concern [91]. Despite the success of salt iodization programs in many countries around the world, some countries still have low coverage of adequately iodized salt [92]. In settings where a large proportion of the population does not have access to adequately iodized salt, WHO and UNICEF recommend high dose iodine supplementation for the most vulnerable groups as an interim measure until salt iodization can be scaled up. Additional research and recommendations suggest the need to complement iodized salt, when it has been used for a short time only or when of low quality, with iodine supplementation in women of child-bearing age [93,94]. To determine if iodized salt in the maternal or child diet has the same effects on mental development as high dose supplementation, effectiveness research will have to take place in these countries. 5. Conclusions Our review found that regardless of study design, iodine deficiency had a biologically important impact on, or association with, mental development. We believe that the best estimate to date of the effect size of iodine supplementation on mental development in children 5 years old and under is 0.49, which translates into 7.4 IQ points lost due to iodine deficiency. Although these intervention studies had relatively rigorous designs and used age-appropriate mental development tests, results must be interpreted with caution due to various limitations in study purchase PG-1016548 design and analysis including small sample size and possible attrition, lack of accommodation for intra-cluster correlation, and inattention to confounding variables. The observational studies, albeit a weak design, support the idea that iodine is important for mental development, and provide similar effects sizes as the intervention studies. To further quantify the importance of iodine for mental development in young children, this review points to the need for well-designed randomized controlled trials with adequate sample sizes as well as studies that assess the effectiveness of iodized salt. Acknowledgments Funding for this research was provided by The Micronutrient Initiative. Conflict of Interest The authors declare no conflict of interest. References 1. 2. 3. Bernal, J.; Pekonen, F. Ontogenesis of the nuclear 3,5,3-triiodothyronine receptor in the human fetal brain. Endocrinology 1984, 114, 677?79. Bernal, J. Thyroid hormones and brain development. Vitam. Horm. 2005, 71, 95?22. Gibson, R.S. Principles of Nutritional Assessment, 2nd ed.; Oxford University Press: Oxford, UK, 2005; p. 908.Nutrients 2013, 5 4.5. 6.7. 8. 9. 10. 11. 12. 13. 14. 15.16.17.18. 19.20.21.Oppenheimer, J.H.; Schwartz, H.L.; Mariash, C.N.; Kinlaw, W.B.; Wong, N.C.; Freake, H.C. Advances in our LOR-253 chemical information understanding of thyroid hormone action at the cellular level. Endocr. Rev. 1987, 8, 288?08. Manzano, J.; Bernal, J.; Morte, B. Influence of thyroid hormones on maturation of rat cerebellar astrocytes. Int. J. Dev. Neurosci. 2007, 25, 171?79. Pedraza, P.E.; Obregon, M.J.; Escobar-Morreale, H.F.; del Rey, F.E.; de Escobar, G.M. Mechanisms of adaptation to iodine deficiency in rats: Thyroid status is tissue.Deficiency. In contrast to studies reported here and other meta-analyses, the meta-analysis of 37 studies from China mainly compared samples that differed in their access to iodized salt [26]. Universal salt iodization is recommended by WHO and UNICEF for the sustainable elimination of iodine deficiency in all countries where iodine deficiency disorders are of public health concern [91]. Despite the success of salt iodization programs in many countries around the world, some countries still have low coverage of adequately iodized salt [92]. In settings where a large proportion of the population does not have access to adequately iodized salt, WHO and UNICEF recommend high dose iodine supplementation for the most vulnerable groups as an interim measure until salt iodization can be scaled up. Additional research and recommendations suggest the need to complement iodized salt, when it has been used for a short time only or when of low quality, with iodine supplementation in women of child-bearing age [93,94]. To determine if iodized salt in the maternal or child diet has the same effects on mental development as high dose supplementation, effectiveness research will have to take place in these countries. 5. Conclusions Our review found that regardless of study design, iodine deficiency had a biologically important impact on, or association with, mental development. We believe that the best estimate to date of the effect size of iodine supplementation on mental development in children 5 years old and under is 0.49, which translates into 7.4 IQ points lost due to iodine deficiency. Although these intervention studies had relatively rigorous designs and used age-appropriate mental development tests, results must be interpreted with caution due to various limitations in study design and analysis including small sample size and possible attrition, lack of accommodation for intra-cluster correlation, and inattention to confounding variables. The observational studies, albeit a weak design, support the idea that iodine is important for mental development, and provide similar effects sizes as the intervention studies. To further quantify the importance of iodine for mental development in young children, this review points to the need for well-designed randomized controlled trials with adequate sample sizes as well as studies that assess the effectiveness of iodized salt. Acknowledgments Funding for this research was provided by The Micronutrient Initiative. Conflict of Interest The authors declare no conflict of interest. References 1. 2. 3. Bernal, J.; Pekonen, F. Ontogenesis of the nuclear 3,5,3-triiodothyronine receptor in the human fetal brain. Endocrinology 1984, 114, 677?79. Bernal, J. Thyroid hormones and brain development. Vitam. Horm. 2005, 71, 95?22. Gibson, R.S. Principles of Nutritional Assessment, 2nd ed.; Oxford University Press: Oxford, UK, 2005; p. 908.Nutrients 2013, 5 4.5. 6.7. 8. 9. 10. 11. 12. 13. 14. 15.16.17.18. 19.20.21.Oppenheimer, J.H.; Schwartz, H.L.; Mariash, C.N.; Kinlaw, W.B.; Wong, N.C.; Freake, H.C. Advances in our understanding of thyroid hormone action at the cellular level. Endocr. Rev. 1987, 8, 288?08. Manzano, J.; Bernal, J.; Morte, B. Influence of thyroid hormones on maturation of rat cerebellar astrocytes. Int. J. Dev. Neurosci. 2007, 25, 171?79. Pedraza, P.E.; Obregon, M.J.; Escobar-Morreale, H.F.; del Rey, F.E.; de Escobar, G.M. Mechanisms of adaptation to iodine deficiency in rats: Thyroid status is tissue.