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      Effects of Iodized Salt and Iodine Supplements on Prenatal and Postnatal Growth: A Systematic Review

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          Abstract

          Hypothyroidism due to iodine deficiency can impair physical development, most visibly in the marked stunting of myxedematous cretinism caused by severe in utero iodine deficiency. Whether iodine repletion improves growth in noncretinous children is uncertain. Therefore, the aim of our systematic review was to assess the effects of iodine fortification or supplementation on prenatal and postnatal growth outcomes in noncretinous children. Following Cochrane methods and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, we searched 10 databases including 2 Chinese databases (latest search February 2017). We included randomized and nonrandomized controlled trials (RCTs; non-RCTs), controlled before-after (CBA) studies, and interrupted time-series studies in pregnant women and children (≤18 y), which compared the effects of iodine (any form, dose, regimen) to placebo, noniodized salt, or no intervention on prenatal and postnatal growth outcomes. We calculated mean differences with 95% CIs, performed random-effects meta-analyses, and assessed the quality of evidence with the use of GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included 18 studies (13 RCTs, 4 non-RCTs, 1 CBA) (n = 5729). Iodine supplementation of severely iodine-deficient pregnant women increased mean birthweight [mean difference (MD): 200 g; 95% CI: 183, 217 g; n = 635; 2 non-RCTs] compared to controls, but the quality of this evidence was assessed as very low. Iodine repletion across the other groups showed no effects on primary growth outcomes (quality of evidence mostly low and very low). Meta-analyses showed a positive effect in moderate-to-mildly iodine-deficient schoolchildren on insulin-like growth factor-1 (MD: 38.48 ng/mL; 95% CI: 6.19, 70.76 ng/mL; n = 498; 2 RCTs, low-quality evidence) and insulin-like growth factor binding protein-3 (MD: 0.46 μg/mL; 95% CI: 0.25, 0.66 μg/mL; n = 498; 2 RCTs, low-quality evidence). In conclusion, we identified few well-designed trials examining the effects of iodine repletion on growth. We are uncertain whether prenatal iodine repletion increases infant growth. Postnatal iodine repletion may improve growth factors but has no clear effects on somatic growth. Our systematic review was registered with PROSPERO as CRD42014012940.

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          Most cited references46

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          Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation.

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            Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles.

            Some authors argue that systematic reviews and meta-analyses of intervention studies should include only randomized controlled trials because the randomized controlled trial is a more valid study design for causal inference compared with the observational study design. However, a review of the principal elements underlying this claim (randomization removes the chance of confounding, and the double-blind process minimizes biases caused by the placebo effect) suggests that both classes of study designs have strengths and weaknesses, and including information from observational studies may improve the inference based on only randomized controlled trials. Furthermore, a review of empirical studies suggests that meta-analyses based on observational studies generally produce estimates of effect similar to those from meta-analyses based on randomized controlled trials. The authors found that the advantages of including both observational studies and randomized studies in a meta-analysis could outweigh the disadvantages in many situations and that observational studies should not be excluded a priori.
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              Thyroid hormones in fetal growth and prepartum maturation.

              The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.
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                Author and article information

                Journal
                Advances in Nutrition
                Oxford University Press (OUP)
                2161-8313
                2156-5376
                May 15 2018
                May 01 2018
                May 2018
                May 15 2018
                May 01 2018
                May 2018
                : 9
                : 3
                : 219-237
                Affiliations
                [1 ]Human Nutrition Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland
                [2 ]Centre for Evidence-Based Health Care, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa
                [3 ]Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China
                [4 ]National Institute for Nutrition and Health, Chinese Centre for Disease Control and Prevention, Key Laboratory of Trace Element Nutrition of the Ministry of Health, Beijing, China
                [5 ]Centre of Excellence for Nutrition, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa
                Article
                10.1093/advances/nmy009
                5952947
                29767700
                8a4e3632-fc7d-4e85-8f69-cc4528c4ab1c
                © 2018

                http://academic.oup.com/journals/pages/about_us/legal/notices

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