Background: Acute excess iodine intake can damage the thyroid, but the effects of chronic excess iodine intake are uncertain. Few data exist for pregnant and lactating women and infants exposed to excessive iodine intake. Methods: This was a multicenter cross-sectional study. At study sites in rural Kenya and urban Tanzania previously reporting iodine excess in children, urinary iodine concentration (UIC), thyrotropin, total thyroxine, and thyroglobulin (Tg) were measured in school-age children (SAC), women of reproductive age, pregnant (PW) and lactating women, and breast-feeding and weaning infants. In a national study in Djibouti, UIC was measured in SAC and PW. At all sites, daily iodine intake was estimated based on UIC, and iodine concentration was measured in household salt and drinking water. Results: The total sample size was 4636: 1390, 2048, and 1198 subjects from Kenya, Tanzania, and Djibouti, respectively. In Kenya and Tanzania: (i) median UIC was well above thresholds for adequate iodine nutrition in all groups and exceeded the threshold for excess iodine intake in SAC; (ii) iodine concentrations >40 mg of iodine/kg were found in approximately 55% of household salt samples; (iii) iodine concentrations ≥10 μg/L were detected in 9% of drinking water samples; (iv) Tg was elevated in all population groups, but the prevalence of thyroid disorders was negligible, except that 5–12% of women of reproductive age had subclinical hyperthyroidism and 10–15% of PW were hypothyroxinemic. In Djibouti: (i) the median UIC was 335 μg/L (interquartile range [IQR] = 216–493 μg/L) in SAC and 265 μg/L (IQR = 168–449 μg/L) in PW; (ii) only 1.6% of Djibouti salt samples ( n = 1200) were adequately iodized (>15 mg/kg); (iii) the median iodine concentration in drinking water was 92 μg/L (IQR = 37–158 μg/L; n = 77). In all countries, UIC was not significantly correlated with salt or water iodine concentrations. Conclusions: Although iodine intake was excessive and Tg concentrations were elevated, there was little impact on thyroid function. Chronic excess iodine intake thus appears to be well tolerated by women, infants, and children. However, such high iodine intake is unnecessary and should be avoided. Careful evaluation of contributions from both iodized salt and groundwater iodine is recommended before any review of iodization policy is considered.

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.

Introduction Iodine is an essential micronutrient and component of the thyroid hormones. Sufficient ingestion of iodine is necessary for normal growth and development. If iodine requirements are not met, growth can be impaired. Salt iodisation and supplementation with iodine can prevent iodine deficiency disorders and stunted growth. No systematic review has yet collated the evidence linking iodine to growth. With an increased emphasis on stunting within the WHO Global Nutrition Targets for 2025, we propose a systematic review to address this question. Methods and analysis We will undertake a systematic review, and if appropriate, meta-analyses, evaluating the effects of iodised salt or iodine supplements on prenatal and postnatal somatic growth, until age 18. We will search a number of databases, including MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, the Cochrane Library, including the CENTRAL register of Controlled Trials and also the WHO library and ICTRP (International Clinical Trials Registry Platform), which includes the Clinicaltrials.gov repository. We will also search Wanfang Data and the China Knowledge Resource Integrated Database. Included studies must have compared exposure to iodised salt, iodine supplements or iodised oil, to placebo, non-iodised salt or no intervention. Primary outcomes will be continuous and categorical markers of prenatal and postnatal somatic growth. Secondary outcomes will cover further measures of growth, including growth rates and indirect markers of growth such as insulin-like growth factor-1 (IGF-1). Ethics and dissemination The systematic review will be published in a peer-reviewed journal, and will be sent directly to the WHO, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders and other stakeholders. The results generated from this systematic review will provide evidence to support future programme recommendations regarding iodine fortification or supplementation and child growth. Trial registration number PROSPERO CRD42014012940.

Adverse pregnancy outcomes and their complications cause increased maternal and neonatal morbidity and mortality and contribute considerably to the global burden of disease. In the last two decades, numerous narrative and systematic reviews have emerged assessing non-essential, potentially harmful, trace element exposure as a potential risk factor. This narrative review summarizes the recent literature covering associations between exposure to cadmium, lead, arsenic, and mercury and pregnancy outcomes and highlights common limitations of existing evidence that may hinder decision-making within public health. Several initial scoping searches informed our review, and we searched PubMed (latest date July 2022) for the literature published within the last five years reporting on cadmium, lead, arsenic, or mercury and pre-eclampsia, preterm birth, or prenatal growth. Pre-eclampsia may be associated with cadmium and strongly associated with lead exposure, and exposure to these metals may increase risk of preterm birth. Many reviews have observed cadmium to be negatively associated with birth weight. Additionally, lead and arsenic exposure may be negatively associated with birth weight, with arsenic exposure also adversely affecting birth length and head circumference. These findings should be interpreted with caution due to the limitations of the reviews summarized in this paper, including high heterogeneity due to different exposure assessment methods, study designs, and timing of sampling. Other common limitations were the low quality of the included studies, differences in confounding variables, the low number of studies, and small sample sizes.