Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95 % CI: -39, -27), Asian (% difference = -43; 95 % CI: -51, -35) and other non-White (% difference = -26; 95 % CI: -35, -14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

Perspectives on the application of CONSORT guidelines to randomised controlled trials in nutrition.

PURPOSE: Reporting guidelines facilitate quality and completeness in research reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement is widely applied to dietary and nutrition trials but has no extension specific to nutrition. Evidence suggests poor reporting in nutrition research. The Federation of European Nutrition Societies led an initiative to make recommendations for a nutrition extension to the CONSORT statement towards a more robust reporting of the evidence base. METHODS: An international working group was formed of nutrition researchers from 14 institutions in 12 different countries and on five continents. Using meetings over a period of one year, we interrogated the CONSORT statement specifically for its application to report nutrition trials. RESULTS: We provide a total of 28 new nutrition-specific recommendations or emphasised recommendations for the reporting of the introduction (three), methods (twelve), results (five) and discussion (eight). We also added two additional recommendations that were not allocated under the standard CONSORT headings. CONCLUSION: We identify a need to provide guidance in addition to CONSORT to improve the quality and consistency of the reporting and propose key considerations for further development of formal guidelines for the reporting of nutrition trials. Readers are encouraged to engage in this process, provide comments and conduct specific studies to inform further work on the development of reporting guidelines for nutrition trials.

Iodine status in western Kenya: a community-based cross-sectional survey of urinary and drinking water iodine concentrations.

Spot urinary iodine concentrations (UIC) are presented for 248 individuals from western Kenya with paired drinking water collected between 2016 and 2018. The median UIC was 271 µg L-1, ranging from 9 to 3146 µg L-1, unadjusted for hydration status/dilution. From these data, 12% were potentially iodine deficient (< 100 µg L-1), whilst 44% were considered to have an excess iodine intake (> 300 µg L-1). The application of hydration status/urinary dilution correction methods was evaluated for UICs, using creatinine, osmolality and specific gravity. The use of specific gravity correction for spot urine samples to account for hydration status/urinary dilution presents a practical approach for studies with limited budgets, rather than relying on unadjusted UICs, 24 h sampling, use of significantly large sample size in a cross-sectional study and other reported measures to smooth out the urinary dilution effect. Urinary corrections did influence boundary assessment for deficiency-sufficiency-excess for this group of participants, ranging from 31 to 44% having excess iodine intake, albeit for a study of this size. However, comparison of the correction methods did highlight that 22% of the variation in UICs was due to urinary dilution, highlighting the need for such correction, although creatinine performed poorly, yet specific gravity as a low-cost method was comparable to osmolality corrections as the often stated 'gold standard' metric for urinary concentration. Paired drinking water samples contained a median iodine concentration of 3.2 µg L-1 (0.2-304.1 µg L-1). A weak correlation was observed between UIC and water-I concentrations (R = 0.11).

Reducing micronutrient deficiencies in Pakistani children: are subsidies on fortified complementary foods cost-effective?

OBJECTIVE: To estimate the cost-effectiveness of price subsidies on fortified packaged complementary foods (FPCF) in reducing iodine deficiency, iron-deficiency anaemia and vitamin A deficiency in Pakistani children. DESIGN: The study proceeded in three steps: (i) we determined the current lifetime costs of the three micronutrient deficiencies with a health economic model; (ii) we assessed the price sensitivity of demand for FPCF with a market survey in two Pakistani districts; (iii) we combined the findings of the first two steps with the results of a systematic review on the effectiveness of FPCF in reducing micronutrient deficiencies. The cost-effectiveness was estimated by comparing the net social cost of price subsidies with the disability-adjusted life years (DALY) averted. SETTING: Districts of Faisalabad and Hyderabad in Pakistan. SUBJECTS: Households with 6-23-month-old children stratified by socio-economic strata. RESULTS: The lifetime social costs of iodine deficiency, iron-deficiency anaemia and vitamin A deficiency in 6-23-month-old children amounted to production losses of $US 209 million and 175 000 DALY. Poor households incurred the highest costs, yet even wealthier households suffered substantial losses. Wealthier households were more likely to buy FPCF. The net cost per DALY of the interventions ranged from a return per DALY averted of $US 783 to $US 65. Interventions targeted at poorer households were most cost-effective. CONCLUSIONS: Price subsidies on FPCF might be a cost-effective way to reduce the societal costs of micronutrient deficiencies in 6-23-month-old children in Pakistan. Interventions targeting poorer households are especially cost-effective.

Iodised salt and iodine supplements for prenatal and postnatal growth: a rapid scoping of existing systematic reviews.

BACKGROUND: Iodine deficiency can adversely affect child development including stunted growth. However, the effect of iodine supplementation or fortification on prenatal and postnatal growth in children (<18 years) is unclear. We identified the potential need for a systematic review to contribute to the evidence base in this area. To avoid duplication and inform the need for a new systematic review and its protocol, we undertook a rapid scoping review of existing systematic reviews investigating the effect of iodised salt and iodine supplements on growth and other iodine-related outcomes. METHODS: We searched TRIP and Epistemokinos (latest search date 15 December 2014). All English language systematic reviews reporting on the effect of iodine supplementation or fortification in any form, dose or regimen on any iodine-related health outcomes (including but not limited to growth) were included. Eligible systematic reviews could include experimental or observational studies in pregnant or lactating women or children to age 18. We tabulated the extracted data to capture the scope of questions addressed, including: author, publication year, most recent search date, participants, pre-specified treatment/exposure and comparator, pre-specified outcomes, outcomes relevant to our question and number and type of studies included. Methodological quality of included reviews was assessed using AMSTAR. RESULTS: Nine hundred and seventy-six records were screened and 10 reviews included. Most studies were of moderate methodological quality. Outcomes included assessments of thyroid function, iodine deficiency disorders, mental development and growth. Populations studied included pregnant women, preterm infants and children into adulthood. Most reviews looked at direct iodine supplementation or fortification, though some reviews considered iodine status, including the relationship between iodine intake and iodine biomarkers. Although five reviews pre-specified inclusion of growth outcomes, none provided synthesised evidence on the effects of iodine supplementation or fortification on prenatal and postnatal somatic growth. CONCLUSIONS: Our rapid scoping review demonstrates a gap in the evidence base with no existing, up-to-date systematic reviews on the effects of all forms of iodine supplementation/fortification in all of the relevant population groups on relevant growth and growth-related outcomes. A new systematic review examining this question will assist in addressing this gap.

Perspective: Peer Evaluation of Recommendations for CONSORT Guidelines for Randomized Controlled Trials in Nutrition.

Creating effective dietary guidance requires a rigorous evidence base that is predominantly developed from robust clinical trials or large-scale cohort studies, with the quality of the data available depending on the completeness and accuracy of their reporting. An international group of academics from 14 institutions in 12 different countries and on 5 continents, working on behalf of the Federation of European Nutrition Societies within its "Improving Standards in the Science of Nutrition" initiative, reviewed the Consolidated Standards of Reporting Trials (CONSORT) statement checklist as it pertains to nutrition trials. This perspective piece documents the procedure followed to gain input and consensus on the checklist previously published by this group, including its presentation and interrogation at the International Union of Nutritional Sciences International Congress of Nutrition 2022 (IUNS-ICN 22), inputs from a survey of journal editors, and its piloting on 8 nutrition trials of diverse designs. Overall, the initiative has been met with considerable enthusiasm. At IUNS-ICN 22, refinements to our proposal were elicited through a World Café method discussion with participating nutrition scientists. The contributing journal editors provided valuable insights, and the discussion led to the development of a potential tool specific to assess adherence to the proposed nutrition extension checklist. The piloting of the proposed checklist provided evidence from real-life studies that reporting of nutrition trials can be improved. This initiative aims to stimulate further discussion and development of a CONSORT-nutrition-specific extension.

Optimizing Growth: The Case for Iodine.

Iodine is an essential micronutrient and component of thyroid hormone. An adequate dietary iodine intake is critical to maintain and promote normal growth and development, especially during vulnerable life stages such as pregnancy and early infancy. The role of iodine in cognitive development is supported by numerous interventional and observational studies, and when iodine intake is too low, somatic growth is also impaired. This can be clearly seen in cases of untreated congenital hypothyroidism related to severe iodine deficiency, which is characterized, in part, by a short stature. Nevertheless, the impact of a less severe iodine deficiency on growth, whether in utero or postnatal, is unclear. Robust studies examining the relationship between iodine and growth are rarely feasible, including the aspect of examining the effect of a single micronutrient on a process that is reliant on multiple nutrients for optimal success. Conversely, excessive iodine intake can affect thyroid function and the secretion of optimal thyroid hormone levels; however, whether this affects growth has not been examined. This narrative review outlines the mechanisms by which iodine contributes to the growth process from conception onwards, supported by evidence from human studies. It emphasizes the need for adequate iodine public health policies and their robust monitoring and surveillance, to ensure coverage for all population groups, particularly those at life stages vulnerable for growth. Finally, it summarizes the other micronutrients important to consider alongside iodine when seeking to assess the impact of iodine on somatic growth.

Effects of Non-Essential "Toxic" Trace Elements on Pregnancy Outcomes: A Narrative Overview of Recent Literature Syntheses.

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.

Improving Iodine Intake in Rural Haiti through Social Enterprise: A Cross-Sectional Study in the Central Plateau.

Iodine intake in Haiti has increased in recent years thanks to the "Bon Sel" social enterprise approach to salt fortification and distribution by the market segment. However, it was uncertain whether this salt reached remote communities. This cross-sectional study aimed to assess the iodine status of school-age children (SAC) and women of reproductive age (WRA) in a remote region of the Central Plateau. A total of 400 children (9-13 years) and 322 women (18-44 years) were recruited through schools and churches, respectively. Urinary iodine (UIC) and urinary creatinine (UCC) concentrations were measured in spot samples, and thyroglobulin (Tg) on dried blood spots. Their iodine intake was estimated, and dietary information collected. The median (IQR) UIC in SAC was 130 µg/L (79-204, n = 399), and in WRA, 115 µg/L (73-173, n = 322). The median (IQR) Tg in SAC was 19.7 µg/L (14.0-27.6, n = 370), and in WRA, 12.2 µg/L (7.9-19.0, n = 183); 10% of SAC had Tg > 40 µg/L. Estimated iodine intake was 77 µg/day and 202 µg/day in SAC and WRA, respectively. Iodized table salt was rarely consumed, though bouillon was used daily; this is hypothesized to be a major contributor to dietary iodine intake. Iodine intake in this remote region seems to have improved considerably since the 2018 national survey, though SAC remain at risk. These results point to the potential effectiveness of using social business principles to deliver humanitarian solutions.

Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Pre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia. METHODS: A systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women. RESULTS: Twenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, -0.15 (-0.27, -0.03, I2 = 83.4%)), and vitamin D (risk difference, -0.09 (-0.17, -0.02, I2 = 0.0%)) supplementation. CONCLUSION: Our findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women.

Estimating habitual iodine intake and prevalence of inadequacy from spot urine in cross-sectional studies: a modeling analysis to determine the required sample size.

BACKGROUND: The habitual/usual iodine intake and the prevalence of iodine inadequacy may be estimated from spot urinary iodine concentrations in cross-sectional studies by collecting a repeat spot urine in a subgroup of the study population and accounting for within-person variability in iodine intake. However, guidance on the required overall sample size (N) and the replicate rate (n) is lacking. OBJECTIVES: To determine the sample size (N) and replicate rate (n) needed to estimate the prevalence of iodine inadequacy in cross-sectional studies. METHODS: We used data from local observational studies conducted in women 17-49 y old in Switzerland (N = 308), South Africa (N = 154), and Tanzania (N = 190). All participants collected 2 spot urine samples. We calculated the iodine intake using urinary iodine concentrations and accounted for urine volume using urinary creatinine concentration. For each study population, we estimated the habitual iodine intake distribution and determined the prevalence of iodine intake below the average requirement using the Statistical Program to Assess habitual Dietary Exposure (SPADE). We used the obtained model parameters in power analyzes and estimated the prevalence of iodine inadequacy for different sample sizes (N = 400, 600, and 900) and replicate rates (n = 50, 100, 200, 400, 600, and 900). RESULTS: The estimated prevalence (95% CI) of inadequate iodine intake was 21% (15, 28%), 5.1% (1.3, 8.7%), and 8.2% (3.4, 13%) for Swiss, South African, and Tanzanian women, respectively. An N of 400 women, with a repeated measure (n) in 100 women, achieved a satisfactory precision of the prevalence estimate in all study populations. Increasing the replicate rate (n) improved the precision more effectively than increasing the N of the study. CONCLUSIONS: The sample size for cross-sectional studies aiming to assess the prevalence of inadequate iodine intake depend on the expected prevalence, the overall variance in intake, and the study design. However, an N of 400 participants with a repeated measure of 25% may be used as guidance when planning observational studies applying simple random sampling. This trial was registered at clinicaltrials.gov as NCT03731312.

Community Pharmacist-Led Interventions to Improve Preconception and Pregnancy Health: A Systematic Review.

Background: Community pharmacist-led interventions are effective in improving health outcomes; however, their impact in improving preconception and pregnancy health is not clear. This study evaluated the effectiveness of community pharmacist-led interventions which aimed to improve health outcomes of preconception and pregnant women. Methods: A systematic review of the literature, consistent with PRISMA guidelines, was performed. Five electronic databases were searched up to February 2021. Results: Four studies, three in pregnant women and one in preconception women, were identified. The studies focused on improving micronutrient status and smoking cessation. The studies increased knowledge about, and use of, iron supplements, and improved iron status and smoking cessation rates in pregnant women, while improving knowledge regarding, and increasing the use of, preconception folic acid. The studies were ranked as weak to moderate quality. Conclusion: This review provides preliminary evidence for the potential benefit of community pharmacist-led interventions to improve the health of women before and during pregnancy.

Iodine status of pregnant women with obesity from inner city populations in the United Kingdom.

BACKGROUND/OBJECTIVES: Iodine is essential for foetal neurodevelopment and growth. Requirements increase in pregnancy to support increased thyroid hormone synthesis for maternal and foetal requirements, and for foetal transfer. Iodine deficiency in pregnancy is widely reported, and obesity has been associated with sub-optimal thyroid function. We evaluated iodine status and its relation with birthweight in a secondary analysis of pregnant women with obesity from multi-ethnic inner-city settings who participated in the UK Pregnancies Better Eating and Activity trial (UPBEAT). SUBJECTS/METHODS: Iodine and creatinine concentrations were evaluated in spot urine samples in the second (15+0-18+6 weeks, n = 954) trimester of pregnancy. We assessed iodine status as urinary iodine concentration (UIC) and urinary iodine-to-creatinine ratio (UI/Cr) and applied WHO/UNICEF/IGN population threshold of median UIC > 150 µg/L for iodine sufficiency. Relationships between iodine status and birthweight were determined using linear and logistic regression with appropriate adjustment, including for maternal BMI and gestational age. RESULTS: Median (IQR) UIC and UI/Cr in the second trimester of pregnancy were 147 µg/L (99-257) and 97 µg/g (59-165), respectively. An UI/Cr <150 µg/g was observed in 70% of women. Compared to women with UI/Cr >150 µg/g, there was a trend for women with UI/Cr <150 µg/g to deliver infants with a lower birthweight (ß = -60.0 g; 95% CI -120.9 to -1.01, P = 0.05). CONCLUSIONS: Iodine status of pregnant women with obesity from this cohort of UK women was suboptimal. Lower iodine status was associated with lower birthweight.

Adequately iodized salt is an important strategy to prevent iodine insufficiency in pregnant women living in Central Java, Indonesia.

Iodine is an essential micronutrient for cognitive development and growth. Optimal intakes are critical during pregnancy. We report the iodine status and thyroid function of pregnant women living in areas previously affected by severe iodine deficiency and in longstanding iodine sufficient areas in Java, Indonesia. This cross-sectional study was conducted in Magelang, Java, from July to November 2015, in four sub-districts; two previously affected by severe iodine deficiency (area 1) and two that were iodine-sufficient (area 2). Iodine intake was estimated using median urinary iodine concentration in spot samples and mean urinary iodine excretion in 3 x 24-hour samples, thyroid hormones (thyroid-stimulating hormone and free thyroxine) were measured in venous blood samples, and iodine content of household salt samples was estimated by titration. We recruited a total of 244 pregnant women, 123 in area 1 and 121 in area 2. Urinary iodine results suggested adequate habitual iodine intakes in both areas (median urinary iodine concentration in area 1: 222 µg/l (interquartile range 189, 276 µg/l), area 2: 264 µg/l (interquartile range 172, 284 µg/l), however, the risk of inadequate intakes increased with advancing trimester (Odds Ratio = 2.59 (95% CI 1.19-5.67) and 3.85 (95% CI 1.64-9.02) at second and third trimesters, respectively). Estimated prevalence of thyroid function disorders was generally low. Salt was iodized to approximately 40 ppm and foods rich in native iodine did not contribute significantly to dietary intakes. Adequately iodized salt continues to prevent iodine insufficiency in pregnant women living in areas previously affected by severe iodine deficiency in Java, Indonesia. Monitoring and surveillance, particularly in vulnerable groups, should be emphasized to ensure iodine sufficiency prevails.

Excess iodine intake: sources, assessment, and effects on thyroid function.

Iodine is essential for thyroid hormone synthesis. High iodine intakes are well tolerated by most healthy individuals, but in some people, excess iodine intakes may precipitate hyperthyroidism, hypothyroidism, goiter, and/or thyroid autoimmunity. Individuals with preexisting thyroid disease or those previously exposed to iodine deficiency may be more susceptible to thyroid disorders due to an increase in iodine intake, in some cases at intakes only slightly above physiological needs. Thyroid dysfunction due to excess iodine intake is usually mild and transient, but iodine-induced hyperthyroidism can be life-threatening in some individuals. At the population level, excess iodine intakes may arise from consumption of overiodized salt, drinking water, animal milk rich in iodine, certain seaweeds, iodine-containing dietary supplements, and from a combination of these sources. The median urinary iodine concentration (UIC) of a population reflects the total iodine intake from all sources and can accurately identify populations with excessive iodine intakes. Our review describes the association between excess iodine intake and thyroid function. We outline potential sources of excess iodine intake and the physiological responses and consequences of excess iodine intakes. We provide guidance on choice of biomarkers to assess iodine intake, with an emphasis on the UIC and thyroglobulin.

Thyroglobulin Is Markedly Elevated in 6- to 24-Month-Old Infants at Both Low and High Iodine Intakes and Suggests a Narrow Optimal Iodine Intake Range.

BACKGROUND: In areas with incomplete salt iodization coverage, infants and children aged 6-24 months weaning from breast milk and receiving complementary foods are at risk of iodine deficiency. However, few data exist on the risk of excessive iodine intake in this age group. Thyroglobulin (Tg) is a sensitive marker of iodine intake in school-age children and adults and may be used to estimate the optimal iodine intake range in infancy. The aim of this study was to assess the association of low and high iodine intakes with Tg and thyroid function in weaning infants. METHODS: This multicenter cross-sectional study recruited infants aged 6-24 months (n = 1543; Mage = 12.2 ± 4.6 months) receiving breast milk with complementary foods, from seven countries in areas with previously documented deficient, sufficient, or excessive iodine intake in schoolchildren or pregnant women. Urinary iodine concentration (UIC) and Tg, total thyroxine, and thyrotropin were measured using dried blood spot testing. RESULTS: Median UIC ranged from 48 µg/L (interquartile range 31-79 µg/L) to 552 µg/L (interquartile range 272-987 µg/L) across the study sites. Median Tg using dried blood spot testing was high (>50 µg/L) at estimated habitual iodine intakes <50 µg/day and >230 µg/day. Prevalence of overt thyroid disorders was low (<3%). Yet, subclinical hyperthyroidism was observed in the countries with the lowest iodine intake. CONCLUSIONS: Tg is a sensitive biomarker of iodine intake in 6- to 24-month-old infants and follows a U-shaped relationship with iodine intake, suggesting a relatively narrow optimal intake range. Infants with low iodine intake may be at increased risk of subclinical thyroid dysfunction. In population monitoring of iodine deficiency or excess, assessment of iodine status using UIC and Tg may be valuable in this young age group.

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

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.

Effect of Excess Iodine Intake from Iodized Salt and/or Groundwater Iodine on Thyroid Function in Nonpregnant and Pregnant Women, Infants, and Children: A Multicenter Study in East Africa.

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.

Societal Costs of Micronutrient Deficiencies in 6- to 59-month-old Children in Pakistan.

BACKGROUND: In Pakistan, nearly half of children younger than 5 years are stunted, and 1 in 3 is underweight. Micronutrient deficiencies, a less visible form of undernutrition, are also endemic. They may lead to increased morbidity and mortality as well as to impaired cognitive and physical development. OBJECTIVE: To estimate the lifetime costs of micronutrient deficiencies in Pakistani children aged between 6 and 59 months. METHODS: We develop a health economic model of the lifetime health and cost consequences of iodine, iron, vitamin A, and zinc deficiencies. We assess medical costs, production losses in terms of future incomes lost, and disability-adjusted life-years (DALYs). The estimation is based on large population surveys, information on the health consequences of micronutrient deficiencies extracted from randomized trials, and a variety of other sources. RESULTS: Total societal costs amount to US$46 million in medical costs, US$3,222 million in production losses, and 3.4 million DALYs. Costs are dominated by the impaired cognitive development induced by iron-deficiency anemia in 6- to 23-month-old children and the mortality caused by vitamin A deficiency. Costs are substantially higher in poorer households. CONCLUSIONS: Societal costs amounted to 1.44% of gross domestic product and 4.45% of DALYs in Pakistan in 2013. These costs hinder the country's development. They could be eliminated by improved nutrition of 6- to 59-month-old children and public health measures. Our results may contribute to the design of cost-effective interventions aiming to reduce micronutrient deficiencies in early childhood and their lifetime consequences.