Iodine intake in the Swiss population 100 years after the introduction of iodised salt: a cross-sectional national study in children and pregnant women.

PURPOSE: The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100 years, but dietary habits are changing and today only one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in children and pregnant women. METHODS: We conducted a nationwide cross-sectional study in children (6-12 years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. RESULTS: The median UIC was 127 µg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97 µg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65 µg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150 µg/day). Compared to non-users, users had higher median UIC (129 vs. 81 µg/L, P < 0.001), lower prevalence of inadequacy (< 160 µg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29 µg/L, P < 0.001). All women were euthyroid. CONCLUSIONS: The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013.

Thyroid function and urinary concentrations of iodine, selenium, and arsenic in vegans, lacto-ovo vegetarians and pescatarians.

PURPOSE: Populations following a plant-based diet may be at particular risk of thyroid dysfunction due to low iodine and selenium intakes. The main purpose was to assess thyroid function and urinary concentration of iodine, selenium, and arsenic, in subjects following a vegan, lacto-ovo vegetarian, or pescatarian diet. METHODS: In Norway, a country without mandatory dietary iodine fortification, 205 adults, following vegan (n = 115), lacto-ovo vegetarian (n = 55) and pescatarian diet (n = 35) were included. Thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and serum anti-TPO (S-anti-TPO) were measured in a venous blood sample and concentrations of iodine (UIC), creatinine (UCC), selenium, and arsenic were measured from single spot urine samples. RESULTS: Subclinical hypothyroidism (TSH > 4.0 mU/L) was observed in 3% of subjects. The overall median (p25, p75) Tg was 17 (9, 30) µg/L and vegans had higher Tg compared to pescatarians. Vegans not consuming iodine-containing supplements (n = 43) had higher Tg, than supplement users (n = 72), 27 (11, 44) vs. 16 (8, 25) µg/L and higher fT4, 16 (15, 17) vs. 15 (14, 17) pmol/L, respectively. The overall median UIC was 57 (28, 130) µg/L, all dietary groups had median UIC below WHO thresholds. Median urinary selenium and arsenic concentration was 13 (6, 22) and 3 (2, 8) µg/L, respectively. CONCLUSION: The prevalence of subclinical hypothyroidism was low and fT4 and fT3 were within the normal range for all dietary groups. Vegans had significantly increased Tg compared to pescatarians.

The amount of SARS-CoV-2 RNA in wastewater relates to the development of the pandemic and its burden on the health system.

Virus surveillance in wastewater can be a useful indicator of the development of the COVID-19 pandemic in communities. However, knowledge about how the amount of SARS-CoV-2 RNA in wastewater relates to different data on the burden on the health system is still limited. Herein, we monitored the amount of SARS-CoV-2 RNA and the spectrum of virus variants in weekly pooled wastewater samples for two years from mid-February 2020 and compared them with several clinical data. The two-year monitoring showed the weekly changes in the amount of viral RNA in wastewater preceded the hospital care needs for COVID-19 and the number of acute calls on adult acute respiratory distress by 1-2 weeks during the first three waves of COVID-19. Our study demonstrates that virus surveillance in wastewater can predict the development of a pandemic and its burden on the health system, regardless of society's test capacity and possibility of tracking infected cases.

IODINE STATUS AND THYROID FUNCTION IN LACTATING WOMEN AND INFANTS - A SURVEY IN THE ZAGREB AREA, CROATIA.

Lactating women (LW) and infants have high dietary iodine requirements and are at risk of iodine deficiency. The aim of the study was to assess iodine status and thyroid function in LW and their breastfed infants in Zagreb, Croatia. The study included 133 LW and breastfed infant pairs. Urinary iodine concentration (UIC) and thyroid function parameters were measured in all subjects. In LW, breast milk iodine concentration (BMIC) was measured and iodine and salt rich food frequency questionnaire data were collected. Results of analysis indicated that 99.2% of the LW used iodized salt in household and 20.4% used iodine-containing vitamin and mineral supplements. Median (IQR) UIC was 75 µg/L (19.0-180.5 µg/L) in LW and 234 µg/L (151.0-367.5 µg/L) in infants, whereas BMIC was 121 µg/kg (87.8-170.8 µg/kg). Multivariate regression analysis revealed BMIC to be a significant predictor of infant UIC (p<0.001). Positive correlation was recorded between LW and infant thyroid function. This was the first study in Croatia demonstrating BMIC to be a reliable biomarker of iodine status during lactation and predicting iodine intake in breastfed infants. The study confirmed that mandatory salt iodization in Croatia ensured sufficient dietary iodine for LW and optimal iodine intake for breastfed infants via breast milk.

GLOBAL ENDOCRINOLOGY: Global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020.

Iodine deficiency has multiple adverse effects on growth and development. Diets in many countries cannot provide adequate iodine without iodine fortification of salt. In 2020, 124 countries have legislation for mandatory salt iodization and 21 have legislation allowing voluntary iodization. As a result, 88% of the global population uses iodized salt. For population surveys, the urinary iodine concentration (UIC) should be measured and expressed as the median, in µg/L. The quality of available survey data is high: UIC surveys have been done in 152 out of 194 countries in the past 15 years; in 132 countries, the studies were nationally representative. The number of countries with adequate iodine intake has nearly doubled from 67 in 2003 to 118 in 2020. However, 21 countries remain deficient, while 13 countries have excessive intakes, either due to excess groundwater iodine, or over-iodized salt. Iodine programs are reaching the poorest of the poor: of the 15 poorest countries in the world, 10 are iodine sufficient and only 3 (Burundi, Mozambique and Madagascar) remain mild-to-moderately deficient. Nigeria and India have unstable food systems and millions of malnourished children, but both are iodine-sufficient and population coverage with iodized salt is a remarkable 93% in both. Once entrenched, iodine programs are often surprisingly durable even during national crises, for example, war-torn Afghanistan and Yemen are iodine-sufficient. However, the equity of iodized salt programs within countries remains an important issue. In summary, continued support of iodine programs is needed to sustain these remarkable global achievements, and to reach the remaining iodine-deficient countries.

Inadequate Status and Low Awareness of Folate in Switzerland-A Call to Strengthen Public Health Measures to Ensure Sufficient Intakes.

BACKGROUND: Folate plays an essential role in the prevention of neural tube defects, yet little is known about the folate status of women of reproductive age or to what degree the general population is aware of the importance of folate in early-life development. We aimed to determine folate status in women of reproductive age and pregnant women in Switzerland, and to assess folate awareness in the Swiss population. METHODS: In a convenience sample of 171 women of reproductive age and 177 pregnant women throughout Switzerland, we measured red blood cell (RBC) folate concentration. In a second convenience sample (n = 784, men and women) we assessed folate knowledge with an online survey. RESULTS: RBC folate concentration (median interquartile range) was 442 (366, 564) nmol/L in women of reproductive age and 873 (677, 1177) nmol/L in pregnant women. Folate deficiency (RBC folate <340 nmol/L) was found in 19.9% of women of reproductive age and 2.8% of pregnant women, while 91.8% of women of reproductive age and 52.0% of pregnant women showed folate concentrations indicating an elevated risk of neural tube defects (RBC folate <906 nmol/L). The online survey showed that a high proportion (≥88%) of participants were aware of folate's role in neural tube defect (NTD) prevention and fetal development, yet knowledge about dietary sources and national recommendations of folate supplementation when planning pregnancy were limited. CONCLUSION: The high prevalence of folate inadequacy in Swiss women suggests an elevated risk of neural tube defects and calls for urgent measures to increase folate intakes.

Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial.

Background: Iodine deficiency during pregnancy may be associated with lower offspring IQ, but there are few data on the safety and efficacy of maternal iodine supplementation on child development. In a previously reported multi-center randomized trial conducted in Thailand and India, we assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on offspring development. In this secondary analysis of that trial, we report data only from the Thai pregnant women in the study, who were more iodine deficient at entry. Methods: Pregnant women in Bangkok, Thailand, were randomized to receive daily 200 µg oral iodine or placebo until delivery. We assessed thyroid size and thyroid function during pregnancy and cognitive and motor development at ages 1, 2, and 5.7 years. The trial was registered at www.clinicaltrials.gov/NCT00791466. Findings: Women (n = 514) entered the trial between November 2008 and March 2011 at a mean ± SD gestational age of 11 ± 2.8 weeks; their median (IQR) UIC was 112 (75, 170) µg/L. Mean compliance with supplementation was 88%. We assessed 397 mothers in the 3rd trimester, 231 infants at age 2 y, and 157 children at mean age 5.7 y. During pregnancy, there was a slightly greater decrease in free and total thyroxine concentrations in the iodine group (p < 0.05). At age 2 years, the iodine group had borderline lower scores for combined fine and gross motor function (p = 0.05), but there were no other significant differences in development. At 5.7 years, there were no significant group differences in child development. Conclusion: Daily iodine supplementation in mildly iodine deficient pregnant women was associated with small negative effects on maternal thyroxine concentrations, but did not affect child development. The safety and efficacy of iodine supplementation in mildly-iodine deficient pregnant women needs to be evaluated further in large randomized controlled trials.

Effects of an Iodine-Containing Prenatal Multiple Micronutrient on Maternal and Infant Iodine Status and Thyroid Function: A Randomized Trial in The Gambia.

Background: Iodine supplementation is recommended to pregnant women in iodine-deficient populations, but the impact in moderate iodine deficiency is uncertain. We assessed the effect of an iodine-containing prenatal multiple micronutrient (MMN) supplement in a rural Gambian population at risk of moderate iodine deficiency. Materials and Methods: This study uses data and samples collected as a part of the randomized controlled trial Early Nutrition and Immune Development (ENID; ISRCTN49285450) conducted in Keneba, The Gambia. Pregnant women (<20 weeks gestation) were randomized to either a daily supplement of MMNs containing 300 µg of iodine or an iron and folic acid (FeFol) supplement. Randomization was double blinded (participants and investigators). The coprimary outcomes were maternal urinary iodine concentration (UIC) and serum thyroglobulin (Tg), assessed at baseline and at 30 weeks' gestation. Secondary outcomes were maternal serum thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) (assessed at baseline and at 30 weeks' gestation), breast milk iodine concentration (BMIC) (assessed at 8, 12, and 24 weeks postpartum), infant serum Tg (assessed at birth [cord], 12, and 24 weeks postpartum), and serum TSH (assessed at birth [cord]). The effect of supplementation was evaluated using mixed effects models. Results: A total of 875 pregnant women were enrolled between April 2010 and February 2015. In this secondary analysis, we included women from the MMN (n = 219) and FeFol (n = 219) arm of the ENID trial. At baseline, median (interquartile range or IQR) maternal UIC and Tg was 51 µg/L (33-82) and 22 µg/L (12-39), respectively, indicating moderate iodine deficiency. Maternal MMN supplement increased maternal UIC (p < 0.001), decreased maternal Tg (p < 0.001), and cord blood Tg (p < 0.001) compared with FeFol. Maternal thyroid function tests (TSH, TT3, TT4, and TT3/TT4 ratio) and BMIC did not differ according to maternal supplement group over the course of the study. Median (IQR) BMIC, maternal UIC, and infant Tg in the MMN group were 51 µg/L (35-72), 39 µg/L (25-64), and 87 µg/L (59-127), respectively, at 12 weeks postpartum, and did not differ between supplement groups. Conclusions: Supplementing moderately iodine-deficient women during pregnancy improved maternal iodine status and reduced Tg concentration. However, the effects were not attained postpartum and maternal and infant iodine nutrition remained inadequate during the first six months after birth. Consideration should be given to ensuring adequate maternal status through pregnancy and lactation in populations with moderate deficiency.

Iodine deficiency in pregnant women in Sweden: a national cross-sectional study.

PURPOSE: Voluntary salt iodization at 50 mg/kg salt ensures adequate iodine nutrition in Swedish school-aged children, but iodine status in pregnant women is uncertain. METHODS: We conducted a cross-sectional national study of 743 pregnant women, at median gestational age of 23 weeks (IQR 9, 38), recruited from maternal health care centers. We measured: urinary iodine concentration (UIC) and urinary creatinine concentration in spot urine samples; thyroglobulin (Tg), thyroid-stimulating hormone (TSH), and total thyroxine (tT4) on dried blood spots (DBS); and thyreoperoxidase antibodies in serum samples. Data on dietary supplement use were obtained, and women were classified as supplement users (consuming multivitamins containing ≥ 150 µg iodine/day) and non-supplement users (no supplements or < 150 µg iodine/day from supplements). RESULTS: Overall median UIC [bootstrapped 95% confidence interval (CI)] was 101 µg/L (95, 108; n = 737): 149 µg/L (132, 164) in supplement users (n = 253) and 85 µg/L (79, 92) in non-supplement users (n = 440) (p < 0.001). Overall geometric mean DBS-Tg (95% CI) was 22.1 µg/L (20.8, 23.5; n = 675) and the prevalence of elevated DBS-Tg was 19%. DBS-Tg was lower in supplement users (n = 229) than in non-supplement users (n = 405) (19.1 vs 24.4 µg/L, p < 0.001). DBS-TSH, DBS-tT4, and S-TPOab positivity did not differ between the two groups. CONCLUSIONS: Pregnant women in Sweden have inadequate iodine nutrition. Women not taking iodine supplements containing ≥ 150 µg iodine/day are affected by mild iodine deficiency and are at higher risk for increased thyroid activity, while maintaining euthyroidism. Iodine intake should be improved in women both before and after conception by promotion of iodized salt instead of non-iodized salt. We urge regular monitoring of iodine status in the general Swedish population, as well as in risk groups.

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.

Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.

BACKGROUND: Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES: Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. DESIGN: In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO4, 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na2EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. RESULTS: The adjusted geometric mean BPb concentration at baseline was 4.3 µg/dL (95% CI: 4.2, 4.3 µg/dL), and at endpoint these values were 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for FeSO4, 2.9 µg/dL (95% CI: 2.7, 3.0 µg/dL) for NaFeEDTA, 3.3 µg/dL (95% CI: 3.1, 3.5 µg/dL) for EDTA, and 3.7 µg/dL (95% CI: 3.5, 3.9 µg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. CONCLUSIONS: Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.

A dose-response crossover iodine balance study to determine iodine requirements in early infancy.

BACKGROUND: Optimal iodine intake during infancy is critical for brain development, but no estimated average requirement (EAR) is available for this age group. OBJECTIVE: We measured daily iodine intake, excretion, and retention over a range of iodine intakes in early infancy to determine the minimum daily intake required to achieve iodine balance. DESIGN: In a dose-response crossover study, we randomly assigned healthy infants (n = 11; mean ± SD age 13 ± 3 wk) to sequentially consume over 33 d 3 infant formula milks (IFMs) containing 10.5, 19.3, and 38.5 µg I/100 kcal, respectively. Each IFM was consumed for 11 d, consisting of a 6-d run-in period followed by a 4-d balance period and 1 run-out day. RESULTS: Iodine intake (mean ± SD: 54.6 ± 8.1, 142.3 ± 23.1, and 268.4 ± 32.6 µg/d), excretion (55.9 ± 8.6, 121.9 ± 21.7, and 228.7 ± 39.3 µg/d), and retention (-1.6 ± 8.3, 20.6 ± 21.6, and 39.8 ± 34.3 µg/d) differed among the low, middle, and high iodine IFM groups (P < 0.001 for all). There was a linear relation between daily iodine intake and both daily iodine excretion and daily iodine retention. Zero balance (iodine intake = iodine excretion, iodine retention = 0 µg/d) was achieved at a daily iodine intake of 70 µg (95% CI: 60, 80 µg). CONCLUSION: Our data indicate the iodine requirement in 2- to 5-mo-old infants is 70 µg/d. Adding an allowance for accumulation of thyroidal iodine stores would produce an EAR of 72 µg and a recommended dietary allowance of 80 µg. This trial was registered at clinicaltrials.gov as NCT02045784.

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.

Systematic review of the effects of iodised salt and iodine supplements on prenatal and postnatal growth: study protocol.

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.

Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women: a randomized study.

BACKGROUND: After the oral administration of iron, the production of circulating non-transferrin-bound iron may contribute to an increased risk of illness in malaria-endemic areas that lack effective medical services. OBJECTIVE: In healthy women with a range of body iron stores, we aimed to determine effects on the production of circulating non-transferrin-bound iron resulting from the oral administration of 1) a supplemental dose of iron (60 mg) with water, 2) a supplemental dose of iron (60 mg) with a standard test meal, and 3) a fortification dose of iron (6 mg) with a standard test meal. DESIGN: With the use of serum ferritin as the indicator, healthy women with replete iron stores (ferritin concentration >25 µg/L; n = 16) and reduced iron stores (ferritin concentration ≤25 µg/L; n = 16) were enrolled in a prospective, randomized, crossover study. After the oral administration of aqueous solutions of ferrous sulfate isotopically labeled with 54Fe, 57Fe, or 58Fe, blood samples were collected for 8 h, and iron absorption was estimated by erythrocyte incorporation at 14 d. RESULTS: At 4 h, serum non-transferrin-bound iron reached peaks with geometric mean (95% CI) concentrations of 0.81 µmol/L (0.56, 1.1 µmol/L) for 60 mg Fe with water and 0.26 µmol/L (0.15, 0.38 µmol/L) for 60 mg Fe with food but was at assay limits of detection (0.1 µmol Fe/L) for 6 mg Fe with food. For the 60 mg Fe without food, the area under the curve over 8 h for serum non-transferrin-bound iron was positively correlated with the amount of iron absorbed (R = 0.49, P < 0.01) and negatively correlated with serum ferritin (R = -0.39, P < 0.05). CONCLUSIONS: In healthy women, the production of circulating non-transferrin-bound iron is determined by the rate and amount of iron absorbed. The highest concentrations of non-transferrin-bound iron resulted from the administration of supplemental doses of iron without food. Little or no circulating non-transferrin-bound iron resulted from the consumption of a meal with a fortification dose of iron.

Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Iodine deficiency in infants can damage the developing brain and increase mortality. Present recommendations state that oral iodised oil should be given to breastfeeding mothers to correct iodine deficiency in infancy when iodised salt is not available, and that direct supplementation should be given to infants who are not being breastfed or receiving iodine-fortified complimentary foods. However, there is little evidence for these recommendations. We aimed to assess the safety and efficacy of direct versus indirect supplementation of the infant. METHODS: We did this double blind, randomised, placebo-controlled trial in Morocco. Healthy breastfeeding mothers and their term newborn babies (aged ≤8 weeks) were block randomised by clinic day to receive either: one dose of 400 mg iodine to the mother and placebo to the infant (indirect infant supplementation), or one dose of about 100 mg iodine to the infant and placebo to the mother (direct infant supplementation). Randomisation was masked to participants and investigators. Coprimary outcomes were: maternal and infant urinary iodine concentrations, breastmilk iodine concentration, maternal and infant thyroid-stimulating hormone (TSH) concentrations, maternal and infant thyroxine (T4) concentrations, and infant growth. These outcomes were measured at baseline, and when infants were aged about 3 months, 6 months, and 9 months, and the two groups were compared using mixed effects models. This study is registered with ClinicalTrials.gov, number NCT01126125. FINDINGS: We recruited 241 mother-infant pairs between Feb 25, and Aug 10, 2010, and completed data collection by Aug 6, 2011. At baseline, median urinary iodine concentration was 35 µg/L (IQR 29-40) in mothers and 73 µg/L (29-237) in infants, suggesting iodine deficiency. During the study, maternal urinary iodine concentration (p=0.011), breastmilk iodine concentration (p<0.0001), and infant urinary iodine concentration (p=0.042) were higher in the indirect infant supplementation group than in the direct supplementation group. Maternal TSH (p=0.276) and T4 (p=0.074) concentrations did not differ between the groups over the course of the study, nor did infant TSH (p=0.597) and T4 (p=0.184) concentrations, but the number of infants with thyroid hypofunction was lower (p=0.023) in the indirect supplementation group than the direct supplementation group. The infant groups did not differ in anthropomorphic measures, except that length-for-age Z score was slightly greater in the direct infant supplementation group (p=0.032). At 3 months and 6 months of age, median infant urinary iodine concentration in the indirect infant supplementation group was sufficient (>100 µg/L), whereas infant urinary iodine concentration was sufficient only at 6 months in the direct supplementation group. There were no serious adverse events in either group. INTERPRETATION: In regions of moderate-to-severe iodine deficiency without effective salt iodisation, lactating women who receive one dose of 400 mg iodine as oral iodised oil soon after delivery can provide adequate iodine to their infants through breastmilk for at least 6 months, enabling the infants to achieve euthyroidism. Direct supplementation is less effective in improving infant iodine status. FUNDING: ETH Zurich, Switzerland; the Medicor Foundation, Vaduz, Lichtenstein.

Potato crop as a source of emetic Bacillus cereus and cereulide-induced mammalian cell toxicity.

Bacillus cereus, aseptically isolated from potato tubers, were screened for cereulide production and for toxicity on human and other mammalian cells. The cereulide-producing isolates grew slowly, the colonies remained small (~1 mm), tested negative for starch hydrolysis, and varied in productivity from 1 to 100 ng of cereulide mg (wet weight)(-1) (~0.01 to 1 ng per 10(5) CFU). By DNA-fingerprint analysis, the isolates matched B. cereus F5881/94, connected to human food-borne illness, but were distinct from cereulide-producing endophytes of spruce tree (Picea abies). Exposure to cell extracts (1 to 10 µg of bacterial biomass ml(-1)) and to purified cereulide (0.4 to 7 ng ml(-1)) from the potato isolates caused mitochondrial depolarization (loss of ΔΨm) in human peripheral blood mononuclear cells (PBMC) and keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine fibroblasts (L-929), and pancreatic insulin-producing cells (MIN-6). Cereulide (10 to 20 ng ml(-1)) exposed pancreatic islets (MIN-6) disintegrated into small pyknotic cells, followed by necrotic death. Necrotic death in other test cells was observed only after a 2-log-higher exposure. Exposure to 30 to 60 ng of cereulide ml(-1) induced K(+) translocation in intact, live PBMC, keratinocytes, and sperm cells within seconds of exposure, depleting 2 to 10% of the cellular K(+) stores within 10 min. The ability of cereulide to transfer K(+) ions across biological membranes may benefit the producer bacterium in K(+)-deficient environments such as extracellular spaces inside plant tissue but is a pathogenic trait when in contact with mammalian cells.