Search

Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting., Objectives: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3)., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons., Results: SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation., Conclusions: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592., (Copyright © 2022 American Society for Nutrition.)

Background: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development., Objectives: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024)., Results: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11)., Conclusions: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons., Results: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation., Conclusions: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers., Results: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics., Conclusions: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Zinc deficiency impairs immune function and is common among children in South-East Asia., Objectives: The effect of zinc supplementation on immune function in young Laotian children was investigated., Methods: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration)., Results: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012)., Conclusions: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation., Objectives: We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted., Methods: Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or α-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRP > 5 mg/L or AGP > 1 g/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach., Results: In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence., Conclusions: Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA., (Copyright © The Author(s) 2020.)

The Global Burden of Disease study (GBD) is an ambitious effort to estimate the disease burden attributable to various risk factors. The results from the GBD are used around the world to monitor the UN established Sustainable Development Goals, set health policies and research strategies, among others. The GBD along with other studies, such as those from the Maternal Child Epidemiology Estimation Group and the Lancet Breastfeeding Series Group, produce estimates of the nutrition-related global burden of disease that exhibit considerable differences. These differences are difficult to reconcile due to the estimation methods, which in recent years have substantially increased in complexity. In this paper, we give a detailed review of the methods used by GBD and other entities to estimate the global burden of disease that is attributable to undernutrition and suboptimal breastfeeding. Further, we compare the methods to determine causes for differences in estimates. We find that the main determinant of differences in estimates is what causes of death are linked to each risk factor. Methods used to estimate nutrition-related disease burden need to be more clearly documented to foster discussion and collaboration on the important assumptions required to produce estimates., (Copyright © American Society for Nutrition 2019.)

Background: The WHO and UNICEF recommend therapeutic zinc supplementation (TZS) for the treatment of diarrhea. In zinc-deficient populations, preventive zinc supplementation might provide greater benefits for reducing diarrhea and malaria incidence and increasing growth and plasma zinc (pZn) concentration. If effective, intermittent preventive zinc supplementation (IPZS) would cost less than daily preventive zinc supplementation (DPZS)., Objective: We assessed the effects of IPZS, DPZS, and TZS in children on the primary outcomes of diarrhea incidence, malaria incidence, growth, and pZn concentration compared with nonsupplemented control groups., Methods: Rural Burkinabe children (n = 7641; 6-30 mo old) in 36 clusters were randomly assigned to 1 of 5 treatment groups for 16, 32, or 48 wk: 1) IPZS (10 mg Zn/d for 10 d every 16 wk); 2) DPZS (7 mg Zn/d); 3) TZS (20 mg Zn/d for 10 d for diarrhea); 4) morbidity surveillance control (MSC); or 5) nonintervention control (NIC). Supplemented groups remained masked until completion of primary analyses with mixed models., Results: At baseline, stunting (28.6%) and low pZn concentration (<65 μg/dL; 43.5%) were common. After 48 wk, mean ± SE pZn increased more (P = 0.008) in the DPZS group (3.9 ± 1.3 μg/dL) than in the TZS (-0.5 ± 1.2 μg/dL) and NIC (-1.2 ± 0.9 μg/dL) groups. All supplemented groups had a moderately lower incidence of reported diarrhea (0.48-0.49 compared with 0.57 episodes/100 d, P = 0.001) and reported fever (1.1-1.2 compared with 1.5 episodes/100d, P < 0.001) and gained slightly less length (3.15-3.20 compared with 3.36 cm/16 wk, P < 0.001) than the MSC group, but did not differ from each other. Prevalence of diarrhea and incidences of confirmed fever and malaria were not different across study groups., Conclusions: The preventive and TZS groups had reduced diarrhea incidence, but it is uncertain whether this resulted from a functional response to zinc or reporting bias. The comparison should be re-examined in populations known to respond to zinc supplementation. This trial was registered at www.clinicaltrials.gov as NCT00944359., (© 2016 American Society for Nutrition.)

Background: Adequate nutrition is necessary for the rapid brain development that occurs during infancy., Objectives: We tested the hypothesis that the provision of small-quantity, lipid-based nutrient supplements (SQ-LNSs) plus malaria and diarrhea treatment positively affects infant development. We also tested the effect of various doses of zinc provided in SQ-LNSs or in a tablet., Methods: In a partially masked, cluster-randomized controlled trial, communities in rural Burkina Faso were stratified by selected characteristics and then randomly assigned within strata to the intervention (IC; 25 communities, 2435 children) or the nonintervention (NIC; 9 communities, 785 children) cohorts. IC children were randomly assigned to 4 groups. As secondary outcomes, a subsample of 3 of these 4 groups (n = 747) and of the NIC (n = 376) were assessed for motor, language, and personal-social development at age 18 mo by using the Developmental Milestones Checklist II. The 3 IC groups received 20 g SQ-LNSs/d containing 0 or 10 mg added zinc with a placebo tablet or 20 g SQ-LNSs/d containing 0 mg added zinc with a tablet containing 5 mg Zn. All IC groups received treatment of malaria and diarrhea from age 9 to 18 mo. Data collectors and participants were aware of allocation to the IC or NIC but did not know the particular IC subgroup., Results: Children in the IC scored 0.34 (95% CI: 0.21, 0.46), 0.30 (95% CI: 0.15, 0.44), and 0.32 (95% CI: 0.16, 0.48) SDs higher in motor, language, and personal-social development, respectively, than did children in the NIC (All P < 0.001). Children who received different amounts of zinc did not differ significantly in any of the scores. No effect on caregiver-child interaction was found., Conclusion: In rural Burkina Faso, the provision of SQ-LNSs to infants from age 9 to 18 mo, regardless of added zinc content, plus malaria and diarrhea treatment positively affected motor, language, and personal-social development at age 18 mo. This trial was registered at clinicaltrials.gov as NCT00944281., (© 2016 American Society for Nutrition.)

Background: Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status., Objective: The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs)., Methods: Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 μg/L were considered indicative of current or recent malaria parasitemia., Results: Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 μg/L vs. 11.1 ± 0.8 μg/L; P < 0.001) and lower RBP (0.79 ± 0.01 μmol/L vs. 0.92 ± 0.01 μmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 μg/dL vs. 64.9 ± 11.1 μg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 μg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 μmol/L) decreased from 33.4% to 27.7%., Conclusions: Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853., (© 2014 American Society for Nutrition.)

The responsiveness of plasma zinc concentration to zinc fortification is uncertain. Our objective in this study was to determine whether plasma zinc concentration changes in response to consuming zinc-fortified foods or liquid zinc supplements. We conducted a 4-wk double-blind, randomized trial among 132 healthy Senegalese men ≥ 18 y. Participants received 1 of 4 interventions: 1) (control) 200 g/d of wheat bread fortified with iron and folic acid, but not zinc, and a liquid multivitamin supplement without zinc between meals; 2) (zinc supplement) the same bread and the same multivitamin supplement with 15 mg zinc as ZnSO(4) added; 3) (moderate zinc fortification) the same bread cofortified with 7.5 mg zinc as ZnO and the same multivitamin supplement without zinc; or 4) (high zinc fortification) the same bread cofortified with 15 mg zinc as ZnO and the same multivitamin supplement without zinc. Fasting blood samples were collected twice at baseline and at d 15 and 29 of the intervention. There was no significant interaction between group and study day (P = 0.11). However, at d 15, the mean change in plasma zinc concentration in the zinc-supplemented group was greater than in the placebo and fortification groups ( 0.72 μmol/L vs. -0.09 to 0.03 μmol/L; P = 0.05). At d 29 there were no significant group-wise differences. Across all time points, the zinc-supplemented group was the only group where plasma zinc concentration increased from baseline (P = 0.006). These results suggest that plasma zinc concentration may not be a sufficiently sensitive indicator to evaluate short-term responses to zinc fortification.

Background: Simple, low-cost methods are needed to evaluate the effect of zinc-fortification programs. Plasma zinc concentration is a useful biomarker of zinc intake from supplementation, but responses to zinc fortification are inconsistent., Objective: The objective was to compare the change in plasma zinc concentrations in young children who received zinc from either a liquid supplement or a zinc-fortified complementary food., Design: A double-blind intervention trial was conducted in 137 young Senegalese children aged 9-17 mo who were randomly assigned to receive one of the following treatments for 15 d: 1) 30 g dry weight of an iron-fortified cereal porridge and a liquid multivitamin supplement without zinc (control group), 2) the same porridge and multivitamin supplement with 6 mg Zn added to the supplement dose (ZnSuppl group), or 3) the same porridge with added zinc to provide 6 mg Zn per 25 g dry weight of porridge and multivitamin without zinc (ZnFort group)., Results: Mean (±SD) plasma zinc concentration (μg/dL) increased by 4.7 ± 1.6 (P = 0.004) in the ZnSuppl group, which was significantly greater (P = 0.009) than the mean change in the control group (-1.0 ± 1.6; P = 0.51) and in the ZnFort group (-1.8 ± 1.7; P = 0.29). The latter 2 groups did not differ from each other (P = 0.99)., Conclusions: Plasma zinc concentration increased in children who received daily zinc supplementation for 15 d but not in those who received a zinc-fortified complementary food containing a similar amount of zinc. Additional longer-term studies are needed to assess the effect of zinc-fortification programs on zinc-related functional outcomes and the usefulness of plasma zinc as a biomarker of program effect. This trial was registered at www.clinicaltrials.gov as study NCT0094398.

To assist with the evaluation of zinc (Zn) intervention programs, information is needed on the magnitude and velocity of response of plasma Zn concentration following changes in Zn intake. Our objective in this study was to measure plasma Zn concentration of healthy adult men before and after initiation and discontinuation of 1 of 2 dosages of Zn supplements or placebo. We conducted a randomized, double-blind, placebo-controlled trial in 58 apparently healthy males aged 19-54 y. Participants received 1 of 3 liquid supplements daily for 21 d: 10 or 20 mg Zn/d, as Zn sulfate, or placebo. Fasting plasma Zn concentrations were measured on 14 occasions before, during, and after supplementation. Data were analyzed using mixed-model ANCOVA. The plasma Zn concentration was related to day of study (P < 0.0001) and study group (P < 0.0001). Controlling for baseline concentrations, plasma Zn concentrations were consistently elevated above baseline by d 5 among individuals in both of the Zn-supplemented groups compared with those receiving placebo supplements, regardless of their initial plasma Zn concentration. There were no significant group-wise differences between those who received either 10 or 20 mg/d Zn. Plasma Zn concentrations of supplemented individuals declined following withdrawal of supplementation and within 2 wk no longer differed from those of the placebo group. Change in the plasma Zn concentration is a useful indicator to monitor compliance with, and possibly effectiveness of, Zn supplementation programs. To ensure accurate interpretation of the results, samples should be collected while the intervention is still in progress.

Deficiencies of micronutrients are highly prevalent in low-income countries. Inadequate intake of iodine impairs thyroid function and results in a spectrum of disorders. Other common deficiencies of micronutrients such as iron, selenium, vitamin A, and possibly zinc may interact with iodine nutrition and thyroid function. Randomised controlled intervention trials in iodine- and iron-deficient populations have shown that providing iron along with iodine results in greater improvements in thyroid function and volume than providing iodine alone. Vitamin A supplementation given alone or in combination with iodised salt can have a beneficial impact on thyroid function and thyroid size. Despite numerous studies of the effect of selenium on iodine and thyroid metabolism in animals, most published randomised controlled intervention trials in human populations failed to confirm an impact of selenium supplementation on thyroid metabolism. Little evidence is available on interactions between iodine and zinc metabolism., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Salt iodization is the main strategy for reducing iodine deficiency disorders worldwide. Characteristics of families not using iodized salt need to be known to expand coverage., Objective: The objective was to determine whether families who do not use iodized salt have a higher prevalence of child malnutrition and mortality and to identify factors associated with not using iodized salt., Design: Use of adequately iodized salt (>or =30 ppm), measured by rapid test kits, was assessed between January 1999 and September 2003 in 145 522 and 445 546 families in urban slums and rural areas, respectively, in Indonesia., Results: Adequately iodized salt was used by 66.6% and 67.2% of families from urban slums and rural areas, respectively. Among families who used adequately iodized salt, mortality in neonates, infants, and children aged <5 y was 3.3% compared with 4.2%, 5.5% compared with 7.1%, and 6.9% compared with 9.1%, respectively (P < 0.0001 for all), in urban slums; among families who did not use adequately iodized salt, the respective values were 4.2% compared with 6.3%, 7.1% compared with 11.2%, and 8.5% compared with 13.3% (P < 0.0001 for all) in rural areas. Families not using adequately iodized salt were more likely to have children who were stunted, underweight, and wasted. In multivariate analyses that controlled for potential confounders, low maternal education was the strongest factor associated with not using adequately iodized salt., Conclusion: In Indonesia, nonuse of adequately iodized salt is associated with a higher prevalence of child malnutrition and mortality in neonates, infants, and children aged <5 y. Stronger efforts are needed to expand salt iodization in Indonesia.

Background: Although elemental iron powders are widely used to fortify cereal products, little data exist on their efficacy in humans., Objective: We compared the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in Thai women with low iron stores., Design: A double-blind intervention was conducted in 18-50-y-old women (n = 330) randomly assigned into 4 groups to receive either no fortification iron or 12 mg Fe/d for 6 d/wk for 35 wk as ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in a baked, wheat-flour-based snack. Snacks were not consumed with meals, and consumption was monitored. At baseline, 20 wk, and 35 wk, hemoglobin status and iron were measured and the groups were compared., Results: Between baseline and 35 wk, geometric mean serum ferritin (SF) increased significantly in all 3 groups receiving iron (P < 0.01), and geometric mean serum transferrin receptor (TfR) decreased significantly in the groups receiving ferrous sulfate and electrolytic iron (P < 0.05). Calculated mean (+/-SD) body iron stores increased from 1.5 +/- 2.8 to 5.4 +/- 2.9 mg/kg in the ferrous sulfate group, from 1.5 +/- 3.5 to 4.4 +/- 3.6 mg/kg in the electrolytic iron group, and from 1.3 +/- 3.2 to 3.2 +/- 4.3 mg/kg in the hydrogen-reduced iron group (P < 0.01 for all 3 groups) but did not change significantly in the control group., Conclusions: Ferrous sulfate, electrolytic iron, and hydrogen-reduced iron, fortified into wheat-based snacks, significantly improved iron status. On the basis of the change in body iron stores during the 35-wk study, the relative efficacy of the electrolytic and hydrogen-reduced iron compared with ferrous sulfate was 77% and 49%, respectively.

Background: There are few data on the adverse effects of chronic exposure to high iodine intakes, particularly in children., Objective: The objective of the study was to ascertain whether high dietary intakes of iodine in children result in high thyroid volume (Tvol), a high risk of goiter, or both., Design: In an international sample of 6-12-y-old children (n = 3319) from 5 continents with iodine intakes ranging from adequate to excessive, Tvol was measured by ultrasound, and the urinary iodine (UI) concentration was measured. Regressions were done on Tvol and goiter including age, body surface area, sex, and UI concentration as covariates., Results: The median UI concentration ranged from 115 microg/L in central Switzerland to 728 microg/L in coastal Hokkaido, Japan. In the entire sample, 31% of children had UI concentrations >300 microg/L, and 11% had UI concentrations >500 microg/L; in coastal Hokkaido, 59% had UI concentrations >500 microg/L, and 39% had UI concentrations >1000 microg/L. In coastal Hokkaido, the mean age- and body surface area-adjusted Tvol was approximately 2-fold the mean Tvol from the other sites combined (P < 0.0001), and there was a positive correlation between log(UI concentration) and log(Tvol) (r = 0.24, P < 0.0001). In the combined sample, after adjustment for age, sex, and body surface area, log(Tvol) began to rise at a log(UI concentration) >2.7, which, when transformed back to the linear scale, corresponded to a UI concentration of approximately 500 microg/L., Conclusions: Chronic iodine intakes approximately twice those recommended-indicated by UI concentrations in the range of 300-500 microg/L-do not increase Tvol in children. However, UI concentrations >/=500 microg/L are associated with increasing Tvol, which reflects the adverse effects of chronic iodine excess.

Background: Although transferrin receptor (TfR) and zinc protoporphyrin (ZnPP) are often used to define iron status in school-age children in developing countries, the diagnostic cutoffs for this age group are uncertain., Objective: The objective was to determine the sensitivity and specificity of TfR and ZnPP in predicting iron deficiency in black and white children in Africa., Design: Hemoglobin, C-reactive protein (CRP), serum ferritin (SF), TfR, and ZnPP were measured in children in Côte d'Ivoire and Morocco. We excluded children with elevated CRP and then used receiver operating characteristic (ROC) curves to evaluate TfR and ZnPP alone and in combination in screening for iron deficiency, defined as an SF concentration <15 mug/L, and iron deficiency anemia (IDA), defined as an SF concentration <15 mug/L and low hemoglobin., Results: The sample included 2814 children aged 5-15 y. The sensitivity and specificity of TfR and ZnPP were limited by considerable overlap between iron-sufficient, nonanemic children and those with IDA. On the basis of ROC curves, we identified diagnostic cutoffs for TfR and ZnPP that achieved specificities and sensitivities of approximately 60-80%. Separate cutoffs for Côte d'Ivoire and Morocco gave the best performance; the cutoffs for both TfR and ZnPP were higher in Côte d'Ivoire. Moreover, a comparison of nonanemic, iron-sufficient subjects showed that Ivorian children had significantly higher TfR and ZnPP concentrations than did Moroccan children (P < 0.01)., Conclusions: New diagnostic cutoffs for TfR and ZnPP, based on ROC curve analyses, may improve the performance of these indexes in defining iron status in children. Significant ethnic differences in TfR and ZnPP suggest that separate cutoffs may be needed for black and white children.

Background: Goiter prevalence in school-age children is an indicator of the severity of iodine deficiency disorders (IDDs) in a population. In areas of mild-to-moderate IDDs, measurement of thyroid volume (Tvol) by ultrasound is preferable to palpation for grading goiter, but interpretation requires reference criteria from iodine-sufficient children., Objective: The study aim was to establish international reference values for Tvol by ultrasound in 6-12-y-old children that could be used to define goiter in the context of IDD monitoring., Design: Tvol was measured by ultrasound in 6-12-y-old children living in areas of long-term iodine sufficiency in North and South America, central Europe, the eastern Mediterranean, Africa, and the western Pacific. Measurements were made by 2 experienced examiners using validated techniques. Data were log transformed, used to calculate percentiles on the basis of the Gaussian distribution, and then transformed back to the linear scale. Age- and body surface area (BSA)-specific 97th percentiles for Tvol were calculated for boys and girls., Results: The sample included 3529 children evenly divided between boys and girls at each year ( +/- SD age: 9.3 +/- 1.9 y). The range of median urinary iodine concentrations for the 6 study sites was 118-288 micro g/L. There were significant differences in age- and BSA-adjusted mean Tvols between sites, which suggests that population-specific references in countries with long-standing iodine sufficiency may be more accurate than is a single international reference. However, overall differences in age- and BSA-adjusted Tvols between sites were modest relative to the population and measurement variability, which supports the use of a single, site-independent set of references., Conclusion: These new international reference values for Tvol by ultrasound can be used for goiter screening in the context of IDD monitoring.

Background: The long-term goal of salt iodization is elimination of iodine deficiency and reduction of the goiter rate to < 5% in school-aged children. Normalization of the goiter rate probably indicates disappearance of iodine deficiency disorders as a public health problem. However, thyroid size may not return to normal for months or years after correction of iodine deficiency., Objective: We described the time course and pattern of changes in thyroid size and goiter rate in response to the introduction of iodized salt in an area of severe endemic goiter., Design: In a 5-y prospective study, we measured thyroid size by ultrasonography and urinary iodine and thyroid hormone concentrations in schoolchildren 6 mo before the introduction of iodized salt and annually for 4 y thereafter., Results: Four years after the introduction of iodized salt and normalization of the median urinary iodine concentration, mean thyroid size had decreased 56% (P < 0.0001). However, 29% of the children remained goitrous, with a significant age shift in the distribution of goiter. At baseline, the goiter rate was significantly higher in younger (age: 5-9 y) than in older (age: 10-14 y) children (P < 0.0001). At 2, 3, and 4 y after salt iodization, the goiter rate was significantly higher in the older than in the younger children (at 4 y: 52% compared with 19%), and the difference increased with time (P < 0.0001)., Conclusion: The goiter rate in school-aged children may remain sharply elevated for up to 4 y after successful introduction of iodized salt, primarily because of persistent goiter in older children.

Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism. However, the mechanism is not yet clear. The objective of this study was to investigate whether iron (Fe) deficiency lowers thyroid peroxidase (TPO) activity. TPO is a heme-containing enzyme catalyzing the two initial steps in thyroid hormone synthesis. Male weanling Sprague-Dawley rats (n = 84) were randomly assigned to seven groups. Three groups (ID-3, ID-7, ID-11) were fed an Fe-deficient diet containing 3, 7 and 11 microg Fe/g, respectively. Because IDA reduces food intake, three control groups were pair-fed Fe-sufficient diets (35 microg Fe/g) to each of the ID groups and one control group consumed food ad libitum. After 4 wk, hemoglobin, triiodothyronine (T(3)) and thyroxine (T(4)) were lower in the Fe-deficient groups than in the ad libitum control group (P < 0.001). By multiple regression, food restriction had a significant, independent effect on T(4) (P < 0.0001), but not on T(3). TPO activity (by both guaiacol and iodine assays) was markedly reduced by food restriction (P < 0.05). IDA also independently reduced TPO activity (P < 0.05). Compared with the ad libitum controls, TPO activity per thyroid determined by the guaiacol assay in the ID-3, ID-7 and ID-11 groups was decreased by 56, 45 and 33%, respectively (P < 0.05). These data indicate that Fe deficiency sharply reduces TPO activity and suggest that decreased TPO activity contributes to the adverse effects of IDA on thyroid metabolism.

Background: In many developing countries, children are at high risk of both goiter and iron deficiency anemia. Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter., Objective: The aim of this study was to determine whether iron supplementation in goitrous, iron-deficient children would improve their response to iodized salt., Design: We conducted a randomized, double-blind, placebo-controlled trial in 5-14-y-old children in Côte d'Ivoire. Goitrous, iron-deficient children (n = 166) consuming iodized salt (10-30 mg I/kg salt at the household level) were supplemented with either iron (60 mg Fe/d, 4 d/wk for 16 wk) or placebo. At 0, 1, 6, 12, and 20 wk, we measured hemoglobin, serum ferritin, serum transferrin receptor, whole-blood zinc protoporphyrin, thyrotropin, thyroxine, urinary iodine, and thyroid gland volume (by ultrasonography)., Results: Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo (P < 0.05). At 20 wk, the mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group (x +/- SD percentage change in thyroid volume from baseline: -22.8 +/- 10.7% compared with -12.7 +/- 10.1%; P < 0.01). At 20 wk, goiter prevalence was 43% in the iron-treated group compared with 62% in the placebo group (P < 0.02). There were no significant differences between groups in whole-blood thyrotropin or serum thyroxine at baseline or during the intervention., Conclusions: Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency. A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis.