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Background: Bouillon is commonly consumed in some countries where micronutrient deficiencies are prevalent, but it has not been widely adopted as a micronutrient fortification vehicle., Objectives: We modeled the potential impacts of bouillon fortification on dietary micronutrient adequacy to inform future discussions around bouillon fortification programs., Methods: We analyzed the dietary intake of women of reproductive age (WRA) and 1- to 5-y-old children from a national dietary survey in Cameroon, and "apparent intake" (using the nutrient density approach) of WRA, children, and men from 3 household surveys in Cameroon, Ghana, and Haiti. We examined (apparent) intake of bouillon and simulated the impacts of bouillon fortification with varying levels of vitamin A, folic acid, vitamin B12, iron, and zinc on inadequate intake (below the estimated average requirement) and intake above the tolerable upper intake level (UL). Scenarios accounted for current mandatory fortification programs and different assumptions about iron absorption from bouillon., Results: Bouillon was consumed by >67% of households in Ghana and >90% in Haiti and Cameroon. Median (apparent) consumption ranged from 1.6 to 2.1 g/d for WRA, 0.7 to 1.0 g/d for children, and 1.8 to 2.2 g/d for men. Bouillon fortification at the highest micronutrient concentration modeled was predicted to reduce dietary inadequacy by 21-52 percentage points (pp) for vitamin A; 3-47pp for folic acid, and 4-90pp for vitamin B12, depending on the country and population group. In contrast, predicted impacts for iron were modest (2-17pp reduction) but would increase if absorption of iron from bouillon were enhanced. Simulated zinc fortification reduced inadequacy by 12-50pp, but zinc intake above the UL exceeded 10% among children in almost all scenarios., Conclusions: Modeling indicates that bouillon fortification could improve dietary micronutrient adequacy beyond existing fortification programs. Further work is needed to identify fortification levels that meet criteria for nutritional benefit, technical and commercial feasibility, affordability, and cost-effectiveness., Competing Interests: Reina Engle-Stone is an Editorial Board Member for Current Developments in Nutrition and played no role in the Journal’s evaluation of the manuscript. All other authors report no conflicts of interest., (© 2024 The Author(s).)

Background: Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID)., Objectives: Objectives were to apply population-based ("super-subject") modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals., Methods: Women ( n = 89) ingested a dose of [ 2 H 6 ]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FD p ) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS . The latter were used in the RID equation TBS (μmol) = FaS × 1/SA p (where SA p is plasma retinol specific activity) to predict TBS at various times., Results: Model-predicted TBS was 973 μmol ( n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252-3848 μmol on day 14 ( n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37., Conclusions: Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS ; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion., Trial Registration Number: Trial is registered (NCT04632771) at https://clinicaltrials.gov., (© 2024 The Author(s).)

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions., (© 2024 The Author(s). Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Undernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNSs) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies., Objectives: We examined the effects of SQ-LNSs provided during pregnancy compared with 1) iron and folic acid or standard of care (IFA/SOC) or 2) multiple micronutrient supplements (MMSs) and identified characteristics that modified the estimates of effects of SQ-LNSs on birth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNSs provided during pregnancy (n = 5273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether the results differed depending on methods for gestational age dating, birth anthropometry, or study design., Results: SQ-LNSs (compared with IFA/SOC) increased birth weight [mean difference: +49 g; 95% confidence interval (CI): 26, 71 g] and all birth anthropometric z-scores (+0.10-0.13 standard deviation); they reduced risk of low birth weight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNSs and MMSs; P values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age: +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNSs compared with IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index <20 kg/m 2 , inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNSs compared with MMSs were greater for certain outcomes among female infants, first-born infants, and mothers <25 y., Conclusions: SQ-LNSs had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNSs and MMSs is needed. Targeting SQ-LNSs to vulnerable subgroups may be worth considering., Clinical Trial Registry: This study was registered at PROSPERO as CRD42021283391., Competing Interests: Conflict of interest N.F.K. is on the Editorial Board of the American Journal of Clinical Nutrition and played no role in the Journal’s evaluation of the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Large-scale food fortification (LSFF) can increase dietary micronutrient intake and improve micronutrient status. Here we used food balance sheet data from the Food and Agriculture Organization of the United Nations to estimate current country-specific prevalences of inadequate zinc intake. We assessed the potential effects of improving existing LSFF programmes for cereal grains or implementing new programmes in 40 countries where zinc deficiency is a potential public health problem. Accounting for LSFF programmes as currently implemented, 15% of the global population (1.13 billion individuals) is estimated to have inadequate zinc intake. In countries where zinc deficiency is a potential public health problem, the implementation of high-quality mandatory LSFF programmes that include zinc as a fortificant would substantially increase the availability of zinc in the national food supply, reducing the estimated prevalence of inadequate zinc intake by up to 50% globally. Investments in strong LSFF programmes could have a substantial impact on population zinc status., (© 2024. The Author(s).)

Introduction: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana., Methods: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development., Discussion: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa., Trial Registration: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Engle-Stone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Information on salt consumption patterns is needed to inform the need for and design of salt reduction strategies., Objectives: In northern Ghana, this study aimed to estimate household consumption of salt, including salt from bouillon, and compare (estimated) women and children's salt intake to global recommendations; to estimate the proportion of salt consumed from bouillon; and to identify factors, including knowledge, attitudes, and practices, associated with household salt consumption., Methods: Employing mixed-methods methodology, we conducted a pilot survey ( n = 369 households enrolled) and focus group discussions (FGDs; n = 20) in Tolon and Kumbungu districts (14 urban, 14 rural clusters) (clinicaltrials.gov registry: NCT04632771). Households reported purchases of discretionary salt (DS, "table salt") and bouillon cubes. DS and total salt (TS; DS+salt from bouillon) consumption for women (15-49 y) and children (2-5 y) were estimated using the Adult Male Equivalent method and compared with global recommendations (<5 g/d women; <3.75 g/d children). Women's salt intake was also predicted from urinary sodium excretion (INTERSALT equation). Associations between DS and TS consumption, as well as household and women's characteristics, were tested with minimally adjusted and multivariable linear mixed-effects models. Qualitative FGD themes were generated using the Framework Method., Results: From household purchase data, estimated TS consumption exceeded global recommendations for 44% of children [median: 2.9 (IQR: 1.9, 5.2) g/d] and 60% of women [6.0 (4.0, 10.2) g/d]; 35% of children and 50% of women exceeded recommendations from DS alone. Bouillon contributed <25% of households' TS consumption. Few characteristics were associated with DS or TS consumption. Salient qualitative themes that shaped salt consumption behaviors included salt's ubiquity as a seasoning, key household members' influence on food procurement and preparation, and perceptions about health., Conclusions: Purchase data suggest salt consumption among women and children exceeds recommendations, even when excluding salt from bouillon; food prepared outside the home likely further contributes. Salt reduction interventions may be warranted in this context., (© 2024 The Author(s).)

Background: Bouillon is a promising large-scale food fortification vehicle, but there is uncertainty regarding the types and concentrations of micronutrients that are feasible to add without compromising consumer acceptability., Objective: The objective of this study was to evaluate the acceptability of 2 different multiple micronutrient-fortified bouillon cube formulations, compared with a bouillon cube fortified with iodine only., Methods: We conducted a double-blind, randomized, controlled acceptability study in 2 districts in northern Ghana. Two nonproprietary, noncommercialized formulations of multiple micronutrient-fortified bouillon cubes containing iron, zinc, folic acid, vitamins A and B12, and iodine at "upper-level" (45-125% CODEX NRV/2.5g) or "lower-level" (15-50% CODEX NRV/2.5g) concentrations, and a control cube that contained iodine only (50% CODEX NRV/2.5g) were evaluated. Eligible women ( n = 84) were invited to participate in 1) center-based sensory evaluations designed to permit within-individual comparisons among the different study products; and 2) in-home evaluation of bouillon acceptability and use, in which participants were randomized to receive 1 of the 3 study products to use in household cooking for a 2-wk period. Acceptance test ratings were based on a 5-point Likert scale (1 = dislike very much, 5 = like very much)., Results: In the center-based evaluations, overall liking of the 3 bouillon cube formulations both dry and in prepared dishes ranged from 4.3 to 4.6 on the 5-point Likert scale and did not differ among formulations ( P > 0.05). After the 2-wk in-home trial, 93.8% of index participants ( n = 75/80) rated their overall liking of the bouillon product formulation to which they were randomly assigned as "like" or "like very much" (4-5 on the 5-point Likert scale) and median apparent intake of study-provided bouillon over 2 wk was 3.6 g/capita/d; neither value differed by study group ( P = 0.91 for both)., Conclusions: All 3 formulations of bouillon cubes assessed were acceptable to women and their households in 2 districts in northern Ghana.This trial was registered at www.clinicaltrials.gov as NCT05177614., (© 2023 The Authors.)

Background: Both small-quantity and medium-quantity lipid-based nutrient supplements (LNS) have been used for the prevention of child undernutrition. A meta-analysis of 14 trials of small-quantity lipid-based nutrient supplements (SQ-LNS) - no LNS showed effects on length-for-age z-score {LAZ, +0.14 [95% confidence interval (CI): 0.11, 0.16]} and weight-for-length z-score [WLZ, +0.08 (0.06, 0.10)] z-scores, as well as prevalence ratios (95% CI) for stunting [LAZ < -2, 0.88 (0.85, 0.91)] and wasting [WLZ < -2, 0.86 (0.80, 0.93)]. However, little is known about the effects of medium-quantity lipid-based nutrient supplements (MQ-LNS) on growth., Objectives: We aimed to examine the effects of preventive MQ-LNS (∼250-499 kcal/d) provided at ∼6-23 mo of age on growth outcomes - no LNS or provision of SQ-LNS., Methods: We conducted a systematic review of studies of MQ-LNS for prevention, and categorized them as providing <6 mo - ≥6 mo of supplementation; for the latter category, we conducted a meta-analysis, with the main outcomes being change in WLZ and LAZ, and prevalence of wasting and stunting., Results: Three studies provided MQ-LNS for 3-5 mo (seasonal) for children 6-36 mo of age, and did not show consistent effects on growth outcomes. Eight studies provided MQ-LNS for 6-18 mo, generally starting at 6 mo of age; in the meta-analysis (max total n = 13,954), MQ-LNS increased WLZ [+0.09 (95% CI: 0.05, 0.13)] and reduced wasting [0.89 (0.81, 0.97)], but had no effect on LAZ [+0.04 (-0.02, 0.11)] or stunting [0.97 (0.92, 1.02)] - no LNS. Two studies directly compared SQ-LNS and MQ-LNS and showed no significant differences in growth outcomes., Conclusions: The current evidence suggests that MQ-LNS offer no added benefits over SQ-LNS, although further studies directly comparing MQ-LNS with SQ-LNS would be useful. One possible explanation is incomplete consumption of the MQ-LNS ration and thus lower than desirable intake of certain nutrients., Trial Registration Number: Registry and registry number for systematic reviews or meta-analyses: Registered with PROSPERO as CRD42022382448 on December 18, 2022: =https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022382448., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)

Objective: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda., Design: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability., Setting: Rural Uganda., Participants: Not applicable., Results: Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242., Conclusions: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

Objectives: To assess (a) the impact of daily preventive zinc tablets (7 mg; PZ), zinc-containing multiple micronutrient powder (10 mg zinc, and 13 other micronutrients; MNP) or placebo, delivered for 9 months, on Insulin-like Growth Factor 1 (IGF1) and IGF Binding Protein 3 (IGFBP3) among Laotian children 6-23 months, and (b) whether the effects of PZ and MNP on length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ) are modified by baseline IGF1 and IGFBP3., Design: A double-blind, placebo-controlled trial (N = 419)., Methods: Plasma IGF1 and IGFBP3 concentrations at baseline and 36 weeks were analyzed by automated chemiluminescent assay. Anthropometry was assessed at baseline, at 18 and 36 weeks. Intervention effects were estimated using ANCOVA., Results: At 36 weeks, geometric mean IGF1 (~39.0-39.2 ng/mL; p = 0.99) and IGFBP3 (2038-2076 ng/mL; p = 0.83) did not differ by group. At 18 weeks (but not at 36 weeks), LAZ in the PZ group (-1.45) was higher than the MNP (-1.70) and control (-1.55) groups ( p = 0.01) among children in the highest baseline IGF1 tertile ( p for interaction = 0.006). At 36 weeks (but not at 18 weeks), WAZ in the PZ group (-1.55) was significantly higher than the MNP (-1.75) and control (-1.65) groups ( p = 0.03), among children in the lowest baseline IGFBP3 tertile ( p for interactions = 0.06)., Conclusions: Although IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ on linear and ponderal growth, suggesting that IGF1 bioavailability may drive catch-up growth in zinc-supplemented children.

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.)

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)-therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)-and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6-23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015)., (© 2022. The Author(s).)

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential., Competing Interests: The authors have read the journal’s policy and have the following competing interests to declare: Neal Craft is a paid employee of Craft Nutrition Consulting. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

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.)

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663., (© 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.)

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (< 65 μg/dL). At endline, geometric mean (95% CI) PZC were greater in the PZ and MNP groups compared with the TZ and control groups (P < 0.01), but hair zinc concentrations did not differ among groups (P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) μg/g) and the MNP (117.8 (113.3, 122.3) μg/g) groups than in the TZ group (110.4 (106.0, 114.8) μg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

Background: Despite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance., Methods: Data were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations., Results: The mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (- 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not., Conclusion: OPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC., Trial Registration: The NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688 . Registered 16 April 2013.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups ( P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations ( P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

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.)

Introduction: Determination of hemoglobins (Hbs) F, A 2, and E is crucial for diagnosis of thalassemia. This study determined the levels of Hbs F, A 2, and E in children aged 6-23 months and investigated the effect of age, sex, and types of thalassemia on the expression of these Hbs., Methods: A total of 698 blood samples of Laotian children including 272 non-Hb E, 271 Hb E heterozygotes, and 155 Hb E homozygotes were collected. Hb profiles were determined using the capillary zone electrophoresis. Coinheritance of α-thalassemia and the homozygosity for Hb E mutation were checked by PCR-based assay., Results: Children heterozygous and homozygous for Hb E had significantly higher Hb F and A 2 levels than non-Hb E children (median Hb F = 1.1% for non-Hb E group, 2.7% for Hb E heterozygotes, and 9.4% for Hb E homozygotes; median Hb A 2  = 2.6% for non-Hb E group, 3.8% for Hb E heterozygotes, and 5.2% for Hb E homozygotes). The median Hb E levels were 21.9% for Hb E heterozygotes and 85.3% for Hb E homozygotes. Comparing within group, there was a statistically significant difference between children with and without an α-gene defect for Hb A 2 and E, but not Hb F. Based on a multiple regression analysis, age and sex were significantly associated with the expression of Hb F and A 2 but not Hb E., Conclusions: Our findings can guide the development of a diagnostic approach to thalassemia in children aged 6-23 months., (© 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Background: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment., Methods: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models., Results: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL). Overall diarrhea incidence (0.61 ± 0.01 episodes/100 days at risk) and duration (2.12 ± 0.03 days/episode) did not differ by study group. Age modified the impact of the interventions on diarrhea incidence ( P  = 0.06) and duration ( P  = 0.01). In children >18 months, TZ reduced diarrhea incidence by 24% vs MNP ( P  = 0.035), and 36% vs Control ( P  = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ ( P  = 0.03), and 16% vs Control ( P  = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P  = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P  = 0.72)., Conclusions: There was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo., Trial Registration: ClinicalTrials.gov: NCT02428647., Competing Interests: Conflicts of interest: KHB and the spouse of SYH worked for the Bill & Melinda Gates Foundation, which provided part of the financial support. The sponsors had no involvement in the study implementation, data analyses or manuscript writing. All authors have completed the ICMJE uniform disclosure form (available upon request from the corresponding author) and declare no further conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

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.)

Environmental enteric dysfunction (EED) may be ameliorated by zinc supplementation. The objective of this study was to investigate the impact of different forms of zinc supplementation on biomarkers of EED (i.e., plasma citrulline, kynurenine, and tryptophan concentrations and the kynurenine:tryptophan [KT] ratio) among young Laotian children. In a double-blind randomized controlled trial, 3,407 children aged 6-23 months were randomized into one of four groups: daily preventive zinc dispersible tablets (PZ; 7 mg zinc), daily multiple micronutrient powders (MNP; 10 mg zinc, 6 mg iron, and 13 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/day for 10 days), or daily placebo powder, and followed up for ∼36 weeks. Plasma samples at baseline and endline for 359 children were analyzed for citrulline, kynurenine, and tryptophan concentrations. At baseline, the prevalence of stunting and zinc deficiency was 37% and 76.5%, respectively. The mean plasma citrulline, kynurenine, and tryptophan concentrations were 24.6 ± 5.4 µmol/L, 3.27 ± 0.83 µmol/L, and 72.3 ± 12.9 µmol/L, respectively; the mean KT ratio (×1,000) was 45.9 ± 12.0. At endline, neither plasma citrulline, kynurenine, or tryptophan concentrations, nor the KT ratio differed among intervention groups ( P > 0.05). In this population, PZ, MNP, and TZ had no overall effect on plasma concentrations of citrulline, kynurenine, and tryptophan, or the KT ratio. The need remains to better understand the etiology of EED, and the development of biomarkers to diagnose EED and evaluate the impact of interventions.

Low gestational weight gain (GWG) and low mid-upper arm circumference (MUAC) are associated with adverse pregnancy outcomes. We aimed to assess the prevalence and determinants of low GWG and low MUAC among pregnant women in rural Zinder, Niger. A community-based survey was conducted among 1,384 pregnant women in the catchment areas of 18 integrated health centers in the region of Zinder, Niger. Weight and MUAC were measured during an in-home visit and again 1 month later, when haemoglobin concentration and micronutrient status were also assessed. The prevalence of low GWG was defined based on the 2009 United States Institute of Medicine (U.S. IOM) guidelines (<0.35 kg/week) and less than the third centile of the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) standards. Factors associated with GWG and MUAC were identified using logistic regression models adjusting for season, village, and gestational age. The median (interquartile range) age was 25.0 (20.7, 30.0) years, and 16.4% were ≤19 years. The prevalence of low GWG were 62.9% and 27.5% according to 2009 IOM and less than the third INTERGROWTH-21st centile, respectively; 24.9% had low MUAC. Higher α-1-acid glycoprotein (OR = 1.7, 95% CI [1.1, 2.8]) and C-reactive protein (OR = 1.2, 95% CI [1.02, 1.50]) increased the odds of low GWG. Adolescents (OR = 2.7, 95% CI [1.8, 4.0]), housewives (OR = 1.97, 95% CI [1.36, 2.86]), and those who reported recent food assistance (OR = 1.80, 95% CI [1.04, 3.11]) had higher odds of low MUAC. Prevalence of low GWG and low MUAC was high among pregnant women. Determinants of GWG and MUAC included socio-economic, demographic, and biological factors, although only markers of inflammation were consistent predictors across different definitions of low GWG., (© 2019 The Authors. Maternal & Child Nutrition published by John Wiley & Sons, Ltd.)

Background: Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown., Objective: Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates., Results: We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10)., Conclusions: LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718., (Copyright © The Author(s) 2019.)

Background: Anaemia is prevalent among pregnant women in rural Niger and antenatal care (ANC) attendance is suboptimal. We designed a programmatic intervention including community-based behaviour change communication, provision of essential drugs (including iron folic acid (IFA) supplements) and quality improvement activities at selected integrated health centres (IHCs)., Objective: To assess the impact of the programmatic intervention on: (1) utilisation of ANC, (2) adherence to daily IFA supplementation and (3) prevalence of adequate gestational weight gain (GWG) and anaemia among pregnant women in Zinder, Niger., Methods: Using a quasi-experimental study design comparing a cohort of women at baseline to another cohort of women at endline, 18 IHCs and surrounding villages were randomly assigned to time of enrolment over 1 year. A baseline survey was implemented among randomly selected pregnant women in 68 village clusters. Subsequently, the intervention was rolled out and an endline survey was implemented 6 months later in the same villages., Results: Mean age in the baseline (n=1385) and endline (n=922) surveys was 25.8±6.4 years. The percentage of pregnant women who reported attending any number of ANC and an adequate number of ANC for their gestational age, respectively, was not significantly different between the endline and the baseline surveys. Pregnant women in the endline survey were more likely to have received IFA (60.0% vs 45.8%, OR: 2.7 (1.2, 6.1)); and the proportion of pregnant women who reportedly consumed IFA daily in the previous 7 days was significantly higher in the endline than in the baseline survey (46.4% vs 32.8%, OR: 2.8 (1.2, 6.5)). There was no impact on the prevalence of adequate GWG or anaemia., Conclusions: The programmatic intervention resulted in a modest increase in the number of pregnant women who reported receiving and consuming IFA supplements as recommended, but did not affect ANC attendance and nutritional status., Competing Interests: Competing interests: BN works for Nutrition International., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dietary phytate inhibits zinc absorption from composite meals in adults., Objective: The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children., Methods: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer., Results: Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 μg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001)., Conclusions: The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133., (Copyright © American Society for Nutrition 2019.)

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6-23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (-1·93 (95 % CI -1·88, -1·97)) v. placebo (-1·88 (95 % CI -1·83, -1·92)), and the opposite occurred among initially anaemic children (final mean LAZ -1·90 (95 % CI -1·86, -1·94) in MNP v. -1·92 (95 % CI -1·88, -1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

Background: Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case., Objectives: The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences., Methods: Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures., Results: In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar., Conclusions: The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853., (Copyright © American Society for Nutrition 2019.)

Objectives: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children., Study Design: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression., Results: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06)., Conclusions: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children., Trial Registration: ClinicalTrials.govNCT02428647., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pregnant and lactating women in rural Niger are at high risk for inadequate intakes of multiple micronutrients. Thus, 24 h dietary recalls were conducted and analyzed for dietary intakes in this population ( n = 202). Using linear programming analyses, micronutrient gaps in women's diets were identified, food-based recommendations (FBR) to improve dietary micronutrient adequacy were developed, and various supplementation strategies were modelled. Energy intakes were below estimated requirements, and, for most micronutrients, >50% of women were at risk of inadequate intakes. Linear programming analyses indicated it would be difficult to select a diet that achieved recommended dietary allowances for all but three (vitamin B₆, iron and zinc) of 11 modeled micronutrients. Consumption of one additional meal per day, and adherence to the selected FBR (daily consumption of dark green leafy vegetables, fermented milk, millet, pulses, and vitamin A fortified oil), would result in a low percentage of women at risk of inadequate intakes for eight modeled micronutrients (vitamin A, riboflavin, thiamin, B 6, folate, iron, zinc, and calcium). Because the promotion of realistic FBRs likely will not ensure that a low percentage of women are at risk of inadequate intakes for all modeled micronutrients, multiple micronutrient supplementation or provision of nutrient-dense foods should be prioritized.

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol concentrations (HCC) in young Laotian children and examined risk factors associated with HCC. In a randomized double-blind controlled trial (NCT02428647), children aged 6⁻23 mo were randomized to one of four intervention groups and followed for ~36 weeks: daily preventive zinc (PZ) tablets (7 mg/day), daily multiple micronutrient powder (MNP) sachets (containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days) or daily placebo powder. HCC of 512 children was assessed at baseline and endline. ANCOVA and linear regression models were used to assess group differences in HCC and to examine the risk factors associated with HCC, respectively. At enrollment, mean HCC was 28.8 ± 43.9 pg/mg. In models adjusted for age at enrollment, health district, and baseline HCC there was no overall effect of the interventions on endline HCC and change in HCC. When controlling for additional predetermined covariates, there was a marginally significant effect on change in HCC ( p = 0.075) with a slightly lower reduction of HCC in TZ compared to PZ (mean change (95% CI): -4.6 (-7.0; -2.3) vs. -9.4 (-11.7; -7.0) pg/mg; p = 0.053). At baseline, consumption of iron rich foods was negatively associated with HCC, whereas AGP (α1-acid glycoprotein) levels, elevated AGP and C-reactive protein and high soluble transferrin receptor were positively associated with HCC. In young Laotian children, MNP, PZ and TZ had no impact on HCC. The marginal difference in change in HCC between the PZ and TZ groups was too small to be considered of health significance.

Background: Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10-14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea., Methods: The present study is a community-based, randomized controlled trial in the Lao People's Democratic Republic (PDR). Three thousand, four hundred children 6-23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA., Discussion: Many countries are now rolling out large-scale programs to include therapeutic zinc supplementation in the treatment of childhood diarrhea, but few have established programs demonstrated to be effective in the prevention of zinc deficiency. This study will address how best to deliver supplemental zinc to prevent zinc deficiency and reduce the severity of diarrhea-related health complications., Trial Registration: Trial registration identifier (NCT02428647) ; Date of registration: April 29, 2015., Competing Interests: Competing interestsKBH is an employee of Nutrition International, formerly the Micronutrient Initiative and GAR was an employee of the Mathile Institute for the Advancement of Human Nutrition at the time of the initial proposal writing. KHB works for the Bill & Melinda Gates Foundation, which provided part of the financial support. The spouse of SYH works for the Bill & Melinda Gates Foundation. KRW, SK, MAB, GMH, SS, KR, CBS, CPL, CDA, GL, SF and RMB declare that they have no competing interests., (© The Author(s). 2018.)

Background: Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated haematology analyser in young children., Aim: To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR., Methods: Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots., Results: Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L)., Conclusion: Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences., Competing Interests: Competing interests: KHB works for the Bill & Melinda Gates Foundation. The spouse of SYH works for the Bill & Melinda Gates Foundation. All other authors have no competing interests to declare., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In Niger, use of antenatal care (ANC) and iron folic acid (IFA) supplements is suboptimal. The objectives of this paper are as follows: (a) to conduct formative research to understand barriers and beliefs among pregnant women related to ANC, IFA supplementation, and pregnancy outcomes; (b) assess the quality of currently provided ANC services; (c) use the findings to guide the development of programmatic interventions to improve coverage of ANC services and IFA supplementation of pregnant women. Structured in-home interviews (n = 72) and focus groups (n = 4) were conducted with pregnant women in 4 randomly selected villages in rural Zinder. ANC consultations (n = 33) were observed in 5 randomly selected health centres, and exit interviews were conducted with all pregnant women and seven health agents following these observations. During workshops with stakeholders, results of the formative research were interpreted, and programmatic interventions were developed. In home interviews, 72% of women reported having attended at least one ANC visit. They also reported husbands (71%), mothers (40%), and friends (33%) supporting ANC attendance. Among those having attended ANC, only 65% reported taking IFA the day prior to the interview. Three of five health centres visited had IFA in stock. Health staff did not provide IFA supplements during 18 of 33 observed ANC consultations of which only 7 cases could be explained by the lack of IFA supplements in stock. Findings were used to design a 3-pronged intervention: (a) behaviour change communication activities in communities; (b) quality improvement activities in health centres to strengthen ANC; and (c) provision of key supplies required for ANC., (© 2017 John Wiley & Sons Ltd.)

The World Health Organization recommends iron and folic acid (IFA) supplementation for pregnant women. The high prevalence of anaemia among pregnant women in Niger warrants better understanding of the utilization of antenatal care (ANC) and IFA. We aimed to assess the prevalence of and factors associated with ANC coverage and adherence to IFA recommendation among pregnant women. Pregnant women (n = 923) from 64 randomly selected villages within the catchment area of 12 health centres were interviewed during a baseline household survey in Zinder, Niger. ANC and IFA coverage were 60.1% and 43.6%, respectively. Only 71.7% of women who attended ANC received IFA. Of the 401 women who reportedly received any IFA supplements, 99.3% had attended any ANC during their current pregnancy and 68.6% reported adherence to recommended IFA supplementation (i.e., consumed IFA every day in the previous week). Women with gestational age ≥27 weeks were more likely to have attended ANC than women with gestational age <27 weeks (85.9% vs. 27.5%, odds ratio [OR]: 21.81, 95% confidence interval [CI]: 13.81, 34.45). Women who reportedly received husbands' advice about attending ANC were more likely to attend ANC (OR: 1.48, 95% CI [1.03, 2.11]) and adhere to IFA recommendations (OR: 1.80, 95% CI [1.04, 3.13]) compared to those who did not receive any advice. ANC attendance is crucial to ensure distribution of IFA supplementation among pregnant women in Zinder. Interventions to improve ANC and IFA adherence will require promotion of early ANC, ensure availability of IFA at ANC, and involve husbands in ANC., (© 2018 John Wiley & Sons Ltd.)

Deficiencies of vitamin A, iron, and iodine are major public health concerns in many low- and middle-income countries, but information on their status in populations is often lacking due to high costs and logistical challenges associated with assessing micronutrient status. Accurate, user-friendly, and low-cost analytical tools are needed to allow large-scale population surveys on micronutrient status. We present the expansion of a 7-plex protein microarray tool for the simultaneous measurement of up to seven biomarkers with relevance to the assessment of the key micronutrients iron, iodine, and vitamin A, and inflammation and malaria biomarkers: α-1-acid glycoprotein, C-reactive protein, ferritin, retinol binding protein 4, soluble transferrin receptor, thyroglobulin, and histidine-rich protein II. Assay performance was assessed using international reference standards and then verified by comparing the multiplexed and conventional immunoassay results on a training panel of plasma samples collected from US adults. These data were used to assign nominal concentrations to the calibrators of the assay to further improve performance which was then assessed by interrogating plasma samples from a cohort of pregnant women from Niger. The correlation between assays for each biomarker measured from this cohort was typically good, with the exception of thyroglobulin, and the sensitivity ranged from 74% to 93%, and specificity from 81% to 98%. The 7-Plex micronutrient assay has the potential for use as an affordable tool for population surveillance of vitamin A, iron, and iodine deficiencies as well as falciparum malarial parasitemia infectivity and inflammation. The assay is easy-to-use, requires minimal sample volume, and is scalable, rapid, and accurate-needing only a low-cost reader and basic equipment present in most reference laboratory settings and so may be employed by low and middle income countries for micronutrient surveillance to inform on status in key populations. Micronutrient deficiencies including iron, iodine, and vitamin A affect a significant portion of the world's population. Efforts to assess the prevalence of these deficiencies in vulnerable populations are challenging, partly due to measurement tools that are inadequate for assessing multiple micronutrients in large-scale population surveys. We have developed a 7-plex immunoassay for the simultaneous measurement of seven biomarkers relevant to assessing iodine, iron, and vitamin A status, inflammation and Plasmodium falciparum parasitemia by measuring levels of thyroglobulin, ferritin, soluble transferrin receptor, retinol binding protein 4, α-1-acid glycoprotein, C-reactive protein, and histidine-rich protein II. This 7-plex immunoassay technique has potential as a rapid and effective tool for use in large-scale surveys and assessments of nutrition intervention programs in low- and middle-income countries.

Objective: To assess iodine status among pregnant women in rural Zinder, Niger and to compare their status with the iodine status of school-aged children from the same households., Design: Seventy-three villages in the catchment area of sixteen health centres were randomly selected to participate in the cross-sectional survey., Setting: Salt iodization is mandatory in Niger, requiring 20-60 ppm iodine at the retail level., Subjects: A spot urine sample was collected from randomly selected pregnant women (n 662) and one school-aged child from the same household (n 373). Urinary iodine concentration (UIC) was assessed as an indicator of iodine status in both groups. Dried blood spots (DBS) were collected from venous blood samples of pregnant women and thyroglobulin (Tg), thyroid-stimulating hormone and total thyroxine were measured. Iodine content of household salt samples (n 108) was assessed by titration., Results: Median iodine content of salt samples was 5·5 ppm (range 0-41 ppm), 98 % had an iodine content 40 µg/l., Conclusions: In this region of Niger, most salt is inadequately iodized. UIC in pregnant women indicated iodine deficiency, whereas UIC of school-aged children indicated marginally adequate iodine status. Thus, estimating population iodine status based solely on monitoring of UIC among school-aged children may underestimate the risk of iodine deficiency in pregnant women.

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages ( n = 88) were included. Capillary and venous blood samples ( n = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B 12 . C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (<15 µg/L) and sTfR (>8.3 mg/L), respectively. In total, 40.7% of women had low pZn (<50 µg/dL), 79.7% had marginal RBP (<1.32 µmol/L), 44.3% of women had low folate (<10 nmol/L) and 34.8% had low B 12 concentrations (<148 pmol/L). Common risk factors associated with MN status included gravidity, mid-upper-arm circumference, geophagy, malaria, and result of the woman's last pregnancy. Interventions to promote the strengthening of antenatal care, and access and adherence to nutrition and health interventions are critical among pregnant women in this population.

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution., Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol., Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa., Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Increasing concentrations of atmospheric carbon dioxide (CO2) lower the content of zinc and other nutrients in important food crops. Zinc deficiency is currently responsible for large burdens of disease globally, and the populations who are at highest risk of zinc deficiency also receive most of their dietary zinc from crops. By modelling dietary intake of bioavailable zinc for the populations of 188 countries under both an ambient CO2 and elevated CO2 scenario, we sought to estimate the effect of anthropogenic CO2 emissions on the global risk of zinc deficiency., Methods: We estimated per capita per day bioavailable intake of zinc for the populations of 188 countries at ambient CO2 concentrations (375-384 ppm) using food balance sheet data for 2003-07 from the Food and Agriculture Organization. We then used previously published data from free air CO2 enrichment and open-top chamber experiments to model zinc intake at elevated CO2 concentrations (550 ppm, which is the concentration expected by 2050). Estimates developed by the International Zinc Nutrition Consultative Group were used for country-specific theoretical mean daily per-capita physiological requirements for zinc. Finally, we used these data on zinc bioavailability and population-weighted estimated average zinc requirements to estimate the risk of inadequate zinc intake among the populations of the different nations under the two scenarios (ambient and elevated CO2). The difference between the population at risk at elevated and ambient CO2 concentrations (ie, population at new risk of zinc deficiency) was our measure of impact., Findings: The total number of people estimated to be placed at new risk of zinc deficiency by 2050 was 138 million (95% CI 120-156). The people likely to be most affected live in Africa and South Asia, with nearly 48 million (32-63) residing in India alone. Global maps of increased risk show significant heterogeneity., Interpretation: Our results indicate that one heretofore unquantified human health effect associated with anthropogenic CO2 emissions will be a significant increase in the human population at risk of zinc deficiency. Our country-specific findings can be used to help guide interventions aimed at reducing this vulnerability., Funding: Bill & Melinda Gates Foundation, Winslow Foundation., (Copyright © 2015 Myers et al. Open access article published under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

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.)