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Inconsistent use of terminology among diverse stakeholders hinders effective communication in micronutrient programs, especially large-scale food fortification (LSFF) which involves stakeholders from different sectors. To align the terminology use, the Micronutrient Data Innovation Alliance (DInA) of the Micronutrient Forum (MNF) created a lexicon of terms related to LSFF and other micronutrient programs. The purpose of this lexicon is to establish a central repository of consensus definitions of key terms to facilitate communication among diverse stakeholders involved in micronutrient programs including public and private sectors, donor agencies, food industries, academic institutions, etc. This paper describes the methodology of lexicon development. Important terms related to micronutrient programs were compiled from multiple sources, including United Nations agencies, program implementation and technical support agencies, relevant websites, and scientific literature. The selection of terms was guided by key micronutrient interventions (fortification, supplementation, dietary diversification) and the program cycle (assessment, planning, implementation, monitoring and evaluation). Definitions of terms were identified from these references and checked for consistency across different sources. For terms with multiple definitions, a modified Delphi method was applied to harmonize the definitions. The first draft lexicon (n = 113 terms) was reviewed by six experts from the University of California, Davis (UCD) and MNF, and second draft (n = 115 terms) was shared with 24 global micronutrient experts for feedback. Fifty-four terms were found to have multiple definitions. Of which, minor modification was made for 12-terms with nominal difference and remaining 42-terms were shared with over 140 micronutrient-experts disseminated via an online survey through newsletters and emails to solicit experts' opinions on the most appropriate definition or a modified one. Nineteen legal terms and 83 micronutrient terms (n = 102 terms) were subsequently added. Overall, 39 experts from diverse areas of expertise (LSFF, micronutrient program planning and implementation, surveys and research, policy development, food industry regulations, food safety, and public health nutrition) participated in the online survey. The terms with >75% agreement among experts were considered as final, while the remaining were reviewed again by experts from UCD and MNF until consensus was reached on harmonized definitions. The current lexicon is available online at the DInA-website. and contains 217 terms and will be maintained as a "living document". The lexicon will facilitate the ability of key stakeholders of micronutrient programs to evaluate and compare program performance in order to make informed decisions on how to ensure future progress in reducing micronutrient deficiencies. [ABSTRACT FROM AUTHOR]

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol‐binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid‐upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron‐containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha‐1‐acid‐glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care‐seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children. Key messages: Anaemia is a public health concern among women and young children due to multiple causes and biological, socioeconomic and ecological risk factors.Anaemia was assessed among women and their young children hospitalised for clinical signs and symptoms suggestive of thiamine deficiency disorders. The risk of anaemia was significantly associated with multiple indicators of micronutrient status and factors related to poverty and health and dietary practices.The present study highlights that anaemia and iron, thiamine, riboflavin and vitamin A deficiencies are highly prevalent in the study population and that multiple strategies are required to prevent anaemia and the other consequences of these micronutrient deficiencies. [ABSTRACT FROM AUTHOR]

Dietary intake and biomarkers of micronutrient status of 100 non-pregnant women of reproductive age (NPWRA) were assessed to determine optimal levels of iron, zinc, vitamin B12, and folic acid to include in multiply-fortified salt (MFS) that will be evaluated in an upcoming trial. Weighed food records were obtained from participants to measure intake of micronutrients and discretionary salt, and to assess adequacy using Indian Nutrient Reference Values (NRVs). Statistical modeling was used to determine optimal fortification levels to reduce inadequate micronutrient intake while limiting intake above the upper limit. Fasting blood samples were obtained to assess iron, zinc, vitamin B12, and folate status. In usual diets, inadequate intake of iron (46%), zinc (95%), vitamin B12 (83%), and folate (36%) was high. Mean intake of discretionary salt was 4.7 g/day. Prevalence estimates of anemia (37%), iron deficiency (67%), zinc deficiency (34%), vitamin B12 insufficiency (37%), and folate insufficiency (70%) were also high. Simulating the addition of optimized MFS to usual diets resulted in percentage point (pp) reductions in inadequate intake by 29 pp for iron, 76 pp for zinc, 81 pp for vitamin B12, and 36 pp for folate. MFS holds potential to reduce the burden of micronutrient deficiencies in this setting. [ABSTRACT FROM AUTHOR]

Purpose: Public health interventions to address stunting and wasting should be evaluated for possibly contributing to obesity risk. The present study tested the hypothesis that small-quantity lipid-based nutrient supplements (SQ-LNS) might increase fat deposition, and that additional zinc provided via SQ-LNS or in the form of dispersible tablets would increase fat-free mass (FFM) accretion. Methods: Using a two-stage, cluster-randomized trial design, 34 communities were randomly assigned to the intervention cohort (IC) or non-intervention cohort (NIC), and family compounds within the IC were randomly assigned to receive different amounts of zinc (0, 5 or 10 mg zinc) incorporated in SQ-LNS or 5 mg zinc in the form of dispersible tablets along with treatment for diarrhea, malaria and fever. Body composition was assessed in a subset of IC (n = 201) and NIC (n = 74) children at 9 and 18 months using the deuterium dilution method. A mixed linear model was used to examine average change in FFM and % fat mass (%FM) among intervention groups and by cohort. Results: Children in the IC had significantly greater change in FFM (Mean (95% Confidence Interval)) (1.57 (1.49, 1.64) kg) compared to the NIC (1.35 (1.23, 1.46) kg; p = 0.005). There were no significant differences in the change in %FM between the NIC and IC or among the intervention groups. Conclusion: SQ-LNS, along with morbidity treatment increased weight gain and FFM in young children from 9 to 18 months of age without increasing FM deposition. Additional zinc supplementation did not affect changes in FFM or %FM. Trial registration: The study was registered as a clinical trial with the US National Institute of Health (www.ClinicalTrials.gov; NCT00944281). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Multiple micronutrient (MN) deficiencies remain highly prevalent among women of reproductive age (WRA) and preschool-aged children (PSC) in many areas within India. Salt is an attractive vehicle for MN fortification in this context, as it is universally consumed in fairly consistent amounts and coverage of iodized salt (IS) is 94%. The overall objective of this trial is to evaluate the nutritional impact of quintuply-fortified salt with iron in the form of encapsulated ferrous fumarate, zinc, vitamin B12, folic acid, and iodine (eFF-Q5S) vs. quintuply-fortified salt with iron in the form of ferric pyrophosphate plus EDTA, zinc, vitamin B12, folic acid, and iodine (FePP-Q5S) vs. IS for the improvement of MN status among non-pregnant WRA and PSC. Methods: The study is a community-based, randomized, controlled trial that will be conducted in Punjab, India. 780 non-pregnant WRA 18–49 years old and 468 PSC 12–59 months old will be enrolled and assigned to one of three intervention groups. Salt will be provided to participants monthly for 12 months. Primary outcomes include changes in mean concentration of biomarkers of iron, zinc, vitamin B12, folate and iodine. Secondary outcomes include changes in the composition of the gut microbiome, and discretionary salt intake of PSC. Discussion: If proven efficacious, multiply-fortified salt (MFS) has the potential to drastically reduce the burden of MN deficiencies in India, and around the world. Although effectiveness research will be needed to examine the impact of MFS under programmatic conditions, salt fortification will piggy-back on existing platforms to produce IS and doubly-fortified salt (DFS), making it possible to scale-up the intervention quickly. Trial registration: Clinicaltrials.gov: NCT05166980; date of registration: December 22, 2021. Clinical Trials Registry-India: CTRI/2022/040332 and CTRI/2022/02/040333; date of registration: February 15, 2022. [ABSTRACT FROM AUTHOR]

Background: The Global Burden of Disease (GBD) Study provides estimates of death and disability from eighty-seven risk factors, including some micronutrient deficiencies. Objectives: To review methodological changes that led to large differences in the disease burden estimates for vitamin A and Zn deficiencies between the GBD 2017 and 2019 Studies. Methods: GBD publications were reviewed; additional information was provided by GBD researchers. Results: Vitamin A deficiency prevalence is based on plasma retinol concentration, whereas the estimate for Zn deficiency prevalence uses dietary adequacy as a proxy. The estimated global prevalence of vitamin A deficiency for children aged 1–4 years in the year 2017 decreased from 0·20 (95 % CI 0·17, 0·24) in GBD 2017 to 0·16 (95 % CI 0·15, 0·19) in GBD 2019, while the global prevalence of Zn deficiency did not change between the two studies (0·09 (95 % CI 0·04, 0·17) and 0·09 (95 % CI 0·03, 0·18)). New to 2019 was that meta-analyses were performed using Meta Regression – Bayesian, Regularized, Trimmed, a method developed for GBD. Due to this and multiple other methodological changes, the estimated number of deaths due to vitamin A deficiency dropped from 233 000 (179 000–294 000) to 24 000 (3000–50 000) from GBD 2017 to 2019, and for Zn deficiency from 29 000 (1000–77 000) to 2800 (700–6500), respectively. Conclusion: The changes in the estimated disease burdens due to vitamin A and Zn deficiencies in the GBD reports from 2017 to 2019 are due primarily to changes in the analytical methods employed, so may not represent true changes in disease burden. Additional effort is needed to validate these results. [ABSTRACT FROM AUTHOR]

Background Young children exposed to high-dose vitamin A supplements (VAS) and vitamin A (VA)–fortified foods may be at risk of high VA intake and high VA total body stores (TBS). Objectives TBS and estimated liver VA concentration were compared among children with adequate or high VA intake and different timing of exposure to VAS, and associations between estimated liver VA concentrations and biomarkers of VA toxicity were examined. Methods Children 12–18 mo of age (n  = 123) were selected for 3 groups: 1) retinol intake >600 µg/d and VAS within the past mo, 2) retinol intake >600 µg/d and VAS in the past 3–6 mo, and 3) VA intake 200–500 µg retinol activity equivalents (RAE)/d and VAS in the past 3–6 mo. Dietary intake data were collected to measure VA intakes from complementary foods, breast milk, and low-dose, over-the-counter supplements. TBS were assessed by retinol isotope dilution, and VA toxicity biomarkers were measured. Main outcomes were compared by group. Results Mean (95% CI) VA intakes excluding VAS were 1184 (942, 1426), 980 (772, 1187), and 627 (530, 724) µg RAE/d, in groups 1–3, respectively; mean VA intake was higher in groups 1 and 2 compared with group 3 (P  < 0.05). Geometric mean (GM) (95% CI) TBS were 589 (525, 661), 493 (435, 559), and 466 (411, 528) µmol, respectively. GM TBS and GM liver VA concentrations were higher in group 1 compared with group 3 (liver VA concentration: 1.62 vs. 1.33 µmol/g; P  < 0.05). Plasma retinyl ester and 4-oxo-retinoic acid concentrations and serum markers of bone turnover and liver damage did not indicate VA toxicity. Conclusions In this sample, most children had retinol intakes above the Tolerable Upper Intake Level (UL) and liver VA concentrations above the proposed cutoff for "hypervitaminosis A" (>1 µmol/g liver). There was no evidence of chronic VA toxicity, suggesting that the liver VA cutoff value should be re-evaluated. This trial was registered at www.clinicaltrials.gov as NCT03030339. [ABSTRACT FROM AUTHOR]

Including biomarkers of micronutrient status in existing or planned national surveys or surveillance systems is a critical step in improving capacity to promote, design, monitor, and evaluate micronutrient policies and programs. We aimed to identify the barriers to and enablers of the inclusion of micronutrient biomarker assessment in national surveys and surveillance systems, to identify the main challenges faced during the survey process, and to review experiences using existing platforms for micronutrient surveys. We conducted a series of key informant interviews with in-country and external representatives from six countries where national-level data on micronutrient status were collected in the past 5 years: Cambodia, Pakistan, Malawi, Uganda, Ghana, and Uzbekistan. Micronutrients associated with specific public health programs were always prioritized for inclusion in the survey. If funding, time, and/or logistics allowed, other considered micronutrients were also included. The most important and frequently reported barrier to inclusion of a more comprehensive panel of micronutrient biomarkers was inadequate funding to cover the laboratory analysis cost for all micronutrients considered at the planning stage. Government support and commitment was stressed as the most important enabling factor by all key informants. Advocacy for funding for micronutrient status assessment is needed. [ABSTRACT FROM AUTHOR]

Safe upper levels (UL) of zinc intake for children were established based on either (1) limited data from just one study among children or (2) extrapolations from studies in adults. Resulting ULs are less than amounts of zinc consumed by children in many studies that reported benefits of zinc interventions, and usual dietary zinc intakes often exceed the UL, with no apparent adverse effects. Therefore, existing ULs may be too low. We conducted a systematic bibliographic review of studies among preadolescent children, in which (1) additional zinc was provided vs. no additional zinc provided, and (2) the effect of zinc on serum or plasma copper, ceruloplasmin, ferritin, transferrin receptor, lipids, or hemoglobin or erythrocyte super-oxide dismutase were assessed. We extracted data from 44 relevant studies with 141 comparisons. Meta-analyses found no significant overall effect of providing additional zinc, except for a significant negative effect on ferritin (p = 0.001), albeit not consistent in relation to the zinc dose. Interpretation is complicated by the significant heterogeneity of results and uncertainties regarding the physiological and clinical significance of outcomes. Current zinc ULs should be reassessed and potentially revised using data now available for preadolescent children and considering challenges regarding interpretation of results. [ABSTRACT FROM AUTHOR]

Background The Lives Saved Tool (LiST) is a mathematical modelling tool for estimating the survival, health, and nutritional impacts of scaling intervention coverage in low- and middle-income countries (LMICs). Various nutrition interventions are included in LiST and are regularly (and independently) reviewed and updated as new data emerge. This manuscript describes our latest in-depth review of nutrition evidence, focusing on intervention efficacy, appropriate population-affected fractions, and new interventions for potential inclusion in the LiST model. Methods An external advisory group (EAG) was assembled to review evidence from systematic reviews on intervention-outcome (I-O) pairs for women and children under five years of age. GRADE quality was assigned to each pair based on a LiST-specific checklist to facilitate consistent decisions during the consideration. For existing interventions with new information, the EAG was asked to recommend whether to update the default efficacy values and population-affected fractions. For the new interventions, the EAG decided whether there was sufficient evidence of benefit, and in affirmative cases, information on the efficacy and affected fraction values that could be used. Decisions were based on expert group consensus. Results Overall, the group reviewed 53 nutrition-related I-O pairs, including 25 existing and 28 new ones. Efficacy and population-affected fractions were updated for seven I-O pairs; three pairs were updated for efficacy estimates only, three were updated for population-affected fractions only; and nine new I-O pairs were added to the model, bringing the total of nutrition-related I-O pairs to 34. Included in the new I-O pairs were two new nutrition interventions added to LIST: zinc fortification and neonatal vitamin A supplementation. Conclusions For modelling tools like LiST to be useful, it is crucial to update interventions, efficacy and population-affected fractions as new evidence becomes available. The present updates will enable LiST users to better estimate the potential health, nutrition, and survival benefits of investing in nutrition. [ABSTRACT FROM AUTHOR]

Information on the prevalence of micronutrient deficiencies is needed to determine related disease burden; underpin evidence-based advocacy; and design, deliver, and monitor safe, effective interventions. Assessing the global prevalence of deficiency requires a valid micronutrient status biomarker with an appropriate cutoff to define deficiency and relevant data from representative surveys across multiple locations and years. The Global Burden of Disease Study includes prevalence estimates for iodine, iron, zinc, and vitamin A deficiencies, for which recommended biomarkers and appropriate deficiency cutoffs exist. Because representative survey data are lacking, only retinol concentration is used to model vitamin A deficiency, and proxy indicators are used for the other micronutrients (goiter for iodine, hemoglobin for iron, and dietary food adequacy for zinc). Because of data limitations, complex statistical modeling is required to produce current estimates, relying on assumptions and proxies that likely understate the extent of micronutrient deficiencies and the consequent global health burden. [ABSTRACT FROM AUTHOR]

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

Severe thiamine (vitamin B1) deficiency is generally regarded as a problem affecting mostly infants in low‐income communities of Southeast Asia and adult alcoholics regardless of their location. However, recent scholarship shows that the disorders associated with thiamine deficiency may also affect heretofore unsuspected populations, and that the scope of disorders, including some long‐lasting neurocognitive consequences, is broader than previously thought. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Meeting children's vitamin A (VA) needs remains a policy priority. Doing so efficiently is a fiscal imperative and protecting at‐risk children during policy transitions is a moral imperative. Using the Micronutrient Intervention Modeling tool and data for Cameroon, we predict the impacts and costs of alternative VA intervention programs, identify the least‐cost strategy for meeting targets nationally, and compare it to a business‐as‐usual (BAU) strategy over 10 years. BAU programs effectively cover ∼12.8 million (m) child‐years (CY) and cost ∼$30.1 m; ∼US$2.34 per CY effectively covered. Improving the VA‐fortified oil program, implementing a VA‐fortified bouillon cube program, and periodic VA supplements (VAS) in the North macroregion for 3 years effectively cover ∼13.1 m CY at a cost of ∼US$9.5 m, or ∼US$0.71 per CY effectively covered. The tool then identifies a sequence of subnational policy choices leading from the BAU toward the more efficient strategy, while addressing VA‐attributable mortality concerns. By year 4, fortification programs are predicted to eliminate inadequate VA intake in the South and Cities macroregions, but not the North, where VAS should continue until additional delivery platforms are implemented. This modeling approach offers a concrete example of the strategic use of data to follow the Global Alliance for VA framework and do so efficiently. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors comment on a study published within the issue which reported on the prevalence of low serum zinc concentrations among children and adolescents in India. Topics covered include the risk factors for low SZC identified by the study, the limitations of the study, and the implications of the study findings for public health.

Anemia is an important public health challenge and accurate prevalence estimates are needed for program planning and tracking progress. While venous blood assessed by automated hematology analyzers is considered gold standard, most population‐based surveys use point‐of‐care diagnostics and capillary blood to estimate population prevalence of anemia. Several factors influence hemoglobin (Hb) concentration, including human and analytic error, analysis method, and type of instrument, but it is unclear whether biological variability exists between venous and capillary blood. The objective of this paper was to systematically review sources of Hb variability and the potential biological basis for venous and capillary differences. We use data from a recent survey in the state of Uttar Pradesh, India, to illustrate the implications on anemia prevalence estimates. Significant differences in Hb concentration between capillary and venous blood samples are common. Most but not all find capillary Hb concentration to be higher than venous. Instrument/method variability and human error play an important role, but cannot fully explain these differences. A normative guide to data collection, analysis, and anemia diagnosis is needed to ensure consistent and appropriate interpretation. Further research is needed to fully understand the biological implications of venous and capillary Hb variability. [ABSTRACT FROM AUTHOR]

Several intervention strategies are available to reduce micronutrient deficiencies, but uncoordinated implementation of multiple interventions may result in excessive intakes. We reviewed relevant data collection instruments and available information on excessive intakes for selected micronutrients and considered possible approaches for weighing competing risks of intake above tolerable upper intake levels (ULs) versus insufficient intakes at the population level. In general, population‐based surveys in low‐ and middle‐income countries suggest that dietary intakes greater than the UL are uncommon, but simulations indicate that fortification and supplementation programs could lead to high intakes under certain scenarios. The risk of excessive intakes can be reduced by considering baseline information on dietary intakes and voluntary supplement use and continuously monitoring program coverage. We describe a framework for comparing risks of micronutrient deficiency and excess, recognizing that critical information for judging these risks is often unavailable. We recommend (1) assessing total dietary intakes and nutritional status; (2) incorporating rapid screening tools for routine monitoring and surveillance; (3) addressing critical research needs, including evaluations of the current ULs, improving biomarkers of excess, and developing methods for predicting and comparing risks and benefits; and (4) ensuring that relevant information is used in decision‐making processes. [ABSTRACT FROM AUTHOR]

Background: Moderate acute malnutrition (MAM) affects 34.1 million children globally. Treatment effectiveness is generally determined by the amount and rate of weight gain. Body composition (BC) assessment provides more detailed information on nutritional stores and the type of tissue accrual than traditional weight measurements alone.Objective: The aim of this study was to compare the change in percentage fat mass (%FM) and other BC parameters among young Malian children with MAM according to receipt of 1 of 4 dietary supplements, and recovery status at the end of the 12-wk intervention period.Methods: BC was assessed using the deuterium oxide dilution method in a subgroup of 286 children aged 6-35 mo who participated in a 12-wk community-based, cluster-randomized effectiveness trial of 4 dietary supplements for the treatment of MAM: 1) lipid-based, ready-to-use supplementary food (RUSF); 2) special corn-soy blend "plus plus" (CSB++); 3) locally processed, fortified flour (MI); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). Multivariate linear regression modeling was used to evaluate change in BC parameters by treatment group and recovery status.Results: Mean ± SD %FM at baseline was 28.6% ± 5.32%. Change in %FM did not vary between groups. Children who received RUSF vs. MI gained more (mean; 95% CI) weight (1.43; 1.13, 1.74 kg compared with 0.84; 0.66, 1.03 kg; P = 0.02), FM (0.70; 0.45, 0.96 kg compared with 0.20; 0.05, 0.36 kg; P = 0.01), and weight-for-length z score (1.23; 0.79, 1.54 compared with 0.49; 0.34, 0.71; P = 0.03). Children who recovered from MAM exhibited greater increases in all BC parameters, including %FM, than children who did not recover.Conclusions: In this study population, children had higher than expected %FM at baseline. There were no differences in %FM change between groups. International BC reference data are needed to assess the utility of BC assessment in community-based management of acute malnutrition programs. This trial was registered at clinicaltrials.gov as NCT01015950. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vitamin D is an essential nutrient for bone health and may influence the risks of respiratory illness, adverse pregnancy outcomes, and chronic diseases of adulthood. Because many countries have a relatively low supply of foods rich in vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from sunlight, an important proportion of the global population is at risk of vitamin D deficiency. There is general agreement that the minimum serum/plasma 25‐hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D deficiency–related bone disease is approximately 30 nmol/L; therefore, this threshold is suitable to define vitamin D deficiency in population surveys. However, efforts to assess the vitamin D status of populations in low‐ and middle‐income countries have been hampered by limited availability of population‐representative 25(OH)D data, particularly among population subgroups most vulnerable to the skeletal and potential extraskeletal consequences of low vitamin D status, namely exclusively breastfed infants, children, adolescents, pregnant and lactating women, and the elderly. In the absence of 25(OH)D data, identification of communities that would benefit from public health interventions to improve vitamin D status may require proxy indicators of the population risk of vitamin D deficiency, such as the prevalence of rickets or metrics of usual UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20% prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is determined to be high based on proxy indicators (e.g., prevalence of rickets >1%), food fortification and/or targeted vitamin D supplementation policies can be implemented to reduce the burden of vitamin D deficiency–related conditions in vulnerable populations. Here we report the outcome of a working group convened in January and March 2017 by the Sackler Institute for Nutrition Science at the New York Academy of Sciences and the Bill & Melinda Gates Foundation to assess the global prevalence and disease burden of vitamin D deficiency, and population‐based strategies to improve vitamin D status, particularly in low‐ and middle‐income countries. The working group aimed to examine definitions of vitamin D deficiency based on biomarkers and correlations with disease or health outcomes. [ABSTRACT FROM AUTHOR]

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month‐specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high‐risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing. This paper describes the current state of thiamine research and the significance of thiamine deficiency in low‐ and middle‐income countries from public health and clinical perspectives. The map shows countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men (in turquoise), and countries where rice or wheat flour fortification are in place to address low thiamine availability (in yellow). [ABSTRACT FROM AUTHOR]

Abstract: Information on the distribution and predictors of obesity in Africa is needed to identify populations at risk and explore intervention options. Our objectives were to (a) examine the prevalence and geographic distribution of overweight and obesity among Cameroonian women; (b) evaluate change in anthropometric indicators among urban women between 2009 and 2012; (c) examine associations between household and individual characteristics and overweight and obesity; and (d) examine relationships between body mass index (BMI), abdominal obesity, and inflammation. We analysed data from a nationally representative survey conducted in 3 geographic strata (North, South, and Yaoundé/Douala) in Cameroon in 2009 and a survey in Yaoundé/Douala in 2012. Participants selected for this analysis were nonpregnant women, ages 15–49 years (n = 704 in 2009; n = 243 in 2012). In 2009, ~8% of women were underweight (BMI < 18.5) and 32% overweight or obese (BMI ≥ 25.0). Underweight was most common in the North (19%) and overweight and obesity in the South (40%) and Yaoundé/Douala (49%). Prevalence of BMI ≥ 25.0 in Yaoundé/Douala did not differ in 2012 compared with 2009 (55.5% vs. 48.7%; P = 0.16). Residence in urban areas, greater maternal age, and TV ownership were independently related to overweight and obesity in national and stratified analyses. In Yaoundé/Douala in 2012, 48% (waist‐to‐hip ratio > 0.85) to 73% (waist circumference > 80 cm) had abdominal obesity. Body mass index was positively associated with abdominal obesity and inflammation. Though causal inferences cannot be drawn, these findings indicate population subgroups at greatest risk for overweight and associated health consequences in Cameroon. [ABSTRACT FROM AUTHOR]

As infectious disease control programs achieve increasing success, further reductions in child mortality in low- and middle-income countries (LMICs)will require focused prevention strategies for birth defects and other noninfectious diseases.Neural tube defects (NTDs) can cause early death or lifelong disability. Preventing NTDs provides a feasible, significant opportunity to decrease the toll of birth defects and contribute to further reducing child mortality globally. The Micronutrient Forum convened a technical consultation on Folate Status in Women and Neural Tube Defects Prevention to develop a roadmap to inform and prioritize investments in NTD prevention in LMICs; help guide implementation efforts in terms of the feasibility of interventions and the potential for acceleration; and identify research and knowledge gaps. Here, we describe the impetus for and approach to the consultation and present the conclusions and a framework for developing a roadmap for action to accelerate NTD prevention in LMICs. The framework (1) provides options for action on folate status assessment; (2) outlines a way forward to develop and implement a time-bound global action plan for NTD prevention; and (3) identifies common impediments to NTD prevention, broad strategies to overcome or minimize these impediments, and basic building blocks necessary to accelerate action. [ABSTRACT FROM AUTHOR]

Background Previous reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD. Methods We conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana ( n = 1,023), Malawi ( n = 675 and 1,385), and Burkina Faso ( n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models ( SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD. Results Out of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts. Conclusions Key elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status. [ABSTRACT FROM AUTHOR]

Background: We previously compared the potential effects of different intervention strategies for achieving dietary vitamin A (VA) adequacy. The Lives Saved Tool (LiST) permits estimates of lives saved through VA interventions but currently only considers periodic VA supplements (VASs).Objective: We aimed to adapt the LiST method for estimating the mortality impact of VASs to estimate the impact of other VA interventions (e.g., food fortification) on child mortality and to estimate the number of lives saved by VA interventions in 3 macroregions in Cameroon.Methods: We used national dietary intake data to predict the effects of VA intervention programs on the adequacy of VA intake. LiST parameters of population affected fraction and intervention coverage were replaced with estimates of prevalence of inadequate intake and effective coverage (proportion achieving adequate VA intake). We used a model of liver VA stores to derive an estimate of the mortality reduction from achieving dietary VA adequacy; this estimate and a conservative assumption of equivalent mortality reduction for VAS and VA intake were applied to projections for Cameroon.Results: There were 2217-3048 total estimated VA-preventable deaths in year 1, with 58% occurring in the North macroregion. The relation between effective coverage and lives saved differed by year and macroregion due to differences in total deaths, diarrhea burden, and prevalence of low VA intake. Estimates of lives saved by VASs (the intervention common to both methods) were similar with the use of the adapted method (in 2012: North, 743-1021; South, 280-385; Yaoundé and Douala, 146-202) and the "usual" LiST method (North: 697; South: 381; Yaoundé and Douala: 147).Conclusions: Linking effective coverage estimates with an adapted LiST method permits estimation of the effects of combinations of VA programs (beyond VASs only) on child mortality to aid program planning and management. Rigorous program monitoring and evaluation are necessary to confirm predicted impacts. [ABSTRACT FROM AUTHOR]

Child growth stunting is common in low-income countries, possibly due to insufficient protein intakes. Most previous studies have concluded that children's protein intakes are adequate in relation to estimated requirements, but these studies did not consider issues of protein digestibility and effects of infection on dietary protein utilization. Using an alternative approach to assess the possible role of protein inadequacy in children's growth restriction, the results of 18 intervention trials in which supplementary protein or amino acids were provided to children ages 6-35months and growth outcomes were reviewed. Eight studies conducted in hospitalized children recovering from acute malnutrition found that the recommended protein intake levels for healthy children supported normal growth rates, but higher intakes were needed for accelerated rates of "catch-up" growth. Ten community-based studies did not demonstrate a consistent benefit of supplemental protein on children's growth. However, weaknesses in the study designs limit the conclusions that can be drawn from these studies, and additional appropriately designed trials are needed to answer this question definitively. Recommendations for optimizing future study designs are provided herein. [ABSTRACT FROM AUTHOR]

Background: Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study. Objectives: We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children’s morbidity. Methods: Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13–16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated. Results: Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4±0.4 and 10.1±2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07±0.44) versus Z-Suppl (-0.21±0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9–12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group. Conclusions: Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS. [ABSTRACT FROM AUTHOR]

Background: Few data are available on the effectiveness of large-scale food fortification programs.Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaoundé and Douala, Cameroon.Methods: We conducted representative surveys 2 y before and 1 y after the introduction of fortified wheat flour. In each survey, 10 households were selected within each of the same 30 clusters (n = ∼300 households). Indicators of inflammation, malaria, anemia, and micronutrient status [plasma ferritin, soluble transferrin receptor (sTfR), zinc, folate, and vitamin B-12] were assessed among women aged 15-49 y and children 12-59 mo of age.Results: Wheat flour was consumed in the past 7 d by ≥90% of participants. Postfortification, mean total iron and zinc concentrations of flour samples were 46.2 and 73.6 mg/kg (target added amounts were 60 and 95 mg/kg, respectively). Maternal anemia prevalence was significantly lower postfortification (46.7% compared with 39.1%; adjusted P = 0.01), but mean hemoglobin concentrations and child anemia prevalence did not differ. For both women and children postfortification, mean plasma concentrations were greater for ferritin and lower for sTfR after adjustments for potential confounders. Mean plasma zinc concentrations were greater postfortification and the prevalence of low plasma zinc concentration in women after fortification (21%) was lower than before fortification (39%, P < 0.001); likewise in children, the prevalence postfortification (28%) was lower than prefortification (47%, P < 0.001). Mean plasma total folate concentrations were ∼250% greater postfortification among women (47 compared with 15 nmol/L) and children (56 compared with 20 nmol/L), and the prevalence of low plasma folate values was <1% after fortification in both population subgroups. In a nonrepresentative subset of plasma samples, folic acid was detected in 77% of women (73% of those fasting) and 93% of children. Mean plasma and breast-milk vitamin B-12 concentrations were >50% greater postfortification.Conclusion: Although the pre-post survey design limits causal inference, iron, zinc, folate, and vitamin B-12 status increased among women and children in urban Cameroon after mandatory wheat flour fortification. [ABSTRACT FROM AUTHOR]

Information on the etiology of anemia is necessary to design effective anemia control programs. Our objective was to measure the prevalence of inherited hemoglobin disorders (IHD) in a representative sample of children in urban Cameroon, and examine the relationships between IHD and anemia. In a cluster survey of children 12-59 months of age (n = 291) in Yaoundé and Douala, we assessed hemoglobin (Hb), malaria infection, and plasma indicators of inflammation and micronutrient status. Hb S was detected by HPLC, and α+thalassemia (3.7 kb deletions) by PCR. Anemia (Hb < 110 g/L), inflammation, and malaria were present in 45%, 46%, and 8% of children. A total of 13.7% of children had HbAS, 1.6% had HbSS, and 30.6% and 3.1% had heterozygous and homozygous α+thalassemia. The prevalence of anemia was greater among HbAS compared to HbAA children (60.3 vs. 42.0%, p = 0.038), although mean Hb concentrations did not differ, p = 0.38). Hb and anemia prevalence did not differ among children with or without single gene deletion α+thalassemia. In multi-variable models, anemia was independently predicted by HbAS, HbSS, malaria, iron deficiency (ID; inflammation-adjusted ferritin <12 µg/L), higher C-reactive protein, lower plasma folate, and younger age. Elevated soluble transferrin receptor concentration (>8.3 mg/L) was associated with younger age, malaria, greater mean reticulocyte counts, inflammation, HbSS genotype, and ID. IHD are prevalent but contribute modestly to anemia among children in urban Cameroon. [ABSTRACT FROM AUTHOR]

Background: Previous research indicates that young children in low-income countries (LICs) generally consume greater amounts of protein than published estimates of protein requirements, but this research did not account for protein quality based on the mix of amino acids and the digestibility of ingested protein.Objective: Our objective was to estimate the prevalence of inadequate protein and amino acid intake by young children in LICs, accounting for protein quality.Methods: Seven data sets with information on dietary intake for children (6-35 mo of age) from 6 LICs (Peru, Guatemala, Ecuador, Bangladesh, Uganda, and Zambia) were reanalyzed to estimate protein and amino acid intake and assess adequacy. The protein digestibility-corrected amino acid score of each child's diet was calculated and multiplied by the original (crude) protein intake to obtain an estimate of available protein intake. Distributions of usual intake were obtained to estimate the prevalence of inadequate protein and amino acid intake for each cohort according to Estimated Average Requirements.Results: The prevalence of inadequate protein intake was highest in breastfeeding children aged 6-8 mo: 24% of Bangladeshi and 16% of Peruvian children. With the exception of Bangladesh, the prevalence of inadequate available protein intake decreased by age 9-12 mo and was very low in all sites (0-2%) after 12 mo of age. Inadequate protein intake in children <12 mo of age was due primarily to low energy intake from complementary foods, not inadequate protein density.Conclusions: Overall, most children consumed protein amounts greater than requirements, except for the younger breastfeeding children, who were consuming low amounts of complementary foods. These findings reinforce previous evidence that dietary protein is not generally limiting for children in LICs compared with estimated requirements for healthy children, even after accounting for protein quality. However, unmeasured effects of infection and intestinal dysfunction on the children's protein requirements could modify this conclusion. [ABSTRACT FROM AUTHOR]

Vitamin A (VA) fortification of cooking oil is considered a cost-effective strategy for increasing VA status, but few large-scale programs have been evaluated. We conducted representative surveys in Yaoundé and Douala, Cameroon, 2 years before and 1 year after the introduction of a mandatory national program to fortify cooking oil with VA. In each survey, 10 different households were selected within each of the same 30 clusters (n = ~300). Malaria infection and plasma indicators of inflammation and VA (retinol-binding protein, pRBP) status were assessed among women aged 15-49 years and children aged 12-59 months, and casual breast milk samples were collected for VA and fat measurements. Refined oil intake was measured by a food frequency questionnaire, and VA was measured in household oil samples post-fortification. Pre-fortification, low inflammation-adjusted pRBP was common among children (33% <0.83 µmol/L), but not women (2% <0.78 µmol/L). Refined cooking oil was consumed by >80% of participants in the past week. Post-fortification, only 44% of oil samples were fortified, but fortified samples contained VA concentrations close to the target values. Controlling for age, inflammation, and other covariates, there was no difference in the mean pRBP, mean breast milk VA, prevalence of low pRBP, or prevalence of low milk VA between the pre- and post-fortification surveys. The frequency of refined oil intake was not associated with VA status indicators post-fortification. In sum, after a year of cooking oil fortification with VA, we did not detect evidence of increased plasma RBP or milk VA among urban women and preschool children, possibly because less than half of the refined oil was fortified. The enforcement of norms should be strengthened, and the program should be evaluated in other regions where the prevalence of VA deficiency was greater pre-fortification. [ABSTRACT FROM AUTHOR]

Millions of children in low-income and middle-income countries falter in linear growth and neurobehavioral development early in life. This faltering may be caused by risk factors that are associated with both growth and development, such as insufficient dietary intake and infection in infancy. Alternatively, these risk factors may be indicative of an environment that constrains both linear growth and development through different mechanisms. In a cluster-randomized trial in Burkina Faso, we previously found that provision of lipid-based nutrient supplements plus malaria and diarrhoea treatment from age 9 to 18 months resulted in positive effects of ~0.3 standard deviation on length-for-age z-score (LAZ) and of ~0.3 standard deviation on motor, language and personal-social development scores at age 18 months. In this paper, we examined whether the effect of the intervention on developmental scores was mediated by the effect on LAZ, or, alternatively, whether the intervention had independent effects on growth and development. For motor, language, and personal-social z-scores, the effect of the intervention decreased from 0.32 to 0.21, from 0.33 to 0.27 and from 0.35 to 0.29, respectively, when controlling for change in LAZ from 9 to 18 months. All effects remained significant. These results indicate that the intervention had independent positive effects on linear growth and development, suggesting that these effects occurred through different mechanisms. © 2016 John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Background: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC).Methods: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 μg of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation.Results: At baseline, 35% of children had low adjusted pZC (<65 μg/dL), 93% were anemic (Hb <110 g/L), 25% had low adjusted pF (<12 μg/L), 90% had high adjusted sTfR (>8.3 mg/L) and 47% had low adjusted RBP (<0.94 μmol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 μmol/L vs. 0.86 μmol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034).Conclusions: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC.Trial Registration: NCT00944281 (July 21, 2009). [ABSTRACT FROM AUTHOR]

Background: Assessment of high-dose vitamin A supplementation (VAS) coverage often relies on postevent coverage (PEC) surveys, but the validity of these methods has rarely been evaluated.Objectives: To assess reported VAS coverage and factors associated with missed coverage and to investigate the reliability of the results.Methods: During a cross-sectional survey, 10 454 caregivers of children <27 months old were asked whether their child had received VAS in the past 6 months. During a 48-week longitudinal study of 6232 children 6 to 30 months old, caregivers were asked every 4 weeks if their child had received VAS in the past 4 weeks.Results: The cross-sectional study showed that 94.4% (95% confidence interval [CI]: 93.8%, 94.9%) of eligible children 6 to 26 months of age reportedly received VAS in the previous 6 months, as did 85.8% (CI: 84.5%, 87.2%) of ineligible, 0 to 5 months old children. The longitudinal study showed that 81.6% of children surveyed within 4 weeks following a VAS campaign reportedly received VAS during the campaign and 13.4% of caregivers incorrectly reported receiving VAS when no campaign had actually occurred. False-positive reporting was more likely when oral polio vaccine (OPV) was distributed during the reporting period (20.6% vs 5.4%; P < .001). Showing a photo of OPV during the interview reduced the odds ratio (OR) of false-positive reports (OR = 0.7 [0.6-0.8]).Conclusions: The PEC surveys should include children outside the target age to assess targeting efficiency, and pictures of both VAS and oral vaccines distributed during the same period should be shown during interviews to enhance reporting accuracy. [ABSTRACT FROM AUTHOR]

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

Background: Vitamin A supplementation (VAS) among children 6 to 59 months of age reduces vitamin A deficiency (VAD)-related mortality. Child health days (CHDs) only reach an estimated 16.7% of children at exactly 6 months, leaving uncovered children at risk of VAD-related mortality; similarly, VAS provided at 9 months of age with measles-containing vaccine leaves infants unprotected for 3 months.Objective: Using data from sub-Saharan Africa, we estimated the mortality benefits and safety of providing VAS at age 6 months, compared to delivery through CHDs and at 9 months.Methods: We modeled VAS-preventable mortality benefits at 6 months as a function of published VAS effect sizes, intervention coverage, and proportion of infant deaths occurring between 6 and 11 months. To evaluate safety, we modeled the effect of different VAS coverage scenarios on maximum hepatic vitamin A concentrations (HVACs).Results: VAS linked to a 6-month visit could reduce infant mortality by an additional 1.95 (95% confidence interval [CI]: 1.38-2.52) and 1.63 (95% CI: 1.15-2.11) percentage points compared to VAS through CHDs and at 9 months, respectively. The HVAC models indicate that VAS at 6 months is safe even in the presence of a second VAS dose 1 month later and other food-based vitamin A control strategies.Conclusion: Advancing the first VAS dose to 6 months should be considered in settings where VAS is currently given first at 9 months. A 6-month VAS dose should also be considered in settings where VAS is delivered through CHDs. VAS delivery at 6 months could also serve as a platform to deliver other high-impact interventions. [ABSTRACT FROM AUTHOR]

Background: Vitamin A (VA) deficiency (VAD) is still a concern in many parts of the world, and multiple intervention strategies are being implemented to reduce the prevalence of VAD and associated morbidity and mortality. Because some individuals within a population may be exposed to multiple VA interventions, concerns have been raised about the possible risk of hypervitaminosis A.Objectives: A consultative meeting was held in Vienna, Austria, in March 2014 to (1) review current knowledge concerning the safety and effectiveness of large-scale programs to control VAD, (2) develop a related research agenda, and (3) review current available methods to assess VA status and risk of hypervitaminosis A.Methods: Multiple countries were represented and shared their experiences using a variety of assessment methods, including retinol isotope dilution (RID) techniques. Discussion included next steps to refine assessment methodology, investigate RID limitations under different conditions, and review programmatic approaches to ensure VA adequacy and avoid excessive intakes.Results: Fortification programs have resulted in adequate VA status in Guatemala, Zambia, and parts of Cameroon. Dietary patterns in several countries revealed that some people may consume excessive preformed VA from fortified foods.Conclusion: Additional studies are needed to compare biomarkers of tissue damage to RID methods during hypervitaminosis A and to determine what other biomarkers can be used to assess excessive preformed VA intake. [ABSTRACT FROM AUTHOR]

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

Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes and proteins and biomarkers of oxidative stress, inflammation, or DNA damage. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess the impact of providing small-quantity lipid-based nutrient supplements (SQ-LNS) on the I status of young Burkinabe children. In total, thirty-four communities were assigned to intervention (IC) or non-intervention cohorts (NIC). IC children were randomly assigned to receive 20 g lipid-based nutrient supplements (LNS)/d containing 90 µg I with 0 or 10 mg Zn from 9 to 18 months of age, and NIC children received no SQ-LNS. All the children were exposed to iodised salt through the national salt iodization programme. Spot urinary iodine (UI), thyroid-stimulating hormone (TSH) and total thyroxine (T4) in dried blood spots as well as plasma thyroglobulin (Tg) concentrations were assessed at 9 and 18 months of age among 123 IC and fifty-six NIC children. At baseline and at 18 months, UI, TSH and T4 did not differ between cohorts. Tg concentration was higher in the NIC v. IC at baseline, but this difference did not persist at 18 months of age. In both cohorts combined, the geometric mean of UI was 339·2 (95 % CI 298·6, 385·2) µg/l, TSH 0·8 (95 % CI 0·7, 0·8) mU/l, T4 118 (95 % CI 114, 122) nmol/l and Tg 26·0 (95 % CI 24·3, 27·7) µg/l at 18 months of age. None of the children had elevated TSH at 18 months of age. Marginally more children in NIC (8·9 %) had low T4 (<65 nmol/l) compared with the IC (1·6 %) (P=0·052). Salt samples (n 106) were collected from randomly selected participants and assessed by titration for I content, which was on average 37 (sd 15) ppm (range 5–86 ppm); 95 % of households had adequately iodised salt (I>15 ppm). A reduction of SQ-LNS I content could be considered in settings with similarly successful salt iodisation programmes. [ABSTRACT FROM PUBLISHER]