Search

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]

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]

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]

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]

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.

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]

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]

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]

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]

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]

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]

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]

Background: Representative data on folate and vitamin B-12 dietary intake and status in low-income countries are rare, despite the widespread adoption of folic acid fortification.Objective: The purpose of this study was to evaluate folate and vitamin B-12 intake, status, and risk factors for deficiency before implementation of a national fortification program in Cameroon.Methods: A nationally representative cross-sectional cluster survey was conducted in 3 ecologic zones of Cameroon (South, North, and the 2 largest cities, Yaoundé/Douala), and information on dietary intake was collected from 10 households in each of 30 randomly selected clusters per zone. In a subset of women and their 12- to 59-mo-old children (n = 396 pairs), plasma folate and vitamin B-12, as well as breast milk vitamin B-12, were analyzed.Results: Vitamin B-12 and folate dietary intake patterns and plasma concentrations were similar for women and children. In the subsample, 18% and 29% of women and 8% and 30% of children were vitamin B-12 (≤ 221 pmol/L) and folate (< 10 nmol/L) deficient, respectively. Mean dietary folate ranged from 351 μg dietary folate equivalents/d in the North to 246 μg dietary folate equivalents/d in Yaoundé/Douala; plasma folate was negatively associated with socioeconomic status (P = 0.001). Plasma vitamin B-12 deficiency was similar in the South and North, 29% and 40%, respectively, but was only 11% in Yaoundé/Douala, and was positively associated with socioeconomic status. Mean breast milk vitamin B-12 was statistically significantly lower in the North (101 pmol/L) than in the South (296 pmol/L) or Yaoundé/Douala (349 pmol/L).Conclusions: Folate intake and status are inadequate among women and young children in Yaoundé/Douala, whereas low vitamin B-12 intake and status are more common in poor and rural areas, especially in the North. Different strategies may be needed to control deficiency of these nutrients in different regions of Cameroon. [ABSTRACT FROM AUTHOR]

Background: Moderate acute malnutrition (MAM), defined as weight-for-length z score between 23 and 22 or midupper arm circumference between 11.5 and 12.5 cm, affects ~33 million children aged < 5 y worldwide. Objective: The objective was to compare the effects of 4 dietary supplements for the treatment of MAM. Design: Twelve community health centers in rural Mali were randomly assigned to provide to 1264 MAM children aged 6-35 mo one of 4 dietary supplements containing ~500 kcal/d for 12 wk: 1) ready-to-use, lipid-based supplementary food (RUSF); 2) special corn-soy blend (CSB++); 3) locally processed, fortified flour (Misola); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). Results: In total, 1178 children (93.2%) completed the study. The adjusted mean (95% CI) change in weight (kg) from baseline was greater with RUSF than with the locally processed blends and was intermediate with CSB++ [1.16 (1.08, 1.24) for RUSF, 1.04 (0.96, 1.13) for CSB++, 0.91 (0.82, 0.99) for Misola, and 0.83 (0.74, 0.92) for LMF; P < 0.001]. For length change, RUSF and CSB++ differed significantly from LMF. Sustained recovery rates were higher with RUSF (73%) than with Misola (61%) and LMF (58%), P < 0.0001; CSB++ recovery rates (68%) did not differ from any of the other groups. Conclusions: RUSF was more effective, but more costly, than other dietary supplements for the treatment of MAM; CSB++ yielded intermediate results. The benefits of treatment should be considered in relation to product costs and availability. This trial was registered at clinicaltrials.gov as NCT01015950. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The WHO recommends assessing food and nutrient intakes to design food-fortification programs, but nationally representative dietary data are seldom available in low-income countries. Objective: Prior to initiation of food fortification in Cameroon, we measured intake of vitamin A (VA) and fortifiable foods (vegetable oil, sugar, wheat flour, and bouillon cube) to simulate the effects of fortification with different foods and VA amounts on prevalence of inadequate and excessive VA intake. Methods: Twenty-four-hour recalls were conducted among 912 women and 883 children (with duplicates in a subset) in a nationally representative cluster survey stratified by region (North, South, Yaounde/Douala). Usual intake distributions were estimated by the National Cancer Institute method. Results: Nationally, 53% of women had a usual intake of <500 pig retinol activity equivalents/d, and 59% of nonbreastfeeding children had an intake of <210 µg retinol activity equivalents/d, although VA intake varied by region. The current fortification program (12 mg/kg VA in oil) would decrease the prevalence of inadequate intakes to 35% among both women and children, without increasing the proportion with retinol intakes >3000 µg/d among women or >600 µg/d among children. However, inadequate VA intake would remain >50% in the North, where VA deficiency was most common. Increasing VA in oil or fortifying a second food (sugar, wheat flour, or bouillon cube) would further decrease the prevalence of inadequate intakes, but, depending on the food vehicle and region, would also increase the prevalence of retinol intakes above the tolerable upper intake level, mainly among children. Conclusions: The current food-fortification program can be expected to improve dietary VA adequacy without increasing the risk of excessive intake among women and children in Cameroon. Modifications to the program must balance the potential to further increase VA intake with the risk of excessive intake among children. [ABSTRACT FROM AUTHOR]

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status and the risk of zinc deficiency in populations. However, the relation between PZC and clinical signs of zinc deficiency remains uncertain. These analyses were conducted to evaluate the relation between PZC and clinical signs of zinc deficiency and to determine a cutoff for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Electronic bibliographic searches were conducted of literature indexed in PubMed, Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies in adults and case reports in children and adults (ages <1 mo-43 y) with acrodermatitis enteropathica (AE). Data extracted included demographic characteristics, PZCs, and the presence or absence of clinical signs likely associated with zinc deficiency (e.g., dermatitis, diarrhea). Mean PZC was significantly lower among adults consuming severely zinc-restricted diets (<1 mg Zn/d) who developed clinical signs compared with those who remained asymptomatic (36.0 ± 16.8 vs. 67.9 ± 13.3 µg/dL, P< 0.034). Likewise, patients with AE had a lower mean PZC when symptomatic compared with post-treatment PZC when they were asymptomatic (38.2 ± 20.7 vs. 102 ± 34.7 µg/dL, P < 0.01). Among individuals with restricted dietary zinc intake, PZC predicted clinical signs with 82% sensitivity and 92% specificity when using a cutoff of 50 µg/dL. Among individuals with AE, PZC predicted clinical signs with 80% sensitivity and 89% specificity when applying a cutoff of 50 µg/dL. These analyses demonstrate a clear relation between PZC and the presence of clinical signs associated with zinc deficiency among presumably healthy individuals undergoing periods of dietary zinc restriction, as well as in individuals with AE, further validating the usefulness of PZC as a biomarker of severe zinc deficiency. [ABSTRACT FROM AUTHOR]

Information is needed on breast milk zinc concentration and amount of zinc transferred to the infant in relation to the time since birth for both appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) infants. Breast milk zinc concentration and total milk volume were measured among mothers of AGA and SGA infants, using deuterium oxide "dose-to-mother" tracer technique and plasma zinc concentrations of mothers and infants. Forty-six mother-infant pairs (20 AGA and 26 SGA infants) were recruited from a low-income community in Bangladesh. Each mother-infant pair was studied 3 times: at 4, 12, and 24 wk postpartum. During each round, 2-wk studies of breast milk transfer were performed, using deuterium oxide dose-to-mother tracer technique. Breast milk samples were collected on days 1 and 5 of each round to determine milk zinc concentration. Mean ± SD birth weight and length were 3.02 ± 0.2 kg and 0.482 ± 0.012 m, respectively, for AGA and 2.34 ± 0.20 kg and 0.462 ± 0.011 m, respectively, for SGA infants, and both variables were different between groups (birth weight, P < 0.001; length, P < 0.001). Breast milk intake increased gradually with time postpartum in both groups. Breast milk zinc concentration decreased with increasing infant age (P < 0.001) but did not differ for mothers of AGA and SGA infants. Breast milk zinc transfer decreased significantly with age in both groups (P < 0.001) but did not differ by birth-weight category. Breast milk zinc concentration among Bangladeshi mothers and patterns of change at 24 wk were similar to those of wealthier countries, and there was no relation between infant birth-weight category and milk zinc concentration or transfer. This trial was registered at www.clinicaltrials.gov as NCT01728766 [ABSTRACT FROM AUTHOR]

Breastmilk vitamin A (BMVA) has been proposed as an indicator of population vitamin A status but has rarely been applied in large-scale surveys or compared with conventional vitamin A biomarkers. We assessed the prevalence of, and risk factors for, low BMVA and its relation to vitamin A intake, plasma retinol-binding protein (pRBP), and markers of inflammation in a national survey in Cameroon. We randomly selected 30 clusters in each of 3 strata (South, North, and Cities). Casual milk samples were collected from approximately 5 women per cluster (n = 440). pRBP, plasma C-reactive protein (pCRP), plasma α1-acid glycoprotein (pAGP), and 24-h vitamin A intake were assessed in 10 women aged 15-49 y and 10 children aged 12-59 mo per cluster, including a subset of lactating women (n = 253). Low BMVA was infrequent: 7.2% (95% CI: 4.7, 9.8) of values were <1.05 μmol/L, and 9.3% (95% CI: 5.8, 12.7) were <8 μg/g fat, consistent with the low prevalence of pRBP <0.78 μmol/L among women (< 5%) but lower than the prevalence of pRBP <0.83 μmol/L among children (35%). Risk factors for both low BMVA and pRBP included living in the North and low maternal education. BMVA was positively associated with inflammation-adjusted pRBP among women in the lowest vitamin A intake tertile [<115 μg retinol activity equivalents (RAEs)/d, P < 0.01] but not in the highest tertile (>644 μg RAEs/d, P > 0.4). Controlling for milk fat, BMVA was negatively associated with pCRP (P < 0.02) but not pAGP (P > 0.5). BMVA and pRBP provide similar estimates of vitamin A deficiency prevalence and identify the same risk groups among women in Cameroon, but BMVA underestimates the prevalence of vitamin A deficiency among young children. [ABSTRACT FROM AUTHOR]

Information is needed on zinc absorption from grain cultivars having higher zinc content. Total absorbed zinc (TAZ) from mixed diets containing high-zinc rice (HZnR), conventional rice (CR), or CR plus zinc fortificant (CR+Zn) was measured. Forty-two nonmalnourished preschool-aged children were enrolled in 1 of 2 groups. Using a crossover design, children in group A (n = 22) received for 1 d each a mixed diet containing 150 g CR or HZnR. Children in group B (n = 20) received HZnR on 1 d and CR+Zn on the other day. Fractional zinc absorption (FZA) was measured during each dietary period by using a dual-isotope tracer ratio technique; TAZ was calculated as the product of zinc intake [total dietary zinc (TDZ)] and FZA. TDZ was 3.83, 4.83, and 6.03 mg/d when the children were fed the CR, HZnR, and CR+Zn-containing diets, respectively. Mean FZA from the CR diet was greater than from the HZnR diet (25.1 vs. 20.1%, P < 0.001), and the mean FZA from the CR+Zn diet (18.8%) was less than from both the CR diet (P < 0.001) and the HZn R diet (P = 0.014). The mean TAZ was 0.96 ± 0.16, 0.97 ± 0.18, and 1.13 ± 0.20 mg/d from the CR, HZnR and CR+Zn diets, respectively. TAZ was not different for the CR and HZnR diets (P = 0.99) but was significantly greater from the CR+Zn diet compared with the other 2 diets (P < 0.001). Rice cultivars with higher zinc and/or lower phytate content are needed to increase TAZ by young children consuming this amount of rice. [ABSTRACT FROM AUTHOR]

Available iron status indicators reflect different aspects of metabolism. We compared the prevalence and distribution of iron deficiency (ID) and iron-deficiency anemia (IDA) among Cameroonian women and children, as measured by plasma ferritin, and soluble transferrin receptor concentrations, body iron stores (BIS), and hemoglobin, and evaluated the impact of adjustments for inflammation on these measures. In a nationally representative survey, we randomly selected 30 clusters in each of 3 zones (north, south, and large cities) and 10 households/cluster, each with a child aged 12-59 mo and a woman 15-49 y. Ferritin and BIS were mathematically adjusted for inflammation, using plasma C-reactive protein and α1-acid glycoprotein both as continuous and categorical variables. Inflammation was present in 48.0% of children and 20.8% of women and anemia was diagnosed in 57.6% of children and 38.8% of women. Depending on the iron status indicator applied, the prevalence of ID ranged from 14.2 to 68.4% among children and 11.5 to 31.8% among women, and the prevalence of IDA ranged from 12.0 to 47.4% among children and 9.0 to 19.4% among women; the proportion of anemia associated with ID ranged from 20.8 to 82.3% among children and 23.2 to 50.0% among women. The different iron indicators generally identified similar groups at greatest risk of deficiency, using both conventional and derived cutoffs: younger children, pregnant women, and women and children in the north and rural areas. Research is needed to clarify the relationships between iron status indicators, particularly in the presence of inflammation, to harmonize global data on prevalence of ID. [ABSTRACT FROM AUTHOR]

Documentation of micronutrient intake inadequacies among developing country populations is important for planning interventions to control micronutrient deficiencies. The objective of this study was to quantify micronutrient intakes by young children and their primary female caregivers in rural Bangladesh. We measured 24-h dietary intakes on 2 nonconsecutive days in a representative sample of 480 children (ages 24-48 mo) and women in 2 subdistricts of northern Bangladesh by using 12-h weighed food records and subsequent 12-h recall in homes. We calculated the probability of adequacy (PA) of usual intakes of 11 micronutrients and an overall mean PA, and evaluated dietary diversity by counting the total number of 9 food groups consumed. The overall adequacy of micronutrient intakes was compared to dietary diversity scores using correlation and multivariate regression analyses. The overall mean prevalence of adequacy of micronutrient intakes for children was 43% and for women was 26%. For children, the prevalence of adequate intakes for each of the 11 micronutrients ranged from a mean of 0 for calcium to 95% for vitamin B-6 and was <50% for iron, calcium, riboflavin, folate, and vitamin B-12. For women, mean or median adequacy was <50% for all nutrients except vitamin B-6 and niacin and was <1% for calcium, vitamin A, riboflavin, folate, and vitamin B-12. The mean PA (MPA) was correlated with energy intake and dietary diversity, and multivariate models including these variables explained 71-76% of the variance in MPA. The degree of micronutrient inadequacy among young children and women in rural Bangladesh is alarming and is primarily explained by diets low in energy and little diversity of foods. [ABSTRACT FROM AUTHOR]

We assessed the effect of daily consumption of orange-fleshed sweet potatoes (OFSP), with or without added fat, on the vitamin A (VA) status of Bangladeshi women with low initial VA status. Women (n = 30/group) received one of the following for 6 d/wk over 10 wk: 1) 0 µg retinol activity equivalents (RAE)/d as boiled white-fleshed sweet potatoes (WFSP) and a corn oil capsule, 2) 600 µg RAE/d as boiled OFSP and a corn oil capsule, 3) fried OFSP and a corn oil capsule, or 4) boiled WFSP and a retinyl palmitate capsule in addition to their home diets. Plasma concentrations of retinol and &bgr;-carotene and total body VA pool size were assessed before and after the 60-d intervention. Initial and final plasma retinol concentrations (mean ± SD) were 0.75 ± 0.18/Amol/Land 0.84 ± 0.19µmol/L, respectively (P= 0.31); final means did not differ by group. Initial and final plasma &bgr;-carotene concentrations were 0.10 ± 00 µmol/L and 0.18 ± 0.09 µmol/L, respectively (P < 0.0001); final mean plasma &bgr;-carotene concentrations were higher in groups that received OFSP (P< 0.0001), and final mean plasma &bgr;-carotene was marginally higher in the group that received fried OFSP compared with boiled OFSP (P = 0.07). Initial and final total body VA pool sizes were 0.060 ± 0.047 mmol and 0.091 ± 0.070 mmol, respectively (P= 0.05, n = 110) and did not differ by group. Despite an increase in plasma &bgr;-carotene concentration, the impact of OFSP on VA status appears to be limited in Bangladeshi women residing in a resource-poor community. [ABSTRACT FROM AUTHOR]

In preparation for a proposed large-scale food fortification program. in Cameroon, we completed a nationally representative, cross-sectional, cluster survey to assess the consumption patterns of four potentially fortifiable foods (refined vegetable oil, wheat flour, sugar, and bouillon cube) by women and children. Thirty clusters were randomly chosen in each of three ecologic zones (south, north, and large cities) and 10 households IHH( per cluster were selected, each with a child 12-59 mo old and a primary female caregiver 15-49 y old (total 1002 HH). Blood samples were collected and food consumption was assessed by FFQ and 24-h dietary recall. Anemia (39% of women, 58% of children) and deficiencies of iron (15-32%, 21-70%), zinc (77%, 70%), vitamin A (22%, 35%), and vitamin B-12 (28%, 27%l were common, especially in the north and among HH with lower socio-economic status (SES). Oil was consumed by 54% of HH, whereas >75% of HH consumed wheat flour, sugar, and bouillon cube. For most foods, coverage was lower among HH with lower SES. On average, oil, wheat flour, and sugar were consumed once per day and bouillon cube was consumed twice per day. Median intakes of oil, wheat flour, sugar, and bouillon cube (among consumers) were 19.8, 79.4, 30.0, and 1.9 g/d for women and 12.0, 49.4, 19.4, and 0.9 g/d for children, respectively. Food consumption patterns of high risk population subgroups must be considered, along with technical feasibility and cost, for the selection of appropriate vehicles for food fortification. [ABSTRACT FROM AUTHOR]

Variation in the relationship between plasma retinol-binding protein (RBP) and retinol (ROH) has implications for vitamin A (VA) status assessment using RBP. Our objectives were to identify factors affecting the RBP:ROH relationship and to derive and evaluate population-specific RBP cutoffs for VA deficiency (VAD) in Cameroon. Plasma RBP, C-reactive protein (CRP), α1-acid-glycoprotein (AGP), and ROH concentrations were compared in a subsample of women 15-49 y (n = 121) and children 12-59 mo (n = 123) included in a national survey conducted in 2009. Plasma RBP and ROH were highly correlated (r = 0.94 for women; r = 0.96 for children; P < 0.001). Pregnancy and lactation altered the RBP:ROH relationship in women, but obesity, elevated CRP and AGP, age, and VA status did not. Among children, age altered the RBP:ROH relationship, but sex, stunting, VA status, and elevated CRP and AGP did not. Cutoffs for VAD derived using regression analysis were <1.17 μmol RBP/L for women (corresponding to <1.05 μmol ROH/L) and <0.83 μmol RBP/L for children (corresponding to <0.70 μmol ROH/L). The sensitivity and specificity of derived cutoffs were 81.8 and 93.0% for women and 94.7 and 88.9% for children, respectively. The infection-adjusted prevalence of low VA status (<1.17 μmol RBP/L) was 21.9% (95% CI = 18.7-25.0%) among women. Among children, the infection-adjusted prevalence of VAD (<0.83 μmol RBP/L) was 35.0% (95% CI = 31.1-39.0%). In conclusion, VAD remains a public health problem in Cameroon. The RBP:ROH relationship should be considered in surveys using RBP to assess VA status, and use of population-specific cutoffs may be advisable. [ABSTRACT FROM AUTHOR]

The responsiveness of plasma zinc concentration to zinc fortification is uncertain. Our objective in this study was to determine whether plasma zinc concentration changes in response to consuming zinc-fortified foods or liquid zinc supplements. We conducted a 4-wk double-blind, randomized trial among 132 healthy Senegalese men ≥ 18 y. Participants received 1 of 4 interventions: 1) (control) 200 gJd of wheat bread fortified with iron and folic acid, but not zinc, and a liquid multivitamin supplement without zinc between meals; 2) (zinc supplement) the same bread and the same multivitamin supplement with 15 mg zinc as ZnSO4 added; 3) (moderate zinc fortification) the same bread cofortified with 7.5 mg zinc as ZnO and the same multivitamin supplement without zinc; or 4) (high zinc fortification) the same bread cofortified with 15 mg zinc as ZnO and the same multivitamin supplement without zinc. Fasting blood samples were collected twice at baseline and at d 15 and 29 of the intervention. There was no significant interaction between group and study day IP = 0.11). However, at d 15, the mean change in plasma zinc concentration in the zinc-supplemented group was greater than in the placebo and fortification groups (≈0.72 μmol/L vs. -0.09 to 0.03 μmol/L; P = 0.05). At d 29 there were no significant group-wise differences. Across all time points, the zinc-supplemented group was the only group where plasma zinc concentration increased from baseline (P = 0.006). These results suggest that plasma zinc concentration may not be a sufficiently sensitive indicator to evaluate short-term responses to zinc fortification. [ABSTRACT FROM AUTHOR]

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

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

The estimated average requirement (EAR) for vitamin A (VA) of adult males is based on the amount of dietary VA required to maintain adequate function and provide a modest liver VA reserve (0.07 μmol/g). In the present study, the paired-deuterated retinol dilution technique was used to estimate changes in VA pool size in Bangladeshi men from low-income, urban neighborhoods who had small initial VA pool sizes (0.059 ± 0.032 mmol, or 0.047 ± 0.025 μmol/g liver; n = 16). The men were supplemented for 60 d with 1 of 8 different levels of dietary VA, ranging from 100 to 2300 μg/d (2 men/dietary VA level). VA pool size was estimated before and after the supplementation period. The mean change (plus or minus) in VA pool size in the men was plotted against their corresponding levels of daily VA intake and a regression line was fit to the data. The level of intake at which the regression line crossed the x-axis (where estimates of VA pool size remained unchanged) was used as an estimate of the EAR. A VA intake of 254-400 μg/d was sufficient to maintain a small VA pool size (0.059 ± 0.032 mmol( in the Bangladeshi men, corresponding to a VA intake of 362-571 μg/d for a 70-kg U.S. man, which is lower than their current EAR of 625 μg/d. The data suggest that the paired-deuterated retinol dilution technique could be used for estimating the EAR for VA for population subgroups for which there are currently no direct estimates. [ABSTRACT FROM AUTHOR]

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

Rural Bangladeshi populations have a high risk of zinc deficiency due to their consumption of a predominantly rice-based diet with few animal-source foods. Breeding rice for higher zinc content would offer a sustainable approach to increase the populations zinc intakes. The objectives of the study were to quantify usual rice and zinc intakes in young children and their adult female primary caregivers and to simulate the potential impact of zinc-biofortified rice on their zinc intakes. We measured dietary intake in a representative sample of 480 children (ages 24-48 mo) and their female caregivers residing in 2 rural districts of northern Bangladesh. Dietary intakes were estimated by 12-h weighed records and 12-h recall in homes on 2 nonconsecutive days. Serum zinc concentrations were determined in a subsample of children. The median (25th, 75th percentilel rice intakes of children and female caregivers were 134 (99, 1721 and 420 (365, 4761 g raw weight/d, respectively. The median zinc intakes were 2.5 (2.1, 2.91 and 5.4 14.8, 6.11 mg/d in children and women, respectively. Twenty-four percent of children had low serum zinc concentrations (<9.9 μmol/L) after adjusting for elevated acute phase proteins. Rice was the main source of zinc intake, providing 49 and 69% of dietary zinc to children and women, respectively. The prevalence of inadequate zinc intakes was high in both the children 122%) and women 173-100%). Simulated increases in rice zinc content to levels currently achievable through selective breeding decreased the estimated prevalence of inadequacy to 9% in children and 20-85% in women, depending on the assumptions used to estimate absorption. Rural Bangladeshi children and women have inadequate intakes of zinc. Zinc biofortification of rice has the potential to markedly improve the zinc adequacy of their diets. [ABSTRACT FROM AUTHOR]

A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children < 5 y of age. To explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 μmol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 μmol; 5 mg), which was used to estimate VA pool size, in 3- to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of [14C2]-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify 14C in stool and urine. Estimates of absorption, retention, and the urinary elimination rate (UER) were 83.8 ± 7.1%, 76.3 ± 6.7%, and 1.9 ± 0.6%/d, respectively, for the HD-VA supplement and 76.5 ± 9.5%, 71.1 ± 9.4%, and 1.8 ± 1.2%/d, respectively, for the SI-labeled VA. Mean estimates of absorption, retention, and the UER did not differ by size of the VA dose administered. Estimated absorption and retention were negatively associated with reported fever (r = -0.83; P = 0.011). The HD-VA supplement and SI-labeled VA were adequately absorbed, retained, and utilized in apparently healthy Zambian preschool-age boys; absorption and retention may be affected by recent fever. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: No studies have examined the independent effects of current and longer-term dietary zinc intakes on zinc absorption. Objective: We determined the effects of current compared with longer-term zinc intake on fractional zinc absorption (FZA). Design:Westudied 9 men whose usual zinc intakes were>11 mg/d. FZA was measured at baseline, depletion (0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and repletion (11 mg Zn/d for 4 wk with 20 mg supplemental Zn/d for first 7 d). During 2 successive days after each dietary period, subjects consumed either adequate-zinc meals (11 mg Zn/d) with a zinc stable isotope tracer for 1 d, followed by low-zinc meals (4 mg Zn/d) with zinc tracer, or vice versa. Five days after oral dosing, a zinc tracer was infused intravenously. FZA was measured with the use of a modified double isotope tracer ratio method with urine samples collected on days 5-7 and 10-12 of absorption studies. Results: Plasma and urinary zinc did not vary by dietary period. Mean FZA was greater from low-zinc meals than from adequatezinc meals (60.9% ± 13.8% compared with 36.1% ± 8.9%; P < 0.0001), whereas mean total absorbed zinc was greater from adequate-zinc meals than from low-zinc meals (3.60 ± 0.91 compared with 2.48 ± 0.56; P < 0.0001), regardless of the longer-term dietary period. Conclusions: FZA was inversely related to current zinc intake, but there was no detectable effect of longer-term dietary zinc. If longerterm zinc intake does modify FZA, such changes are smaller than those caused by current zinc intake, or they occur only after more severe zinc depletion. [ABSTRACT FROM AUTHOR]

The exact mechanism whereby zinc influences growth is unknown, although it has been postulated that zinc may stimulate appetite and energy intake or enhance fat-free mass (FFM) accrual directly. We compared energy intake, reported appetite, and body composition of 6-to 8-mo-old Peruvian children with initial length-for-age Z-score (LAZ) < -0.5 SD who were randomly assigned to receive daily for 6 mo: 1) 3 mg/d zinc in a liquid supplement; 2) 3 mg/d zinc in a fortified porridge; or 3) no extra zinc in either the supplement or porridge. There were no group-wise differences in changes in dietary energy intakes or body composition or in the prevalence of reported poor appetite. However, among children with an initial LAZ less than the median (-1.1 SD), those who received zinc as a liquid supplement had a 0.41 kg greater increase in FFM than those who did not receive zinc (P < 0.05). We concluded that daily provision of 3 mg of supplemental zinc did not affect energy intake or reported appetite. Among children with initial mild-to-moderate stunting, those who received the zinc supplement had a greater increase in FFM than those who did not receive additional zinc. It is possible that the growth-restricted children were more likely to be zinc deficient and that FFM accrual may be an early growth response to supplemental zinc. Zinc supplements may be more efficacious than the same dose of zinc provided in fortified food; therefore, further research is needed on the optimal level of zinc fortification that will result in improved health outcomes in populations with high rates of zinc deficiency. [ABSTRACT FROM AUTHOR]

Background: It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture. Objective: The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants. Design: We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly. Results: Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables. Conclusions: The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture. [ABSTRACT FROM AUTHOR]

Background: Information is needed to design studies of the effects of complementary feeding regimens on children's intakes of complementary foods (CFs) and breast milk. Objective:We evaluated the effects of varied energy density of CFs on the time until stabilization of dietary intakes and on total daily energy intakes (EIs) and breast-milk intakes. Design: CFs with low [0.4 kcal/g (LD)] and high [1.5 kcal/g (HD)] energy density were fed 3 times/d to 10 children (aged 9-18 mo) during 2 randomly assigned sequences of three 8-d diet periods (HD-LD-HD or LD-HD-LD) along with ad libitum breastfeeding. CF and breast-milk intakes were measured. Results: Intakes of the HD diet and breast milk did not vary by day of period, but intake of the LD diet increased progressively. During days 5-7 of the last 2 diet periods in each sequence, more of the LD than of the HD diet was consumed (752 ± 252 and 439 ± 111 g/d, respectively; P<0.001), but EIs from CFs were greater with theHD diet. Breast-milk consumption was slightly less (192 ± 115 and 234±121 g/d, respectively; P=0.03) but total daily EI was greater (774±175 and 441±85 kcal/d, respectively; P<0.001) during the HD than during the LD diet period. Conclusions: New information on the effects of newly introduced diets on daily intakes of these diets and of breast milk can be used to design future studies. Total daily EIs were greater with the HD diet despite its negative effects on breast-milk intakes. [ABSTRACT FROM AUTHOR]

Background: The effect of breastfeeding on the nutrition of HIV-infected (HIV+) mothers is unknown. Simple, valid methods are needed for body-composition assessment of HIV+ women. Objective: We compared the ability of bioimpedance spectroscopy (BIS) and anthropometry with that of isotope dilution (2H2O) to measure fat-free mass (FFM) and fat mass (FM) in HIV+ and HIV uninfected (HIV-) breastfeeding South African mothers. Design: Total body water (TBW) content of 68 lactating mothers (20 HIV+, 48 HIV-) was measured 10 wk after delivery by using BIS and 2H2O to measure FFM and FM. Anthropometric measurements included body mass index (BMI; in kg/m2), midupper arm circumference (MUAC), and 4 skinfold thicknesses. Results: TBW, FFM, and FM measurements determined by BIS were correlated with 2H2O measurements in HIV+ (r = 0.664, 0.621, and 0.872, respectively; P < 0.01) and HIV- (r = 0.876, 0.868, and 0.932, respectively; P<0.001) mothers. TBW measured by BIS was greater than that measured by the 2H2O method in both HIV+ (1.8 L) and HIV- (1.5 L) women; FM or FFM did not differ significantly by method. BMI, MUAC, and all skinfold-thickness measurements correlated strongly (r > 0.62, P < 0.001) with FM measured by 2H2O in both groups. BMI and MUAC correlated (r> 0.64, P < 0.001) with FFM in HIV- mothers but not in HIV+ mothers. Conclusions: In HIV+and HIV-breastfeeding mothers, BIS provides an estimate of body composition comparable to that obtained with the 2H2Omethod. BMI and MUAC are useful in predicting FM in both groups but are not valid measures of FFM in HIV+ mothers. [ABSTRACT FROM AUTHOR]

We assessed the adequacy of nutrient intakes of 135 rural Bangladeshi breast-fed infants 6-12 mo of age and examined nutritional trade-offs due to possible displacement of breast milk by complementary foods. Observers completed 12-h daytime measurements of breast milk and complementary food intakes; data for the previous 12 h were obtained from maternal recall, yielding estimates of total 24-h intakes. On average, infants were mildly wasted (mean +/- SD weight-for-length Z-score = -0.92 +/- 0.88) and moderately stunted (length-for-age Z-score = -1.49 +/- 0.96). Total energy intakes at 6-8 and 9-12 mo were 88 and 86% of absolute energy requirements (kJ/d), 106 and 105% of requirements per kg body weight, and 97 and 94% of requirements per kg median weight-for-length, respectively. Breast milk contributed 78% of energy intake at 6-8 mo and 75% at 9-12 mo. Mean meal frequency and energy density of complementary foods were generally consistent with recommendations, but only small amounts of food were offered. Nevertheless, only 72% of the food energy offered was consumed. Total energy intake was positively correlated with meal frequency, quantity consumed per meal, and energy intake from breast milk, but not with energy density of complementary foods. Energy intake from complementary foods was inversely related to energy intake from breast milk. The diets fell short of recommended intakes for numerous vitamins and minerals. We conclude that although greater intakes of complementary foods were associated with higher total energy intake, micronutrient intake remained low due to the low micronutrient density of the complementary foods consumed and the partial displacement of breast milk. [ABSTRACT FROM AUTHOR]

Background: Information is needed on the fractional absorption of zinc (FAZ) and absorbed zinc (AZ) during prolonged exposure to zinc-fortified foods. Objective: The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over ≈7 wk. Design: Forty-one stunted, moderately anemic children received daily, at breakfast and lunch, 100 g wheat products fortified with 3 mg Fe (ferrous sulfate) and 0 (group Zn-0), 3 (group Zn-3), or 9 (group Zn-9) mg Zn (zinc sulfate) per 100 g flour. FAZ was measured on days 2-3 and 51-52; meal-specific AZs were calculated as the product of FAZ and zinc intake. Results: For the breakfast and lunch meals combined, mean total zinc intakes were 2.14, 4.72, and 10.04 mg/d in groups Zn-0, Zn-3, and Zn-9, respectively, during the initial absorption studies; mean (±SD) FAZ values were 0.341 ± 0.111, 0.237 ± 0.052, and 0.133 ± 0.041, respectively, on days 2-3 (P < 0.001) and did not change significantly on days 51-52 in the subset of 31 children studied twice. Mean initial AZ was positively related to zinc intake (0.71 ± 0.18, 1.11 ± 0.21, and 1.34 ± 0.47 mg/d, respectively; P < 0.001); final values did not differ significantly from the initial values. Conclusions: AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during ≈7-wk periods of consumption. Although consumption of zinc-fortified foods may reduce FAZ, zinc fortification at the levels studied positively affects total daily zinc absorption, even after nearly 2 mo of exposure to zinc-fortified diets. [ABSTRACT FROM AUTHOR]