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

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)., (© 2022. The Author(s).)

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

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.

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

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

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

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

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

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

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

Background: 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).

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

Objective: Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children., Design, Setting and Populations: This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso., Interventions: Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community., Main Outcomes: Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group., Results: The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively)., Conclusions: Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population., Trial Registration Number: NCT00944281., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unlabelled: Small-quantity lipid-based nutrient supplements (SQ-LNS) are promising home fortification products, but the optimal zinc level needed to improve growth and reduce morbidity is uncertain. We aimed to assess the impact of providing SQ-LNS with varied amounts of zinc, along with illness treatment, on zinc-related outcomes compared with standard care. In a placebo-controlled, cluster-randomized trial, 34 communities were stratified to intervention (IC) or non-intervention cohorts (NIC). 2435 eligible IC children were randomly assigned to one of four groups:1) SQ-LNS without zinc, placebo tablet; 2) SQ-LNS containing 5mg zinc, placebo tablet; 3) SQ-LNS containing 10mg zinc, placebo tablet; or 4) SQ-LNS without zinc and 5mg zinc tablet from 9–18 months of age. During weekly morbidity surveillance, oral rehydration salts were provided for reported diarrhea and antimalarial therapy for confirmed malaria. Children in NIC (n = 785) did not receive SQ-LNS, tablets, illness surveillance or treatment. At 9 and 18 months, length, weight and hemoglobin were measured in all children. Reported adherence was 97 ± 6% for SQ-LNS and tablets. Mean baseline hemoglobin was 89 ± 15g/L. At 18 months, change in hemoglobin was greater in IC than NIC (+8 vs -1g/L, p<0.0001), but 79.1% of IC were still anemic (vs. 91.1% in NIC). Final plasma zinc concentration did not differ by group. During the 9-month observation period, the incidence of diarrhea was 1.10 ± 1.03 and of malaria 0.54 ± 0.50 episodes per 100 child-days, and did not differ by group. Length at 18 months was significantly greater in IC compared to NIC (77.7 ± 3.0 vs. 76.9 ± 3.4 cm; p<0.001) and stunting prevalence was significantly lower in IC (29.3%) than NIC (39.3%; p<0.0001), but did not differ by intervention group within IC. Wasting prevalence was also significantly lower in IC (8.7%) than in NIC (13.5%; p = 0.0003). Providing SQ-LNS daily with or without zinc, along with malaria and diarrhea treatment, significantly increased growth and reduced stunting, wasting and anemia prevalence in young children., Trial Registration: ClinicalTrials.gov NCT00944281.

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

Objectives: Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation., Methods: We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days., Results: At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 μg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) μmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 μg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 μg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC., Conclusions: Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Background: Zinc supplementation of young children in lower-income countries reduces morbidity from diarrhea and pneumonia and all-cause mortality, but the most cost-effective approach for distributing zinc supplements is unknown., Objective: To examine the potential impact of four possible strategies for delivering zinc supplements on disease prevention and deaths averted among children 6 to 59 months of age in sub-Saharan Africa., Methods: We analyzed different zinc supplementation strategies to assess their likely impact on morbidity and mortality of preschool children in sub-Saharan Africa and to estimate their possible costs., Results: Preventive zinc supplementation reduces diarrhea incidence by 27% among children 12 to 59 months of age, pneumonia incidence by 21% among children 6 to 59 months of age, and all-cause mortality by 18% among children 12 to 59 months of age. The likely average total program costs of zinc supplementation programs were estimated from the outlays of existing service delivery platforms, such as child health days, community-based nutrition programs, and clinic-based treatment of diarrhea, assuming different levels of coverage and target age ranges of children., Conclusions: We found that the average total costs per life saved ranged from approximately US$462 to US$3,111, and the most cost-effective interventions were weekly or intermittent preventive zinc supplementation, because of the possibility of high coverage and fewer supplements required. Empirical data from zinc supplementation programs will be needed to confirm these estimates.

Objective: To assess zinc absorption from dispersible tablets by investigating the effects of short-term zinc supplementation, provided either as zinc (Zn) sulfate dispersible tablets or solution, on changes in plasma Zn concentration in young children., Study Design: We conducted a randomized, partially-masked, placebo-controlled trial in 451 children 6 to 23 months of age in Burkina Faso, randomly assigned to receive a dispersible tablet containing 5 mg Zn, a Zn solution containing 5 mg Zn/5 mL, or a placebo solution, daily for 3 weeks. The main outcome measure was change in plasma zinc concentration after supplementation compared with baseline., Results: The mean plus or minus SD change in plasma Zn concentration (μg/dL) was significantly greater in both Zn supplemented groups (tablets: 16.9±13.1μg/dL, liquid: 16.6±14.2 μg/dL), compared with the placebo group (0.2±10.9 μg/dL; P<.001, ANOVA). In both Zn supplemented groups, but not in the placebo group, change in plasma Zn concentration was progressively less with increasing age in months (-0.79 μg/dL/mo and -1.15 μg/dL/mo, respectively; P<.001); this effect did not differ in the Zn supplemented groups (P=.18)., Conclusions: Short-term supplementation results in a large increase in plasma Zn concentration, regardless of whether the additional Zn is provided as a dispersible tablet or solution., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Micronutrient deficiencies are a public health concern among young children in low-income countries, and novel strategies are needed to improve the nutritional status of children at risk. One promising approach is the use of lipid-based nutrient supplements (LNS), which can be added to complementary food at the time of consumption. The optimal amount of zinc to include in LNS is uncertain, and concerns have been expressed about possible adverse effects of zinc on sensory characteristics of LNS. We conducted a series of acceptability studies of LNS containing either 0 or 10 mg of zinc per daily 20 g LNS dose among Burkinabe children 9-15 months old and their mothers. These acceptability studies included observations of children's consumption, maternal and child sensory reaction to the products using a 5-unit hedonic scale, a triangle test for detection of differences and a review of maternal reports of their child-feeding experiences during a 2-week home-feeding trial. The LNS products were well appreciated by the mothers and children during the sensory trials and the 2-week home-feeding trial. The addition of 10 mg zinc to LNS did not affect the consumed proportion of the offered porridge-LNS-mixture (P = 0.43). Results of the triangle test with mothers confirmed that there was no detectable difference between products containing 0 or 10 mg zinc per 20 g LNS dose. Most importantly, interviews and focus groups following the 2-week home-feeding trial indicated good acceptability of the products by mothers and their children., (© 2010 Blackwell Publishing Ltd.)

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

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

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

Observational studies in human populations suggest that maternal zinc deficiency during pregnancy may cause adverse pregnancy outcomes for the mother and fetus. Therefore, we reviewed the current evidence from studies of zinc supplementation, with or without other micronutrients, during pregnancy and lactation to assess its impact on maternal, fetal, and infant health. A meta-analysis of supplementation trials indicates a 14% reduction in premature delivery among zinc-supplemented women. Most studies found no significant impact of maternal zinc supplementation on infant birthweight, but a subset of studies conducted in underweight or zinc-deficient women suggests that there may be a positive effect of zinc supplementation in such women. However, the number of relevant studies is limited, and more information is needed to confirm these observations. The results for other pregnancy outcomes are inconsistent, and the number of available studies is small. Likewise, the impact of maternal zinc supplementation during pregnancy on infant postnatal growth and risk of infection is variable, and few studies are available. Thus, more research will be needed to allow definitive conclusions to be drawn, especially for the second half of infancy and later childhood. Studies found no adverse effects of maternal zinc supplementation on iron status during pregnancy. More information is required on other potential adverse effects, particularly with regard to a possible modifying effect of preexisting maternal zinc status. In view of the possible benefits of zinc supplementation for reducing the risk of premature delivery, the possible positive impact of zinc supplementation on infant birthweight among undernourished women, and the lack of reported adverse effects, zinc should be included in maternal supplements given during pregnancy in populations at risk for zinc deficiency.

Zinc deficiency increases the risk and severity of a variety of infections, restricts physical growth, and affects specific outcomes of pregnancy. Global recognition of the importance of zinc nutrition in public health has expanded dramatically in recent years, and more experience has accumulated on the design and implementation of zinc intervention programs. Therefore, the Steering Committee of the International Zinc Nutrition Consultative Group (IZiNCG) completed a second IZiNCG technical document that reexamines the latest information on the intervention strategies that have been developed to enhance zinc nutrition and control zinc deficiency. In particular, the document reviews the current evidence regarding preventive zinc supplementation and the role of zinc as adjunctive therapy for selected infections, zinc fortification, and dietary diversification or modification strategies, including the promotion and protection of breastfeeding and biofortification. The purposes of this introductory paper are to summarize new guidelines on the assessment of population zinc status, as recommended by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), the International Atomic Energy Agency (IAEA), and IZiNCG, and to provide an overview on several new advances in zinc metabolism. The following papers will then review the intervention strategies individually.

Objective: To make the best use of limited resources for supporting health-related research to reduce child mortality, it is necessary to apply a suitable method to rank competing research options. The Child Health and Nutrition Research Initiative (CHNRI) developed a new methodology for setting health research priorities. To broaden experience with this priority-setting technique, we applied the method to rank possible research priorities concerning the control of Zn deficiency. Although Zn deficiency is not generally recognized as a direct cause of child mortality, recent research indicates that it predisposes children to an increased incidence and severity of several of the major direct causes of morbidity and mortality., Design: Leading experts in the field of Zn research in child health were identified and invited to participate in a technical working group (TWG) to establish research priorities. The individuals were chosen to represent a wide range of expertise in Zn nutrition. The seven TWG members submitted a total of ninety research options, which were then consolidated into a final list of thirty-one research options categorized by the type of resulting intervention., Results: The identified priorities were dominated by research investment options targeting Zn supplementation, and were followed by research on Zn fortification, general aspects of Zn nutrition, dietary modification and other new interventions., Conclusions: In general, research options that aim to improve the efficiency of an already existing intervention strategy received higher priority scores. Challenges identified during the implementation of the methodology and suggestions to modify the priority-setting procedures are discussed.

Food fortification is increasingly recognized as an effective approach to improve a population's micronutrient status. The present report provides a critical review of the scientific evidence currently available on the impact of zinc fortification on zinc nutrition. The available studies clearly show that zinc fortification can increase dietary zinc intake and total daily zinc absorption. Most absorption studies also indicate that adding zinc to food does not adversely affect the absorption of other minerals, such as iron. Despite the positive effect of zinc fortification on total zinc absorption, only a few studies have found positive impacts of zinc fortification on serum zinc concentrations or functional indicators of zinc status. The reasons for these inconsistent results are uncertain but may relate to the choice of food vehicles, the age group and zinc status of the study populations, or particular aspects of the study design. Thus, additional research is needed to determine the impact of zinc fortification, with or without other micronutrients, in populations at risk for zinc deficiency. Because of the benefits of increasing intake in populations at high risk for zinc deficiency, the documented increase in total zinc absorption that occurs following zinc fortification, the absence of any adverse effects, and the relatively low cost of adding zinc, public health planners should consider including zinc in mass and targeted fortification programs in such populations. Because of the limited available information on program impact, it will be important to evaluate the outcomes of such programs.

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by approximately 20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by approximately 15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on children's behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individual's serum zinc concentration does not reliably predict that person's response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a population's risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Zinc fortification is considered a potentially useful strategy for the control of zinc deficiency, but the success of such intervention programs depends on the population's access to and consumption of zinc-fortified foods and adequate absorption of zinc from these foods. The latter issue has been assessed by a variety of studies that applied zinc isotopic tracers to assess zinc uptake from zinc-fortified foods. These studies show that the additional zinc provided by zinc fortification decreases fractional absorption of zinc, but increases total zinc absorption from these foods. Available studies show no significant difference in zinc absorption from foods fortified with either zinc oxide or zinc sulfate, which are the two cheapest chemical forms of zinc that are generally recognized as safe for human consumption. It appears that high-phytate meals depress zinc absorption from zinc-fortified foods, although total zinc absorption from such foods is still likely to be greater than if the foods were not fortified with zinc. With the possible exception of Na2EDTA, putative enhancers of zinc absorption do not seem to confer major benefits for zinc absorption from zinc-fortified foods. There is little information on the effect of fortification with other micronutrients on zinc absorption from co-fortified foods, and zinc fortification does not seem to suppress iron absorption from iron-fortified foods in most studies.

ObjectivesTo evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children.Study designIn total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression.ResultsAt baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P

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

BackgroundZinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10-14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea.MethodsThe present study is a community-based, randomized controlled trial in the Lao People's Democratic Republic (PDR). Three thousand, four hundred children 6-23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA.DiscussionMany countries are now rolling out large-scale programs to include therapeutic zinc supplementation in the treatment of childhood diarrhea, but few have established programs demonstrated to be effective in the prevention of zinc deficiency. This study will address how best to deliver supplemental zinc to prevent zinc deficiency and reduce the severity of diarrhea-related health complications.Trial registrationTrial registration identifier (NCT02428647) ; Date of registration: April 29, 2015.

Optimal infant and young child feeding (IYCF) practices can help ensure nutrient adequacy and support healthy growth and development. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been proposed to help fill nutrient gaps, but little is known about the impact of provision of SQ-LNS on breastfeeding or complementary feeding practices. In the context of four coordinated randomized controlled nutrient supplementation trials in diverse sites in Africa, we compared IYCF practices at infant age 18 months (after 9-12 months of supplementation) between those receiving and not receiving SQ-LNS. Practices were assessed by caregiver recall. Continued breastfeeding ranged from 74% (Ghana site) to 97% (Burkina Faso site) and did not differ between groups in any site; prevalence of frequent breastfeeding also did not differ. In two sites (Burkina Faso and Malawi), infants receiving SQ-LNS were more likely to meet the World Health Organization recommendations for frequency of feeding (percentage point differences of 12-14%, P

BackgroundOf 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.ObjectivesWe explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity.MethodsChildren 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.ResultsMean 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

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages (n = 88) were included. Capillary and venous blood samples (n = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B12. C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (8.3 mg/L), respectively. In total, 40.7% of women had low pZn (

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]

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]

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: 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]

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]