Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial.

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 < .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).ConclusionsDespite 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 registrationClinicalTrials.govNCT02428647

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B ₁₂ status among young Laotian children:a randomized controlled trial

PURPOSE: To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B(12) status among young Laotian children. METHODS: Children (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B(12) along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B(12) concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline. RESULTS: There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B(12) concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B(12) deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015). CONCLUSIONS: Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B(12) status in young Laotian children. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial.

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

Evidence-Based Road Safety Practice in India: Assessment of the Adequacy of Publicly Available Data in Meeting Requirements for Comprehensive Road Safety Data Systems

Objective: To assess the availability and coverage of publicly available road safety data at the national and state levels in India. Methods: We reviewed the 2 publicly accessible data sources in India for the availability of data related to traffic injuries and deaths: (1) the National Crime Records Bureau (NCRB) and (2) the Ministry of Road Transport and Highways (MORTH). Using the World Health Organization (WHO) manual for the comprehensive assessment of road safety data, we developed a checklist of indicators required for comprehensive road safety assessment. These indicators were then used to assess the availability of road safety data in India using the NCRB and MORTH data. We assessed the availability of data on outcomes and exposures indicators (i.e., number of crashes, injuries, deaths, timing of deaths, gender and age distribution of injuries and deaths), safety performance indicators (i.e., with reference to select risk factors of speeding, alcohol, and helmet use), and cost indicators (i.e., medical costs, material costs, intervention costs, productivity costs, time costs, and losses to quality of life). Results: Information on outcome indicators was the most comprehensive in terms of availability. Both NCRB and MORTH databases had data for most of the need areas specified by the WHO under outcomes and exposure indicators. Regarding outcome and exposure indicators, data were available for 81 and 91 percent of specified need areas at the national level from NCRB and MORTH databases, respectively. At the state level, data on outcome and exposure indicators were available for only 54 percent of need areas from either of the 2 sources. There were no data on safety performance indicators in the NCRB database. From the MORTH database, data availability on safety performance indicators was 60 percent at both national and state levels. Data availability on costs and process indicators was found to be below 20 percent at the national and state levels. Conclusion: Overall, there is an urgent need to improve the publicly available road safety data in India. This will enhance monitoring of the burden of traffic injuries and deaths, enable sound interpretation of national road safety data, and allow the formulation effective road safety policies

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial

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

Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein-3 (IGFBP3) and Growth Response to Daily Zinc Supplementation: A Randomized Trial in Rural Laotian Children.

ObjectivesTo 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.DesignA double-blind, placebo-controlled trial (N = 419).MethodsPlasma 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.ResultsAt 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).ConclusionsAlthough 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

Age‐specific differences in the magnitude of malaria‐related anemia during low and high malaria seasons in rural Zambian children

Abstract Background Malaria causes anemia by destruction of red blood cells and inhibition of erythropoiesis. Objective We assessed whether the magnitude of the malaria‐specific effect on anemia differs by age, during low and high malaria seasons. Method In rural Zambian children participating in a pro‐vitamin A efficacy trial, we estimated differences in the prevalence of anemia (defined as hemoglobin < 110 g/L for children < 60 months. and < 115 g/L in older children) by malaria status and assessed malaria‐age interactions. Regression models (with anemia as the outcome) were used to model malaria‐age interaction in both the low and high malaria seasons, controlling for potential confounders. Results Average age was 68 months at baseline (n = 820 children). In the low malaria season, anemia prevalence was 29% in malaria‐negative children and 54% in malaria‐positive children (p < 0.001), with no malaria‐age interactions (p = 0.44). In the high malaria season, anemia prevalence was 41% in malaria‐negative children and 54% in malaria‐positive children (p < 0.001), with significant malaria‐age interactions (p = 0.02 for anemia). Age‐stratified prevalence of anemia in malaria positive versus negative children was 67.0% versus 37.1% (in children < 60 months); 57.0% versus 37.2% (in 60–69 months.); 46.8% versus 37.2% (in 70–79 months.); 37.0% versus 37.3% (in 80–89 months) and 28.0% versus 37.4% (in 90+ months). Conclusions Malarial anemia is most severe in younger children, especially when transmission is intense. Anemia control programs must prioritize this vulnerable group