To assess a) the impact of daily preventive zinc tablets (7 mg; PZ), multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP) or placebo on Insulin-like Growth Factor 1 ...(IGF1), IGF Binding Protein 3 (IGFBP3) and IGF1 bioavailability (indexed by molar IGF1: IGFBP3 ratio), among Laotian children aged 6–23 mo; b) potential effect modification by baseline physical growth status.
Plasma samples from 419 children participating in the parent trial (n = 3407) were collected at baseline and after ∼9 mo (endline). Determination of IGF1 and IGFBP3 were done via an automated chemiluminescent assay. Linear regression models were used to assess main and modifying effects of PZ and MNP on IGF1 and IGFBP3, controlling for age, sex, district and baseline values of each biomarker.
The parent trial found no overall treatment effects on physical growth. In this subgroup, mean age at baseline was 14.2 ± 5.1 mo and ∼38% were stunted. IGF1 and IGFBP3 at baseline were 45.9 ng/ml and 2143.0 ng/ml, respectively. At endline, geometric mean IGF1 (∼39.0–39.2 ng/ml; P = 0.99), IGFBP3 (2038–2076 ng/ml; P = 0.83) and molar IGF1: IGFBP3 ratio (0.071–0.073; P = 0.74) did not differ by group. Baseline weight-for-age z-score (WAZ) modified the treatment effect on IGFBP3 (p for interaction = 0.05) and molar IGF1: IGFBP3 (p for interaction = 0.04). In non-underweight children (WAZ ≥ -2), mean IGFBP3 in the PZ group (2000 ng/ml) was significantly lower than in the placebo (2148 ng/ml; P = 0.03) and MNP (2157 ng/ml; P = 0.03) groups. In underweight children, however, the IGFBP3 in the PZ group (2039 ng/ml) was higher than the placebo (1774 ng/ml; P = 0.05) but not the MNP (1881 ng/ml; P = 0.15) group. PZ (relative to placebo and MNP) appeared to reduce the bioavailability of IGF1 in underweight children, while increasing IGF1 bioavailability in non-underweight children (p interaction = 0.04).
IGF1 in this population did not respond to PZ or MNP. PZ (relative to placebo and MNP) was associated with higher endline IGFBP3 concentrations in underweight children but lower values in non-underweight children. These results suggest that PZ affected activity in the GH-IGF axis in these children, but additional evidence is needed to understand long term implications for growth in this population.
By The Thrasher Research Fund, with support from the Mathile Institute for the Advancement of Human Nutrition, Nutrition International and the Bill & Melinda Gates Foundation.
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.
Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations. We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (~15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children. This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ~400-km2 area were identified and grouped by proximity into clusters of ~15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and a1-acid glycoprotein. Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms. In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol.
Background: Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to ...improve vitamin A status in maize-consuming populations.
Objective: We evaluated the efficacy of regular provitamin A carotenoid–biofortified “orange” maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
Design: This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km2 area were identified and grouped by proximity into clusters of ∼15–25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Results: Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
Conclusion: In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
Vitamin A (VA) deficiency remains a nutritional concern in Sub‐Saharan Africa. We conducted a cluster‐randomized controlled trial to test the impact of proVA biofortified maize flour consumption on ...VA status. All 4‐8 y old children (n=1,226) in a study area of ~400 km² in Mkushi, Zambia were enrolled and grouped by proximity into clusters of ~15‐25. We randomized clusters to: a) biofortified “orange” maize flour (n=25 clusters); b) white maize flour (n=25); or 3) non‐intervened control (n=14). Intervened clusters received 200 g maize flour, 6 d/wk for 6 mo prepared as per standardized recipes. Food packages were given in non‐intervened clusters after the trial. At baseline and follow‐up, we collected venous blood to measure serum retinol, beta‐carotene, CRP, and AGP. Groups were comparable at baseline. Although attendance did not differ (85%), median daily intake was higher in white (156 g/d) vs orange (140 g/d; providing ~75% RDA for VA) clusters. At follow‐up, serum β‐carotene was 0.3 μmol/L (95% CI: 0.2‐0.4) higher in orange clusters (p<0.001), but mean serum retinol (1.06 ± 0.43 μmol/L overall) and VA deficiency prevalence (18.6% overall; <0.7 μmol/L) did not differ by trial arm. In this marginally nourished population, regular biofortified maize flour consumption did not improve VA status.
Grant Funding Source: Supported by HarvestPlus and the Canadian International Development Agency
Poor iron status, assessed by low serum ferritin (SF), may protect against malaria. We evaluated the association of SF, and SF corrected for inflammation and malaria status (SFcorr), with ...microscopy‐confirmed incident malaria in a cohort of 954 4‐8 y old Zambian children participating in a 6 mo trial to improve vitamin A status (August 2012 to March 2013). Analyses were stratified by age (<5 y and >5 y) to account for the age‐specific risk of malaria. Baseline SFcorr was determined by proportionately reducing SF based on categories of inflammation defined by AGP > 1g/L, CRP > 5 mg/L, and by concurrent malaria status assessed by microscopy, relative to SF observed in unaffected children. SF and SFcorr levels were classified as deficient, medium, and high using cutoffs of <12 or 15 ug/L (depending on age), up to 60 ug/L (but not deficient), and >60 ug/L, respectively. Malaria‐infected children were treated at baseline. Among children <5 y, having medium or high SFcorr resulted in relative risks for incident malaria after 6 mo of 1.61 (95%CI: 1.05‐2.50) and 1.67 (95%CI: 1.06‐2.61), respectively. This pattern was not observed with uncorrected SF. Our findings demonstrate the necessity of adjusting for inflammation and concurrent malaria infection when assessing the relationship between iron status and malaria, and are consistent with evidence that iron status modifies malaria risk, particularly in young children.
Grant Funding Source: Supported by HarvestPlus and Canadian International Development Agency
To assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO) and calprotectin (CAL) among young Laotian children and explore modifying ...effects of MPO, CAL and NEO on growth
In a double-blind controlled trial, children 6–23 mo of age were randomized to receive either daily preventive zinc tablets (PZ; 7 mg/d), daily micronutrient powder sachets (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/d 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 were determined in a randomly selected sub-sample of 720 children using commercially available ELISA kits. Linear regression models were used to assess main and modifying effects while controlling for baseline value, age and district
The baseline prevalence of stunting was 39.3%, and there was no overall treatment effect on physical growth in the parent trial. At endline, geometric mean fecal MPO, NEO and CAL concentrations did not differ among the 4 groups (all P > 0.23). There was an effect modification by baseline concentrations of NEO and CAL on endline stunting (p for interaction = 0.01 and 0.02, respectively). Among children in the lowest quintile of NEO concentrations, there was a trend towards a higher stunting prevalence at endline in the TZ 47.1% (35.6, 58.7) and the MNP 45.3% (32.7, 57.9) groups compared to the PZ 33.6% (21.0, 46.3) and the control 33.9% (22.8, 44.9) groups. Similar results were found among children in the lowest quintile of CAL concentrations. Moreover, baseline concentration of CAL, modified the impact of the interventions on weight-for-height z-scores (WHZ) (p for interaction = 0.074). Among children in the lowest quintile of CAL concentrations, there was a trend towards a higher WHZ at endline in the MNP −0.57 (−0.73, −0.42) and TZ −0.68 (−0.86, −0.51) groups compared to the control −0.79 (−0.97, −0.61) and the PZ −0.88 (−1.05, −0.72) groups.
In this population of young Laotian children PZ, MNP and TZ had no overall impact on EED or growth, but intestinal function modified the growth response to supplementation suggesting its potential role in the pathways of growth impairment.
Funded by the Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.
To investigate the impact of different forms of zinc supplementation on plasma citrulline (CIT), kynurenine (KYN) and tryptophan (TRP) concentrations and the kynurenine: tryptophan ratio (KTR), ...considered as markers of intestinal function and systemic inflammatory response, among young Lao children.
In a randomized controlled double-blind trial, 3407 children aged 6–23 mo were randomized into one of four groups and followed for ∼36 weeks: daily preventive zinc dispersible tablet (7 mg zinc; PZ), daily multiple micronutrient powder (10 mg zinc, 6 mg iron and 13 other micronutrients; MNP), therapeutic zinc supplements for the treatment of diarrhea (20 mg/d for 10 days with each diarrhea episode; TZ), or daily placebo powder (Control). Plasma samples at baseline and endline for 359 children participating in the parent trial were analyzed at the NIH West Coast Metabolomics Center (UC Davis); plasma CIT, KYN and TRP concentrations were determined by hydrophilic interaction chromatography (HILIC) quadrupole time of flight mass spectrometer (QTOF) tandem mass spectrometry (MS/MS). Linear regression models were used to assess the treatment effect, controlling for baseline value, child age and district.
The parent trial found no overall group-wise effects on linear growth or diarrhea outcomes. In the subgroup included in the present analyses, mean age at enrollment was 16.0 ± 4.9 mo, 37% were stunted and 83% were zinc deficient. At baseline, mean plasma CIT, KYN and TRP concentrations were 24.6 ± 5.4 μM, 3.27 ± 0.83 μM and 72.3 ± 12.9 μM, respectively; the mean KT ratio was 0.046 ± 0.013. 5% of children had low CIT (< 17 μM) and no children had low TRP (< 35 μM). At endline, there were no differences among intervention groups in mean plasma CIT (25.0–26.6 μM, P = 0.287), KYN (2.96–3.11 μM, P = 0.115), TRP (66.1–70.0 μM, P = 0.151) or the KTR (0.046–0.047, P = 0.981).
In this population, PZ, MNP and TZ had no overall effect on plasma concentrations of CIT, KYN, TRP and the KTR. We plan to further explore if these markers of intestinal function were predictive of subsequent linear growth, or modified the growth response to supplementation.
The Bill & Melinda Gates Foundation, Nutrition International and the Mathile Institute for the Advancement of Human Nutrition.
Determine if children (6 to 23 mo) who received daily preventive zinc (PZ; 7 mg/d), daily high-zinc, low-iron micronutrient powder (MNP; 10 mg/d zinc, 6 mg/d iron) or therapeutic zinc during episodes ...of diarrhea (TZ; 20 mg/d for 10 d per episode) have improved markers of innate and adaptive immune function, compared to placebo (PL).
Rural Laotian children were recruited into a double-blind, randomized, controlled intervention trial for 9 mo. Venous blood was collected at baseline (BL) and endline (EL) for analysis. Primary outcomes included T-cell subsets (naïve and memory CD4, CD8, Tregs) measured by flow cytometry and production of T-cell cytokines (IL-2, IL-10, IL-13, IL-17A, INF-γ) and LPS-induced cytokines (IL-1β, IL-6, IL-10, TNF-α by whole blood cultures. Blood leukocytes (including lymphocytes, neutrophils, monocytes and eosinophils) were measured as secondary outcome variables. Group means at EL were compared by analysis of covariance (controlling for BL values of the outcome, sex, child age, district, month of enrollment and plasma zinc concentration). If an interaction with BL plasma zinc (above/below median) was observed, group means were compared separately in children above and below the median.
Mean BL plasma zinc in all children (N = 574) was 0.55 ± 0.12 mg/L. No significant group differences were seen at EL in the primary outcomes. For secondary outcomes, the counts (^103/μL) of lymphocytes from the PZ group (5.02 ± 0.16) were significantly lower than the PL group (5.64 ± 0.16; P = 0.032). The EL counts (^103/μL) of from the PZ group (0.144 ± 0.026) were significantly lower than in the PL (0.279 ± 0.048; P = 0.036) and TZ (0.285 ± 0.047; P = 0.025) groups among children with baseline zinc below the median.
Primary outcomes (T-cell subsets, and cytokine production) were not affected by the zinc intervention. Lymphocyte and eosinophil concentrations may be affected by zinc treatment but this result requires confirmation.
ARS Project 2032-53000-001-00-D, Mathile Institute for the Advancement of Human Nutrition.
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