Abstract
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).
Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids.
We tested the impact of ...provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children.
We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m
) in a dark-adapted state.
At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m
), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness.
The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148.
To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children.
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.
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).
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.
ClinicalTrials.govNCT02428647.
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 (
= 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;
= 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.
Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated ...haematology analyser in young children.
To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR.
Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots.
Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L).
Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences.
Objectives/Hypothesis:
To assess whether practice on a virtual‐reality (VR) temporal bone simulator improves acquisition of technical skills in mastoid surgery.
Study Design:
Prospective blinded ...study.
Methods:
Using a previously validated objective structured assessment of technical skills (OSATS) tool, performance was assessed in 12 residents for two tasks of cortical mastoidectomy: 1) identifying and defining the tegmen and 2) defining the sigmoid sinus and sinodural angle. These surgical tasks were chosen as key steps in mastoid dissection because they were of intermediate complexity. Videos of virtual dissections were captured at baseline and again after practicing each task four to six times.
Results:
OSATS scores for the tegmen task increased from 2.125 ± 1.25 to 3.1 ± 0.85 (P = .026), whereas for the sigmoid task scores increased from 2 ± 0.45 to 2.75 ± 1.125 (P = .0098). The time to complete the tasks decreased from 8.37 ± 4.78 minutes to 5.39 ± 3.06 minutes (P = .018) for the tegmen task and from 8.99 ± 6.7 minutes to 8.68 ± 5.98 minutes (P = .594) for the sigmoid task. There was a decline in number of injuries from 0.5 ± 1.5 to 0 ± 0.5 (P = .594) for the tegmen task and from 2.5 ± 4 to 0.5 ± 1 (P = .029) for the sigmoid task.
Conclusions:
Technical skills in mastoidectomy surgery can be acquired during even brief practice on the VR temporal bone simulator. It is anticipated that longer periods of practice presented within the fundamentals of comprehensive curriculum will facilitate procedural learning. Further studies are required to elucidate evidence of transference of these skills to the operating room and to procedures of greater complexity.
Zinc deficiency impairs immune function and is common among children in South-East Asia.
The effect of zinc supplementation on immune function in young Laotian children was investigated.
Children (n ...= 512) aged 623 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).
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).
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 http://www.clinicaltrials.gov as NCT02428647.
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 (
= 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (
= 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.
Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating ...biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants.
We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.
Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.
Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM 1.15 μmol/L (0.96, 1.39 μmol/L) and VA 1.17 μmol/L (0.99, 1.38 μmol/L) groups than in the WM group 0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13, and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).
Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.
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.
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