Determination of hemoglobins (Hbs) F, A
and E is crucial for diagnosis of thalassemia. This study determined the levels of Hbs F, A
and E in children aged 6-23 months and investigated the effect of ...age, sex, and types of thalassemia on the expression of these Hbs.
A total of 698 blood samples of Laotian children including 272 non-Hb E, 271 Hb E heterozygotes, and 155 Hb E homozygotes were collected. Hb profiles were determined using the capillary zone electrophoresis. Coinheritance of α-thalassemia and the homozygosity for Hb E mutation were checked by PCR-based assay.
Children heterozygous and homozygous for Hb E had significantly higher Hb F and A
levels than non-Hb E children (median Hb F = 1.1% for non-Hb E group, 2.7% for Hb E heterozygotes, and 9.4% for Hb E homozygotes; median Hb A
= 2.6% for non-Hb E group, 3.8% for Hb E heterozygotes, and 5.2% for Hb E homozygotes). The median Hb E levels were 21.9% for Hb E heterozygotes and 85.3% for Hb E homozygotes. Comparing within group, there was a statistically significant difference between children with and without an α-gene defect for Hb A
and E, but not Hb F. Based on a multiple regression analysis, age and sex were significantly associated with the expression of Hb F and A
but not Hb E.
Our findings can guide the development of a diagnostic approach to thalassemia in children aged 6-23 months.
Introduction
Determination of hemoglobins (Hbs) F, A2, and E is crucial for diagnosis of thalassemia. This study determined the levels of Hbs F, A2, and E in children aged 6‐23 months and ...investigated the effect of age, sex, and types of thalassemia on the expression of these Hbs.
Methods
A total of 698 blood samples of Laotian children including 272 non‐Hb E, 271 Hb E heterozygotes, and 155 Hb E homozygotes were collected. Hb profiles were determined using the capillary zone electrophoresis. Coinheritance of α‐thalassemia and the homozygosity for Hb E mutation were checked by PCR‐based assay.
Results
Children heterozygous and homozygous for Hb E had significantly higher Hb F and A2 levels than non‐Hb E children (median Hb F = 1.1% for non‐Hb E group, 2.7% for Hb E heterozygotes, and 9.4% for Hb E homozygotes; median Hb A2 = 2.6% for non‐Hb E group, 3.8% for Hb E heterozygotes, and 5.2% for Hb E homozygotes). The median Hb E levels were 21.9% for Hb E heterozygotes and 85.3% for Hb E homozygotes. Comparing within group, there was a statistically significant difference between children with and without an α‐gene defect for Hb A2 and E, but not Hb F. Based on a multiple regression analysis, age and sex were significantly associated with the expression of Hb F and A2 but not Hb E.
Conclusions
Our findings can guide the development of a diagnostic approach to thalassemia in children aged 6‐23 months.
Inflammation-induced hyporetinolemia (IIH), a reduction in serum retinol (SR) during inflammation, may bias population estimates of vitamin A deficiency (VAD). The optimal adjustment for IIH depends ...on the type and extent of inflammation. In rural Zambian children (4–8 years, N = 886), we compared three models for defining inflammation: α-1-acid glycoprotein (AGP) only (inflammation present if > 1 g/L or normal if otherwise), C-reactive protein (CRP) only (moderate inflammation, 5–15 mg/L; high inflammation, > 15 mg/L; or normal if otherwise) and a combined model using both AGP and CRP to delineate stages of infectious episode. Models were compared with respect to 1) the variance in SR explained and 2) comparability of inflammation-adjusted VAD estimated in low and high malaria seasons. Linear regression was used to estimate the variance in SR explained by each model and in estimating the adjustment factors used in generating adjusted VAD (retinol < 0.7 μmol/L). The variance in SR explained were 2% (AGP-only), 11% (CRP-only), and 11% (AGP–CRP) in the low malaria season; and 2% (AGP-only), 15% (CRP-only), and 12% (AGP–CRP) in the high malaria season. Adjusted VAD estimates in the low and high malaria seasons differed significantly for the AGP (8.2 versus 13.1%) and combined (5.5 versus 9.1%) models but not the CRP-only model (6.1 versus 6.3%). In the multivariate regression, a decline in SR was observed with rising CRP (but not AGP), in both malaria seasons (slope = −0.06; P < 0.001). In this malaria endemic setting, CRP alone, as opposed to CRP and AGP, emerged as the most appropriate model for quantifying IIH.
Background:
Measurements of mid-upper arm circumference (MUAC) may result in measurement error due to incorrect placement along the arm or tight pulling of tape. To reduce the risk of these ...measurement errors, a new wider tape was developed.
Objective:
To compare the measurement agreement and precision and the ease of use of the standard and wide MUAC tapes.
Methods:
Mid-upper arm circumference was measured in 814 children aged 9 to 32 months with both tapes. The midpoint of the upper arm was measured with the standard tape and estimated with the wide tape. Standardization sessions were implemented to assess intra- and interobserver precision.
Results:
Mid-upper arm circumference with the wide MUAC tape was significantly larger than the standard tape (mean standard deviation: 14.3 1.0 cm vs 13.9 1.0 cm; P < .001), resulting in a consistent bias of +0.41 cm. Forty-six (5.7%) children were identified with low MUAC <12.5 cm by standard tape compared with 10 (1.2%) by the wide tape (P <.001). Because a new tape could be reproduced by correcting for this bias, we corrected measured results by subtracting 0.41 cm and mean MUAC by tape type was no longer significantly different. Intra- and interobserver technical error of measurement suggested a better precision with the wide MUAC tape.
Conclusions:
Despite simplifying the measurement by approximating the midpoint of the upper arm, the wide MUAC tape tended to have better precision than the standard MUAC tape. However, there was a consistent measurement bias of +0.41 cm in mean MUAC. This first field test yielded promising results and led to further product adjustments.
Zinc 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.
The 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.
Many 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 registration identifier (NCT02428647) ; Date of registration: April 29, 2015.
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.
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.
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 (
= 0.06) and duration (
= 0.01). In children >18 months, TZ reduced diarrhea incidence by 24% vs MNP (
= 0.035), and 36% vs Control (
= 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 (
= 0.03), and 16% vs Control (
= 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,
= 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days,
= 0.72).
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.
ClinicalTrials.gov: NCT02428647.
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
Background: 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.
Objective: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.
Methods: 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.
Results: 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).
Conclusions: 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.
Background: 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.
Objective: ...We tested the impact of provitamin A carotenoid–biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children.
Methods: 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/m2) in a dark-adapted state.
Results: 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/m2), 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.
Conclusions: 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 assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B
status among young Laotian children.
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
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
concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.
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
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
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).
Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B
status in young Laotian children.
The trial was registered at www.
gov (NCT02428647) on April 29 2015.
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