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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.

BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting.ObjectivesWe aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3).MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation.ConclusionsIncluding SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

PurposeTo assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children.MethodsChildren (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 B12 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 B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.ResultsThere 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 B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 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

Access to and utilisation of antenatal care (ANC) is important for optimising health and nutrition during pregnancy. This study aimed to assess adherence to and factors associated with ANC and antenatal supplement use among Laotian women, and consider culturally appropriate strategies to increase micronutrient intakes. Mother-child (aged 21 d to

Culturally determined food restrictions are common among pregnant and postpartum women in Asia. This study aimed to describe perinatal dietary restrictions, factors associated with food avoidances and attainment of minimum dietary diversity (MDD-W) among women in Lao PDR. Mother-child (aged 21 days to

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

BackgroundDespite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance.MethodsData were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations.ResultsThe mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (- 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not.ConclusionOPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC.Trial registrationThe NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688 . Registered 16 April 2013.

BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (

BackgroundSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.ObjectivesWe aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).ResultsIn 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsChild SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers.ResultsSQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin 12 mo and provided 9 (as opposed to

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support.

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 (

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at

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.

BackgroundZinc deficiency impairs immune function and is common among children in South-East Asia.ObjectivesThe effect of zinc supplementation on immune function in young Laotian children was investigated.MethodsChildren (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).ResultsT-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).ConclusionsZinc 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.

BackgroundDiarrhea 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.MethodsChildren 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.ResultsBaseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (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).ConclusionsThere 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 registrationClinicalTrials.gov: NCT02428647.

BackgroundThe 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.ObjectivesWe 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.MethodsCross-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.ResultsIn 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.ConclusionsRelations 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.

IntroductionDiagnosis of infantile thiamine deficiency disorders (TDD) is challenging due to the non-specific, highly variable clinical presentation, often leading to misdiagnosis. Our primary objective is to develop a case definition for thiamine responsive disorders (TRD) to determine among hospitalised infants and young children, which clinical features and risk factors identify those who respond positively to thiamine administration.Methods and analysisThis prospective study will enrol 662 children (aged 21 days to

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.

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6-23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (-1·93 (95 % CI -1·88, -1·97)) v. placebo (-1·88 (95 % CI -1·83, -1·92)), and the opposite occurred among initially anaemic children (final mean LAZ -1·90 (95 % CI -1·86, -1·94) in MNP v. -1·92 (95 % CI -1·88, -1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

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

Stunting prevalence is an indicator of a country's progress towards United Nations' Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%-62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress.

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.

Pregnant and lactating women in rural Niger are at high risk for inadequate intakes of multiple micronutrients. Thus, 24 h dietary recalls were conducted and analyzed for dietary intakes in this population (n = 202). Using linear programming analyses, micronutrient gaps in women's diets were identified, food-based recommendations (FBR) to improve dietary micronutrient adequacy were developed, and various supplementation strategies were modelled. Energy intakes were below estimated requirements, and, for most micronutrients, >50% of women were at risk of inadequate intakes. Linear programming analyses indicated it would be difficult to select a diet that achieved recommended dietary allowances for all but three (vitamin B₆, iron and zinc) of 11 modeled micronutrients. Consumption of one additional meal per day, and adherence to the selected FBR (daily consumption of dark green leafy vegetables, fermented milk, millet, pulses, and vitamin A fortified oil), would result in a low percentage of women at risk of inadequate intakes for eight modeled micronutrients (vitamin A, riboflavin, thiamin, B6, folate, iron, zinc, and calcium). Because the promotion of realistic FBRs likely will not ensure that a low percentage of women are at risk of inadequate intakes for all modeled micronutrients, multiple micronutrient supplementation or provision of nutrient-dense foods should be prioritized.

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.

Inconsistent use of terminology among diverse stakeholders hinders effective communication in micronutrient programs, especially large-scale food fortification (LSFF) which involves stakeholders from different sectors. To align the terminology use, the Micronutrient Data Innovation Alliance (DInA) of the Micronutrient Forum (MNF) created a lexicon of terms related to LSFF and other micronutrient programs. The purpose of this lexicon is to establish a central repository of consensus definitions of key terms to facilitate communication among diverse stakeholders involved in micronutrient programs including public and private sectors, donor agencies, food industries, academic institutions, etc. This paper describes the methodology of lexicon development. Important terms related to micronutrient programs were compiled from multiple sources, including United Nations agencies, program implementation and technical support agencies, relevant websites, and scientific literature. The selection of terms was guided by key micronutrient interventions (fortification, supplementation, dietary diversification) and the program cycle (assessment, planning, implementation, monitoring and evaluation). Definitions of terms were identified from these references and checked for consistency across different sources. For terms with multiple definitions, a modified Delphi method was applied to harmonize the definitions. The first draft lexicon (n = 113 terms) was reviewed by six experts from the University of California, Davis (UCD) and MNF, and second draft (n = 115 terms) was shared with 24 global micronutrient experts for feedback. Fifty-four terms were found to have multiple definitions. Of which, minor modification was made for 12-terms with nominal difference and remaining 42-terms were shared with over 140 micronutrient-experts disseminated via an online survey through newsletters and emails to solicit experts' opinions on the most appropriate definition or a modified one. Nineteen legal terms and 83 micronutrient terms (n = 102 terms) were subsequently added. Overall, 39 experts from diverse areas of expertise (LSFF, micronutrient program planning and implementation, surveys and research, policy development, food industry regulations, food safety, and public health nutrition) participated in the online survey. The terms with >75% agreement among experts were considered as final, while the remaining were reviewed again by experts from UCD and MNF until consensus was reached on harmonized definitions. The current lexicon is available online at the DInA-website. and contains 217 terms and will be maintained as a "living document". The lexicon will facilitate the ability of key stakeholders of micronutrient programs to evaluate and compare program performance in order to make informed decisions on how to ensure future progress in reducing micronutrient deficiencies. [ABSTRACT FROM AUTHOR]

BackgroundHaemoglobin (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.AimTo compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR.MethodsCapillary 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.ResultsMean 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

BackgroundWe 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).MethodsUsing 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.ResultsAt baseline, 35% of children had low adjusted pZC (8.3 mg/L) and 47% had low adjusted RBP (

BackgroundPrevious reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD.MethodsWe conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n = 1,023), Malawi (n = 675 and 1,385), and Burkina Faso (n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD.ResultsOut of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts.ConclusionsKey elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status.

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

Millions of children in low-income and middle-income countries falter in linear growth and neurobehavioral development early in life. This faltering may be caused by risk factors that are associated with both growth and development, such as insufficient dietary intake and infection in infancy. Alternatively, these risk factors may be indicative of an environment that constrains both linear growth and development through different mechanisms. In a cluster-randomized trial in Burkina Faso, we previously found that provision of lipid-based nutrient supplements plus malaria and diarrhoea treatment from age 9 to 18 months resulted in positive effects of ~0.3 standard deviation on length-for-age z-score (LAZ) and of ~0.3 standard deviation on motor, language and personal-social development scores at age 18 months. In this paper, we examined whether the effect of the intervention on developmental scores was mediated by the effect on LAZ, or, alternatively, whether the intervention had independent effects on growth and development. For motor, language, and personal-social z-scores, the effect of the intervention decreased from 0.32 to 0.21, from 0.33 to 0.27 and from 0.35 to 0.29, respectively, when controlling for change in LAZ from 9 to 18 months. All effects remained significant. These results indicate that the intervention had independent positive effects on linear growth and development, suggesting that these effects occurred through different mechanisms. © 2016 John Wiley & Sons Ltd.

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 (

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol‐binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid‐upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron‐containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha‐1‐acid‐glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care‐seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children. Key messages: Anaemia is a public health concern among women and young children due to multiple causes and biological, socioeconomic and ecological risk factors.Anaemia was assessed among women and their young children hospitalised for clinical signs and symptoms suggestive of thiamine deficiency disorders. The risk of anaemia was significantly associated with multiple indicators of micronutrient status and factors related to poverty and health and dietary practices.The present study highlights that anaemia and iron, thiamine, riboflavin and vitamin A deficiencies are highly prevalent in the study population and that multiple strategies are required to prevent anaemia and the other consequences of these micronutrient deficiencies. [ABSTRACT FROM AUTHOR]

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]