Multiple Micronutrient Powders Research Articles

Effects of iron supplements and iron-containing micronutrient powders on the gut microbiome in Bangladeshi infants: a randomized controlled trial

Anemia is highly prevalent globally, especially in young children in low-income countries, where it often overlaps with a high burden of diarrheal disease. Distribution of iron interventions (as supplements or iron-containing multiple micronutrient powders, MNPs) is a key anemia reduction strategy. Small studies in Africa indicate iron may reprofile the gut microbiome towards pathogenic species. We seek to evaluate the safety of iron and MNPs based on their effects on diversity, composition, and function of the gut microbiome in children in rural Bangladesh as part of a large placebo-controlled randomized controlled trial of iron or MNPs given for 3 months (ACTRN12617000660381). In 923 infants, we evaluate the microbiome before, immediately following, and nine months after interventions, using 16S rRNA gene sequencing and shotgun metagenomics in a subset. We identify no increase in diarrhea with either treatment. In our primary analysis, neither iron nor MNPs alter gut microbiome diversity or composition. However, when not adjusting for multiple comparisons, compared to placebo, children receiving iron and MNPs exhibit reductions in commensal species (e.g., Bifidobacterium, Lactobacillus) and increases in potential pathogens, including Clostridium. These increases are most evident in children with baseline iron repletion and are further supported by trend-based statistical analyses.

Suboptimal micronutrient intake among children aged 6 to 23 months in Ethiopia: Further analysis of the demographic and health survey.

The recommended essential micronutrient such as food rich in vitamin-A or iron, multiple micronutrient powder or iron supplement, routine daily consumption of iodine, and vitamin-A supplement are deficient among children in Ethiopia. This has been a significant public health problem despite the government efforts. Although few studies have examined the micronutrient intake among children, they are limited in scope and methodological measurements. Analyzing the micronutrient intake among children across all regions and leveraging all essential micronutrient elements are crucial for generating improved evidence to better inform policy. Thus, we examined the micronutrient intake among children aged 6 to 23 months in Ethiopia. We used data from the Ethiopian Demographic and Health Survey. A two-stage stratified sampling technique was employed, and 1392 children aged 6 to 23 months were included in our analysis. We conducted a multilevel mixed-effect binary logistic regression analysis to identify determinants of micronutrient intake. In the final model, we used a p-value of less than 0.05 and Adjusted Odds Ratio (AOR) with their 95% confidence interval (CI). We found that only 27.6% (95% CI: 26.8-31.6) of children aged 6 to 23 months were received the recommended micronutrients in Ethiopia. We identified that maternal educational status (Educated mothers (AOR = 2.09, 95%CI:1.23-3.58)), health facility delivery (AOR = 2.14, 95%CI:1.42-2.98), household wealth status (middle quantile (AOR = 1.80, 95%CI:1.01-3.21)), children's age (12 to 23 months age (AOR = 2.36, 95% CI: 1.33-4.21)), and mother's exposure to media (AOR = 1.70, 95%CI: 1.42-2.04) were increased micronutrient intake, whereas residing in the rural communities (AOR = 0.27, 95%CI: 0.21-0.34) decreased micronutrient intake. Nearly three-fourths of children aged 6 to 23 months did not receive the recommended essential micronutrients in Ethiopia. Therefore, there is a need to broaden strategies aimed at enhancing the intake by improving information and knowledge dissemination among mothers during facility visits and through media channels.

Prevalence of multiple micronutrient powders consumption and its determinants among 6- to 23-month-old children in East Africa: a mixed effect analysis using the recent population based cross sectional national health survey

BackgroundTo address iron deficiency anemia, Multiple Micronutrient Powders (MMNPs) can be sprinkled onto any semisolid diet and given to young children. There is currently no data on actual MMNPs uptake by children; hence, the study’s goal was to investigate MMNPs and determinants among children aged 6–23 months in East Africa.MethodsData from the 2016–2022 East Africa demographic and health survey extracted from Kids Records (KR) files were used in this study. A total of 33,324 weighted 6- to 23-month-old child samples were included. For assessing model fitness and contrast, the intra-class correlation coefficient, median odds ratio, proportional change in variance, and deviance were used. A multilevel logistic regression model was applied to identify variables that may influence MMNPs intake. In the multivariable multilevel logistic regression analyses, variables were judged to be significantly linked with MMNPs intake if their p-values were < 0.05.ResultsIn East Africa, the prevalence of MMNPs intake among infants aged 6–23 months was 6.45% (95% CI, 6.19%, 6.22%). Several factors were found to be significantly associated with MMNPs consumption. These factors include older maternal age (AOR = 1.23, 95% CI, 1.09, 1.39) and (AOR = 1.46, 95% CI, 1.23, 1.73), poorer (AOR = 0.73, 95% CI, 0.64, 0.84), middle (AOR = 0.75, 95% CI, 0.66, 0.86), richer (AOR = 0.61, 95% CI, 0.52, 0.71), and richest (AOR = 0.49, 95% CI, 0.41, 0.59) as compared to poorest, having employment status (AOR = 0.65, 95% CI, 0.59, 0.71), mass media exposure (AOR = 1.61, 95% CI, 1.35, 1.78), longer birth interval (AOR = 1.19, 95% CI, 1.28, 1.36), place of delivery (AOR = 1.46, 95% CI, 1.28,1.66), and mothers from rural areas (AOR = 0.71, 95% CI, 0.62,0.80).ConclusionsOverall, MMNPs intake was lower than the national and international recommendations. Only seven out of every hundred children received MMNPs. Improving maternal preventive health care and supporting marginalized women will have a positive impact.

Micronutrient gaps during the complementary feeding period in seven countries in Southeast Asia: A Comprehensive Nutrient Gap Assessment

AbstractThe complementary feeding period is a critical stage of child development when micronutrient needs are high and challenging to meet. Understanding if specific micronutrient gaps exist during this period is critical for effective programming. A Comprehensive Nutrient Gap Assessment (CONGA) was conducted in seven countries in Southeast Asia to estimate gaps in micronutrients commonly lacking in the diets of children aged 6–23 months and to establish the certainty of available evidence for each identified gap. Sixty‐eight evidence sources were identified during this analysis, and 310 micronutrient‐specific data points were identified across all seven countries. Data points varied in recency, representativeness and evidence type. The CONGA methodology enabled the estimation of a gap burden rating for each micronutrient in each country, as well as a rating of their evidence certainty. Micronutrient gaps were identified in vitamin D, zinc and iron and a potential gap was identified in calcium during the complementary feeding period in the region. Evidence relevant to intake and deficiency of folate, vitamin B12, thiamine, niacin, vitamin C and vitamin B6 was limited across the region. Proven strategies to address these gaps include increasing the availability and consumption of nutrient‐dense foods, micronutrient supplementation, large‐scale fortification of staple foods and condiments and point‐of‐use fortification through multiple micronutrient powders and fortified speciality foods. More recent data on micronutrient availability, intake and deficiency is urgently needed in Southeast Asia.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial

IntroductionApproximately 40% of children aged 6–59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of...

Micronutrient intake status and associated factors in children aged 6–23 months in sub-Saharan Africa

Micronutrient deficiency has serious consequences across all ages worldwide, particularly in sub-Saharan Africa. Poor micronutrient (MN) consumption among children remains a major public health concern in many countries. Low literacy, poor diets, a lack of access to healthcare, and insufficient agricultural productivity made proper micronutrient consumption difficult, despite numerous interventions. Thus, this research aimed to determine the adequate intake of MNs among 6–23 months of age children in sub-Saharan Africa. Initially, a two-stage stratified sampling technique was applied for the selected recent demographic and health survey data. The data source was the (2015–2020) standard demographic and health surveys (DHS) among 20 Sub-Saharan African countries. Micronutrient intake status (the outcome variable) was determined using either food rich in Vitamin A or iron consumed within the previous 24 hr or multiple micronutrient powder or iron supplementation within the previous 07 days or vitamin A supplementation or deworming within 06 months. A generalized linear mixed model based on Modified Poisson regression and robust error variance was used to identify factors associated with children’s adequate micronutrient intake. An adjusted Prevalence Ratio (aPR) with a 95% confidence interval was used to identify factors, strength and direction of the association. The total samples of 65,187 children aged 6–23 months were included. Of all, 73.99% (95% CI: 73.65, 74.32) of children had adequate intake of micronutrients. Maternal education (primary (aPR = 1.04, 95% CI: 1.02, 1.06) and secondary (aPR = 1.07, 95% CI: 1.04, 1.09)), father’s education (primary (aPR = 1.03, 95% CI: 1.01, 1.05) and secondary (aPR = 1.04, 95% CI: 1.02, 1.06)), occupational status of the mother (aPR = 1.04, 95% CI: 1.02, 1.06), pregnancy interval (aPR = 0.97, 95% CI: 0.95, 0.99), exclusive breastfeeding status (aPR = 0.83, 95% CI: 0.82, 0.85), birthweight (average (aPR = 1.03, 95% CI: 1.01, 1.05) and larger than average (aPR = 1.04, 95% CI: 1.02, 1.06)), multiple/twin at birth (aPR = 0.94, 95% CI: 0.91, 0.98), child age (aPR = 1.22, 95% CI: 1.19, 1.25), number of children in home (aPR = 1.02, 95% CI: 1.01, 1.03), ANC utilization (aPR = 1.20, 95% CI: 1.15, 1.27), place of birth (AOR = 0.93, 95% CI: 0.91, 0.95), rich households (aPR = 1.03, 95% CI: 1.01, 1.05), and countries from Central (aPR = 1.07, 95% CI: 1.04, 1.09), South Africa (aPR = 1.07, 95% CI: 1.03, 1.11), and West African (aPR = 0.95, 95% CI: 0.92, 0.99) were associated with level of micronutrients intake status. The prevalence of adequate intake of MN was considerable. Variables at the child, family and community levels were associated with adequate intake of micronutrients. Consequently, stakeholders’ involvement is required in healthcare and community settings.

The Prevalence of Anemia in Children Aged 6–23 Months and its Correlates Differ by District in Kapilvastu and Achham Districts in Nepal

BackgroundAnalyses of predictors of anemia or malnutrition often pool national or regional data, which may hide variability at subnational levels. ObjectivesWe sought to identify the risk factors for anemia in young Nepali children aged 6–23 mo in 2 districts: Kapilvastu and Achham. MethodsThis is an analysis of two cross-sectional surveys that were conducted as part of a program evaluation of an infant and young child feeding and micronutrient powder intervention that included anemia as a primary outcome. Baseline and endline surveys in each district (in 2013 and 2016) included hemoglobin assessments in n = 4709 children who were representative of children 6–23 mo in each district. Log-binomial regression models accounting for the survey design were used to estimate univariable and multivariable prevalence ratios for risk factors at multiple levels—underlying, direct, and biological causes. Average attributable fractions (AFs) for the population were calculated for significant predictor biomarkers of anemia in multivariable models. ResultsIn Accham, the prevalence of anemia was 31.4%; significant predictors included child’s age, household asset ownership, length-for-age z-score, inflammation (CRP concentration > 0.5 mg/L; α-1 acid glycoprotein concentration > 1 mg/mL), and iron deficiency (serum ferritin concentration < 12 μg/L with BRINDA-inflammation adjustment). In Kapilvastu, the prevalence of anemia was 48.1%; significant predictors included child’s sex and ethnicity, wasting and weight-for-length z-score, any morbidity in the previous 2 wk, consumption of fortified foods, receipt of multiple micronutrient powder distributions, iron deficiency, zinc deficiency (nonfasting serum zinc concentration of <65 μg/dL in the morning and that of <57 μg/dL in the afternoon), and inflammation. In Achham, average AFs were 28.2% and 19.8% for iron deficiency and inflammation, respectively. Average AFs for anemia in Kapilvastu were 32.1%, 4.2%, and 4.9% for iron deficiency, zinc deficiency, and inflammation, respectively. ConclusionsThe prevalence of anemia and its risk factors varied between districts, with inflammation contributing to a greater share of anemia in Achham than in Kapilvastu. The estimated AF for iron deficiency was around 30% in both districts; iron-delivering interventions and multisectoral approaches to anemia are warranted.

Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders Alters Resting Brain Activity in Bangladeshi Children

BackgroundAnemia and iron deficiency have been associated with poor child cognitive development. A key rationale for the prevention of anemia using supplementation with iron has been the benefits to neurodevelopment. However, little causal evidence exists for these gains. ObjectivesWe aimed to examine effects of supplementation with iron or multiple micronutrient powders (MNPs) on brain activity measures using resting electroencephalography (EEG). MethodsChildren included in this neurocognitive substudy were randomly selected from the Benefits and Risks of Iron Supplementation in Children study, a double-blind, double-dummy, individually randomized, parallel-group trial in Bangladesh, in which children, starting at 8 mo of age, received 3 mo of daily iron syrup, MNPs, or placebo. Resting brain activity was recorded using EEG immediately after intervention (month 3) and after a further 9-month follow-up (month 12). We derived EEG band power measures for delta, theta, alpha, and beta frequency bands. Linear regression models were used to compare the effect of each intervention with that of placebo on the outcomes. ResultsData from 412 children at month 3 and 374 at month 12 were analyzed. At baseline, 43.9% were anemic and 26.7% were iron deficient. Immediately after intervention, iron syrup, but not MNPs, increased the mu alpha-band power, a measure that is associated with maturity and the production of motor actions (iron vs. placebo: mean difference = 0.30; 95% CI: 0.11, 0.50 μV2; P = 0.003; false discovery rate adjusted P = 0.015). Despite effects on hemoglobin and iron status, effects were not observed on the posterior alpha, beta, delta, and theta bands, nor were effects sustained at the 9-month follow-up. ConclusionsThe effect size for immediate effects on the mu alpha-band power is comparable in magnitude with psychosocial stimulation interventions and poverty reduction strategies. However, overall, we did not find evidence for long-lasting changes in resting EEG power spectra from iron interventions in young Bangladeshi children. This trial was registered at www.anzctr.org.au as ACTRN12617000660381.

Effects of iron supplementation on neural indices of habituation in Bangladeshi children

BackgroundIron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. ObjectiveWe aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). MethodsThis substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. ResultsData were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07μV [95% CI: −1.22, 1.37]; MNPs compared with placebo: MD = 0.58μV [95% CI: −0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. ConclusionIn Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation.This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.

A comprehensive intervention package improves the linear growth of children under 2-years-old in rural Bangladesh: a community-based cluster randomized controlled trial

Approximately one-third of children under the age of five are stunted in developing countries and many of them are micronutrient-deficient. We designed a comprehensive intervention package including egg/milk-based snacks to improve linear growth and dietary diversity among 6 to 12-month-old children in rural Bangladesh. In this 1-year community-based cluster randomized controlled longitudinal experiment, 412 mother–infant pairs were randomly assigned to receive either monthly food vouchers (for eggs, milk, semolina, sugar, and oil) to prepare egg and milk-based snacks for their children, along with multiple micronutrient powder (MNP), counseling on child feeding and handwashing, or regular government health communication alone (control; n = 206, treatment; n = 206). The trial was conducted in 12 clusters (small administrative units of sub-district). The primary inclusion criteria were ultra-poor households with limited resources and having children under 2-years-old. The primary and secondary outcomes were differences in children's length gain and dietary diversity. The effect of intervention on child growth was examined using a mixed effect linear regression model. Mean weight and length of the children did not significantly differ between groups at baseline. Around 90% of the children in both groups were breastfed. After receiving intervention for 12 months, LAZ score increased by 0.37 (CI 0.24, 0.51, p < 0.001) and risk of stunting reduced by 73% (OR: 0.27, CI 0.13, 0.58, p = 0.001). This comprehensive intervention package improved the growth and dietary diversity of children in extremely poor Bangladeshi households. A scaling-up of this intervention in contexts with limited resources should be taken into consideration.Trial registration: This trial registered retrospectively at ClinicalTrials.gov as NCT03641001, 21/8/2018.

Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial

Iron deficiency is the most prevalent nutritional disorder worldwide. Iron supplementation has modest efficacy, causes gastrointestinal side-effects that limit compliance, and has been associated with serious adverse outcomes in children across low-income settings. We aimed to compare two hepcidin-guided screen-and-treat regimens designed to reduce overall iron dosage by targeting its administration to periods when children were safe and ready to receive iron supplementation, with WHO's recommendation of universal iron supplementation. We conducted an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial in 12 rural communities across The Gambia. Eligible participants were children aged 6-23 months with anaemia. Participants were randomly assigned (1:1:1) to either the WHO recommended regimen of one sachet of multiple micronutrient powder (MMP) daily containing 12·0 mg iron as encapsulated ferrous fumarate (control group); to MMP with 12·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 μg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 μg/L (12 mg screen-and-treat group); or to MMP with 6·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 μg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 μg/L (6 mg screen-and-treat group). Randomisation was done by use of a permuted block design (block size of 9), with stratification by haemoglobin and age, using computer-generated numbers. Participants and the research team (except for the data manager) were masked to group allocation. The primary outcome was haemoglobin concentration, with a non-inferiority margin of -5 g/L. A per-protocol analysis, including only children who had consumed at least 90% of the supplements (ie, supplement intake on ≥75 days during the study), was done to assess non-inferiority of the primary outcome at day 84 using a one-sided t test adjusted for multiple comparisons. Safety was assessed by use of ex-vivo growth tests of Plasmodium falciparum in erythrocytes and three species of sentinel bacteria in plasma samples from participants. This trial is registered with the ISRCTN registry, ISRCTN07210906. Between April 23, 2014, and Aug 7, 2015, we prescreened 783 children, of whom 407 were enrolled into the study: 135 were randomly assigned to the control group, 136 to the 12 mg screen-and-treat group, and 136 to the 6 mg screen-and-treat group. 345 (85%) children were included in the per-protocol population: 115 in the control group, 116 in the 12 mg screen-and-treat group, and 114 in the 6 mg screen-and-treat group. Directly observed adherence was high across all groups (control group 94·8%, 12 mg screen-and-treat group 95·3%, and 6 mg screen-and-treat group 95·0%). 82 days of iron supplementation increased mean haemoglobin concentration by 7·7 g/L (95% CI 3·2 to 12·2) in the control group. Both screen-and-treat regimens were significantly less efficacious at improving haemoglobin (-5·6 g/L [98·3% CI -9·9 to -1·3] in the 12 mg screen-and-treat group and -7·8 g/L [98·3% CI -12·2 to -3·5] in the 6 mg screen-and-treat group) and neither regimen met the preset non-inferiority margin of -5 g/L. The 12 mg screen-and-treat regimen reduced iron dosage to 6·1 mg per day and the 6 mg screen-and-treat regimen reduced dosage to 3·0 mg per day. 580 adverse events were observed in 316 participants, of which eight were serious adverse events requiring hospitalisation mainly due to diarrhoeal disease (one [1%] participant in the control group, three [2%] in the 12 mg screen-and-treat group, and four [3%] in the 6 mg screen-and-treat group). The most common causes of non-serious adverse events (n=572) were diarrhoea (145 events [25%]), upper respiratory tract infections (194 [34%]), lower respiratory tract infections (62 [11%]), and skin infections (122 [21%]). No adverse events were deemed to be related to the study interventions. The hepcidin-guided screen-and-treat strategy to target iron administration succeeded in reducing overall iron dosage, but was considerably less efficacious at increasing haemoglobin and combating iron deficiency and anaemia than was WHO's standard of care, and showed no differences in morbidity or safety outcomes. Bill & Melinda Gates Foundation and UK Medical Research Council.

Iron Supplementation May Selectively Reprofile the Gut Microbiome in Iron-Deficient Bangladeshi Infants

Children in low- and middle-income countries (LMICs) have a high burden of anemia, much of which is attributable to iron deficiency. The World Health Organization (WHO) recommends universal iron interventions in preschool-aged children in countries where there is a high anemia prevalence. However, oral iron supplementation is associated with increased risks of infection, including diarrhea. In small studies in Africa, iron has been shown to reprofile the intestinal microbiota leading to a reduction in commensal bacteria and an increase in pathogenic taxa. Gut dysbiosis has been implicated in the pathogenesis of gastrointestinal, autoimmune and inflammatory disease. The BRISC (Benefits and Risks of Iron Interventions in Children) trial was a double-blind, placebo-controlled randomized controlled trial of oral iron supplementation in 3,300 infants in Bangladesh. Children were randomized to receive one of iron syrup, iron-containing multiple micronutrient powder (MNP) or placebo daily for three months. The primary outcome of the trial was child cognitive development. Key findings from the trial were an improvement in hematological indices with iron but no effect on the functional outcomes assessed (Pasricha et al New Engl J Med 2021). We aimed to study the effect of iron on microbiome composition, diversity and function in the BRISC participants. To achieve this aim we undertook a substudy in which we collected stool samples from 925 children at the three time points of the main BRISC trial: at recruitment, end of intervention and at nine-month follow up. DNA was extracted and analyzed by 16S ribosomal RNA gene (rRNA) amplicon sequencing (2,339 samples across three timepoints) and shotgun metagenomics (965 samples across three timepoints). Episodes of infection were documented as per the main BRISC trial and included diarrhea, respiratory symptoms, antibiotic use, and clinic/hospital visits. The V4 hypervariable region of the 16S rRNA gene was amplified and sequenced on the Illumina MiSeq instrument together with negative and positive controls. Demultiplexed forward and reverse FASTQ files for each sample were trimmed and processed using the DADA2 package in RStudio, and taxonomy was assigned using the SILVA 138 SSU Ref NR 99 reference database. Control samples and samples with fewer than 500 reads were removed (2,284 samples met this minimum read threshold). Taxonomic, alpha diversity and beta diversity measures were conducted using phyloseq and microbiomeSeq packages in RStudio. Differential abundance was calculated by two separate methods: i. limma voom (using trimmed mean of M values [TMM] normalization and log transformation) and ii. ANCOM-BC (using additive log-ratio transformation). Prior to implementing differential abundance methods a filter was applied such that operational taxonomic units (OTUs) found in under 10% of samples were pruned from the samples. As previously reported, there was no overall significant increase in diarrhea incidence among participants receiving iron compared to those given placebo among BRISC trial participants. Baseline iron deficiency, anemia and iron deficiency anemia prevalence among substudy participants was 33%, 42% and 26% respectively. 16S rRNA analysis demonstrated that recent antibiotic (12% of children at end of intervention) was associated with a significant reduction in alpha diversity. Accordingly, analysis was conducted to exclude recent antibiotic use from analysis by intervention arm. Using this analysis, there were no significant differences in alpha or beta diversity between trial intervention groups at the end of intervention (alpha diversity by Shannon index shown in Figure 1). Members of Ruminococcus torques group (limma voom and ANCOM-BC) and Leuconostoc (limma voom only) were more abundant in the intestinal microbiota of children randomized to iron, but no genus was found to be differentially abundant when controlling for multiple comparisons. However, several bacterial genera were differentially abundant in children who were iron deficient at baseline who received iron. Two forms of analyses (Limma voom and ANCOM-BC) showed agreement in finding a reduction in Sutterella and Lactococcus species in iron deficient children receiving iron. These results are shown in Table 1. These data indicate that reprofiling of the intestinal microbiota in response to iron supplementation is dependent on baseline host iron status. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cost-effectiveness of universal iron supplementation and iron-containing micronutrient powders for anemia among young children in rural Bangladesh: analysis of a randomized, placebo-controlled trial

Universal provision of iron supplements or iron-containing multiple micronutrient powders (MNPs) is widely used to prevent anemia in young children in low- and middle-income countries. The BRISC (Benefits and Risks of Iron Interventions in Children) trial compared iron supplements and MNPs with placebo in children <2 y old in rural Bangladesh. We aimed to assess the cost-effectiveness of iron supplements or iron-containing MNPs among young children in rural Bangladesh. We did a cost-effectiveness analysis of MNPs and iron supplements using the BRISC trial outcomes and resource use data, and programmatic data from the literature. Health care costs were assessed from a health system perspective. We calculated incremental cost-effectiveness ratios (ICERs) in terms of US$ per disability-adjusted life-year (DALY) averted. To explore uncertainty, we constructed cost-effectiveness acceptability curves using bootstrapped data over a range of cost-effectiveness thresholds. One- and 2-way sensitivity analyses tested the impact of varying key parameter values on our results. Provision of MNPs was estimated to avert 0.0031 (95% CI: 0.0022, 0.0041) DALYs/child, whereas iron supplements averted 0.0039 (95% CI: 0.0030, 0.0048) DALYs/child, over 1 y compared with no intervention. Incremental mean costs were $0.75 (95% CI: 0.73, 0.77) for MNPs compared with no intervention and $0.64 ($0.62, $0.67) for iron supplements compared with no intervention. Iron supplementation dominated MNPs because it was cheaper and averted more DALYs. Iron supplementation had an ICER of $1645 ($1333, $2153) per DALY averted compared with no intervention, and had a 0% probability of being the optimal strategy at cost-effectiveness thresholds of $200 (reflecting health opportunity costs in Bangladesh) and $985 [half of gross domestic product (GDP) per capita] per DALY averted. Scenario and sensitivity analyses supported the base case findings. These findings do not support universal iron supplementation or micronutrient powders as a cost-effective intervention for young children in rural Bangladesh. This trial was registered at anzctr.org.au as ACTRN1261700066038 and trialsearch.who.int as U1111-1196-1125.

Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

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).

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial

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 < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015).ConclusionsCompared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B12 status in young Laotian children.Trial registrationThe trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015.

Gender differences in nutritional status and determinants among infants (6\u201311\xa0m): a cross-sectional study in two regions in Ethiopia

BackgroundA limited number of studies suggest that boys may have a higher risk of stunting than girls in low-income countries. Little is known about the causes of these gender differences. The objective of the study was to assess gender differences in nutritional status and its determinants among infants in Ethiopia.MethodsWe analyzed data for 2036 children (6–11 months old) collected as the baseline for a multiple micronutrient powders effectiveness study in two regions of Ethiopia in March–April 2015. Child, mother, and household characteristics were investigated as determinants of stunting and wasting. Multiple logistic regression models were used separately for boys and girls to check for gender differences while adjusting for confounders. The study is registered at http://www.clinicaltrials.gov/ with the clinical trials identifier of NCT02479815.ResultsStunting and wasting prevalence is significantly higher among boys compared to girls, 18.7 vs 10.7% and 7.9 vs 5.4%, respectively. Untimely initiation of breastfeeding, not-exclusive breastfeeding at the age of 6 months, region of residence, and low maternal education are significant predictors of stunting in boys. Untimely introduction to complementary food and low consumption of legumes/nuts are significant predictors of stunting in both boys and girls, and low egg consumption only in girls. Region of residence and age of the mother are significant determinants of wasting in both sexes. Analysis of interaction terms for stunting, however, shows no differences in predictors between boys and girls; only for untimely initiation of breastfeeding do the results for boys (OR 1.46; 95%CI 1.02,2.08) and girls (OR 0.88; 95%CI 0.55,1.41) tend to be different (p = 0.12).ConclusionIn Ethiopia, boys are more malnourished than girls. Exclusive breastfeeding and adequate dietary diversity of complementary feeding are important determinants of stunting in boys and girls. There are no clear gender interactions for the main determinants of stunting and wasting. These findings suggest that appropriate gender-sensitive guidance on optimum infant and young child feeding practices is needed.

Micronutrient intake status and associated factors among children aged 6-23 months in the emerging regions of Ethiopia: A multilevel analysis of the 2016 Ethiopia demographic and health survey.

Micronutrient (MN) deficiency among children is recognised as a major public health problem in Ethiopia. The scarcity of MNs in Ethiopia, particularly in pastoral communities, might be severe due to poor diets mitigated by poor healthcare access, drought, and poverty. To reduce MNs deficiency, foods rich in vitamin A (VA) and iron were promoted and programs like multiple micronutrient powder (MNP), iron and vitamin A supplements (VAS) and or deworming have been implemented. Nationally for children aged 6-23 months, consumption of four or more food groups from diet rich in iron and VA within the previous 24 hours, MNP and iron supplementation within seven days, and VAS and >75% of deworming within the last 6 months is recommend; however, empirical evidence is scarce. Therefore, this study aimed to assess the recommended MN intake status of children aged 6-23 months in the emerging regions of Ethiopia. Data from the Ethiopia Demographic and Health Survey 2016 were used. A two-stage stratified sampling technique was used to identify 1009 children aged 6-23 months. MN intake status was assessed using six options: food rich in VA or iron consumed within the previous 24 hours, MNP or iron supplementation with the previous seven days, VAS or deworming within six months. A multilevel mixed-effect logistic regression analysis was computed, and a p-value of < 0.05 and Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) were used to identify the individual and community-level factors. In this analysis, 37.3% (95% CI: 34.3-40.3) of children aged 6-23 months had not received any to the recommended MNs sources. The recommended MNs resulted; VAS (47.2%), iron supplementation (6.0%), diet rich in VA (27.7%), diet rich in iron (15.6%), MNP (7.5%), and deworming (7.1%). Antenatal care visit (AOR: 1.9, 95% CI: 1.4-2.8), work in the agriculture (AOR: 2.2, 95% CI: 1.3-3.8) and children aged 13 to 23 months (AOR: 1.7, 95% CI: 1.2-2.4) were the individual-level factors and also Benishangul (AOR: 2.2, 95% CI: 1.3-4.9) and Gambella regions (AOR: 1.9, 95% CI: 1.0-3.4) were the community-level factors that increased micronutrient intake whereas residence in rural (AOR: 0.4, 95% CI: 0.1-0.9) was the community-level factors that decrease micronutrient intake. Micronutrient intake among children aged 6-23 months in the pastoral community was low when compared to the national recommendation. After adjusting for individual and community level factors, women's occupational status, child's age, antenatal visits for recent pregnancy, residence and region were significantly associated with the MN intake status among children aged 6-23 months.

High adherence and its influencing factors on multiple micronutrient powders (MNPs).

Adherence to home fortification of foods with multiple micronutrient powders (MNPs) is an essential indicator of effective implementation of MNP programmes. A meta‐analysis was conducted to evaluate the high adherence rate (HAR) to MNPs and further investigate the factors that influence HAR. We searched PubMed, Web of Science, Embase, CAB s, MEDLINE (OVID), Cochrane Library, China National Knowledge Infrastructure, Wanfang and VP, from the date of database inception to 9 November 2020. We included peer‐reviewed observational studies that investigated adherence to MNPs. Data on the HAR to MNPs and influencing factors on HAR were extracted and then pooled together. A total of 10 studies were included. The pooled HAR to MNPs was 63.28% (51.12%–74.64%). Among HARs, rates were higher in middle‐income countries (65.21%) than low‐income countries (55.23%). Parental age over 30 years (maternal age OR = 1.25, 95% CI: 1.08–1.44; paternal age OR = 1.17, 95% CI: 1.04–1.32), children aged 18–36 months (OR = 1.45, 95% CI: 1.12–1.88), maternal educational attainment of college or above (OR = 1.38, 95% CI:1.10–1.73), caregiver with the perception that other mothers use MNPs (OR = 1.52, 95% CI:1.19–1.95), caregiver being aware of the importance of iron (OR = 1.42, 95% CI: 1.18–1.71), caregiver having correct knowledge of MNPs (OR = 1.36, 95% CI:1.19–1.57) and caregiver reporting children have no side effects from MNPs (OR = 2.77, 95% CI: 2.46–3.11) were contributing factors to high adherence to MNPs. The overall HAR to MNPs was relatively low; hence, effective and trusted communication channels need to be established, along with more thorough dissemination of the knowledge of MNPs to caregivers, to improve MNPs adherence rates, especially in low‐income countries.

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children.

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.

Perspective: Putting the youngest among us into the nutrition “call for action” for food fortification strategies

ABSTRACTAdequate iron intake is essential for optimal child development, but iron deficiency and anemia among infants and young children are widespread in low- and middle-income countries. Large-scale food fortification strategies hold great promise for reducing micronutrient deficiencies; however, for children <2 y of age, the impact of such strategies is limited because their intake of staple foods is relatively low and fortification levels are targeted at the adult population. Iron supplementation, iron fortification of foods targeted to infants, and point-of-use fortification with iron-containing products such as multiple micronutrient powders (MNPs) and small-quantity lipid-based nutrient supplements are evidence-based approaches recommended to reduce anemia among infants and young children when used in the right context. Since 2003, the WHO, with support from UNICEF, has recommended the use of MNPs to control iron deficiency. However, the percentage of children with anemia has changed very little over the past 10 y. Five years ago the UN declared a decade of action on nutrition, including World Health Assembly (WHA) targets for maternal, infant, and young child nutrition, yet the WHA set no anemia targets for children. In July 2020 the leaders of 4 UN agencies issued a call for action to protect children's right to nutrition in the face of the COVID-19 pandemic and beyond. Given persistently high rates of anemia among young children, the negative developmental impact, the challenge of meeting iron needs from typical complementary food diets, and the availability of successful evidence-based fortification strategies for this age group, we encourage planners, speakers, and donors at this year's UN Food Systems Summit and the Tokyo Nutrition for Growth Summit to 1) call for the WHA to set anemia targets for infants and young children and 2) promote investment in evidence-based interventions to improve the iron status of young children.