Micronutrient Powder Research Articles

Development of a Screening Tool to Estimate Vitamin A Intake and Comparison with Detailed Dietary Assessment Methods

Abstract Objectives We aimed to develop and validate a tool to estimate vitamin A (VA) intake and identify children at risk of intake above the tolerable upper intake level (UL). Methods We developed, pilot-tested, and refined a screening tool to estimate VA intake among Filipino children 12–18 mo of age. Data were entered into tablets with pre-loaded food composition data to calculate VA intake immediately. The screening tool was used to identify children likely to have “adequate” (one group: 200–500 µg retinol activity equivalents, RAE/d) or “high” (two groups: >600 µg retinol/d) intake. Interviewers administered four 24-h recalls, one 12-h observed weighed record with 12-h recall, and a 30-d supplement questionnaire. Breastmilk intake and VA concentration were measured among breastfeeding children. We compared the screening tool and detailed dietary assessment (DDA) results for primary VA sources, group mean usual intake, and prevalence of intakes above the UL. Results Major VA sources were similar between methods: fortified milk powders, multivitamin supplements, and breastmilk; contributions from intervention programs (e.g., micronutrient powders, fortified staple foods) were low. Mean usual retinol intakes for the high groups (n = 47 and 39, respectively) were 1218 and 1313 µg/d by screening tool vs. 1096 and 931 by DDA; 70 and 77% had usual intake above 600 µg/d. In the adequate group (n = 37), mean total VA intake was 375 and 559 µg RAE/d by screening and DDA, respectively. Conclusions This screening tool provides a reasonably good rapid estimate of VA intake among Filipino children and can be useful for identifying groups with adequate to excessive intakes. Funding Sources Bill & Melinda Gates Foundation.

Child Diet and Maternal Responsiveness Mediate Effects of a Responsive Stimulation and Nutrition Intervention on Child Growth and Development: Evidence from Rural Pakistan

Abstract Objectives To test the hypothesis that child diet and maternal responsiveness mediated the effects of an integrated responsive stimulation (RS) and enhanced nutrition (EN) intervention on child growth and development. Methods We used data from the Pakistan Early Child Development Scale-up (PEDS) cluster-randomized controlled trial which evaluated the effectiveness of the Lady Health Worker (LHW) Program in rural Pakistan from 2010–2012. LHWs were randomized into one of four intervention arms (20 LHWs each): (1) RS: UNICEF-WHO Care for Child Development package (locally adapted), (2) EN: EN education and multiple micronutrient powders for children 6–24 mo, (3) RS + EN, and (4) Control. LHWs delivered the interventions in routine monthly home visits and group sessions. Mother-child pairs were enrolled form birth to 24 mo (N = 1324). Primary outcomes were child growth (assessed with length-for-age Z-score (LAZ)) and development (assessed with the Bayley Scales of Infant and Toddler Development, Third Edition) at 12 and 24 mo. We examined whether child diet (assessed with the WHO indicator for minimum acceptable diet) and maternal responsiveness (assessed with the Observation of Mother-Child Interaction tool) at 12 mo mediated intervention effects at 24 mo. Structural equation modelling was used to estimate the total, direct and indirect (via child diet and maternal responsiveness) intervention effects on child growth and development at 24 mo. Results The RS, EN and RS + EN interventions improved cognitive, language and motor development at 24 mo, but had no significant effect on LAZ and socio-emotional development. Child diet and maternal responsiveness mediated intervention effects on cognitive development, whereas maternal responsiveness alone mediated intervention effects on language and motor development. Despite the lack of significant total intervention effects on LAZ and socio-emotional development, there were significant positive indirect effects on LAZ via maternal responsiveness and child diet, and on socio-emotional development via maternal responsiveness. Conclusions Child diet and maternal responsiveness are two important mechanisms which mediated the effect of a RS and EN intervention on child growth and development. Leveraging these mechanisms can help enhance the effectiveness of RS and EN interventions. Funding Sources None.

Ferrous Sulfate-Iron (60 mg/d) Does Not Increase Risks to Malarial Infectivity, Pathogenic Bacterial Proliferation or Other Adverse Effects in Non-Anemic Healthy Adults

Abstract Objectives A double-blind, placebo-controlled, randomized clinical trial was conducted to determine the effects of different modalities of supplementation with ferrous sulfate (FeSO4)-iron on the safety profiles of non-anemic, healthy adults. Methods Eligible volunteers (194) were screened for general health; 108 were enrolled and randomized to four treatment groups (n = 27): a placebo (corn starch), daily doses of FeSO4 providing 60 mg Fe/d with or without a 15-component multiple micronutrient powder (UNICEF), or single weekly doses of FeSO4 providing 420 mg Fe. Treatment materials were provided in opaque capsules that were physically similar. The following safety profile indicators were assessed both before and after 28 days of intervention: infectivity of subjects’ RBCs to Plasmodium falciparum determined ex vivo; proliferation potential of 5 species of pathogenic bacteria (Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia, Staphylococcus aureus, and Salmonella typhimurium) in subjects’ sera determined ex vivo; markers of inflammation (fecal calprotectin; serum myeloperoxidase, alpha-1 antitrypsin and TNFα); parameters of iron status (serum Fe, Hb, transferrin, % transferrin saturation, and ferritin). Adverse events were assessed by the study physician. Results Results showed that no treatment affected: i) 28-day changes in either fasting or post-prandial levels of any parameter of Fe status; ii) 28-day changes in markers of gut or systemic inflammation; iii) RBC susceptibility to P. falciparum; iv) ex vivo proliferation of and bacterial species except A. baumannii, for which the 28-day change in post-prandial peak growth rate index was less than that of the placebo treatment group; or v) subject reported adverse events, which were minimal. Conclusions These results indicate that administration of FeSO4 in these modalities to non-anemic, healthy adults are well tolerated and do not increase their risks to malarial infection and bacterial proliferation. Funding Sources The Bill and Melinda Gates Foundation U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. #58–1950-4–003.

The Benefits and Risks of Iron interventionS in Children (BRISC) trial: Statistical analysis plan.

Background: The Benefits and Risks of Iron interventionS in Children (BRISC) trial will evaluate the impact of universal supplementation with iron supplements or iron-containing multiple micronutrient powders (MNPs) compared with placebo given for 3 months on child development, growth, morbidity, laboratory indices of anaemia, iron deficiency, and inflammation at end of intervention and after a further 9 months post intervention in children aged 8 months living in rural Bangladesh. This paper describes the statistical analysis plan. Methods: BRISC is a multi-site, three-arm, double-dummy blinded, parallel group, randomised control superiority trial in 3300 children. The statistical analysis plan was developed by the trial statistician in consultation with the trial steering committee and trial management committee based on the protocol, data collection forms, and study outcomes available in the blinded study database. Conclusion: This detailed statistical analysis plan published prior to unblinding the allocated treatments will support the statistical analyses and reporting of the BRISC trial to be undertaken after unblinding. It allows for transparency as well as reproducibility of statistical analyses and reporting. Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000660381 (registered on 8 May 2017); World Health Organization Universal Trial Number U1111-1196-1125.

Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial

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 (< 65 μg/dL). At endline, geometric mean (95% CI) PZC were greater in the PZ and MNP groups compared with the TZ and control groups (P < 0.01), but hair zinc concentrations did not differ among groups (P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) μg/g) and the MNP (117.8 (113.3, 122.3) μg/g) groups than in the TZ group (110.4 (106.0, 114.8) μg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

An Integrated Infant and Young Child Feeding and Micronutrient Powder Intervention Does Not Affect Anemia, Iron Status, or Vitamin A Status among Children Aged 12–23 Months in Eastern Uganda

Background:Micronutrient powders (MNP) can reduce iron deficiency and anemia in children. Objective:We evaluated the impact of an integrated infant and young child feeding (IYCF)–MNP intervention on anemia and micronutrient status among children aged 12–23 mo in Eastern Uganda. The intervention focused on MNP distribution, IYCF education, and caregiver behavior change. Methods:Population-based cross-sectional surveys representative of children aged 12–23 mo in Amuria (intervention) and Soroti (nonintervention) districts were collected in June/July 2015 at baseline (n = 1260) and 12 mo after implementation at endline in 2016 (n = 1490). From pooled capillary blood, we assessed hemoglobin, malaria, ferritin, retinol binding protein (RBP), C-reactive protein, and α1-acid glycoprotein. Ferritin and RBP were regression-adjusted to correct for inflammation. Caregivers reported sociodemographic characteristics and MNP knowledge and practices. Linear regression estimated the difference-in-difference (DiD) effect of MNP on hemoglobin, ferritin, and RBP, and logistic regression estimated DiD effect of MNP on anemia (hemoglobin <11.0 g/dL), iron deficiency (ferritin <12.0 µg/L), iron deficiency anemia (hemoglobin <11.0 g/dL and ferritin <12.0 µg/L), and vitamin A deficiency (VAD; RBP equivalent to <0.70 µmol/L retinol: <0.79 µmol/L at baseline and RBP <0.67 µmol/L at endline). Results:In Amuria, 96% of children had ever consumed MNP versus <1% of children in Soroti. Fifty-four percent of caregivers reported organoleptic changes when MNP were added to foods cooked with soda ash. Adjusting for age, sex, malaria, recent morbidity, and household-level factors, the intervention was associated with –0.83 g/dL lower hemoglobin (95% CI, –1.36, –0.30 g/dL;P = 0.003) but not with anemia, ferritin, iron deficiency, iron deficiency anemia, RBP, or VAD. Conclusions:Despite high program fidelity, the intervention was associated with reduced hemoglobin concentrations but not with change in anemia or micronutrient status among children aged 12–23 mo in Eastern Uganda. Contextual factors, such as cooking with soda ash, might explain the lack of effectiveness.

Age, Ethnicity, Glucose-6-Phosphate Dehydrogenase Deficiency, Micronutrient Powder Intake, and Biomarkers of Micronutrient Status, Infection, and Inflammation Are Associated with Anemia Among Children 6–59 Months in Nepal

Anemia is a major concern for children in Nepal; however, little is known about context-specific causes of anemia. We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anemia in a nationally representative, population-based sample of children 6-59mo (n=1367). Hemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood samples. Soil-transmitted helminth (STH) and Helicobacter pylori infections were assessed from stool. Anthropometry was measured with standard procedures. Sociodemographic and household characteristics, diet, micronutrient powder (MNP) intake, pica, and morbidity recall were ascertained by caregiver interview. Multivariable logistic regression that accounted for complex sampling design, determined predictors of anemia (hemoglobin <11.0g/dL, altitude adjusted); candidate predictors were variables with P<0.05 in bivariate models. Anemia prevalence was 18.6% (95% CI: 15.8, 21.4). MNP intake [adjusted OR (AOR): 0.25, 95% CI: 0.07, 0.86], log (ln) ferritin (μg/L) (AOR: 0.49, 95% CI: 0.38, 0.64), and ln RBP (μmol/L) (AOR: 0.42, 95% CI: 0.18, 0.95) were associated with reduced odds of anemia. Younger age (6-23 mo compared with 24-59 mo; AOR: 2.29, 95% CI: 1.52, 3.46), other Terai ethnicities (AOR: 2.59, 95% CI: 1.25, 5.35) and Muslim ethnicities (AOR: 3.15, 95% CI: 1.30, 7.65) relative to Brahmin/Chhetri ethnicities, recent fever (AOR: 1.68, 95% CI: 1.08, 2.59), ln C-reactive protein (mg/L) (AOR: 1.23, 95% CI: 1.03, 1.45), and glucose-6-phosphate dehydrogenase deficiency (AOR: 2.84, 95% CI: 1.88, 4.30) were associated with increased odds of anemia. Both nonmodifiable and potentially modifiable factors were associated with anemia. Thus some but not all anemia might be addressed through effective public health policy, programs, and delivery of nutrition and infection prevention and control.

Malnutrition trends in Rohingya children aged 6-59 months residing in informal settlements in Cox's Bazar District, Bangladesh: An analysis of cross-sectional, population-representative surveys.

BackgroundMore than 700,000 ethnic Rohingya have crossed the border from Rakhine State, Myanmar to Cox’s Bazar District, Bangladesh, following escalated violence by Myanmar security forces. The majority of these displaced Rohingya settled in informal sites on previously forested land, in areas without basic infrastructure or access to services.Methods and findingsThree cross-sectional population-representative cluster surveys were conducted, including all informal settlements of Rohingya refugees in the Ukhia and Teknaf Upazilas of Cox’s Bazar District. The first survey was conducted during the acute phase of the humanitarian response (October–November 2017), and the second and third surveys were conducted 6 (April–May 2018) and 12 (October–November 2018) months later. Anthropometric indices (weight, height, mid-upper arm circumference [MUAC], oedema) and haemoglobin (Hb) were measured in children aged 6–59 months following standard procedures. Final samples for survey rounds 1, 2, and 3 (R1, R2, and R3) included 1,113, 628, and 683 children, respectively, of which approximately half were male (50.7%–53.5% per round) and a third were 6–23 months of age (32.4%–33.3% per round). Prevalence of global acute malnutrition (GAM) as assessed by weight for height in R2 (12.1%, 95% CI: 9.6–15.1) and R3 (11.0%, 95% CI: 8.4–14.2) represent a significant decline from the observed prevalence in R1 (19.4%, 95% CI: 16.8–22.3) (p < 0.001 for both comparisons). Overall, the prevalence of anaemia significantly declined (p < 0.001) between the first 2 rounds (47.9%, 95% CI: 44.1–51.7 and 32.3%, 95% CI: 27.8–37.1, respectively); prevalence increased significantly (p = 0.04) to 39.8% (95% CI, 34.1–45.4) during R3 but remained below R1 levels. Reported receipt of both fortified blended foods (12.8%) and micronutrient powders (10.3%) were low during R1 but increased significantly (p < 0.001 for both) within the first 6 months to 49.8% and 29.9%, respectively. Although findings demonstrate improvement in anthropometric indicators during a period in which nutrition programme coverage increased, causation cannot be determined from the cross-sectional design.ConclusionsThese data document significant improvements in both acute and micronutrient malnutrition among Rohingya children in makeshift settlements. These declines coincide with a scaleup of services aimed at prevention and treatment of malnutrition. Ongoing activities to improve access to nutritional services may facilitate further reductions in malnutrition levels to sustained below-crisis levels.

Use of concurrent evaluation to improve implementation of a home fortification programme in Bangladesh: a methodological innovation.

This paper focuses on the use of 'concurrent evaluation' to evaluate a nationally scaled-up programme in Bangladesh that was implemented by BRAC (an international development organisation) using Shasthya Shebika (SS) - volunteer community health workers - to promote home fortification with micronutrient powders (MNP) for children under-five. We developed a programme impact pathway to conceptualise the implementation and evaluation strategy and developed a strategic partnership among the key programme stakeholders for better use of evaluation evidence. We developed a multi-method concurrent evaluation strategy to provide insights into the BRAC programme and created provision for course correction to the implementation plan while it was in operation. One hundred sixty-four sub-districts and six urban slums in Bangladesh. Caregivers of children 6-59 months, SS and BRAC's staff members. The evaluation identified low awareness about home fortification among caregivers, inadequate supply and frequent MNP stockouts, and inadequate skills of BRAC's SS to promote MNP at the community level as hindrances to the achievement of programme goals. The partners regularly discussed evaluation results during and after implementation activities to assess progress in programme coverage and any needs for modification. BRAC initiated a series of corrections to the original implementation plan to address these challenges, which improved the design of the MNP programme; this resulted in enhanced programme outcomes. Concurrent evaluation is an innovative approach to evaluate complex real-world programmes. Here it was utilised in implementing a large-scale nutrition programme to measure implementation process and effectiveness.

Role of home visits by volunteer community health workers: to improve the coverage of micronutrient powders in rural Bangladesh.

We assessed the role of home visits by Shasthya Shebika (SS) - female volunteer community health workers (CHWs) - in improving the distribution of micronutrient powder (MNP), and explored the independent effects of caregiver-provider interaction on coverage variables. We used data from three cross-sectional surveys undertaken at baseline (n 1927), midline (n 1924) and endline (n 1540) as part of an evaluation of a home fortification programme. We defined an exposure group as one that had at least one SS visit to the caregiver's household in the 12 months preceding the survey considering three outcome variables - message (ever heard), contact (ever used) and effective coverage (regular used) of MNP. We performed multiple logistic regressions to explore the determinants of coverage, employed an 'interaction term' and calculated an odds ratio (OR) to assess the modifying effect of SS's home visits on coverage. Sixty-eight sub-districts from ten districts of Bangladesh. Children aged 6-59 months and their caregivers. A home visit from an SS positively impacts message coverage at both midline (ratio of OR 1·70; 95 % CI 1·25, 2·32; P < 0·01) and endline (ratio of OR 3·58; 95 % CI 2·22, 5·78; P < 0·001), and contact coverage both at midline (ratio of OR 1·48; 95 % CI 1·06, 2·07; P = 0·021) and endline (ratio of OR 1·74; 95 % CI 1·23, 2·47; P = 0·002). There was no significant effect of a SS's home visit on effective coverage. The households visited by BRAC's volunteer CHWs have better message and contact coverage among the children aged 6-59 months.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

Daily Supplementation With Egg, Cow Milk, and Multiple Micronutrients Increases Linear Growth of Young Children with Short Stature

Background:Childhood stunting is the most prevalent public health nutrition problem in low- and middle-income countries. Objective:This study aimed to determine whether daily supplementation in 12–18-mo-old undernourished Bangladeshi children with egg, cow milk, and multiple micronutrients improves linear growth. Methods:In the Bangladesh Environmental Enteric Dysfunction (BEED) study, a community-based intervention study, 12–18-mo-old children with length-for-age z score (LAZ) <1 were supplemented daily with an egg and 150 mL of milk for 90 feeding days, and 1 sachet of multiple micronutrient powder was provided daily for 60 feeding days. The change in LAZ over this period was compared with that in children of the same age and same baseline LAZ who were enrolled in the recently completed Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Dhaka birth cohort study conducted in the same community where no nutrition intervention was provided. Difference-in-difference (DID) analysis was done and the effect size was adjusted for other possible covariates using a generalized estimating equation in a regression model. Results:A total of 472 children with LAZ <1 completed the intervention and data were available for 174 children in the comparison group. Compared with the comparison group, adjusted DID analysis revealed a change in LAZ in the intervention group of +0.23 (95% CI: 0.18, 0.29; P < 0.05). In a subgroup analysis, the changes were +0.27 (95% CI: 0.18, 0.35; P < 0.05) in stunted (LAZ <2) children and +0.19 (95% CI: 0.12, 0.27; P< 0.05) in children at risk of stunting (LAZ -1 to -2). No allergic reactions or other adverse events related to milk and egg consumption were observed. Results:Daily directly observed milk, egg, and multiple micronutrient supplementation may improve linear growth of stunted children. A randomized controlled trial with longer duration of supplementation coupled with an additional intervention aimed at reducing pathogen burden is warranted to confirm these results. This trial was registered at clinicaltrials.gov as NCT02812615.

Factors associated with home visits by volunteer community health workers to implement a home-fortification intervention in Bangladesh: a multilevel analysis.

BRAC, an international development organization based in Bangladesh, engages community health workers called Shasthya Shebikas (SS) to implement home fortification of foods with micronutrient powders (MNP). We identified factors associated with home visits by SS, at different levels of the BRAC programme-delivery hierarchy, to implement home-fortification interventions. We conducted a cross-sectional survey, semi-structured interviews, and collected programme-related data from sub-districts included in the caregiver survey of BRAC's home-fortification programme and performed multilevel logistic regression modelling to investigate factors associated with home visits by SS. Sixty-eight sub-districts in Bangladesh. Caregivers of children aged 6-59 months (n 1408) and BRAC's SS (n 201). Households with older children (0·55; 0·42, 0·72; P < 0·001) and located >300 m from the SS's house (0·67; 0·50, 0·89; P = 0·006) were less likely to have been visited by the SS, whereas those with caregivers who had ≥5 years of schooling (1·53; 1·10, 2·12; P = 0·011) were more likely to have been visited by the SS (adjusted OR; 95 % CI). Households in the catchment area of older SS aged >50 years (0·44; 0·21, 0·90; P = 0·025) were less likely to have been visited by the SS, whereas those with SS who received incentives of >800 BDT (3·00; 1·58, 5·58; P = 0·001) were more likely to have been visited by the SS (adjusted OR; 95 % CI). The number of home visits is a function of the characteristics of SS, factors that characterize the households they serve and characteristics of their organizational context, particularly to implement home fortification of foods with MNP.

Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective strategies now exist to prevent them. This kind of malnutrition can have several immediate and long-term consequences, including stunted growth, a higher risk of acquiring infections, and poor development outcomes, all of which may lead to a child not achieving his or her full potential. This review systematically synthesizes the available evidence on the strategies used to prevent micronutrient malnutrition among children under-five in LMICs, including single and multiple micronutrient (MMN) supplementation, lipid-based nutrient supplementation (LNS), targeted and large-scale fortification, and point-of-use-fortification with micronutrient powders (MNPs). We searched relevant databases and grey literature, retrieving 35,924 papers. After application of eligibility criteria, we included 197 unique studies. Of note, we examined the efficacy and effectiveness of interventions. We found that certain outcomes, such as anemia, responded to several intervention types. The risk of anemia was reduced with iron alone, iron-folic acid, MMN supplementation, MNPs, targeted fortification, and large-scale fortification. Stunting and underweight, however, were improved only among children who were provided with LNS, though MMN supplementation also slightly increased length-for-age z-scores. Vitamin A supplementation likely reduced all-cause mortality, while zinc supplementation decreased the incidence of diarrhea. Importantly, many effects of LNS and MNPs held when pooling data from effectiveness studies. Taken together, this evidence further supports the importance of these strategies for reducing the burden of micronutrient malnutrition in children. Population and context should be considered when selecting one or more appropriate interventions for programming.

Balancing Safety and Potential for Impact in Universal Iron Interventions.

Almost 300 million children under 5 years of age are anemic worldwide. International policymakers recommend universal distribution of iron-based interventions - either iron supplements or iron-containing multiple micronutrient powders - to alleviate the burden of anemia in young children. When considering whether to implement universal iron interventions, it is essential to balance the putative benefits with possible risks. The key rationale for deploying universal iron interventions to reduce anemia in young children is to improve development, growth, and well-being. While plausible, few randomized controlled trials (RCTs) of iron interventions have carefully assessed these outcomes and there is currently inadequate evidence to support the hypothesis that universal iron interventions provide benefits on functional child health outcomes. Conversely, several important RCTs have found that when iron interventions are given to all children in a population, they may increase infection risk. Other possible risks of iron interventions have not yet been extensively described but include a risk of iron overdose and long-term iron loading in high-risk individuals. Identifying whether these interventions provide a net benefit or harm to populations is challenging. Until the quality of evidence for benefits improves, implementation of universal iron interventions in young children should be undertaken with caution.

Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial.

.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.

Effectiveness of a locally produced ready-to-use supplementary food in preventing growth faltering for children under 2 years in Cambodia: a cluster randomised controlled trial.

This cluster randomised controlled trial tested the effectiveness of a locally produced, fish‐based, ready‐to‐use supplementary food (RUSF) to prevent growth faltering (decline in z‐scores). Cambodian infants (n= 485), aged 6 to 11 months, were randomised by site to receive the RUSF, Corn‐Soy Blend++ (CSB++), micronutrient powders (MNP), or no supplement (control). The intervention was for 6 months. In unadjusted analysis, the control group had statistically significantly decreased weight‐for‐age z‐scores (WAZ; ‐0.02, 95%CI = ‐0.03 ‐ ‐0.01, P= 0.001) and height‐for‐age z‐scores (HAZ; ‐0.07, 95%CI = ‐0.09 ‐ ‐0.05, P < 0.001), and increased mid‐upper arm‐circumference (MUAC; 0.02cm, 95%CI = 0.01 ‐ 0.04, P = 0.010), but no statistically significant change in weight‐for‐height z‐scores (WHZ). The RUSF group did not differ significantly from the control for WAZ, HAZ or WHZ (in other words, WAZ and HAZ decreased and WHZ did not change), but had increased MUAC in comparison to the control (0.04cm, 95%CI = 0.01 ‐ 0.06, P = 0.008). There were no statistically significant differences between the RUSF group and the CSB++ or MNP groups with respect to WAZ, HAZ, WHZ or MUAC. Interestingly, in adjusted analysis, low consumers of RUSF had increased WAZ, WHZ and MUAC (0.03, 95%CI = 0.01‐0.06, P = 0.006; 0.04, 95%CI = 0.01‐0.08, P = 0.026; and 0.05cm, 95%CI = 0.02‐0.09, P = 0.004, respectively) compared with the control. The novel RUSF, particularly in small quantities, protected against ponderal growth faltering, but the improvements were of limited clinical significance.

Safe and effective delivery of supplemental iron to healthy older adults: The double-blind, randomized, placebo-controlled trial protocol of the Safe Iron Study

The forms of iron currently available to correct iron deficiency have adverse effects, including infectious diarrhea, increased susceptibility to malaria, inflammation and detrimental changes to the gut microbiome. These adverse effects limit their use such that the growing burden of iron deficiency has not abated in recent decades. Here, we summarize the protocol of the “Safe Iron Study”, the first clinical study examining the safety and efficacy of novel forms of iron in healthy, iron-replete adults. The Safe Iron Study is a double-blind, randomized, placebo-controlled trial conducted in Boston, MA, USA. This study compares ferrous sulfate heptahydrate (FeSO 4·H 2O) with two novel forms of iron supplements (iron hydroxide adipate tartrate (IHAT) and organic fungal iron metabolite (Aspiron™ Natural Koji Iron)). In Phase I, we will compare each source of iron administrated at a low dose (60 mg Fe/day). We will also determine the effect of FeSO 4 co-administrated with a multiple micronutrient powder and weekly administration of FeSO 4. The forms of iron found to produce no adverse effects, or adverse effects no greater than FeSO 4 in Phase I, Phase II will evaluate a higher, i.e., a therapeutic dose (120 mg Fe/day). The primary outcomes of this study include ex vivo malaria ( Plasmodium falciparum) infectivity of host erythrocytes, ex vivo bacterial proliferation (of selected species) in presence of host plasma and intestinal inflammation assessed by fecal calprotectin. This study will test the hypotheses that the novel forms of iron, administered at equivalent doses to FeSO 4, will produce similar increases in iron status in iron-replete subjects, yet lower increases in ex vivo malaria infectivity, ex vivo bacterial proliferation, gut inflammation. Ultimately, this study seeks to contribute to development of safe and effective forms of supplemental iron to address the global burden of iron deficiency and anemia. Registration: ClinicalTrials.gov identifier: NCT03212677; registered: 11 July 2017.

PROCOMIDA, a Food-Assisted Maternal and Child Health and Nutrition Program, Contributes to Postpartum Weight Retention in Guatemala: A Cluster-Randomized Controlled Intervention Trial

ABSTRACTBackgroundFood-assisted maternal and child health and nutrition (FA-MCHN) programs are widely used to reduce household food insecurity and maternal and child undernutrition in low- and middle-income countries. These programs, however, may unintentionally lead to excessive energy intake and unhealthy weight gain, especially in food-secure populations.ObjectiveWe evaluated the impact of an FA-MCHN program implemented in Guatemala on maternal weight from pregnancy to 24 mo postpartum. The program was earlier shown to reduce stunting.MethodsWe used a longitudinal, cluster-randomized controlled trial with arms varying in family ration size [full (FFR), reduced (RFR), none (NFR)] and individual maternal ration type [corn–soy blend (CSB), lipid-based nutrient supplement (LNS), micronutrient powder (MNP)]: A: FFR + CSB; B: RFR + CSB; C: NFR + CSB; D: FFR + LNS; E: FFR + MNP; F: control. Weight was measured during pregnancy and at 1, 4, 6, 9, 12, 18, and 24 mo postpartum. We used linear mixed models controlling for pregnancy weight with random cluster and mother effects. Data on 3535 women were analyzed.ResultsSignificant (P < 0.05) or marginally significant (P < 0.10) effects of 0.50–0.65 kg were found at all time points (except 9 mo) in arm A. Similar-sized effects were found in arms B (1, 4, 6, and 12 mo) and C (1 and 12 mo). Marginally significant effects (0.51–0.66 kg) were found in arm D (1, 6, 9, and 12 mo); in arm E, marginally significant effects (0.48–0.75 kg) were found from 6 to 24 mo.ConclusionsThe effect on maternal postpartum weight is of concern because of the high existing prevalence of overweight. Programs need to include “double-duty” objectives and actions, to ensure that addressing child undernutrition does not exacerbate the problem of unhealthy weight gain. This trial was registered at clinicaltrials.gov as NCT01072279.

A Fortified Food Can Be Replaced by Micronutrient Supplements for Distribution in a Mexican Social Protection Program Based on Results of a Cluster-Randomized Trial and Costing Analysis

ABSTRACTBackgroundDespite positive nutrition impacts, the prevalence of malnutrition among beneficiaries of Mexico's conditional cash transfer (CCT) program remains high. Greater nutrition impact may have been constrained by the type of nutritional supplements provided.ObjectiveThe objective of this study was to inform a potential modification to the supplements distributed to pregnant and lactating women and children.MethodsImpact was assessed using 2 cluster-randomized trials (pregnant women, children) run simultaneously. Communities (n = 54) were randomly assigned to the fortified foods provided by the program (Nutrivida women, Nutrisano children) or alternatives: tablets (women), syrup (children), or micronutrient powders for women (MNP-W) and children (MNP-C). Each supplement for women/children contained the same micronutrients based on the formulations of Nutrivida and Nutrisano, respectively. Pregnant women (aged >18 y) were recruited before 25 weeks of gestation and followed to 3 mo postpartum. Children aged 6–12 mo were recruited and followed to age 24 mo. Primary outcomes were anemia for women and length growth for children. Statistical analyses appropriate for cluster-randomized designs were used, and structural equation modeling to estimate dose-response effects. Supplement costs per beneficiary (daily dose for 18 mo) were estimated for production and distribution.ResultsThere was no significant difference in change of anemia prevalence between supplement groups in women, or in length growth between groups in children. One daily dose of any supplement was associated with 0.8 cm greater length growth. From baseline to age 24 mo, the prevalence of anemia in the Nutrisano, syrup, and MNP-C groups decreased by 36.7, 40.8, and 37.9 percentage points, respectively (within-group, P < 0.05; between groups, P > 0.05). Costs per beneficiary ranged from $12.1 (MNP-C) to $94.8 (Nutrivida).ConclusionsThe CCT program could distribute alternative supplements at lower cost per beneficiary without compromising potential for impact. Acceptance among beneficiaries should also be considered in choice of alternatives. This trial was registered at www.clinicaltrials.gov as NCT00531674.