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Background: Complementary food supplements (CFSs) can enhance growth where stunting is common, but substitution for the usual diet may reduce observed benefits. Objective: We aimed to characterize dietary diversity from home foods in a CFS efficacy trial and determine whether supplementation reduced breastfeeding frequency or displaced home foods. Design: In a cluster-randomized controlled trial in rural Bangladesh, children (n = 5499) received, for 1 y starting at age 6 mo, periodic child feeding counseling for mothers (control) or counseling plus 1 of 4 CFSs fed as a daily snack. Breastfeeding status and past 24-h diet were assessed at enrollment and every 3 mo thereafter until 18 mo of age. A 7-food group dietary diversity score (DDS) was calculated from home foods only, and a DDS ≥4 constituted minimum dietary diversity (MDD). Results: Most children (97%) were breastfed through 18 mo of age, and 24-h breastfeeding frequency did not differ by supplementation group. Child dietary diversity was low; only 51% of children met the MDD by 18 mo. Rice, potatoes, and biscuits (cookies) were the most frequently consumed foods, whereas the legumes, dairy, eggs, and vitamin A-rich fruit and vegetable food groups were each consumed by <50% of children. The odds of meeting the MDD through the consumption of home foods were equal or greater in the supplemented groups compared with the control group at all ages. High socioeconomic status and any maternal education were associated with increased odds of MDD at age 18 mo, whereas child sex and household food security were not associated with MDD. Conclusions: In a setting where daily complementary food supplementation improved linear growth, there was no evidence that supplementation displaced breastfeeding or home foods, and the supplementation may have improved dietary diversity. Pathways by which supplementation with fortified foods may enhance dietary diversity, such as an improved appetite and increased body size, need elucidation. This trial was registered at clinicaltrials.gov as NCT01562379. [ABSTRACT FROM AUTHOR]

Background: Childhood undernutrition may have prenatal origins, and the impact of prenatal interventions on postnatal growth is not well known. Objective: We assessed the effects of prenatal multiple micronutrient (MM) supplementation on child growth and cognitive development. Design: In a cluster-randomized controlled trial in rural Bangladesh, prenatal MM supplementation compared with iron-folic acid (IFA) supplementation was examined for its impact on growth assessed longitudinally from birth up to 24 mo of age (n = 8529) and, in a subsample (n = 734), on cognitive function at 24 mo of age by use of the Bayley scales of infant and toddler development–third edition test. Results: Prevalence of stunting at birth [length for age z score (LAZ): <−2] was 31.9% in the MM and 35.7% in the IFA groups (P < 0.001); however, LAZ increased during the first 3–4 mo in both groups. With the use of a linear random-effects model, prenatal MM-exposed children sustained a higher mean predicted LAZ of ∼0.10 at 1 and 3 mo and 0.06 at 6 mo of age compared with children in the IFA group. Supplementation reduced the prevalence of stunting at 1 (RR: 0.95; 95% CI: 0.92, 0.98) and 3 (RR: 0.91; 95% CI: 0.88, 0.94) mo of age. Differences between groups were absent by 6, 12, and 24 mo of age, when nearly 50% of children had stunted growth. Ponderal and linear growth velocities were somewhat slower from 3 to 12 mo of age in the MM group than in the IFA group, but not from 12 to 24 mo of age. There was no difference between groups on composite scores of cognition, language, and motor performance at 24 mo of age. Conclusions: In this Bangladeshi trial, maternal pre- and postnatal MM supplementation resulted in improvements in LAZ and reduction in stunting through 3 mo of age, but not thereafter and had no impact on cognitive and motor function at 2 y. This trial was registered at clinicaltrials.gov as NCT000860470. [ABSTRACT FROM AUTHOR]

Background: The term vitamin E describes a family of 8 vitamers, 1 of which is α-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations.Objective: To improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with α- and γ-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6-8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (α-tocopherol <12 μmol/L).Methods: Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between α-tocopherol status and relative protein abundance and to predict deficiency.Results: We quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with α-tocopherol (false discovery rate, q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo)C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma α-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma γ-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability.Conclusions: In this undernourished population of children in South Asia, quantitative proteomics identified a large plasma α-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered with clinicaltrials.gov as NCT00115271. [ABSTRACT FROM AUTHOR]

Background: Growth faltering in the first 2 years of life is high in South Asia where prevalence of stunting is estimated at 40-50%. Although nutrition counselling has shown modest benefits, few intervention trials of food supplementation exist showing improvements in growth and prevention of stunting.Methods: A cluster-randomized controlled trial was conducted in rural Bangladesh to test the effect of two local, ready-to-use foods (chickpea and rice-lentil based) and a fortified blended food (wheat-soy-blend++, WSB++) compared with Plumpy'doz, all with nutrition counselling vs nutrition counselling alone (control) on outcomes of linear growth (length and length-for-age z-score, LAZ), stunting (LAZ < -2), weight-for-length z-score (WLZ) and wasting (WLZ < -2) in children 6-18 months of age. Children (n = 5536) were enrolled at 6 months of age and, in the food groups, provided with one of the allocated supplements daily for a year.Results: Growth deceleration occurred from 6 to 18 months of age but deceleration in LAZ was lower (by 0.02-0.04/month) in the Plumpy'doz (P = 0.02), rice-lentil (< 0.01), and chickpea (< 0.01) groups relative to control, whereas WLZ decline was lower only in Plumpy'doz and chickpea groups. WSB++ did not impact on these outcomes. The prevalence of stunting was 44% at 18 months in the control group, but lower by 5-6% (P ≤ 0.01) in those receiving Plumpy'doz and chickpea. Mean length and LAZ at 18 months were higher by 0.27-0.30 cm and 0.07-0.10 (all P < 0.05), respectively, in all four food groups relative to the control.Conclusions: In rural Bangladesh, small amounts of daily fortified complementary foods, provided for a year in addition to nutrition counselling, modestly increased linear growth and reduced stunting at 18 months of age. [ABSTRACT FROM AUTHOR]

Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those <5 years of age. Folic acid taken in early pregnancy can prevent neural tube defects. Folate is essential for DNA synthesis and repair, and deficiency results in macrocytic anemia. Vitamin A deficiency is the leading cause of blindness worldwide and also impairs immune function and cell differentiation. Single MNDs rarely occur alone; often, multiple MNDs coexist. The long-term consequences of MNDs are not only seen at the individual level but also have deleterious impacts on the economic development and human capital at the country level. Perhaps of greatest concern is the cycle of MNDs that persists over generations and the intergenerational consequences of MNDs that we are only beginning to understand. Prevention of MNDs is critical and traditionally has been accomplished through supplementation, fortification, and food-based approaches including diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions. © 2015 National Institutes of Health (NIH). Annals of Nutrition and Metabolism published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. Objective: We sought to determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh. Design: A case-cohort study in 1605 pregnant Bangladeshi women [median (IQR) gestational age: 10 wk (8-13 wk)] who participated in a placebo-controlled vitamin A- or β-carotene-supplementation trial was done to assess ORs of miscarriage in women with low α-tocopherol (<12.0 μmol/L) and γ-tocopherol (<0.81 μmol/L; upper tertile cutoff of the γ-tocopherol distribution in women who did not miscarry). Results: In all women, plasma α- and γ-tocopherol concentrations were low [median (IQR): 10.04 mmol/L (8.07-12.35 μmol/L) and 0.66 μmol/L (0.50-0.95 μmol/L), respectively]. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m²) ≥18.5 and serum ferritin concentration ≤150 mg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. Conclusions: In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822. [ABSTRACT FROM AUTHOR]

Background Inadequate energy and micronutrient intake during childhood is a major public health problem in developing countries. Ready-to-use supplementary food (RUSF) made of locally available food ingredients can improve micronutrient status and growth of children. The objective of this study was to develop RUSF using locally available food ingredients and test their acceptability. Methods A checklist was prepared of food ingredients available and commonly consumed in Bangladesh that have the potential of being used for preparing RUSF. Linear programming was used to determine possible combinations of ingredients and micronutrient premix. To test the acceptability of the RUSF compared to Pushti packet (a cereal based food-supplement) in terms of amount taken by children, a clinical trial was conducted among 90 children aged 6- 18 months in a slum of Dhaka city. The mothers were also asked to rate the color, flavor, mouth-feel, and overall liking of the RUSF by using a 7-point Hedonic Scale (1 = dislike extremely, 7 = like extremely). Results Two RUSFs were developed, one based on rice-lentil and the other on chickpea. The total energy obtained from 50 g of rice-lentil, chickpea-based RUSF and Pushti packet were 264, 267 and 188 kcal respectively. Children were offered 50 g of RUSF and they consumed (mean ± SD) 23.8 ± 14 g rice-lentil RUSF, 28.4 ± 15 g chickpea based RUSF. Pushti packet was also offered 50 g but mothers were allowed to add water, and children consumed 17.1 ± 14 g. Mean feeding time for two RUSFs and Pushti packet was 20.9 minutes. Although the two RUSFs did not differ in the amount consumed, there was a significant difference in consumption between chickpea-based RUSF and Pushti packet (p = 0.012). Using the Hedonic Scale the two RUSFs were more liked by mothers compared to Pushti packet. Conclusions Recipes of RUSF were developed using locally available food ingredients. The study results suggest that rice-lentil and chickpea-based RUSF are well accepted by children. [ABSTRACT FROM AUTHOR]

Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple nutrient:protein associations that reflect biological function and nutritional status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y-old Nepalese children, we estimated cross-sectional correlations between vitamins A (retinol), D (25-hydroxwitamin D), and E (α-tocopherol), copper, and selenium, measured by conventional assays, and relative abundance of their major plasma-bound proteins, measured by quantitative proteomics using 8-plex iTRAQ mass tags. The prevalence of low-to-deficient status was 8.8% (<0.70/µmol/L) for retinol, 19.2% (<50 nmol/L) for 25-hydroxyvitamin D, 17.6% (<9.3/µmol/L) for α-tocopherol, 0% (<10/µmol/L) for copper, and 13.6% (<0.6/µmol/L) for selenium. We identified 4705 proteins, 982 in >50 children. Employing a linear mixed effects model, we observed the following correlations: retinol:retinol-binding protein 4 (r = 0.88), 25-hydroxyvitamin D:vitamin D-binding protein (r = 0.58), α-tocopherol:apolipoprotein C-Ill (r= 0.64), copper:ceruloplasmin (r = 0.65), and selenium: selenoprotein P isoform 1 (r = 0.79) (all P < 0.0001), passing a false discovery rate threshold of 1% (based on P value-derived q values). Individual proteins explained 34-77% (R² of variation in their respective nutrient concentration. Adding second proteins to models raised R² to 48-79%, demonstrating a potential to explain additional variation in nutrient concentration by this strategy. Plasma proteomics can identify and quantify protein biomarkers of micronutrient status in undernourished children. The maternal micronutrient supplementation trial, from which data were derived as a follow-up activity, was registered at clinical trials. gov as NCT00115271. [ABSTRACT FROM AUTHOR]

Background: Micronutrient deficiencies may be related to poor fetal growth and short gestation. Few studies have investigated the contribution of maternal vitamin A deficiency to these outcomes. Objective: In rural northwestern Bangladesh, we examined the effects of weekly antenatal vitamin A and β-carotene supplementation on birth weight, length, circumferential body measures, and length of gestation. Design: With the use of a cluster-randomized, placebo-controlled trial design, pregnant women were enrolled in the first trimester and began receiving their allocated supplements (vitamin A, β-carotene, or placebo) weekly until 3 mo postpartum. Birth anthropometric measures were made at home. Results: Of 13,709 newborns whose birth weight was measured within 72 h of birth, mean (±SD) weight was 2.44 ± 0.42 kg, the prevalence of low birth weight (LBW) was 54.4%, and that of small-for-gestational age (SGA) was 70.5%. Birth weight, length, and chest, head, and arm circumferences did not differ between supplementation and placebo groups nor did rates of LBW and SGA. Mean gestational age at birth was 38.3 ± 2.9 wk, and 25.6% of births occurred before 37 wk. Neither gestational age nor preterm birth rate differed with vitamin A or β-carotene supplementation. Conclusions: In this rural South Asian population with a high burden of LBW and preterm birth but modest levels of maternal vitamin A deficiency, antenatal vitamin A or /β-carotene supplementation did not benefit these birth outcomes. Other nutritional and nonnutritional interventions should be examined to reduce risks of these adverse outcomes in rural South Asia. This trial was registered at clinicaltrials. gov as NCT00198822. [ABSTRACT FROM AUTHOR]

Plasma volume expansion has been associated with fetal growth. Our objective was to examine the associations between maternal nutritional status in early pregnancy and extracellular water (ECW), total body water (TBW), and percentage plasma volume change across pregnancy. In a subsample of 377 pregnant women participating in a cluster-randomized trial of micronutrient supplementation, hemoglobin, hematocrit, and multi-frequency bioelectrical impedance were measured at ~10, 20, and 32 wk of gestation. In early pregnancy, women were short (mean ± SD, 148.9 ± 5.3 cm) and thin (19.5 ± 2.5 kg/m(2)). In mixed-effects multiple regression models, a 1-unit higher BMI at ~10 wk was associated with higher ECW and TBW (0.27 and 0.66 kg per kg/m(2), respectively; P < 0.01) at ~10, ~20, and ~32 wk. Height was also positively associated with ECW and TBW at each time point. Early pregnancy BMI was negatively associated with gains in ECW and TBW (-0.06 and -0.14 kg per kg/m(2), respectively; P < 0.01) from 10 to 20 wk, but not with 20- to 32-wk gains after accounting for weight gain. BMI was positively associated with percentage changes in plasma volume from 20 to 32 wk (0.57% per kg/m(2); P < 0.05). Height was not associated with changes in body water or plasma volume. Women with low BMI and height in early pregnancy have lower ECW and TBW in early, mid, and late pregnancy and lower late pregnancy plasma volume expansion, potentially increasing risk of fetal growth restriction. [ABSTRACT FROM AUTHOR]

Nasopharyngeal (NP) carriage of S. pneumoniae (Spn) is a risk factor for pneumococcal disease and its transmission. We assessed the impact of vitamin A (VA) supplementation shortly after birth in reducing Spn colonization in early infancy in rural Bangladesh. We recruited 500 infants participating in a cluster-randomized trial that reported a 15% reduction in mortality following receipt of an oral dose of VA (52.25 μmol( compared to placebo. NP specimens were collected at the age of 3 mo to study the effect of VA on the prevalence of culture-confirmed Spn. Analyses were conducted by intention to treat. Spn carriage prevalence did not differ between VA and placebo recipients [OR = 0.83 195% Cl: 0.55-1.27); P = 0.390]. Spn carriage at the age of 3 mo was not lowered by VA given at birth. Results are similar to those from an Indian study in which impact on Spn carriage was assessed at the age of 4 mo [OR = 0.73 195% Cl: 0.48-1.10); P= 0.128]. The point estimate of the pooled effect size for the 2 studies is OR = 0.78 [(95% Cl: 0.58-1.04); P= 0.095], which may imply a modest impact on carriage. If so, then the evidence thus far would suggest that Spn carriage reduction is unlikely to be a primary ancillary benefit of newborn VA supplementation. [ABSTRACT FROM AUTHOR]

The long-term benefits of antenatal iron supplementation in child survival are not known. In 1999–2001, 4,926 pregnant women in rural Nepal participated in a cluster-randomized, double-masked, controlled trial involving 4 alternative combinations of micronutrient supplements, each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls, who received vitamin A only. They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival. Of 4,130 livebirths, 209 infants died in the first 3 months and 8 were lost to follow-up. Of those remaining, 3,761 were followed, 150 died between ages 3 months and 7 years, and 152 were lost to follow-up. Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group, as follows: folic acid, 13.4; folic acid-iron, 10.3; folic acid-iron-zinc, 12.0; multiple micronutrients; 14.0; and controls, 15.2. Hazard ratios were 0.90 (95% confidence interval (CI): 0.65, 1.22), 0.69 (95% CI: 0.49, 0.99), 0.80 (95% CI: 0.58, 1.11), and 0.93 (95% CI: 0.66, 1.31), respectively, in the 4 supplementation groups. Maternal iron-folic acid supplementation reduced mortality among these children by 31% between birth and age 7 years. These results provide additional motivation for strengthening antenatal iron-folic acid programs. [ABSTRACT FROM PUBLISHER]

Iron deficiency is one of the main causes of anemia during pregnancy, although other micronutrient deficiencies may play a role. We examined the effects of daily antenatal and postnatal supplementation with four combinations of micronutrients on maternal hematologic indicators in a double-masked randomized controlled community trial. Communities, called sectors, were randomly assigned to supplementation with folic acid (400 microg), folic acid plus iron (60 mg), folic acid plus iron and zinc (30 mg) and folic acid plus iron, zinc and 11 other micronutrients, each at the approximate recommended daily allowance for pregnancy all given with vitamin A as retinol acetate (1000 microg retinol equivalent), or vitamin A alone as the control group. Hemoglobin (Hb) and indicators of iron status were assessed at baseline and at 32 wk of gestation. At 6-wk postpartum, Hb assessment was repeated using a finger stick. Severely anemic women (Hb < 70 g/L) were treated according to WHO recommendations. Folic acid alone had no effect on maternal anemia or iron status. Hb concentrations were 14 g/L, [95% confidence limits (CL), 8.3-19.2], 10.0 g/L (CL, 5.2-14.8) and 9.4 g/L (CL, 4.7-14.1) higher in the groups receiving folic acid plus iron, folic acid plus iron and zinc and folic acid plus iron, zinc and multiple micronutrients, respectively, relative to the control. Anemia in the third trimester was reduced by 54% with folic acid plus iron, by 48% with folic acid plus iron and zinc and by 36% with folic acid plus iron, zinc and multiple micronutrients supplementation, relative to the control (P < 0.05). Thus, the combinations of folic acid plus iron and zinc and folic acid plus iron, zinc and multiple micronutrients provided no additional benefit in improving maternal hematologic status during pregnancy compared with folic acid plus iron. The level of compliance and baseline Hb concentrations modified the effect of iron. [ABSTRACT FROM AUTHOR]

A randomized community trial was carried out in Aceh, Indonesia, 1982-1984, to assess the impact of semiannual vitamin A (VA) supplementation (60 000 µg RE) on preschool child growth: 229 villages were randomized to VA program and 221 to control status. One thousand thirty-two program and 980 control children aged 1-5 y were assessed and followed for 12 mo. VA program males gained an additional ~110 g weight at age 2-3 y (NS), 190 g at age 4 y (p < 0.05), and 263 g at age 5 y over control males (p < 0.01). Arm circumference and muscle area expanded 2 mm (p < 0.05) and ~36 mm² (p < 0.05) more per year, respectively, from ages 3 to 5 y of age and more arm fat was retained at every age (p < 0.05 at 1 and 3 y) in VA males. There were no group differences in ponderal growth for females or in linear growth for either sex. VA supplementation may improve growth where endemic deficiency exists. [ABSTRACT FROM AUTHOR]

Mortality of Sumatran children living in villages randomized to participate in a vitamin A capsule (200 000 IU) distribution program who received the capsule (n = 9776) was compared with those who did not (n = 2447) and with children living in villages randomized to serve as control subjects (n = 12 173). During the 4 mo after completion of the first distribution, mortality among preschool capsule recipients was < 4% that of nonrecipients (p < 0.001). Mortality among preschool nonrecipients was three times that of controls (p < 0.05), suggesting strong selection bias. The potential biologic impact on childhood mortality attributable to vitamin A supplementation is estimated to exceed the 34% previously derived from the more conservative intent-to-treat analysis. One capsule every 6 mo may provide adequate protection for the vast majority of children. The single major limitation to maximum impact appears to be inadequate program coverage. [ABSTRACT FROM AUTHOR]