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Adequate micronutrient intake and status are global public health goals. Vitamin and mineral deficiencies are widespread and known to impair health and survival across the life stages. However, knowledge of molecular effects, metabolic pathways, biological responses to variation in micronutrient nutriture, and abilities to assess populations for micronutrient deficiencies and their pathology remain lacking. Rapidly evolving methodological capabilities in genomics, epigenomics, proteomics, and metabolomics offer unparalleled opportunities for the nutrition research community to link micronutrient exposure to cellular health; discover new, arguably essential micronutrients of microbial origin; and integrate methods of molecular biology, epidemiology, and intervention trials to develop novel approaches to assess and prevent micronutrient deficiencies in populations. In this review article, we offer new terminology to specify nutritional application of multiomic approaches and encourage collaboration across the basic to public health sciences to advance micronutrient deficiency prevention. [ABSTRACT FROM AUTHOR]

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated the relative quantification of plasma proteins assessed via a multiplexed aptamer assay (SOMAScan®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate <0.05. We examined potential pathways using principal component analysis. A total of 147 and 879 of 6431 detected plasma proteins correlated with AGP and CRP, respectively, of which 61 overlapped with both biomarkers. Positive correlates included serum amyloid, complement, interferon-induced, and immunoregulatory proteins. Negative correlates were micronutrient and lipid transporters and pregnancy-related anabolic proteins. The principal components (PCs) of AGP were dominated by negatively correlated anabolic proteins associated with gestational homeostasis, angiogenesis, and neurogenesis. The PCs of CRP were more diverse in function, reflecting cell surface and adhesion, embryogenic, and intracellular and extra-hepatic tissue leakage proteins. The plasma proteome of AGP or CRP reveals wide proteomic variation associated with early gestational inflammation, suggesting mechanisms and pathways that merit future research. [ABSTRACT FROM AUTHOR]

BackgroundWe had a unique opportunity to examine demographic determinants of household mobile phone ownership in rural Bangladesh using socioeconomic data collected as part of a multiyear longitudinal cohort study of married women of reproductive age. ObjectivesThis paper explores how the demographics of household mobile phone owners have changed over time in a representative population of rural Bangladesh. MethodsWe present data collected between 2008 and 2011 on household mobile phone ownership and related characteristics including age, literacy, education, employment, electricity access, and household wealth among 35,306 individuals. Respondents were enrolled when found to be newly pregnant and contributed socioeconomic information once over the course of the time period serving as a “sample” of families within the population at that time. Univariate and multiple logistic regressions analyses were performed to identify the socioeconomic determinants of household phone ownership. ResultsAcross 3 fiscal years, we found that reported household ownership of at least 1 working mobile phone grew from 29.85% in the first fiscal year to 56.07% in the third fiscal year. Illiteracy, unavailability of electricity, and low quartiles of wealth were identified as overall demographic constraints to mobile phone ownership. However, over time, these barriers became less evident and equity gaps among demographic status began to dissipate as access to mobile technology became more democratized. We saw a high growth rate in ownership among households in lower economic standing (illiterate, without electricity, low and lowest wealth index), likely a result of competitive pricing and innovative service packages that improve access to mobile phones as the mobile phone market matures. In contrast, as market saturation is rapidly attained in the most privileged demographics (literate, secondary schooling, electricity, high wealth index), members of the lower wealth quartiles seem to be following suit, with more of an exponential growth. ConclusionsUpward trends in household mobile phone ownership in vulnerable populations over time underline the potential to leverage this increasingly ubiquitous infrastructure to extend health and finance services across social and economic strata.

OBJECTIVES: Early infant mortality has not declined as rapidly as child mortality in many countries. Identification of risk factors for early infant mortality may help inform the design of intervention strategies. METHODS: Over the period 1994-97, 15 469 live-born, singleton infants in rural Nepal were followed to 24 weeks of age to identify risk factors for mortality within 0-7 days, 8-28 days, and 4-24 weeks after the birth. FINDINGS: In multivariate models, maternal and paternal education reduced mortality between 4 and 24 weeks only: odds ratios (OR) 0.28 (95% confidence interval (CI) = 0.12-0.66) and 0.63 (95% CI = 0.44-0.88), respectively. Miscarriage in the previous pregnancy predicted mortality in the first week of life (OR =1.98, 95% CI = 1.37-2.87), whereas prior child deaths increased the risk of post-neonatal death (OR =1.85, 95% CI 1.24-2.75). A larger maternal mid_upper arm circumference reduced the risk of infant death during the first week of life (OR = 0.88, 95% CI = 0.81-0.95). Infants of women who did not receive any tetanus vaccinations during pregnancy or who had severe illness during the third trimester were more likely to die in the neonatal period. Maternal mortality was strongly associated with infant mortality (OR = 6.43, 95% CI = 2.35-17.56 at 0-7 days; OR =11.73, 95% CI = 3.82-36.00 at 8-28 days; and OR = 51.68, 95% CI = 20.26-131.80 at 4-24 weeks). CONCLUSION: Risk factors for early infant mortality varied with the age of the infant. Factors amenable to intervention included efforts aimed at maternal morbidity and mortality and increased arm circumference during pregnancy.

OBJECTIVE: To investigate the length of time following pregnancy during which the risk of mortality was elevated among women in rural Nepal. METHODS: An analysis was performed of prospective data on women participating in the control group of a large, population-based trial. Weekly visits were made for three years to 14 805 women aged 14-45 years. Pregnancy and vital status were assessed. A total of 7325 pregnancies were followed. Mortality during and following pregnancy, expressed on a person-time basis, was compared to referent mortality unrelated to pregnancy (52 weeks after pregnancy) in the same cohort. FINDINGS: The relative risk (RR) of death during pregnancy but before the onset of labour was 0.93 (95% confidence interval (CI): 0.38-2.32). During the perinatal period, defined as lasting from the onset of labour until seven days after outcome, the RR of death was 37.02 (95% CI: 15.03-90.92). The RR for 2 to 6 weeks, 7 to 12 weeks, and 13 to 52 weeks after pregnancy were 4.82, 2.59 and 1.01 with 95% CI of 1.77-13.07, 0.81-8.26 and 0.40-2.53, respectively. The RR of death was 2.21 (95% CI. 1.03-4.71) during the conventional maternal mortality period (pregnancy until 6 weeks after outcome). It was 2.26 (95% CI: 1.05-4.90) when the period was extended to 12 weeks after pregnancy outcome. CONCLUSION: The risk of mortality associated with pregnancy should be assessed over the first 12 weeks following outcome instead of over the first 6 weeks.

Introduction Impaired nutritional status is a recognized risk factor for bacterial infections[1], and both are common causes of morbidity and mortality among institutionalized elderly people[2, 3]. Vitamin A, termed the [...]

Palestine refugees comprise the largest refugee population in the world, most of whom are encamped in Middle Eastern countries. In the Gaza Strip, where ∼1.4 million Palestinians reside, there are high prevalences of anemia and multiple micronutrient deficiencies (MNDs), including those of iron, zinc, vitamins A, B12, D, and E, ranging from 11.4% to 84.7% among pregnant women and 2.9% to 70.9% among preschool children. Dietary diversification and adequate food fortification are framed in policies but remain aspirational goals. Alternative, effective, targeted preventive approaches include, for women, replacement of antenatal iron-folic acid with multiple micronutrient supplementation, and for young children, point-of-use multiple micronutrient powder fortification to prevent anemia, both of which can reduce other MNDs and may bring additional health benefits. These interventions coupled with monitoring of dietary intakes, periodic assessment of MNDs, and implementation research to improve existing nutrition interventions are warranted to protect the health of the Middle East Palestinian diaspora. [ABSTRACT FROM AUTHOR]

Background: Preschool child anthropometric status has been assessed nationally in Nepal since 1975, with semi-decadal surveys since 1996, plus several recent, short-interval surveys to track progress toward achieving a World Health Assembly (WHA) goal to reduce stunting to 24% by 2025.Objective: We report prevalence of preschool child stunting and wasting from a national survey in 2016 and place findings into the context of national trends and alignment for Nepal to attain its WHA 2025 goal.Methods: A representative, midyear Policy and Science for Health, Agriculture and Nutrition (PoSHAN) survey was conducted in 2016 on 5479 children <60 months in 4051 households in 21 village development committees. Child weight and height were measured, and sociodemographic factors were assessed. Data from previous surveys (Nepal Demographic Health Surveys, PoSHAN) were also acquired, and rates of stunting (<-2 height-for-age z score) and wasting (<-2 weight-for-height z score) were compared to current World Health Organization standards. Trends were expressed as average annual rates of reduction (AARR).Results: Nationally, in 2016, 34.1% of preschoolers were stunted and 13.7% wasted. Stunting was highest in the Mountains (40.6%) and wasting highest in the Tarai (18.9%). Trend analysis revealed a steady decline (3.8% AARR) in stunting from 2001 to 2013, with virtually no decline from 2013 to 2016. Wasting has been continually high and variable, at ≥8%, since 1975.Conclusions: Following a steady decline in prevalence, preschool child stunting has plateaued at ∼35% in Nepal, while wasting has changed little over time, offering the opportunity to inform, reassess, and adjust, as needed, efforts to reach WHA 2025 goals. [ABSTRACT FROM AUTHOR]

The Training Gap Investigators who conduct research with human subjects are responsible for the protection of participants' rights, safety, and welfare, and for scientific integrity [1-6]. Each investigator and research [...]

Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein. [ABSTRACT FROM AUTHOR]

Abstract: In South Asia, childhood undernutrition persists while overweight is increasing. Internationally recommended infant and young child feeding (IYCF) practices promote healthy nutritional status; however, little is known about IYCF in Bhutan, investigated here using 2015 National Nutrition Survey data. WHO/UNICEF IYCF indicators, anthropometry and household socio‐economic status were available for 441 children <24 months. Stunting, wasting, and underweight prevalence (<−2Z length‐for‐age [LAZ], weight‐for‐age, [WAZ] and weight‐for‐length [WLZ], respectively) were 15%, 9%, and 5%, respectively, whereas overweight (WLZ >2) prevalence was 6%. In survey‐design‐adjusted analyses, 52% of mothers of 0‐ to 5‐month olds reported exclusive breastfeeding (EBF), with EBF less common for girls than boys (OR: 0.2 [95% CI: 0.1–0.9]). Although 61% of children were breastfed at 2 years and 75% of children >6 months met a minimum daily meal frequency, only 18% of children 6–23 months met minimum dietary diversity. IYCF was unassociated with risk of stunting, wasting, or underweight, possibly due to relatively low prevalence of anthropometric failure and small sample size. However, currently‐breastfed children were less often overweight [OR: ~0.1 (95% upper limit ≤1.0)]. Neither breastfeeding nor most complementary feeding practices differed by socio‐economic status, but children in the highest two fifth of a wealth index had 7.8 (1.3–46.9) and 5.3 (1.1–25.2) times greater odds than children in the lowest fifth of meeting minimum dietary diversity criteria. Low rates of EBF, given possible protection of breastfeeding against overweight, and inadequate dietary diversity offer evidence to guide future program interventions to improve nutritional status of young children. [ABSTRACT FROM AUTHOR]

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Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 μg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 μg/L, excluding deficient), or high (≥75 μg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline).Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148. [ABSTRACT FROM AUTHOR]

Background: The impact of early vitamin A supplementation on neurodevelopmental function has not been adequately studied. In rural Bangladesh we examined cognitive and motor function and scholastic achievement in a cohort of children who were exposed to vitamin A in utero or at birth. Objective: The aim of this study was to examine independent and combined effects of antenatal and newborn supplementation with vitamin A on the cognitive function of children at 8 y of age. Design: A cohort of rural Bangladeshi children from 2 previous double-blind, placebo-controlled cluster-randomized trials were revisited at age 8 y between February 2013 and June 2014. Data on sociodemographic, social, and physical conditions; schooling; child care behavior; anthropometric measures; and cognitive function were collected with the use of various psychometric assessment tools. Results: Among 11,950 children from the parent trial who were last known to be alive, a subset of 1803 children balanced by treatment group in a selected contiguous study area were re-enrolled and 1613 (89%) provided consent for assessments. Of these, 1577 (87%) children had a complete cognitive evaluation. All groups were highly comparable on baseline variables collected in the previous trials and factors measured at re-enrollment. Overall, there was no impact of either maternal or newborn supplementation with vitamin A on intelligence, memory, and motor function. Compared with placebo, children who received both interventions had significantly better performance in reading, spelling, and math computation, with increased mean (95% CI) scores of 8.0 (2.2, 13.8), 6.8 (1.9, 11.7), and 4.8 (0.6, 9.0), respectively. Conclusions: General intelligence or memory and motor functions were not affected by antenatal or newborn supplementation with vitamin A. Scholastic performance and aspects of executive function improved when both interventions were provided. These trials were registered at clinicaltrials.gov as NCT00198822 and NCT00128557. [ABSTRACT FROM AUTHOR]

Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology. Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children. Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age. Height-for-age z scores (HAZs), weight-forage z scores (WAZs), and body mass index-for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q) <5%. Results: Among 982 proteins, 1, 10, 14, and 17 proteinswere associatedwith BAZ, HAZ,MUAC, and AMA, respectively (q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest (n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others. [ABSTRACT FROM AUTHOR]

Background: Early and exclusive breastfeeding may improve neonatal survival in low resource settings, but suboptimal breastfeeding still exists in areas with high infant mortality. Prelacteal feeding, the practice of giving a non-breastmilk food as a neonate's first food, has been associated with suboptimal breastfeeding practices. We examined the association of feeding a non-breastmilk food in the first three days of life (early neonatal food, or ENF) with time from birth to initiation of breastfeeding among 25,286 Bangladeshi mother-neonate pairs, in a secondary analysis of a randomized controlled trial in northwestern rural Bangladesh conducted from 2001-2007. Methods: Trained interviewers assessed the demographic characteristics during pregnancy. At three months postpartum, the interviewers visited participants again and retrospectively assessed demographic and breastfeeding characteristics surrounding the birth. We assessed the relationship between ENF and time to initiation of breastfeeding in hours in both unadjusted and adjusted linear regression analyses. We also calculated reverse cumulative distribution curves for time to initiation of breastfeeding and analyses were stratified by an infant's ability to breastfeed normally at birth. Results: The mean ± SD time from birth to initiation of breastfeeding was 30.6 ± 27.9 hours. Only 2,535 (10.0%) of women reported initiating breastfeeding in the first hour after birth and 10,207 (40.4%) reported initiating breastfeeding in the first 12 hours after birth. In adjusted linear regression analyses, feeding ENF was associated with a significant increase in time, in hours, to breastfeeding initiation both among children not able to breastfeed at birth (37.4; 95% CI 33.3, 41.5) and among children able to breastfeed at birth (13.3; 95% CI 12.7, 14.0). Conclusions: Feeding ENF was strongly associated with delayed initiation of breastfeeding, even after adjusting for other related factors and stratifying on the neonate's ability to suckle normally after birth. More research is needed to understand the impact of these findings on optimal breastfeeding in this setting. It is possible that ENF feeding and the ability to breastfeed immediately after birth are interrelated in their respective associations to suboptimal breastfeeding initiation. This study in a large population representative of other populations in rural South Asia, demonstrates significantly longer times to breastfeeding initiation than previously appreciated, with a possible important role of ENF feeding. Trial registration: The randomized controlled trial on which this analysis is based, "Impact of Maternal Vitamin A or Beta-Carotene Supplementation on Maternal and Infant Mortality in Bangladesh", was registered with ClinicalTrials. gov as trial number ID GHS-A-00-03-00019-00 and identifier NCT00198822. The identifier was first received September 12, 2005 (retrospectively registered). The first participant was enrolled in August 2001. [ABSTRACT FROM AUTHOR]

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: In Nepal, limited availability and affordability of nutritious foods contribute to malnutrition.Objectives: To identify nutrient deficiencies in commonly consumed diets and model lowest cost changes that could improve diet quality in 3 agroecological zones of Nepal.Methods: In August to September 2014, we collected market price and women's food frequency data from 3 representative villages in Nepal's mountains (Mahat Gaun, Jumla, n = 181 households), hills (Sitapur, Arghakhanchi, n = 166), and terai (Saigaun, Banke, n = 232) and verified local diets during women's group discussions. Using the Cost of the Diet method, we compared models of the most nutritious version of a commonly consumed diet given locally available foods ("common diet") with the cheapest possible diet meeting nutrient requirements, including foods not currently available ("optimal diet").Results: The household common diet lacks sufficient vitamin B12, riboflavin, and calcium in the mountains; B6, B12, calcium, and iron in the hills; vitamin A, calcium, and iron in the terai. Adding fish to the mountain and hill diets and increasing dark green leafy vegetable consumption in all zones yielded nutritional adequacy. Optimal diets are more expensive than the common diet in the mountains and hills but less expensive in the terai.Conclusion: The modeled lowest cost diet commonly eaten in 3 Nepalese communities lacks key nutrients. Policies and interventions that increase market availability and consumption of vitamin B12- and calcium-rich fish and dark green leafy vegetables could improve local diets, particularly in the mountains and hills. [ABSTRACT FROM AUTHOR]

Background: Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants.Objective: We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.Methods: Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.Results: Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM [1.15 μmol/L (0.96, 1.39 μmol/L)] and VA [1.17 μmol/L (0.99, 1.38 μmol/L)] groups than in the WM group [0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13], and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).Conclusions: Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713. [ABSTRACT FROM AUTHOR]

Background: Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin A status in maize-consuming populations. Objective: We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (~15 mg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children. Design: This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ~400-km² area were identified and grouped by proximity into clusters of ~15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n =25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein. Results: Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol < 0.7 µmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum b-carotene was 0.14 µmol/L (95% CI: 0.09, 0.20 µmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 µmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms. Conclusion: In this marginally nourished population, regular bio- fortified maizemeal consumption increased serum b-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148. [ABSTRACT FROM AUTHOR]

Researchers conducting large community-based studies among underserved populations may collect data on health conditions that are little-acknowledged in the local setting, and for which there are few if any services for referral of participants who need follow-up diagnosis and care. In the design and planning of studies for such settings, investigators and research ethics committees may struggle to determine what constitutes effective referral and whether it is reasonably available. We offer a guiding framework for referral planning, informed by our experiences of research in the field and of service on research ethics committees, to support evaluation of local referral resources and consideration of the benefits, burdens and risks of referral in the local setting. The framework addresses both the impact of referral on the well-being of the people who would be referred and the impact that referral of study participants would have on local people outside the study. We use a sustained discussion of three field-based case examples to illustrate the ethical concerns at issue and to demonstrate the use of the referral planning framework. [ABSTRACT FROM AUTHOR]

Asian populations have a higher percentage body fat (%BF) and are at higher risk for CVD and related complications at a given BMI compared with those of European descent. We explored whether %BF was disproportionately elevated in rural Bangladeshi women with low BMI. Height, weight, mid-upper arm circumference, triceps and subscapular skinfolds and bioelectrical impedance analysis (BIA) were measured in 1555 women at 3 months postpartum. %BF was assessed by skinfolds and by BIA. BMI was calculated in adults and BMI Z-scores were calculated for females <20 years old. Receiver operating characteristic (ROC) curves found the BMI and BMI Z-score cut-offs that optimally classified women as having moderately excessive adipose tissue (defined as >30% body fat). Linear regressions estimated the association between BMI and BMI Z-score (among adolescents) and %BF. Mean BMI was 19·2 (SD 2·2) kg/m², and mean %BF was calculated as 23·7 (SD 4·8) % by skinfolds and 23·3 (SD 4·9) % by BIA. ROC analyses indicated that a BMI value of approximately 21 kg/m² optimised sensitivity (83·6%) and specificity (84·2%) for classifying subjects with >30% body fat according to BIA among adults. This BMI level is substantially lower than the WHO recommended standard cut-off point of BMI = 25 kg/m2. The equivalent cut-off among adolescents was a BMI Z-score of -0·36, with a sensitivity of 81·3% and specificity of 80·9%. These findings suggest that Bangladeshi women exhibit excess adipose tissue at substantially lower BMI compared with non-South Asian populations. This is important for the identification and prevention of obesity-related metabolic diseases. [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]