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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]

Background: Early and exclusive breastfeeding may reduce neonatal and post-neonatal mortality in low-resource settings. However, prelacteal feeding (PLF), the practice of giving food or liquid before breastfeeding is established, is still a barrier to optimal breastfeeding practices in many South Asian countries. We used a prospective cohort study to assess the association between feeding non-breastmilk food or liquid in the first three days of life and infant size at 3–5 months of age. Methods: The analysis used data from 3,332 mother-infant pairs enrolled in a randomized controlled trial in northwestern rural Bangladesh conducted from 2018 to 2019. Trained interviewers visited women in their households during pregnancy to collect sociodemographic data. Project staff were notified of a birth by telephone and interviewers visited the home within approximately three days and three months post-partum. At each visit, interviewers collected data on breastfeeding practices and anthropometric measures. Infant length and weight measurements were used to produce length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores. We used multiple linear regression to assess the association between anthropometric indices and PLF practices, controlling for household wealth, maternal age, weight, education, occupation, and infant age, sex, and neonatal sizes. Results: The prevalence of PLF was 23%. Compared to infants who did not receive PLF, infants who received PLF may have a higher LAZ (Mean difference (MD) = 0.02 [95% CI: -0.04, 0.08]) score, a lower WLZ (MD=-0.06 [95% CI: -0.15, 0.03]) score, and a lower WAZ (MD=-0.02 [95% CI: -0.08, 0.05]) score at 3–5 months of age, but none of the differences were statistically significant. In the adjusted model, female sex, larger size during the neonatal period, higher maternal education, and wealthier households were associated with larger infant size. Conclusion: PLF was a common practice in this setting. Although no association between PLF and infant growth was identified, we cannot ignore the potential harm posed by PLF. Future studies could assess infant size at an earlier time point, such as 1-month postpartum, or use longitudinal data to assess more subtle differences in growth trajectories with PLF. Trial registration: ClinicalTrials.gov: NCT03683667 and NCT02909179. [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.

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]

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]

Background: Perception-based Likert scale are commonly used to assess household food insecurity. The aim of this study was to evaluate the psychometric properties and external construct validity of the 9-item Food Access Survey Tool (FAST) in a population-based randomized controlled trial. Methods: Participating women (n=11,992) were asked to recall the frequencies of nine food insecurity experiences over the past 6 months on a 5-point Likert scale. The Rasch partial credit model was used to study the item category severity and differential item functioning (DIF) by literacy status, respondents' age, land ownership and household sizes. Principal component analysis (PCA), non-parametric methods, and cumulative ordinal logistic regression models were applied to examine the Rasch model assumptions, namely unidimensionality, monotonicity and measurement invariance (non-DIF). Results: All items demonstrated good model fit with acceptable values of fit statistics (infit). PCA as well as other indices (Cronbach's alpha = 0.85, scalability coefficient = 0.48) indicated that all items fit in a single statistical dimension. The ordered responses of nine items displayed monotonic increasing item category severity as expected theoretically. All nine items were flagged with statistically significant DIF between key demographic--and socioeconomic subgroups (p < 0.001); however, none of the detected DIF was considered practically significant given small effect sizes (variance explained by group membership and interaction term < 1 %). The total summed score over the polytomous FAST was inversely associated with household wealth, dietary diversity score and maternal body mass index, demonstrating external construct validity. Conclusion: The polytomous FAST is internally and externally valid tool to measure household food insecurity in rural Bangladesh. Validation of this type of studies are recommended for similar Likert food insecurity scales. [ABSTRACT FROM AUTHOR]

Background: Aberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field. Methods: The Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (-2.9 to 0.1 log cd/m²). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response. Results: The PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size. Conclusions: The consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications. [ABSTRACT FROM AUTHOR]

Background: In communities with low rates of institutional delivery, little data exist on care-seeking behavior for potentially life-threatening obstetric complications. In this analysis, we sought to describe care-seeking patterns for self-reported complications and near misses in rural Bangladesh and to identify factors associated with care seeking for these conditions. Methods: Utilizing data from a community-randomized controlled trial enrolling 42,214 pregnant women between 2007 and 2011, we used multivariable multinomial logistic regression to explore the association of demographic and socioeconomic factors, perceived need, and service availability with care seeking for obstetric complications near misses. We also used multivariable multinomial logistic regression to analyze the factors associated with care seeking by type of obstetric complication (eclampsia, sepsis, hemorrhage, and obstructed labor). Results: Out of 9,576 women with data on care seeking for obstetric complications, 77% sought any care, with 29% (n = 2,150) visiting at least one formal provider and 70% (n = 5,149) visiting informal providers only. The proportion of women seeking at least one formal provider was highest among women reporting eclampsia (57%), followed I hemorrhage (28%), obstructed labor (22%), and sepsis (17%) (p < 0.001). In multivariable analyses, socioeconomic factors such as living in a household from the highest wealth quartile (Relative Risk Ratio of 1.49; 95% G of [1.33-1.73]), women's literacy (RRR of 1.21; 95% G of [1.05-1.42]), and women's employment (RRR of 1.10; 95% G of [1.01-1.18]) were significantly associated with care seeking from formal providers. Service factors including living less than 10 kilometers from a health facility (RRR of 1.16; 95% G of [1.05-1.28]) and facility availability of comprehensive obstetric services (RRR of 1.25; 95% G of 1.04-1.36) were also significantly associated with seeking care from formal providers. Conclusions: While the majority of women reporting obstetric complications sought care, less than a third visited health facilities. Improvements in socioeconomic factors such as maternal literacy, coupled with improve geographic access and service availability, may increase care seeking from formal facilities. Enhancing community awareness on symptoms of hemorrhage, sepsis, and obstructed labor and their consequences may promote care seeking for obstetric complications in rural Bangladesh. Trial registration: Trial Registration Number: NCT00860470. [ABSTRACT FROM AUTHOR]

Objectives Self-harm and interpersonal violence are important causes of death among women in Nepal. We analysed prospectively collected data to investigate the extent and nature of injury-related deaths among married women aged 15-49 years, recorded through verbal autopsy in rural Sarlahi District, Nepal. Methods Verbal autopsies were systematically collected on all deaths of married women of reproductive age (15-49 years) over a 3-year period (1994-1997) as part of a randomised community-based trial of maternal vitamin A and β-carotene supplementation. This analysis included a three-way comparison of verbal autopsy data: qualitative free-response narratives, closed-ended responses, and physician-assigned consensus cause of death. Results We focused on 46 of 559 deaths (8.2%) that were determined to be injury-related. Of the 46, 28% were identified as intentionally self-inflicted, and 11% as intentionally inflicted by another. Inconsistencies were noted between verbal autopsy reports of causes of deaths and physician assessments. Conflicts within the family figured prominently in the narratives. Women with unstable family situations and suffering from mental illness were often described as having experienced violent deaths. Conclusions Findings highlight that intervention efforts might be necessary especially in situations where there are poor family dynamics or mental health issues in order to prevent potential intrafamily violence and possible death. Results also point to the need for further documentation of violent deaths in rural Nepal. [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: Although safe motherhood strategies recommend that women seek timely care from health facilities for obstetric complications, few studies have described facility availability of emergency obstetric care (EmOC). We sought to describe and compare availability and readiness to provide EmOC among public and private health facilities commonly visited for pregnancy-related complications in two districts of northwest Bangladesh. We also described aspects of financial and geographic access to healthcare and key constraints to EmOC provision. Methods: Using data from a large population-based community trial, we identified and surveyed the 14 health facilities (7 public, 7 private) most frequently visited for obstetric complications and near misses as reported by women. Availability of EmOC was based on provision of medical services, assessed through clinician interviews and record review. Levels of EmOC availability were defined as basic or comprehensive. Readiness for EmOC provision was based on scores in four categories: staffing, equipment, laboratory capacity, and medicines. Readiness scores were calculated using unweighted averages. Costs of C-section procedures and geographic locations of facilities were described. Textual analysis was used to identify key constraints. Results: The seven surveyed private facilities offered comprehensive EmOC compared to four of the seven public facilities. With 100% representing full readiness, mean EmOC readiness was 81% (range: 63%-91%) among surveyed private facilities compared to 67% (range: 48%-91%) in public facilities (p = 0.040). Surveyed public clinics had low scores on staffing and laboratory capacity (69%; 50%). The mean cost of the C-section procedure in private clinics was $77 (standard deviation: $16) and free in public facilities. The public sub-district facilities were the only facilities located in rural areas, with none providing comprehensive EmOC. Shortages in specialized staff were listed as the main barrier to EmOC provision in public facilities. Conclusions: Although EmOC availability and readiness was higher among the surveyed seven most commonly visited private clinics, public facilities appeared to be more affordable for C-section and more geographically accessible. Strategies to retain anesthesiologists and surgeons, such as non-financial incentives, are needed to improve EmOC provision in the public sector. Centralized blood banks are recommended to streamline safe blood acquisition for obstetric surgeries. [ABSTRACT FROM AUTHOR]