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BACKGROUND: Delayed onset of lactogenesis (OL) is most common in primiparas and increases the risk of excess neonatal weight loss, formula supplementation, and early weaning. OBJECTIVE: We examined variables associated with delayed OL among first-time mothers who delivered at term and initiated breastfeeding (n = 431). DESIGN: We conducted in-person interviews during pregnancy and at days 0, 3, and 7 postpartum and extracted obstetric and newborn information from medical records. We defined OL as delayed if it occurred after 72 h and used chi-square analysis to examine its association with potential risk factors across 6 dimensions: 1) prenatal characteristics, 2) maternal anthropometric characteristics, 3) labor and delivery experience, 4) newborn characteristics, 5) maternal postpartum factors, and 6) infant feeding variables. We examined independent associations by using multivariable logistic regression analysis. RESULTS: Median OL was 68.9 h postpartum; 44% of mothers experienced delayed OL. We observed significant bivariate associations between delayed OL and variables in all 6 dimensions (P < 0.05). In a multivariate model adjusted for prenatal feeding intentions, independent risk factors for delayed OL were maternal age >/=30 y, body mass index in the overweight or obese range, birth weight >3600 g, absence of nipple discomfort between 0-3 d postpartum, and infant failing to 'breastfeed well' >/=2 times in the first 24 h. Postpartum edema was significant in an alternate model excluding body mass index (P < 0.05). CONCLUSIONS: The risk factors for delayed OL are multidimensional. Public health and obstetric and maternity care interventions are needed to address what has become an alarmingly common problem among primiparas. © 2010 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Objectives: Adequate zinc nutriture is critically important for human health, but the development of programmes to control zinc deficiency is limited by the lack of reliable information on population zinc status. The present analyses were conducted to: (1) estimate the absorbable zinc content of national food supplies; (2) compare this information with theoretical population requirements for zinc; and (3) use these results to predict national risks of inadequate zinc intake.Setting and Design: National food balance data were obtained for 176 countries from the Food and Agriculture Organization of the United Nations. The amount of absorbable zinc in these foods was estimated from food composition data, and zinc absorption was predicted using a model developed by the International Zinc Nutrition Consultative Group (IZiNCG). Demographic data were obtained from United Nations estimates, and age- and sex-specific physiological requirements for absorbable zinc were estimated using IZiNCG recommendations.Results and Conclusions: The mean per capita absorbable zinc content of national food supplies ranged from 2.98-3.01 mg day(-1) in Western Europe and USA & Canada to 2.09 mg day(-1) in Southeast Asia. The estimated percentage of individuals at risk of inadequate zinc intake ranged from 9.3-9.5% in the regions of North Africa & Eastern Mediterranean and USA & Canada to 33.1% in Southeast Asia. Overall, approximately 20.5% of the world's population is estimated to be at risk of inadequate zinc intake. Data on the absorbable zinc content of national food supplies can be used to determine whether further assessments of population zinc status and development of intervention programmes are warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Information is needed on the fractional absorption of zinc (FAZ) and absorbed zinc (AZ) during prolonged exposure to zinc-fortified foods. OBJECTIVE: The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over approximately 7 wk. DESIGN: Forty-one stunted, moderately anemic children received daily, at breakfast and lunch, 100 g wheat products fortified with 3 mg Fe (ferrous sulfate) and 0 (group Zn-0), 3 (group Zn-3), or 9 (group Zn-9) mg Zn (zinc sulfate) per 100 g flour. FAZ was measured on days 2-3 and 51-52; meal-specific AZs were calculated as the product of FAZ and zinc intake. RESULTS: For the breakfast and lunch meals combined, mean total zinc intakes were 2.14, 4.72, and 10.04 mg/d in groups Zn-0, Zn-3, and Zn-9, respectively, during the initial absorption studies; mean (+/-SD) FAZ values were 0.341 +/- 0.111, 0.237 +/- 0.052, and 0.133 +/- 0.041, respectively, on days 2-3 (P < 0.001) and did not change significantly on days 51-52 in the subset of 31 children studied twice. Mean initial AZ was positively related to zinc intake (0.71 +/- 0.18, 1.11 +/- 0.21, and 1.34 +/- 0.47 mg/d, respectively; P < 0.001); final values did not differ significantly from the initial values. CONCLUSIONS: AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during approximately 7-wk periods of consumption. Although consumption of zinc-fortified foods may reduce FAZ, zinc fortification at the levels studied positively affects total daily zinc absorption, even after nearly 2 mo of exposure to zinc-fortified diets. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: The risk of zinc deficiency in populations can be estimated by comparing serum zinc data with statistically defined lower cutoffs derived from a presumably healthy population. Serum zinc data are available from a large sample of the US population assessed during the second National Health and Nutrition Examination Survey (NHANES II). Although the original analysis of these data considered fasting status and the time of day of blood sampling, it did not account for potentially confounding variables that may affect the serum zinc concentration, such as age, sex, and health status. OBJECTIVE: The objective was to describe variations in serum zinc concentration by age, sex, and other characteristics and to recommend lower cutoffs for presumably healthy persons. DESIGN: Serum zinc data from NHANES II were analyzed by using analysis of variance and covariance models to identify and describe variables significantly associated with serum zinc concentration; 2.5th percentile curves were produced and used to establish age- and sex-based lower cutoffs. RESULTS: Age and sex were significant confounders of serum zinc concentration, so separate lower cutoffs were derived for children and adolescent and adult males and females. Other minor confounding variables were identified. Tentative lower cutoffs for pregnancy and oral contraceptive use were also derived. CONCLUSIONS: The interpretation of population serum zinc data with the use of lower cutoffs should account for the age and sex of the subjects, pregnancy and oral contraceptive use, and fasting status and time of day of blood collection. Copyright © 2003 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: The deuterated-retinol-dilution (DRD) technique provides a quantitative estimate of total body stores of vitamin A. However, it is not known whether the technique can detect changes in vitamin A pool size in response to different intakes of vitamin A. Objective: Our objective was to determine the responsiveness of the DRD technique to 3 different daily supplemental vitamin A intakes during a period of 2.5-4 mo. Design: Two oral doses of [2H4]retinyl acetate [52.4 mu mol retinol equivalent (RE)] were administered on study days 1 and 91 to 26 men (18-32 y of age) who were consuming controlled, low-vitamin A diets, and receiving daily either 0, 5.2, or 10.5 mu mol RE of unlabeled supplemental retinyl palmitate during a 75- or 129-d period. Plasma isotopic ratios of [2H4]retinol to retinol on day 115 were used to estimate final vitamin A body stores per Furr et al (Am J Clin Nutr 1989;49:713-6). Results: Final (x +/= SD) estimated vitamin A pool sizes were 0.048 +/= 0.031, 0.252 +/= 0.045, and 0.489 +/= 0.066 mmol in the treatment groups receiving 0, 5.2, and 10.5 mu mol RE/d, respectively (P < 0.001). Estimated mean changes in vitamin A pool sizes were similar to those expected for the vitamin A-supplemented groups [estimated: expected (95% CI of change in pool size): 1.08 (0.8, 1.2) and 1.17 (1.0, 1.3)]. Conclusions: The DRD technique can detect changes in total body stores of vitamin A in response to different daily vitamin A supplements. However, abrupt changes in dietary vitamin A intake can affect estimates of total-body vitamin A stores. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Koko, a fermented maize porridge used as the primary complementary food in Ghana, has been implicated in the high prevalence of child malnutrition. Weanimix, a cereal-legume blend developed by the United Nations Children's Fund and the Ghanaian government, has been promoted as an alternative. OBJECTIVE: We evaluated the effect of feeding Weanimix and 3 other locally formulated, centrally processed complementary foods on the nutritional status of 208 breast-fed infants. DESIGN: Infants were randomly assigned to receive 1 of 4 foods from 6 to 12 mo of age: Weanimix (W), Weanimix plus vitamins and minerals (WM), Weanimix plus fish powder (WF), and koko plus fish powder (KF). Dietary and anthropometric data were collected regularly. Blood was collected at 6 and 12 mo of age to assess iron, zinc, vitamin A, and riboflavin status. Before and after the intervention, cross-sectional data on the anthropometric status of infants not included in the intervention (NI; n = 464) were collected. RESULTS: There were no significant differences between intervention groups in weight or length gain or in hemoglobin, hematocrit, transferrin saturation, plasma zinc, or erythrocyte riboflavin values between 6 and 12 mo of age. From 9 to 12 mo of age, z scores were lower in NI infants than in the combined intervention groups [at 12 mo: -1.71 +/- 0.90 compared with -1.19 +/- 0.93 for weight and -1.27 +/- 1.02 compared with -0.63 +/- 0.84 for length (P < 0.001 for both), respectively]. The percentage of infants with low ferritin values increased significantly between 6 and 12 mo of age in groups W, WF, and KF but not in group WM. Change in plasma retinol between 6 and 12 mo of age was significantly greater in group WM than in the other 3 groups combined (0.14 +/- 0.3 compared with -0.04 +/- 0.3 micromol/L, P = 0. 003). CONCLUSIONS: All 4 foods improved growth relative to the NI group. Infants fed WM had better iron stores and vitamin A status than those fed nonfortified foods. [ABSTRACT FROM AUTHOR]

BACKGROUND: Results of prior studies of the effect of viscosity reduction of high-energy-density, starch-containing diets on young children's energy intakes are inconsistent, possibly because of differences in the characteristics of the unmodified diets with which the low-viscosity diets were compared. OBJECTIVE: Our objective was to determine the effects of dietary viscosity and energy density on total daily energy consumption by young, non-breast-fed children. DESIGN: We measured the amount of food consumed and the duration of meals during 3 substudies, in each of which 3 study diets were offered for 4 consecutive days each in random sequence: high energy density, high viscosity (HD-HV); high energy density, low viscosity (HD-LV); and low energy density, low viscosity (LD-LV). The viscosity and energy density of the unmodified starch-containing HD-HV diet were varied across substudies to determine whether the effect of amylase liquefaction was related to the initial characteristics of the HD-HV diet. The viscosity of the HV diets ranged from 79000 to 568000 mPa s; energy density of the HD diets ranged from approximately 4.18 to 4.93 kJ (1.00-1.18 kcal)/g. Viscosity of the LV diets was approximately 3000 mPa s and the energy density of the LD diets was approximately 2.47 kJ (0.6 kcal)/g. RESULTS: In each substudy, children consumed more of the LD-LV diet (g kg body wt(-)(1) d(-)(1)) than of the other diets and more of the HD-LV diet than of the HD-HV diet (P < 0.001). Energy consumption from the HD-LV diet was greater than from the other diets (P < 0.001), but the energy intakes from the latter diets were not significantly different. CONCLUSION: Amylase liquefaction of HD-HV porridges resulted in increased energy consumption by young children. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVE. To assess the effects of continued feeding of nonhuman milks or formulas to young children during acute diarrhea on their treatment failure rates, stool frequency and amount, diarrheal duration, and change in body weight. METHODS. A total of 29 randomized clinical trials of 2215 patients were identified by computerized bibliographic search and review of published articles. Data were abstracted and analyzed using standard meta-analytic procedures. RESULTS. Among studies that compared lactose-containing milk or formula diets with lactose-free regimens, those children who received the lactose-containing diets during acute diarrhea were twice as likely to have a treatment failure as those who received a lactose-free diet (22% vs 12%, respectively; P < .001). However, the excess treatment failure rates occurred only in those studies that included patients whose initial degree of dehydration, as reported by authors, was severe, or that were conducted before 1985, when appropriate diarrhea treatment protocols were first widely accepted. Among studies of patients with mild diarrhea, all but one of which were completed after 1985, the overall treatment failure rates in the lactose groups were similar to the rates in the lactose-free groups (13% vs 15%). These results suggest that children with mild or no dehydration and those who are managed according to appropriate treatment protocols, such as that promoted by the World Health Organization, can be treated as successfully with lactose-containing diets as with lactose-free ones. The pooled information from studies that compared undiluted lactose-containing milks with the same milks offered at reduced concentration concluded that (1) children who received undiluted milks were marginally more likely to experience treatment failure than those who received diluted milk (16% vs 12%, P = .05), (2) the differences in stool output were small and of limited clinical importance, and (3) children who received the undiluted milk diets gained 0.25 SD more weight than those who received the diluted ones (P = .004). In addition, as with the previous set of studies, there were no differences in the pooled treatment failure rates between the respective groups in those studies of mildly dehydrated patients conducted after 1985 (14% vs 12%). CONCLUSIONS. The vast majority of young children with acute diarrhea can be successfully managed with continued feeding of undiluted nonhuman milks. Routine dilution of milk and routine use of lactose-free milk formula are therefore not necessary, especially when oral rehydration therapy and early feeding (in addition to milk) form the basic approach to the clinical management of diarrhea in infants and children. [ABSTRACT FROM AUTHOR]

Background: Multiple micronutrient supplements could increase hemoglobin and improve micronutrient status of pregnant women more than iron supplements alone or iron with folic acid.Objective: To compare the effects of multiple micronutrients with those of iron supplements alone or iron with folic acid, on hemoglobin and micronutrient status of pregnant women.Methods: Studies were identified in which pregnant women were randomized to treatment with multiple micronutrients, or with iron with or without folic acid. A pooled analysis was conducted to compare the effects of these supplements on maternal hemoglobin, anemia, and micronutrient status. Effect size was calculated for individual and combined studies, based on mean change from baseline to final measure in the group receiving iron, with or without folic acid, minus the mean change in the group, divided by the pooled standard deviation of the two groups. The effect on the relative risk of anemia or iron deficiency was calculated as the probability of anemia or iron deficiency in the group receiving multiple micronutrients divided by the probability in the group receiving iron, with or without folic acid.Results: Multiple micronutrient supplements had the same impact on hemoglobin and iron status indicators as iron with or without folic acid. There was no overall effect on serum retinol or zinc. In the only study in which status of other micronutrients was analyzed, a high prevalence of multiple deficiencies persisted in the group receiving multiple micronutrients provided with daily recommended intakes of each nutrient.Conclusions: Multiple micronutrient supplements increased hemoglobin synthesis to the same extent as supplementation with iron with or without folic acid, although often they contained lower amounts of iron. The amount of supplemental iron and other nutrients that can enable pregnant women with micronutrient deficiencies to achieve adequate status remains to be determined. [ABSTRACT FROM AUTHOR]

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 μg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 μg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc.

Background: Attributable fractions (AF) of anemia are often used to understand the multifactorial etiologies of anemia, despite challenges interpreting them in cross-sectional studies. We aimed to compare different statistical approaches for estimating AF for anemia due to inflammation, malaria, and micronutrient deficiencies including iron, vitamin A, vitamin B12, and folate., Methods: AF were calculated using nationally representative survey data among preschool children (10 countries, total N = 7,973) and nonpregnant women of reproductive age (11 countries, total N = 15,141) from the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project. We used the following strategies to calculate AF: 1) Levin's formula with prevalence ratio (PR) in place of relative risk (RR), 2) Levin's formula with odds ratio (OR) in place of RR, and 3) average (sequential) AF considering all possible removal sequences of risk factors. PR was obtained by 1) modified Poisson regression with robust variance estimation, 2) Kleinman-Norton's approach, and 3) estimation from OR using Zhang-Yu's approach. Survey weighted country-specific analysis was performed with and without adjustment for age, sex, socioeconomic status, and other risk factors., Results: About 20-70% of children and 20-50% of women suffered from anemia, depending on the survey. Using OR yielded the highest and potentially biased AF, in some cases double those using PR. Adjusted AF using different PR estimations (Poisson regression, Kleinman-Norton, Zhang-Yu) were nearly identical. Average AF estimates were similar to those using Levin's formula with PR. Estimated anemia AF for children and women were 2-36% and 3-46% for iron deficiency, <24% and <12% for inflammation, and 2-36% and 1-16% for malaria. Unadjusted AF substantially differed from adjusted AF in most countries., Conclusion: AF of anemia can be estimated from survey data using Levin's formula or average AF. While different approaches exist to estimate adjusted PR, Poisson regression is likely the easiest to implement. AF are a useful metric to prioritize interventions to reduce anemia prevalence, and the similarity across methods provides researchers flexibility in selecting AF approaches., Competing Interests: The authors have read the journal’s policy and have the following competing interests: JPW is an employee of GroundWork LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences., Objectives: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children., Methods: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA., Results: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05)., Conclusions: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Little valid information is available on human milk nutrient concentrations, especially for micronutrients (MNs), and there are no valid reference values (RVs) across lactation. In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 mo postpartum. Well-nourished, unsupplemented women in Bangladesh, Brazil, Denmark, and The Gambia ( n  = 250/site) were recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and their infants are collected identically at 3 visits (1-3.49, 3.5-5.99, 6.0-8.49 mo postpartum). Milk analyses include macronutrients, selected vitamins, trace elements and minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. We measure milk volume; maternal and infant diets, anthropometry, and morbidity; infant development, maternal genome, and the infant and maternal microbiome. RVs will be constructed based on methods for the WHO Child Growth Standards and the Intergrowth-21st Project. This trial was registered at clinical trials.gov as NCT03254329., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system., Objective: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated., Methods: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight., Results: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y., Conclusions: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Zinc deficiency impairs immune function and is common among children in South-East Asia., Objectives: The effect of zinc supplementation on immune function in young Laotian children was investigated., Methods: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration)., Results: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012)., Conclusions: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case., Objectives: The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences., Methods: Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures., Results: In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar., Conclusions: The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853., (Copyright © American Society for Nutrition 2019.)

Background: Pregnancy and childbirth complications and cesarean delivery are common in Bangladesh. Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on pregnancy and childbirth complications and cesarean delivery. Methods: We conducted the Rang-Din Nutrition Study, a cluster-randomized controlled effectiveness trial within a community health program in rural Bangladesh. We enrolled 4011 pregnant women in early pregnancy. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Pregnancy and childbirth complications and the cesarean delivery rate were secondary outcomes of the study. Results: Women in the LNS-PL group did not differ significantly from the IFA group with respect to mean systolic blood pressure at 36 wk gestation (113 and 112 mm Hg; P = 0.17), diastolic blood pressure at 36 wk gestation (68.9 and 68.7 mmHg; P = 0.88), or mean total number of pregnancy and childbirth complications (0.32 and 0.31; P = 0.86). They also did not differ significantly with respect to the prevalence of high blood pressure at 36 wk (1.74% and 2.03%; P = 0.62), antepartum hemorrhage (0.83% and 1.39%; P = 0.21), prolonged labor (8.34% and 8.79%; P = 0.68), early rupture of membranes (9.30% and 8.45%; P = 0.43), convulsions (1.57% and 1.08%; P = 0.24), high blood pressure in labor (1.54% and 1.19%; P = 0.46), obstructed labor (2.83% and 2.91%; P = 0.90), any complications during pregnancy or childbirth (35.9% and 37.1%; P = 0.64), episiotomy (6.31% and 6.44%; P = 0.90), or cesarean delivery (15.6% and 14.2%; P = 0.48). Conclusion: Compared with IFA, antenatal LNS-PL did not increase or decrease pregnancy and childbirth complications or cesarean delivery among women in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038., Competing Interests: Author disclosures: MKM, SLM, RRP, SH, MS, MH, JMP, SAV, and KGD, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Of two community-based trials among young children in neighboring health districts of Burkina Faso, one found that small-quantity lipid-based nutrient supplements (LNS) increased child growth compared with a non-intervention control group, but zinc supplementation did not in the second study., Objectives: We explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity., Methods: Children in the LNS study received 20g LNS daily containing different amounts of zinc (LNS). Children in the zinc supplementation study received different zinc supplementation regimens (Z-Suppl). Children in both studies were visited weekly for morbidity surveillance. Free malaria and diarrhea treatment was provided by the field worker in the LNS study, and by a village-based community-health worker in the zinc study. Anthropometric assessments were repeated every 13-16 weeks. For the present analyses, study intervals of the two studies were matched by child age and month of enrollment. The changes in length-for-age z-score (LAZ) per interval were compared between LNS and Z-Suppl groups using mixed model ANOVA or ANCOVA. Covariates were added to the model in blocks, and adjusted differences between group means were estimated., Results: Mean ages at enrollment of LNS (n = 1716) and Z-Suppl (n = 1720) were 9.4±0.4 and 10.1±2.7 months, respectively. The age-adjusted change in mean LAZ per interval declined less with LNS (-0.07±0.44) versus Z-Suppl (-0.21±0.43; p<0.0001). There was a significant group by interval interaction with the greatest difference found in 9-12 month old children (p<0.0001). Adjusting for demographic characteristics and morbidity did not reduce the observed differences by type of intervention, even though the morbidity burden was greater in the LNS group., Conclusions: Greater average physical growth in children who received LNS could not be explained by known cross-trial differences in baseline characteristics or morbidity burden, implying that the observed difference in growth response was partly due to LNS.

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia. Objectives: The aims of the project were to 1 ) identify factors associated with inflammation, 2 ) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3 ) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA). Design: The BRINDA database inclusion criteria included surveys that 1 ) were conducted after 2004, 2 ) had target groups of PSC, WRA, or both, and 3 ) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis. Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses. Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to which real-world data can be applied. Findings can inform guidelines and strategies to prevent and control micronutrient deficiencies and anemia globally.

BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts. Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category. Design: Cross-sectional data from 16 surveys ( n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group. Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively. Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs.

Recently, in a randomized, double-blind crossover study, we reported that consumption of grape powder by obese human subjects increased the production of the proinflammatory cytokines interleukin (IL)-1β and IL-6 by peripheral blood monocytes after ex vivo stimulation with bacterial lipopolysaccharide compared with the placebo treatment. We hypothesized that dietary grape powder increased the production of these cytokines by stimulated monocytes. To test this hypothesis, we used 24-hour dietary recall data to determine if differences in dietary patterns played a role in increased cytokine production. No differences in total energy, protein, carbohydrates, or fat intake in the diets were observed between the grape powder and placebo intervention periods. There were no differences observed in consumption of meats and poultry, eggs, fish, vegetables, grains, total dairy, or nuts and seeds by the participants between the 2 intervention periods. When participants received the grape powder, the recall data showed decreased intakes of butyric and capric acids (P<.05), and a possible trend toward decreased intake of cheese and total fruit (P<.1). Positive associations between the intakes of margaric acid, butter, total dairy, or whole grain and IL-6 production were observed (P<.05). However, path analysis showed that total energy, protein, carbohydrates, and fats, and individual fatty acids did not influence the production of cytokines by monocytes. The path analysis indicated that the increased cytokine production by lipopolysaccharide-stimulated monocytes from obese human subjects was caused by the grape powder and not mediated by differences in dietary intake., (Published by Elsevier Inc.)

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Background: Childhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life., Objective: We evaluated the efficacy of small-quantity, lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age., Design: In this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age., Results: At endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and -0.83, respectively, and 12% of the children were stunted (LAZ <-2). In analysis based on the intended treatment, mean ± SD length and LAZ for the LNS group (79.7 ± 2.9 cm and -0.69 ± 1.01, respectively) were significantly greater than for the IFA (79.1 ± 2.9 cm and -0.87 ± 0.99) and MMN (79.1 ± 2.9 cm and -0.91 ± 1.01) groups (P = 0.006 and P = 0.009, respectively). Differences were also significant for weight and weight-for-age z score but not head or midupper arm circumference, and the prevalence of stunting in the LNS group was 8.9%, compared with 13.7% in the IFA group and 12.9% in the MMN group (P = 0.12). In analysis based on actual supplement provided at enrollment, stunting prevalences were 8.9% compared with 15.1% and 11.5%, respectively (P = 0.045)., Conclusion: Provision of SQ-LNSs to women from pregnancy to 6 mo postpartum and to their infants from 6 to 18 mo of age may increase the child's attained length by age 18 mo in similar settings. This trial was registered at clinicaltrials.gov as NCT00970866.

Background: Saturated fatty acids (FAs) released from triglyceride-rich lipoproteins (TGRLs) activate Toll-like receptor 2 (TLR-2) and induce the expression of proinflammatory cytokines in monocytes. Certain plant polyphenols inhibit TLR-mediated signaling pathways., Objective: We determined whether plasma free FAs (FFAs) after a moderately high-fat (MHF, 40% kcal from fat) breakfast modulate the inflammatory status of postprandial blood, and whether blueberry intake suppresses FFA-induced inflammatory responses in healthy humans., Methods: Twenty-three volunteers with a mean ± SEM age and body mass index (in kg/m(2)) of 30 ± 3 y and 21.9 ± 0.4, respectively, consumed an MHF breakfast with either a placebo powder or 2 or 4 servings of blueberry powder in a randomized crossover design. The placebo powder was provided on the first test day and the blueberry powder doses were randomized with a 2-wk washout period. Plasma concentrations of lipids, glucose, and cytokines were determined. To determine whether FFAs derived from TGRL stimulate monocyte activation, and whether this is inhibited by blueberry intake, whole blood was treated with lipoprotein lipase (LPL)., Results: The median concentrations of FFAs and cytokines [tumor necrosis factor-α, interleukin (IL)-6 and IL-8] in postprandial plasma (3.5 h) decreased compared with fasting plasma regardless of the blueberry intake (P < 0.001 for FFAs and P < 0.05 for cytokines). However, concentrations of FFAs and cytokines including IL-1β increased in LPL-treated whole blood compared with untreated blood samples from participants who consumed the placebo powder. Blueberry intake suppressed IL-1β and IL-6 production in LPL-treated postprandial blood compared with the placebo control when fasting changes were used as a covariate., Conclusions: The plasma FFA concentration may be an important determinant affecting inflammatory cytokine production in blood. Supplementation with blueberry powder did not affect plasma FFA and cytokine concentrations; however, it attenuated the cytokine production induced by ex vivo treatment of whole blood with LPL. This trial was registered at clinicaltrials.gov as NCT01594008., (© 2016 American Society for Nutrition.)

Background: Few interventions directly compare equivalent calcium and vitamin D from dairy vs. supplements on the same bone outcomes. The radioisotope calcium-41 ((41)Ca) holds promise as a tracer method to directly measure changes in bone resorption with differing dietary interventions., Objective: Using (41)Ca tracer methodology, determine if 4 servings/day of dairy foods results in greater (41)Ca retention than an equivalent amount of calcium and vitamin D from supplements. Secondary objective was to evaluate the time course for the change in (41)Ca retention., Methods: In this crossover trial, postmenopausal women (n = 12) were dosed orally with 100 nCi of (41)Ca and after a 180 day equilibration period received dairy (4 servings/day of milk or yogurt; ~ 1300 mg calcium, 400 IU cholecalciferol (vitamin D3/day)) or supplement treatments (1200 mg calcium carbonate/day and 400 IU vitamin D3/day) in random order. Treatments lasted 6 weeks separated by a 6 week washout (WO). Calcium was extracted from weekly 24 h urine collections; accelerator mass spectrometry (AMS) was used to determine the (41/40)Ca ratio. Primary outcome was change in (41/40)Ca excretion. Secondary outcome was the time course for change in (41)Ca excretion during intervention and WO periods., Results: The (41/40)Ca ratio decreased significantly over time during both treatments; there was no difference between treatments. Both treatments demonstrated a significant retention of (41)Ca within 1-2 weeks (p = 0.0007 and p < 0.001 for dairy and supplements, respectively). WO demonstrated a significant decrease (p = 0.0024) in (41)Ca retention within 1-2 weeks, back to pre-intervention levels., Conclusion: These data demonstrate that urinary (41)Ca retention is increased with an increase in calcium and vitamin D intake regardless of the source of calcium, and the increased retention occurs within 1-2 weeks.

Objectives: Breast milk contains a high concentration of osteopontin (OPN), a protein having multiple functions. In contrast, infant formula is low in OPN. A randomized clinical trial was performed to evaluate effects of adding a highly enriched bovine OPN fraction to formula, and infants whose mothers had already decided not to breast-feed were recruited. They were fed regular formula (F0) or the same formula with bovine OPN at 65 (F65) or 130 (F130) mg/L (50% and 100% of human milk level, respectively) from 1 to 6 months of age and were compared with a reference group of breast-fed (BF) infants., Methods: Morbidity was recorded daily and 3-day dietary records collected monthly. Anthropometry was assessed monthly, and blood samples were taken at 1, 4, and 6 months of age. Hematology and iron status, serum cytokines, plasma amino acids, and blood urea nitrogen were analyzed., Results: Formulas were well tolerated and there were no significant differences in formula intake or growth among the formula-fed groups. The F130 group had significantly lower plasma threonine than the F0 and F65 groups, and significantly lower plasma branched-chain amino acids (BCAAs) than the F0 group and, thus, was closer to BF infants. Plasma TNF-α was higher in formula-fed infants than in BF infants. Among the formula-fed groups, the proinflammatory cytokine TNF-α was significantly lower in the F65 and F130 groups than in the F0 group, suggesting that OPN downregulates inflammatory cytokines and thus affects immune function., Conclusions: Addition of OPN to infant formula changes amino acid metabolism and cytokine responses of FF infants and makes them more similar to BF infants. The lower prevalence of pyrexia in the F130 infants than in F0 infants suggests that adding OPN may confer health benefits.

Background: Maternal undernutrition and newborn stunting [birth length-for-age z score (LAZ) <-2] are common in Bangladesh., Objective: The objective was to evaluate the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PLs) on birth outcomes., Design: We conducted a cluster-randomized effectiveness trial (the Rang-Din Nutrition Study) within a community health program in rural Bangladesh. We enrolled 4011 pregnant women at ≤20 gestational weeks; 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid) and 16 clusters received LNS-PLs (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Both of the supplements were intended for daily consumption until delivery. Primary outcomes were birth weight and length., Results: Infants in the LNS-PL group had higher birth weights (2629 ± 408 compared with 2588 ± 413 g; P = 0.007), weight-for-age z scores (-1.48 ± 1.01 compared with -1.59 ± 1.02; P = 0.006), head-circumference-for-age z scores (HCZs; -1.26 ± 1.08 compared with -1.34 ± 1.12; P = 0.028), and body mass index z scores (-1.57 ± 1.05 compared with -1.66 ± 1.03; P = 0.005) than those in the IFA group; in adjusted models, the differences in length (47.6 ± 0.07 compared with 47.4 ± 0.04 cm; P = 0.043) and LAZ (-1.15 ± 0.04 compared with -1.24 ± 0.02; P = 0.035) were also significant. LNS-PLs reduced the risk of newborn stunting (18.7% compared with 22.6%; RR: 0.83; 95% CI: 0.71, 0.97) and small head size (HCZ <-2) (20.7% compared with 24.9%; RR: 0.85; 95% CI: 0.73, 0.98). The effects of LNS-PL on newborn stunting were greatest in infants born before a 10-wk interruption in LNS-PL distribution (n = 1301; 15.7% compared with 23.6%; adjusted RR: 0.69; 95% CI: 0.53, 0.89) and in infants born to women ≤24 y of age or with household food insecurity., Conclusion: Prenatal lipid-based nutrient supplements can improve birth outcomes in Bangladeshi women, especially those at higher risk of fetal growth restriction. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2016 American Society for Nutrition.)

Background: The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women., Objective: We evaluated the effects of prenatal LNS supplementation on fetal growth., Design: In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length., Results: This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women., Conclusion: Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866., (© 2015 American Society for Nutrition.)

Obese individuals are at an increased risk of developing CVD, hypertension, type 2 diabetes, and bacterial and viral infections when compared with the normal-weight population. In a 9-week randomised, double-blind, cross-over study, twenty-four obese subjects aged between 20 and 60 years and with a BMI between 30 and 45 kg/m2 were fed grape or placebo powder for 3-week intervals to determine the effects of dietary grapes on blood lipid profiles, plasma inflammatory marker concentrations and immune cell function. Blood samples were collected on days 1 and 8 for obtaining baseline information and at weeks 3, 4, 8 and 9. Comprehensive chemistry panels, lipid profile analyses by NMR, measurement of plasma inflammatory marker concentrations, and analyses of cytokine production by activated T lymphocytes and monocytes were performed for each blood draw. Dietary grape powder reduced the plasma concentrations of large LDL-cholesterol and large LDL particles compared with the placebo powder (P< 0·05). The concentrations of interferon-γ, TNF-α, IL-4 and IL-10 were measured in supernatants from peripheral blood mononuclear cells (PBMC) activated with anti-CD3/CD28 antibodies and those of TNF-α, IL-1β, IL-6 and IL-8 were measured in supernatants from PBMC activated with lipopolysaccharide (LPS). No difference in the production of T-cell cytokines was observed between the two intervention groups. The production of IL-1β and IL-6 was increased in supernatants from LPS-activated PBMC in the grape powder group compared with the placebo powder group (P< 0·05). These data suggest that dietary grapes may decrease atherogenic lipid fractions in obese individuals and increase the sensitivity of monocytes in a population at a greater risk of developing infections.

Objective: To evaluate in-hospital formula supplementation among first-time mothers who intended to exclusively breastfeed and determined if in-hospital formula supplementation shortens breastfeeding duration after adjusting for breastfeeding intention., Study Design: We assessed strength of breastfeeding intentions prenatally in a diverse cohort of expectant primiparae and followed infant feeding practices through day 60. Among mothers planning to exclusively breastfeed their healthy term infants for ≥1 week, we determined predictors, reasons, and characteristics of in-hospital formula supplementation, and calculated the intention-adjusted relative risk (ARR) of not fully breastfeeding days 30-60 and breastfeeding cessation by day 60 with in-hospital formula supplementation (n = 393)., Results: Two hundred ten (53%) infants were exclusively breastfed during the maternity stay and 183 (47%) received in-hospital formula supplementation. The most prevalent reasons mothers cited for in-hospital formula supplementation were: perceived insufficient milk supply (18%), signs of inadequate intake (16%), and poor latch or breastfeeding (14%). Prevalence of not fully breastfeeding days 30-60 was 67.8% vs. 36.7%, ARR 1.8 (95% CI, 1.4-2.3), in-hospital formula supplementation vs exclusively breastfed groups, respectively, and breastfeeding cessation by day 60 was 32.8% vs. 10.5%, ARR 2.7 (95% CI, 1.7-4.5). Odds of both adverse outcomes increased with more in-hospital formula supplementation feeds (not fully breastfeeding days 30-60, P = .003 and breastfeeding cessation, P = .011)., Conclusions: Among women intending to exclusively breastfeed, in-hospital formula supplementation was associated with a nearly 2-fold greater risk of not fully breastfeeding days 30-60 and a nearly 3-fold risk of breastfeeding cessation by day 60, even after adjusting for strength of breastfeeding intentions. Strategies should be sought to avoid unnecessary in-hospital formula supplementation and to support breastfeeding when in-hospital formula supplementation is unavoidable., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Information is needed on zinc absorption from grain cultivars having higher zinc content. Total absorbed zinc (TAZ) from mixed diets containing high-zinc rice (HZnR), conventional rice (CR), or CR plus zinc fortificant (CR+Zn) was measured. Forty-two nonmalnourished preschool-aged children were enrolled in 1 of 2 groups. Using a crossover design, children in group A (n = 22) received for 1 d each a mixed diet containing 150 g CR or HZnR. Children in group B (n = 20) received HZnR on 1 d and CR+Zn on the other day. Fractional zinc absorption (FZA) was measured during each dietary period by using a dual-isotope tracer ratio technique; TAZ was calculated as the product of zinc intake [total dietary zinc (TDZ)] and FZA. TDZ was 3.83, 4.83, and 6.03 mg/d when the children were fed the CR, HZnR, and CR+Zn-containing diets, respectively. Mean FZA from the CR diet was greater than from the HZnR diet (25.1 vs. 20.1%, P < 0.001), and the mean FZA from the CR+Zn diet (18.8%) was less than from both the CR diet (P < 0.001) and the HZnR diet (P = 0.014). The mean TAZ was 0.96 ± 0.16, 0.97 ± 0.18, and 1.13 ± 0.20 mg/d from the CR, HZnR and CR +Zn diets, respectively. TAZ was not different for the CR and HZnR diets (P = 0.99) but was significantly greater from the CR+Zn diet compared with the other 2 diets (P < 0.001). Rice cultivars with higher zinc and/or lower phytate content are needed to increase TAZ by young children consuming this amount of rice.