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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) Levins formula with prevalence ratio (PR) in place of relative risk (RR), 2) Levins 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-Nortons approach, and 3) estimation from OR using Zhang-Yus 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 Levins formula with PR. Estimated anemia AF for children and women were 2-36% and 3-46% for iron deficiency,

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.

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.

BackgroundVitamin A (VA) stores are low in early infancy and may impair development of the immune system.ObjectiveThis 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.MethodsIn 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.ResultsVAS 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.ConclusionsNeonatal 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.

BackgroundZinc deficiency impairs immune function and is common among children in South-East Asia.ObjectivesThe effect of zinc supplementation on immune function in young Laotian children was investigated.MethodsChildren (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).ResultsT-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).ConclusionsZinc 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.

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 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.

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.

BackgroundOf 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.ObjectivesWe explored whether the disparate growth outcomes were associated with differences in intervention components, household demographic variables, and/or children's morbidity.MethodsChildren 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.ResultsMean 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

BackgroundChildhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life.ObjectiveWe 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.DesignIn 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.ResultsAt 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

BackgroundSaturated 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.ObjectiveWe 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.MethodsTwenty-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).ResultsThe 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.ConclusionsThe 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.

BackgroundMaternal undernutrition and newborn stunting [birth length-for-age z score (LAZ)

ObjectiveTo 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 designWe 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).ResultsTwo 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).ConclusionsAmong 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.

BackgroundAlcoholic steatohepatitis (ASH) is caused in part by the effects of ethanol (EtOH) on hepatic methionine metabolism.MethodsTo investigate the phenotypic and epigenetic consequences of altered methionine metabolism in this disease, we studied the effects of 4-week intragastric EtOH feeding with and without the methyl donor betaine in cystathionine beta synthase (CβS) heterozygous C57BL/6J mice.ResultsThe histopathology of early ASH was induced by EtOH feeding and prevented by betaine supplementation, while EtOH feeding reduced and betaine supplementation maintained the hepatic methylation ratio of the universal methyl donor S-adenosylmethionine (SAM) to the methyltransferase inhibitor S-adenosylhomocysteine (SAH). MethylC-seq genomic sequencing of heterozygous liver samples from each diet group found 2 to 4% reduced methylation in gene bodies, but not promoter regions of all autosomes of EtOH-fed mice, each of which were normalized in samples from mice fed the betaine-supplemented diet. The transcript levels of nitric oxide synthase (Nos2) and DNA methyltransferase 1 (Dnmt1) were increased, while those of peroxisome proliferator receptor-α (Pparα) were reduced in EtOH-fed mice, and each was normalized in mice fed the betaine-supplemented diet. DNA pyrosequencing of CβS heterozygous samples found reduced methylation in a gene body of Nos2 by EtOH feeding that was restored by betaine supplementation and was correlated inversely with its expression and positively with SAM/SAH ratios.ConclusionsThe present study has demonstrated relationships among EtOH induction of ASH with aberrant methionine metabolism that was associated with gene body DNA hypomethylation in all autosomes and was prevented by betaine supplementation. The data imply that EtOH-induced changes in selected gene transcript levels and hypomethylation in gene bodies during the induction of ASH are a result of altered methionine metabolism that can be reversed through dietary supplementation of methyl donors.

To assist with the evaluation of zinc (Zn) intervention programs, information is needed on the magnitude and velocity of response of plasma Zn concentration following changes in Zn intake. Our objective in this study was to measure plasma Zn concentration of healthy adult men before and after initiation and discontinuation of 1 of 2 dosages of Zn supplements or placebo. We conducted a randomized, double-blind, placebo-controlled trial in 58 apparently healthy males aged 19-54 y. Participants received 1 of 3 liquid supplements daily for 21 d: 10 or 20 mg Zn/d, as Zn sulfate, or placebo. Fasting plasma Zn concentrations were measured on 14 occasions before, during, and after supplementation. Data were analyzed using mixed-model ANCOVA. The plasma Zn concentration was related to day of study (P < 0.0001) and study group (P < 0.0001). Controlling for baseline concentrations, plasma Zn concentrations were consistently elevated above baseline by d 5 among individuals in both of the Zn-supplemented groups compared with those receiving placebo supplements, regardless of their initial plasma Zn concentration. There were no significant group-wise differences between those who received either 10 or 20 mg/d Zn. Plasma Zn concentrations of supplemented individuals declined following withdrawal of supplementation and within 2 wk no longer differed from those of the placebo group. Change in the plasma Zn concentration is a useful indicator to monitor compliance with, and possibly effectiveness of, Zn supplementation programs. To ensure accurate interpretation of the results, samples should be collected while the intervention is still in progress. J. Nutr. 140: 2128-2133, 2010. doi: 10.3945/jn.110.122812

A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children < 5 y of age. To explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 [micro]mol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 [micro]mol; 5 mg), which was used to estimate VA pool size, in 3- to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of [14C2]-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify 14C in stool and urine. Estimates of absorption, retention, and the urinary elimination rate (UER) were 83.8 [+ or -] 7.1%, 76.3 [+ or -] 6.7%, and 1.9 [+ or -] 0.6%/d, respectively, for the HD-VA supplement and 76.5 [+ or -] 9.5%, 71.1 [+ or -] 9.4%, and 1.8 [+ or -] 1.2%/d, respectively, for the SI-labeled VA. Mean estimates of absorption, retention, and the UER did not differ by size of the VA dose administered. Estimated absorption and retention were negatively associated with reported fever (r = -0.83; P = 0.011). The HD-VA supplement and SI-labeled VA were adequately absorbed, retained, and utilized in apparently healthy Zambian preschool-age boys; absorption and retention may be affected by recent fever. J. Nutr. 140:1588-1594, 2010. doi: 10.39454/jn.110.125500.

Deficiencies of multiple micronutrients (MMN) usually coexist in developing countries, but supplements have usually provided only 1 or 2 micronutrients (MN). To inform policy, in this article we compared the relative benefits of supplying MMN vs. a placebo or 1 or 2 MN on the following: children's growth, health, and development; pregnancy outcome; nutritional status; and HIV/AIDS mortality and morbidity in adults. Sufficient data were available to perform random-effects meta-analyses of randomized controlled trials (RCT) for the effects of MMN on child growth and nutritional status. Results for other outcomes are presented as effect sizes (ES) when available. In children, MMN interventions resulted in small but significantly greater improvements in length or height (ES = 0.13; 95% CI: 0.055, 0.21) and weight (ES = 0.14; 95% CI: 0.029, 0.25), hemoglobin (ES = 0.39; 95% CI: 0.25, 0.53), serum zinc (ES = 0.23; 95% Cl: 0.18, 0.43), serum retinol (ES = 0.33; 95 % CI: 0.050, 0.61), and motor development. A Cochrane review reported that compared with no supplementation or a placebo, MMN supplementation during pregnancy reduced the relative risk of low birth weight (0.83), small-for-gestational age (0.92), and anemia (0.61); however, MMN were not more effective than iron +folic acid alone. There is some evidence that MMN supplementation improves CD4 counts and HIV-related morbidity and mortality in adults. The efficacy of MMN varies across trials, but overall there is evidence that outcomes are better than when providing [less than or equal to] 2 MN. The policy implications of these studies are discussed.

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 [+ or -] 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (

The essential design and quality control aspects of dietary assessment, randomized controlled trials (RCT) in developing countries and their subsequent meta-analysis are reviewed. Dietary assessment protocols consist of three stages: measurement of food intakes using a method appropriate for the study objectives, calculation of nutrient intakes and finally an evaluation of their nutrient adequacy. The latter may involve: 1) assessment of dietary diversity (average number of different foods consumed per day) and selected indices of dietary quality such as intakes of animal source foods (g/d); 2) percentage of energy from protein, fat and animal protein; 3) selected nutrient densities; and 4) dietary phytate:zinc molar ratio, as well as the prevalence of inadequate nutrient intakes calculated using a probability approach. To establish causality between the nutrient inadequacies identified and adverse health outcomes, RCT must be undertaken. A prerequisite of RCT is double-blind randomization, a procedure designed to eliminate biases arising from baseline confounding variables, unintended interventions and ascertainment bias. Results from existing RCT can be summarized via meta-analysis to gain a better understanding of the population relationship. Meta-analysis is a statistical technique involving linear models or generalized linear models, which can be performed after locating the individual studies, and selecting and abstracting all the necessary data. KEY WORDS: * dietary assessment * probability analysis * randomized clinical trials * double blinding * meta-analysis

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. [ABSTRACT FROM AUTHOR]

Growth patterns among breastfed infants appear to vary from infants fed formula or solids. Seven studies have plotted weights and lengths for a total of 453 North American or European breastfed infants. Overall, 226 were breastfed for 12 months or more and of those, 141 were not given other milks or formula during that period. Forty-two percent were started on solids at four to five months, 38% at six to seven months, and 17% at eight to nine months. Infant growth rates followed the same pattern in all seven studies. Compared with standard growth charts, breastfed babies grew more rapidly for the first two months and then more slowly for months three through twelve. In particular, weight gain was slower after month eight, but gain in length was not. Babies weaned at six to eight months did not show the same drop in weight gain. Standard growth curve charts do not appear to be appropriate for breastfed infants., Objective. To compare growth patterns of a large sample of breast-fed infants with the current World Health Organization (WHO)/Centers for Disease Control and Prevention (CDC) reference data. Methods. Data from seven longitudinal studies of infant growth in North America and northern Europe were pooled (n = 453 breast-fed infants). Weight, length and head circumference were compared with the WHO/CDC reference, and repeated-measures analysis of variance was used to examine associations between growth patterns and breast-feeding duration, age of introduction of solid foods, and use of other milks. Results. In comparison with WHO/CDC reference data, infants breast-fed for at least 12 months (n = 226) grew more rapidly in the first 2 months and less rapidly (particularly in weight) from 3 to 12 months; the mean z score at 12 months was -0.53 for weight for age, -0.29 for length for age, and -0.32 for weight for length. In contrast, mean head circumference was well above the WHO/CDC median throughout the first year of life. These patterns were generally consistent across studies. In the full sample (n = 453), a longer duration of breast-feeding was associated with a greater decline in weight for age and weight for length but not length for age. Conclusion. These results suggest that if growth charts are to reflect patterns consistent with those of infants following WHO feeding recommendations, new reference data based on breast-fed infants are needed. Pediatrics 1995;96:495-503; breast-feeding, growth monitoring, growth references, anthropometry, weight, recumbent length, infant feeding practices., The World Health Organization/Centers for Disease Control and Prevention (WHO/CDC) growth charts' currently used throughout the world for monitoring growth of children are based on the US National Center for [...]

Oral rehydration of children with acute diarrhea and mild-to-moderate dehydration may be slightly more effective using rice flour (RF) oral rehydration solution (ORS), but conventional ORS may still be adequate. A total of 134 male infants between 3 and 36 months of age with diarrhea were randomly assigned to one of three ORS treatment groups. Forty-three children were treated with glucose ORS, 46 with rice dextrin ORS and 45 with RF-ORS. Time until rehydration was similar between the three groups. During the first six hours of treatment, stool output decreased by 24% to 27% among infants receiving RF-ORS. By 12 hours there were no significant differences in stool output between the groups. ORS with rice components may reduce stool output better than other carbohydrates because of its low osmolality and additional organic substances. RF-ORS may be more difficult to prepare and may have a higher risk of microbial contamination compared to the other ORSs., Objective. To assess the effects of glucose (G)-oral rehydration solution (ORS), rice dextrin (RD)-ORS, and rice flour (RF)-ORS on fluid intake, rapidity of rehydration, and stool output of children with acute diarrhea and mild or moderate dehydration. Methods. The study was a randomized, double-asked clinical trial. One hundred forty-six male infants, ages 3 to 36 months, were randomly assigned to one of three treatment groups. Clinical evaluations and fluid balances were conducted every 2 to 4 hours for 48 hours. Principal outcome variables were ORS consumption, recovery of hydration status, and fecal output. Results. The groups were similar at admission with regard to age, nutritional status, history of the current episode, and clinical status. There were no differences in ORS consumption by treatment group during any period of study. During the first 6-hour period, patients in group RF had less stool output (16 [+ or -] 14 g/kg/body weight) than those in group G (22 [+ or -] 20 g/kg) or RD (21 [+ or -] 19 g/kg; P < .05). After 12 hours of hospitalization, there were no differences by treatment group. Recovery of hydration status, changes in serum sodium and potassium, and duration of diarrhea in the hospital were similar in all three groups. Conclusion. There was a 24% to 27% reduction in stool output during the first 6 hours of treatment among children who received RF-ORS compared with those who received G-ORS or RD-ORS, but this effect did not persist after the first 12 hours of therapy. Because this difference was of small magnitude and limited duration, it has minor clinical importance. Thus, we conclude that the three solutions had similar efficacy for children with acute, watery diarrhea and mild or moderate dehydration. Pediatrics 1995;95:191-197; diarrhea, rehydration therapy, electrolytes, oral rehydration solution, clinical trial., ABBREVIATIONS. ORS, oral rehydration solution; G-ORS, glucose-ORS; RD-ORS, rice dextrin-ORS; RF-ORS, rice flour-ORS; SD, standard deviation. Therapy for diarrheal dehydration consists of providing fluid and electrolytes either orally or intravenously, [...]

Young children with severe diarrhea may be able to safely tolerate a diet of undiluted, nonhuman milk. In a meta-analysis of 14 clinical studies, researchers studied the treatment, outcome and diet of children up to 59 months old. In six of 13 studies which discussed treatment outcomes, treatment failure rates were much greater among children who received diets containing lactose. Overall, 22% percent of the children with lactose-containing diets were therapeutic failures versus 12% of those without lactose in their diets. The bowel movements of those with lactose-containing diets were not much more frequent than in the lactose-free diet group. Treatment failure rates for those receiving diluted versus undiluted milk were not statistically different. The number of bowel movements were greater in the undiluted milk group. The overall results from these trials indicate that a majority of children with acute diarrhea may be able to safely continue a diet of undiluted, nonhuman milk if severe dehydration and malnutrition are not complicating factors., ABSSTRACT. 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 metal-anlytic procedures. Results. Among studies that compared lactose-containing milk of formula diets with lactose-free regimens, those children who received the lactose-containing diets during acute diahhrea were twice as likely to have a treatment failure as those who received a lactose-free diet (22% vs 12%, respectively; P