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BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and postnatally were previously shown to improve high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) and length in the children of supplemented mothers at 18 mo of age in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. However, the effects of SQ-LNS on maternal HDL functionality during pregnancy are unknown.ObjectiveThe goal of this cross-sectional, secondary outcome analysis was to compare HDL function in mothers supplemented with SQ-LNS vs. iron and folic acid (IFA) during gestation.MethodsHDL CEC and the activities of 3 HDL-associated enzymes were analyzed in archived plasma samples (N = 197) from a subsample of females at 36 weeks of gestation enrolled in the iLiNS-DYAD trial in Ghana. Correlations between HDL function and birth outcomes, inflammatory markers C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), and the effects of season were explored to determine the influence of these factors on HDL function in this cohort of pregnant females.ResultsThere were no statistically significant differences in HDL CEC, plasma lecithin-cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer protein (CETP) activity, or phospholipid transfer protein (PLTP) activity between mothers supplemented with SQ-LNS compared with IFA control, and no statistically significant relationships between maternal HDL function and childbirth outcomes. LCAT activity was negatively correlated with plasma AGP (R = -0.19, P = 0.007) and CRP (R = -0.28, P < 0.001), CETP and LCAT activity were higher during the dry season compared to the wet season, and PLTP activity was higher in the wet season compared to the dry season.ConclusionsMothers in Ghana supplemented with SQ-LNS compared with IFA during gestation did not have measurable differences in HDL functionality, and maternal HDL function was not associated with childbirth outcomes. However, seasonal factors and markers of inflammation were associated with HDL function, indicating that these factors had a stronger influence on HDL functionality than SQ-LNS supplementation during pregnancy.Clinical trial registry numberThe study was registered as NCT00970866. https://clinicaltrials.gov/study/NCT00970866.

BackgroundAflatoxin (AF) exposure is associated with child growth faltering in cross-sectional studies, with limited findings from longitudinal studies.ObjectivesTo evaluate the relationship between maternal AF B1-lysine adduct concentration, child AF B1-lysine adduct concentration, and child growth in the first 30 mo of life.MethodsAF B1-lysine adduct was measured in mother-child dyad plasma samples using isotope dilution mass spectrometry. Using linear regression, we assessed the relationship between AF B1-lysine adduct concentration and child weight, height, and head and mid-upper arm circumferences at 1 wk, 6, 12, 18, 24, and 30 mo of age.ResultsIn adjusted models, maternal prenatal AF B1-lysine adduct (pg/μL) was positively associated with newborn anthropometric outcomes; largest beta coefficients for associations between standardized values were for newborn weight-for-age z-score [β = 0.13; 95% confidence interval (CI): 0.02, 0.24; P < 0.05 and β = 0.11; 95% CI: 0.00, 0.22; P < 0.05 for second and third trimester AF, respectively]. Child AF B1-lysine adduct (pg/μL) at 6 mo was negatively associated with head circumference-for-age z-score at 6, 18, 24, and 30 mo, with beta coefficients ranging from β = -0.15; 95% CI: -0.28, -0.02 to β = -0.17; 95% CI: -0.31, -0.03; P < 0.05); 18-mo AF was negatively associated with anthropometric outcomes at 18, 24, and 30 mo, most consistently with length-for-age z-score (β = -0.18; 95% CI: -0.32, -0.04, β = -0.21; 95% CI: -0.35, -0.07, β = -0.18; 95% CI: -0.32, -0.03 at 18, 24 and 30 mo, respectively).ConclusionsChild AF exposure was associated with impaired child growth, but maternal AF exposure was not. Exposure during infancy was linked to persistent deficit in head circumference, implying reduced brain size lasting beyond the age of 2 years. Exposure at 18 mo was linked to persistent linear growth deficit. Further research should elucidate mechanisms through which AF affects child growth.

Little is known about the impact of small-quantity lipid-based nutrient supplements (SQ-LNSs) on maternal morbidity. This secondary outcome analysis aimed to compare morbidity symptoms among women in two trials evaluating the efficacy of SQ-LNSs. From enrolment (≤20-week gestation) to 6 months postpartum, Ghanaian (n = 1320) and Malawian (n = 1391) women were assigned to consume daily: 60 mg iron and 400 µg folic acid until childbirth and placebo thereafter (iron and folic acid [IFA] group); or multiple micronutrients (MMN); or 20 g/day SQ-LNSs. Within country, we used repeated measures logistic regression and analysis of variance models to compare group differences in the period prevalence and percentage of days of monitoring when women had fever, gastrointestinal, reproductive, and respiratory symptoms during the second and third trimesters of pregnancy (n ~ 1243 in Ghana, 1200 in Malawi) and 0-3 and 3-6 months postpartum (n ~ 1212 in Ghana, 730 in Malawi). Most outcomes did not differ significantly among groups, with the following exceptions: in Ghana, overall, the prevalence of vomiting was lower in the LNS (21.5%) than MMN (25.6%) group, with the IFA group (23.2%) in-between (p = 0.046); mean ± SD percentage of days with nausea was greater in the LNS (3.5 ± 10.3) and MMN (3.3 ± 10.4) groups than the IFA (2.7 ± 8.3) group (p = 0.002). In Malawi, during 3-6 month postpartum, the prevalence of severe diarrhoea was greater in the LNS (8.1%) than the MMN (2.9%) group, with IFA (4.6%) in-between, p = 0.041). We conclude that the type of nutrient supplement received during pregnancy and lactation generally does not influence morbidity symptoms in these settings. Clinicaltrials.gov identifiers: NCT00970866; NCT01239693.

Information on fortifiable food consumption is essential to design, monitor and evaluate fortification programmes, yet detailed methods like 24-h recalls (24HRs) that provide such data are rarely conducted. Simplified questionnaire-based methods exist but their validity compared with 24HRs has not been shown. We compared two simplified methods (i.e., a household food acquisition and purchase questionnaire [FAPQ] and a 7-day semiquantitative food frequency questionnaire [SQ-FFQ]) against 24HRs for estimating fortifiable food consumption. We assessed the consumption of fortifiable wheat flour and oil using a FAPQ and, for wheat flour only, a 7-day SQ-FFQ and compared the results against 24HRs. The participants included children 12-18 months (n = 123) and their mothers 18-49 years selected for a study assessing child vitamin A intake and status in Mandaluyong City, Philippines. For fortifiable wheat flour, the FAPQ estimated considerably lower mean intakes compared to 24HRs for children and mothers (2.2 vs. 14.1 g/day and 5.1 vs. 42.3 g/day, respectively), while the SQ-FFQ estimated slightly higher mean intakes (15.7 vs. 14.1 g/day and 51.5 vs. 42.3 g/day, respectively). For fortifiable oil, the FAPQ estimated considerably higher mean intakes compared to 24HRs for children and mothers (4.6 vs. 1.8 g/day and 12.5 vs. 6.1 g/day, respectively). The SQ-FFQ, but not the FAPQ, generated useful information on fortifiable food consumption that can inform fortification programme design and monitoring decisions in the absence of more detailed individual-level data. Potential adaptations to improve the FAPQ, such as additional questions on foods prepared away from home and usage patterns, merit further research.

ObjectivesTo assess (a) the impact of daily preventive zinc tablets (7 mg; PZ), zinc-containing multiple micronutrient powder (10 mg zinc, and 13 other micronutrients; MNP) or placebo, delivered for 9 months, on Insulin-like Growth Factor 1 (IGF1) and IGF Binding Protein 3 (IGFBP3) among Laotian children 6-23 months, and (b) whether the effects of PZ and MNP on length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ) are modified by baseline IGF1 and IGFBP3.DesignA double-blind, placebo-controlled trial (N = 419).MethodsPlasma IGF1 and IGFBP3 concentrations at baseline and 36 weeks were analyzed by automated chemiluminescent assay. Anthropometry was assessed at baseline, at 18 and 36 weeks. Intervention effects were estimated using ANCOVA.ResultsAt 36 weeks, geometric mean IGF1 (~39.0-39.2 ng/mL; p = 0.99) and IGFBP3 (2038-2076 ng/mL; p = 0.83) did not differ by group. At 18 weeks (but not at 36 weeks), LAZ in the PZ group (-1.45) was higher than the MNP (-1.70) and control (-1.55) groups (p = 0.01) among children in the highest baseline IGF1 tertile (p for interaction = 0.006). At 36 weeks (but not at 18 weeks), WAZ in the PZ group (-1.55) was significantly higher than the MNP (-1.75) and control (-1.65) groups (p = 0.03), among children in the lowest baseline IGFBP3 tertile (p for interactions = 0.06).ConclusionsAlthough IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ on linear and ponderal growth, suggesting that IGF1 bioavailability may drive catch-up growth in zinc-supplemented children.

Choline is an essential micronutrient that may influence growth and development; however, few studies have examined postnatal choline status and children's growth and development in low- and middle-income countries. The aim of this observational analysis was to examine associations of plasma choline with growth and development among Malawian children aged 6-15 months enrolled in an egg intervention trial. Plasma choline and related metabolites (betaine, dimethylglycine and trimethylamine N-oxide) were measured at baseline and 6-month follow-up, along with anthropometric (length, weight, head circumference) and developmental assessments (the Malawi Developmental Assessment Tool [MDAT], the Infant Orienting with Attention task [IOWA], a visual paired comparison [VPC] task and an elicited imitation [EI] task). In cross-sectional covariate-adjusted models, each 1 SD higher plasma choline was associated with lower length-for-age z-score (-0.09 SD [95% confidence interval, CI -0.17 to -0.01]), slower IOWA response time (8.84 ms [1.66-16.03]) and faster processing speed on the VPC task (-203.5 ms [-366.2 to -40.7]). In predictive models, baseline plasma choline was negatively associated with MDAT fine motor z-score at 6-month follow-up (-0.13 SD [-0.22 to -0.04]). There were no other significant associations of plasma choline with child measures. Similarly, associations of choline metabolites with growth and development were null except higher trimethylamine N-oxide was associated with slower information processing on the VPC task and higher memory scores on the EI task. In this cohort of children with low dietary choline intake, we conclude that there were no strong or consistent associations between plasma choline and growth and development.

BackgroundHealthy nutrition during the first year of life is critical for optimal growth and development. Limited techniques are available to assess diet quality in infancy, and few have been shown to be predictive of dietary and adiposity outcomes in low-income children.ObjectiveThe objectives of this study were to construct an Infant Diet Quality Index (IDQI) to assess the diet quality from birth to 12 mo and to determine whether the IDQI exhibits predictive validity by estimating the longitudinal associations of IDQI scores with diet quality and weight status at 2 to 4 y.DesignData were analyzed from the longitudinal Women, Infants, and Children Infant and Toddler Feeding Practices Study-2 (unweighted, n = 2858; weighted. N = 392,439) using one 24-h dietary recall and survey responses during infancy. The newly constructed IDQI consists of 16 equally-weighted components: 1) breastfeeding duration; 2) exclusive breastfeeding; age of first introduction of: 3) solids, 4) iron-rich cereals, 5) cow milk, 6) sugar-sweetened beverages, 7) salty/sweet snacks, 8) other drinks/liquids, and 9) textured foods; frequency of consuming 10) fruit or 11) vegetables; frequency of consuming different 12) fruit or 13) vegetables; 14) nonrecommended bottle-feeding practices; 15) use of commercial baby foods; and 16) number of meals and snacks. Regression analysis was used to estimate associations between the total IDQI score (range, 0-1) and Healthy Eating Index-2015 (HEI-2015) scores and body mass index z-scores (BMIz) at 2 to 4 y of age, adjusted for covariates (e.g., child age, sex and race/ethnicity; maternal education level, etc.) RESULTS: The total IDQI score was positively associated with HEI-2015 at the age of 2 y (β = 16.7; 95% CI: 12.6, 20.9; P < 0.001), 3 y (β = 14.5; 95% CI: 8.1, 21.0; P < 0.001), and 4 y (β = 15.4; 95% CI: 8.4, 22.4; P < 0.001); and negatively associated with BMIz at the age of 2 y (β = -1.24; 95% CI: -2.01, -0.47; P = 0.002) and 4 y (β = -0.92; 95% CI: -1.53, -0.30; P = 0.003).ConclusionsThe IDQI has predictive validity for diet quality and weight status in low-income US children.

BackgroundVitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods.ObjectivesThis analysis aimed to determine the impact of supplementing children's diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD.MethodsChildren age 6-9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol 5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 μmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 μmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)].ConclusionsProvision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx.This trial was registered at [clinicaltrials.gov] as [NCT03385252].

Proline betaine (Pro-B) has been identified as a biomarker of dietary citrus intake, yet gaps remain in its validation as a quantitative predictor of intake during various physiological states. This study quantified sources of within-individual variation (WIV) in urinary Pro-B concentration during pregnancy and assessed its correlation with the reported usual intake of citrus fruit and juice. Pro-B concentrations were determined by 1H-NMR spectroscopy in spot and 24-h urine specimens (n = 255) collected throughout pregnancy from women participating in the MARBLES cohort study. Adjusted linear or log mixed effects models quantified WIV and tested potential temporal predictors of continuous or elevated Pro-B concentration. Pearson or Spearman correlations assessed the relationship between averaged repeated biomarker measures and usual citrus intake reported by food frequency questionnaires. The proportion of variance in urinary Pro-B attributable to WIV ranged from 0.69 to 0.74 in unadjusted and adjusted models. Citrus season was a significant predictor of Pro-B in most analyses (e.g., adjusted β [95% CI]: 0.52 [0.16, 0.88] for non-normalized Pro-B), while gestational age predicted only non-normalized Pro-B (adjusted β [95% CI]: -0.093 [-0.18, -0.0038]). Moderate correlations (rs of 0.40 to 0.42) were found between reported usual citrus intake and averaged repeated biomarker measurements, which were stronger compared to using a single measurement. Given the high degree of WIV observed in urinary Pro-B, multiple samples per participant are likely needed to assess associations between citrus consumption and health outcomes.

Mineral deficiencies are common in children living in low-resource areas. Eggs are a rich source of essential nutrients and have been shown to improve growth in young children, although little is known about their impact on mineral status. Children aged 6-9 months (n = 660) were randomized to receive either one egg/day for 6-months or no intervention. Anthropometric data, dietary recalls, and venous blood were collected at baseline and 6-months follow-up. Quantification of plasma minerals (n = 387) was done using inductively coupled plasma-mass spectroscopy. Difference-in-difference mean plasma mineral concentrations was determined from baseline and follow-up values and assessed between groups by intention-to-treat using ANCOVA regression models. Prevalence of zinc deficiency was 57.4% at baseline and 60.5% at follow-up. Mean difference (MD) of plasma magnesium, selenium, copper, and zinc levels were not different between groups. Plasma iron concentrations were significantly lower in the intervention compared to the control group (MD = - 9.29; 95% CI: - 15.95, - 2.64). Zinc deficiency was widely prevalent in this population. Mineral deficiencies were not addressed with the egg intervention. Further interventions are needed to improve the mineral status of young children.

BackgroundThe National Cancer Institute (NCI) method has been used widely by researchers to make inferences about usual dietary intake distributions of foods and nutrients based on a limited number of 24-hour dietary recalls (24HRs). Although the NCI method does not provide individual estimates of usual intake, it can be used to address many research questions, including modeling effects of nutrition interventions on population distributions of usual intake. Software for implementing the NCI method and corresponding code examples is publicly available in the form of SAS macros, but little formal guidance exists for conducting advanced analyses.ObjectivesWe aim to present advanced techniques for working with NCI macros to conduct both basic and advanced dietary analyses and modeling.MethodWe first present the three basic building blocks of analyses using the NCI method: 1) dataset preparation; 2) application of the MIXTRAN macro to estimate parameters of the usual intake distribution, including effects of covariates, after transformation of 24HRs to approximate normality; and 3) application of the DISTRIB macro to estimate the distribution of usual nutrient intake. Then, we illustrate how researchers can employ these building blocks to answer questions beyond typical descriptive analyses.ResultsResearchers can adapt the building blocks to 1) account for factors such as demographic changes or nutrition interventions such as food fortification, 2) estimate the prevalence of dietary inadequacy via the full probability method, 3) incorporate nutrient intake from sources not always captured by 24HRs, such as dietary supplements and human milk, and 4) carry out multiple subgroup analyses. This paper describes the theoretical basis and operational guidance for these techniques.ConclusionWith this paper as a detailed resource, researchers can leverage the basic NCI building blocks to investigate a wide range of questions about usual dietary intake distribution.

BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting.ObjectivesWe aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3).MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation.ConclusionsIncluding SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

BackgroundIn the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain.ObjectivesWe describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings.MethodsCross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications.ResultsIn 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines.ConclusionsWhere having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

PurposeTo assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children.MethodsChildren (n = 1704) aged 6-23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B12 along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.ResultsThere was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p

BackgroundYoung children exposed to high-dose vitamin A supplements (VAS) and vitamin A (VA)-fortified foods may be at risk of high VA intake and high VA total body stores (TBS).ObjectivesTBS and estimated liver VA concentration were compared among children with adequate or high VA intake and different timing of exposure to VAS, and associations between estimated liver VA concentrations and biomarkers of VA toxicity were examined.MethodsChildren 12-18 mo of age (n = 123) were selected for 3 groups: 1) retinol intake >600 µg/d and VAS within the past mo, 2) retinol intake >600 µg/d and VAS in the past 3-6 mo, and 3) VA intake 200-500 µg retinol activity equivalents (RAE)/d and VAS in the past 3-6 mo. Dietary intake data were collected to measure VA intakes from complementary foods, breast milk, and low-dose, over-the-counter supplements. TBS were assessed by retinol isotope dilution, and VA toxicity biomarkers were measured. Main outcomes were compared by group.ResultsMean (95% CI) VA intakes excluding VAS were 1184 (942, 1426), 980 (772, 1187), and 627 (530, 724) µg RAE/d, in groups 1-3, respectively; mean VA intake was higher in groups 1 and 2 compared with group 3 (P 1 µmol/g liver). There was no evidence of chronic VA toxicity, suggesting that the liver VA cutoff value should be re-evaluated. This trial was registered at www.clinicaltrials.gov as NCT03030339.

ObjectiveThis study aimed to determine the prevalence of anemia and overweight/obesity and assess the relationships between hematocrit (Hct) and body mass index (BMI), and between fatigue and Hct, among a sample of farmworkers in California.MethodsWe estimated the prevalence of anemia (using Hct), overweight/obesity (BMI ≥25 kg/m 2 ), and self-reported fatigue in 587 farmworkers. Multivariable linear and logistic regression models were used to examine the associations between Hct and BMI, and between fatigue and Hct.ResultsAnemia prevalence was 3.1%, overweight/obesity prevalence was 80.7%, and 78% of workers reported fatigue at work. There was no association between Hct and BMI or between Hct and reported fatigue. Women were more likely than men to have lower Hct and higher BMI.ConclusionsA majority of farmworkers in this sample were overweight/obese, but anemia was uncommon. Anemia among more vulnerable subgroups of farmworkers should be explored.

BackgroundYoung children with diets lacking diversity with low consumption of animal source foods are at risk of iron deficiency anemia (IDA).ObjectivesOur objectives were to determine the impact of supplementing diets with 1 egg/d on 1) plasma ferritin, soluble transferrin receptor (sTfR), body iron index (BII), and hemoglobin concentrations and 2) the prevalence of iron deficiency (ID), anemia, and IDA.MethodsMalawian 6-9-mo-old infants in the Mazira trial (clinicaltrials.gov; NCT03385252) were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329). In this secondary analysis, hemoglobin, plasma ferritin, sTfR, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) were measured at enrollment and 6-mo follow-up. Iron biomarkers were corrected for inflammation. Ferritin, sTfR, BII, and hemoglobin were compared between groups using linear regression. Prevalence ratios (PRs) for anemia (hemoglobin 8.3 mg/L, or BII

BackgroundPregnant women in Malawi are at risk of selenium deficiency, which can have adverse effects on pregnancy outcomes. Interventions for improving selenium status are needed.ObjectivesTo assess the effect of provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to Malawian women during pregnancy on their plasma selenium concentrations at 36 wk of gestation.MethodsPregnant women (≤20 wk of gestation) were randomly assigned to receive daily either: 1) iron and folic acid (IFA); 2) multiple micronutrients (MMN; 130 µg selenium per capsule); or 3) SQ-LNS (130 µg selenium/20 g). Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry at baseline and after ≥16 wk of intervention (at 36 wk of gestation) and compared by intervention group.ResultsAt 36 wk of gestation, median (quartile 1, quartile 3) plasma selenium concentrations (micromoles per liter) were 0.96 (0.73, 1.23), 0.94 (0.78, 1.18), and 1.01 (0.85, 1.28) in the IFA, MMN, and SQ-LNS groups, respectively. Geometric mean (GM) plasma selenium concentration was 5.4% (95% CI: 1.8%, 9.0%) higher in the SQ-LNS group than in the MMN group and tended to be higher than in the IFA group (+4.2%; 95% CI: 1.0%, 7.8%). The prevalence of adjusted plasma selenium concentrations

BackgroundEggs are a rich source of choline, an essential nutrient important for child growth and development. In a randomized trial of 1 egg/d in young children in Ecuador, an egg intervention led to significant improvements in growth, which were partially mediated by increased plasma choline concentration. A similar trial in Malawi (clinicaltrials.gov: NCT03385252) found little improvement in child growth or development.ObjectivesWe aimed to evaluate the effect of 1 egg/d for 6 mo on plasma choline concentrations in Malawian children enrolled in a randomized trial.MethodsInfants aged 6-9 mo in rural Malawi were randomly assigned to receive 1 egg/d (n = 331) or serve as a nonintervention control (n = 329) for 6 mo. Anthropometric, developmental, and dietary data were collected at baseline and 6-mo follow-up, along with a blood draw. Plasma choline, betaine, dimethylglycine, trimethylamine N-oxide (TMAO), and DHA were measured at both time points using ultrahigh performance liquid chromatography-tandem MS (n = 200 per group). Linear regression analysis was used to determine the difference in plasma choline and related metabolites between groups after 6 mo of intervention.ResultsPlasma choline, betaine, dimethylglycine, and DHA concentrations did not differ between groups at 6-mo follow-up. Plasma TMAO was significantly (26%; 95% CI: 7%, 48%) higher in the egg intervention group in a fully adjusted model.ConclusionsProvision of 1 egg/d for 6 mo did not result in increases in plasma choline or related metabolites, except TMAO. This could partially explain the lack of effect on growth and development. Additional interventions are needed to improve choline status, growth, and development in this population.

BackgroundIn utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation.ObjectivesAflatoxin exposure and selected determinants thereof were characterized in mother-child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh.MethodsCirculating aflatoxin B1 (AFB1)-lysine albumin adducts were measured in dyads from Bangladesh (n = 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (n = 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB1-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimated daily AFB1 intake.ResultsMaternal AFB1-lysine was higher in Malawi (98% detectable; median: 0.469, IQR: 0.225-1.027 pg/µL) than in Bangladesh (59%; 0.030, nondetectable [nd]-0.077 pg/µL). Although estimated dietary exposure in Malawi was temporally stable (648 ng AFB1/day), estimated intake in Bangladesh was reduced by 94% between rainy and winter seasons (98 to 6 ng/day). AFB1-lysine was low in cord blood from Bangladesh (15% detectable; 0.045, 0.031-0.088 pg/µL among detectable) and in Malawian infants at 6 mo of age (0.072, nd-0.236 pg/µL), but reached maternal concentrations by 18 or 24 mo (Bangladesh: 0.034, nd-0.063 pg/µL; Malawi: 0.370, 0.195-0.964 pg/µL). In Malawian infants, exclusive breastfeeding at 3 mo was associated with 58% lower AFB1-lysine concentrations at 6 mo compared with other feeding modes (P = 0.010).ConclusionsAmong pregnant women, aflatoxin exposure was persistently high in Malawi, while lower and seasonal in Bangladesh. Infants were partially protected from exposure in utero and with exclusive breastfeeding, but exposures reached adult levels by 18-24 mo of age. The Bangladesh and Malawi trials are registered at clinicaltrials.gov as NCT00860470 and NCT01239693.

Access to and utilisation of antenatal care (ANC) is important for optimising health and nutrition during pregnancy. This study aimed to assess adherence to and factors associated with ANC and antenatal supplement use among Laotian women, and consider culturally appropriate strategies to increase micronutrient intakes. Mother-child (aged 21 d to

Culturally determined food restrictions are common among pregnant and postpartum women in Asia. This study aimed to describe perinatal dietary restrictions, factors associated with food avoidances and attainment of minimum dietary diversity (MDD-W) among women in Lao PDR. Mother-child (aged 21 days to

BackgroundMultiple micronutrient (MN) deficiencies remain highly prevalent among women of reproductive age (WRA) and preschool-aged children (PSC) in many areas within India. Salt is an attractive vehicle for MN fortification in this context, as it is universally consumed in fairly consistent amounts and coverage of iodized salt (IS) is 94%. The overall objective of this trial is to evaluate the nutritional impact of quintuply-fortified salt with iron in the form of encapsulated ferrous fumarate, zinc, vitamin B12, folic acid, and iodine (eFF-Q5S) vs. quintuply-fortified salt with iron in the form of ferric pyrophosphate plus EDTA, zinc, vitamin B12, folic acid, and iodine (FePP-Q5S) vs. IS for the improvement of MN status among non-pregnant WRA and PSC.MethodsThe study is a community-based, randomized, controlled trial that will be conducted in Punjab, India. 780 non-pregnant WRA 18-49 years old and 468 PSC 12-59 months old will be enrolled and assigned to one of three intervention groups. Salt will be provided to participants monthly for 12 months. Primary outcomes include changes in mean concentration of biomarkers of iron, zinc, vitamin B12, folate and iodine. Secondary outcomes include changes in the composition of the gut microbiome, and discretionary salt intake of PSC.DiscussionIf proven efficacious, multiply-fortified salt (MFS) has the potential to drastically reduce the burden of MN deficiencies in India, and around the world. Although effectiveness research will be needed to examine the impact of MFS under programmatic conditions, salt fortification will piggy-back on existing platforms to produce IS and doubly-fortified salt (DFS), making it possible to scale-up the intervention quickly.Trial registrationClinicaltrials.gov: NCT05166980; date of registration: December 22, 2021. Clinical Trials Registry-India: CTRI/2022/040332 and CTRI/2022/02/040333; date of registration: February 15, 2022.

BackgroundDespite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance.MethodsData were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations.ResultsThe mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (- 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not.ConclusionOPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC.Trial registrationThe NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688 . Registered 16 April 2013.

Prenatal plus postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) improved child growth at 18 months in the International Lipid-Based Nutrient Supplements DYAD trial in Ghana. In this secondary outcome analysis, we determined whether SQ-LNS versus prenatal iron and folic acid (IFA) supplementation improves the cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) particles and alters their lipidomic, proteomic, or glycoproteomic composition in a subset of 80 children at 18 months of age. HDL CEC was higher among children in the SQ-LNS versus IFA group (20.9 ± 4.1 vs 19.4 ± 3.3%; one-tailed p = 0.038). There were no differences in HDL lipidomic or proteomic composition between groups. Twelve glycopeptides out of the 163 analyzed were significantly altered by SQ-LNS, but none of the group differences remained significant after correction for multiple testing. Exploratory analysis showed that 6 out of the 33 HDL-associated proteins monitored differed in glycopeptide enrichment between intervention groups, and 6 out of the 163 glycopeptides were correlated with CEC. We conclude that prenatal plus postnatal SQ-LNS may modify HDL protein glycoprofiles and improve the CEC of HDL particles in children, which may have implications for subsequent child health outcomes. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundMeta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (

BackgroundSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.ObjectivesWe aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).ResultsIn 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11).ConclusionsChild SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663.

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers.ResultsSQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin 12 mo and provided 9 (as opposed to

ObjectivesInadequate iodine intake during pregnancy increases the risk of neonatal morbidity and mortality. We aimed to evaluate whether prenatal supplements containing iodine affect urinary iodine concentrations (UIC) of pregnant women in Malawi.DesignA randomised controlled trial. Pregnant women (n 1391) were assigned to consume 60 mg/d Fe and 400 µg/d folic acid (IFA) or 18 vitamins and minerals including 250 µg/d iodine (MMN) or 20 g/d small-quantity lipid-based nutrient supplements (SQ-LNS) with similar nutrient contents as MMN group, plus macronutrients (LNS) until childbirth. In a sub-study (n 317), we evaluated group geometric mean urinary iodine concentration (UIC) (µg/L) at 36 weeks of gestation controlling for baseline UIC and compared median (baseline) and geometric mean (36 weeks) UIC with WHO cut-offs: UIC < 150, 150-249, 250-499 and ≥500 reflecting insufficient, adequate, above requirements and excessive iodine intakes, respectively.SettingMangochi District, Malawi.ParticipantsWomen ≤20 weeks pregnant.ResultsGroups had comparable background characteristics. At baseline, overall median (Q1, Q3) UIC (319 (167, 559)) suggested iodine intakes above requirements. At 36 weeks, the geometric mean (95 % CI) UIC of the IFA (197 (171, 226)), MMN (212 (185, 243)) and LNS (220 (192, 253)) groups did not differ (P = 0·53) and reflected adequate intakes.ConclusionsIn this setting, provision of supplements containing iodine at the recommended dose to pregnant women with relatively high iodine intakes at baseline, presumably from iodised salt, has no impact on the women's UIC. Regular monitoring of the iodine status of pregnant women in such settings is advisable. Clinicaltrials.gov identifier: NCT01239693.

Eggs are a rich source of multiple nutrients that support child growth and development. Provision of eggs as a complementary food may improve dietary adequacy among young children at risk for undernutrition. Our objective was to test the impact of an egg intervention on the adequacy of total nutrient intakes and micronutrient density among 6- to 15-month-old Malawian children. Children 6 to 9 months old, living in Mangochi District, Malawi, were randomly assigned to the intervention group (n = 331) receiving an egg per day or a control group (n = 329) consuming their usual diet. Dietary intakes of macronutrients, vitamins and minerals were assessed using 24-h recalls at baseline, 3-month midline and 6-month endline, with repeat recalls in a subsample. Usual nutrient intake and micronutrient density distributions were modelled to estimate group means and prevalence of inadequacy. Group differences at midline and endline were tested using unequal variance t tests with bootstrapped standard errors. The egg intervention resulted in higher intakes of fat and protein and lower intakes of carbohydrates. The egg group had lower prevalence of inadequacy for selenium, vitamin A, riboflavin, vitamin B5 , vitamin B12 and choline. Micronutrient density inadequacy was lower in the egg group for vitamin A and choline at midline and endline, riboflavin at midline and vitamin B5 at endline. Inadequacy of nutrient intakes or density remained highly prevalent in both groups for multiple micronutrients. Though the egg intervention increased intakes of protein and several micronutrients, total intakes and micronutrient density of multiple micronutrients remained far below recommendations.

BackgroundDietary supplements, like small-quantity lipid-based nutrient supplements (SQ-LNS), are used in intervention programs to prevent undernutrition among women and young children in low-income countries. An objective marker is needed to track consumption of supplements to evaluate the effectiveness of these programs.ObjectiveThe aim of this study was to evaluate saccharin and resveratrol as potential adherence markers for tracking recent consumption of a single serving of SQ-LNS in women.MethodsForty-seven healthy nonpregnant women 18-45 y of age were assigned to consume a single dose of SQ-LNS (20 g) containing either 10 mg sodium saccharin or 5 mg trans-resveratrol, under supervision. On the day before and for 2 d following SQ-LNS consumption, urine samples were collected each day for 24 h as 3 consecutive 4-h collections and one 12-h overnight collection. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate, a resveratrol metabolite, were measured by ultra-high-performance liquid chromatography interfaced to a mass spectrometer with electrospray ionization [UHPLC-(ESI-)MS/MS]. Urinary concentrations (μmol/L urine) of saccharin and trans-resveratrol-3-O-sulfate were plotted against time, and receiver operating characteristic (ROC) curves were used to determine the discriminative capacity of each compound, at each post-consumption time point compared with baseline, to detect recent consumption of SQ-LNS. Cutoff values to differentiate supplement consumption from nonconsumption of each marker were developed using the closest-to-(0,1)-corner cut-point approach.ResultsForty-five participants were included in the analysis. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate increased within 4 h of SQ-LNS consumption. Urinary concentration cutoff values for saccharin (13.4 µmol/L) and trans-resveratrol-3-O-sulfate (0.7 µmol/L) allowed for 78% and 89% sensitivity, respectively, and 100% specificity in detecting consumption of SQ-LNS within the first 12 h after consumption.ConclusionsUrinary concentrations of saccharin and trans-resveratrol-3-O-sulfate reflect consumption of SQ-LNS containing those compounds during the first 12 h post-consumption with high sensitivity and specificity in healthy women and may be useful objective adherence markers for tracking consumption of SQ-LNS.

BackgroundInformation on long-term dietary intake is often required for research or program planning, but surveys routinely use short-term assessments such as 24-h recalls (24HRs). Methods to reduce the impact of within-person variation in 24HRs, such as the National Cancer Institute (NCI) method, typically require extensive training and skill.ObjectivesWe introduce the Simulating Intake of Micronutrients for Policy Learning and Engagement (SIMPLE) macro, a new tool to increase the accessibility of 24HR analysis. We explain the underlying theory behind the tool and provide examples of potential applications.MethodsThe SIMPLE macro connects the core NCI statistical code to estimate usual intake distributions and includes additional code to enable advanced analyses such as predictive modeling. The related SIMPLE-Iron macro applies the full probability method to estimate inadequate iron intake, and the SIMPLE-1D macro is used for descriptive or modeling analyses of data with a single 24HR per person. The macros and associated documentations are freely available. We analyzed data from the US National Health and Nutrition Examination Survey (NHANES) and the Cameroon National Micronutrient Survey to compare the SIMPLE macro to 1) the core NCI code using the Estimated Average Requirement cut point method, and 2) the IMAPP software for iron only, and to demonstrate the applications of the SIMPLE macro for estimating usual intake and predictive modeling.ResultsThe SIMPLE macro generates identical results to the core NCI code. The SIMPLE-Iron macro also produces estimates of inadequate iron intake comparable to the IMAPP software. The examples demonstrate application of the SIMPLE macro to 1) descriptive analyses of nutrient intake from food and supplements (NHANES), and 2) analyses accounting for breast-milk nutrient intake and modeling fortification and supplementation programs (Cameroon).ConclusionsThe SIMPLE macros may facilitate the analysis and modeling of dietary data to inform nutrition research, programs, and policy.

BackgroundVitamin A (VA) deficiency is prevalent in preschool-aged children in sub-Saharan Africa.ObjectivesWe assessed the effect of small-quantity lipid-based nutrient supplements (SQ-LNS) given to women during pregnancy and lactation and their children from 6 to 18 mo of age on women's plasma and milk retinol concentrations in Malawi, and children's plasma retinol concentration in Malawi and Ghana.MethodsPregnant women (≤20 wk of gestation) were randomized to receive daily: 1) iron and folic acid (IFA) during pregnancy only; 2) multiple micronutrients (MMN; 800 μg retinol equivalent (RE)/capsule), or 3) SQ-LNS (800 μg RE/20g) during pregnancy and the first 6 mo postpartum. Children of mothers in the SQ-LNS group received SQ-LNS (400 μg RE/20 g) from 6 to 18 mo of age; children of mothers in the IFA and MMN groups received no supplement. Plasma retinol was measured in mothers at ≤20 and 36 wk of gestation and 6 mo postpartum, and in children at 6 and 18 mo of age. Milk retinol was measured at 6 mo postpartum. VA status indicators were compared by group.ResultsAmong Malawian mothers, geometric mean (95% CI) plasma retinol concentrations at 36 wk of gestation and 6 mo postpartum were 0.97 μmol/L (0.94, 1.01 μmol/L) and 1.35 μmol/L (1.31, 1.39 μmol/L), respectively; geometric mean (95% CI) milk retinol concentration at 6 mo postpartum was 1.04 μmol/L (0.97, 1.13 μmol/L); results did not differ by intervention group. Geometric mean (95% CI) plasma retinol concentrations for Malawian children at 6 and 18 mo of age were 0.78 μmol/L (0.75, 0.81 μmol/L) and 0.81 μmol/L (0.78, 0.85 μmol/L), respectively, and for Ghanaian children they were 0.85 μmol/L (0.82, 0.88 μmol/L) and 0.88 μmol/L (0.85, 0.91 μmol/L), respectively; results did not differ by intervention group in either setting.ConclusionsSQ-LNS had no effect on VA status of mothers or children, possibly because of low responsiveness of the VA status indicators.

Determining the proportion of a population at risk of inadequate or excessive nutrient intake is a crucial step in planning and managing nutrition intervention programs. Multiple days of 24-h dietary intake data per subject allow for adjustment of modeled usual nutrient intake distributions for the proportion of total variance in intake attributable to within-individual variation (WIV:total). When only single-day dietary data are available, an external adjustment factor can be used; however, WIV:total may vary by population, and use of incorrect WIV:total ratios may influence the accuracy of prevalence estimates and subsequent program impacts. WIV:total values were compiled from publications and from reanalyses of existing datasets to describe variation in WIV:total across populations and settings. The potential impact of variation in external WIV:total on estimates of prevalence of inadequacy was assessed through simulation analyses using the National Cancer Institute 1-d method. WIV:total values were extracted from 40 publications from 24 countries, and additional values were calculated from 15 datasets from 12 nations. Wide variation in WIV:total (from 0.02 to 1.00) was observed in publications and reanalyses. Few patterns by population characteristics were apparent, but WIV:total varied by age in children (< vs. >1 y) and between rural and urban settings. Simulation analyses indicated that estimates of the prevalence of inadequate intake are sensitive to the selected ratio in some cases. Selection of an external WIV:total estimate should consider comparability between the reference and primary studies with regard to population characteristics, study design, and statistical methods. Given wide variation in observed ratios with few discernible patterns, the collection of ≥2 days of intake data in at least a representative subsample in population dietary studies is strongly encouraged. In the case of single-day dietary studies, sensitivity analyses are recommended to determine the robustness of prevalence estimates to changes in the variance ratio.

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (

Complementary feeding diets in low- and middle-income countries are generally inadequate to meet requirements for growth and development. Food-based interventions may prevent nutrient inadequacies provided that they do not displace other nutrient-rich foods. We conducted a randomized controlled trial in rural Malawi in which 660 children aged 6 to 9 months were provided an egg a day for 6 months or assigned to a control group. Dietary intake of complementary foods and drinks was assessed at baseline, 3-month midline and 6-month endline visits using a tablet-based multipass 24-h recall. Up to two repeat recalls were collected at each time point in a subsample of 100 children per treatment group. At midline and endline, usual energy intake from eggs was about 30 kcal/day higher in the egg group compared with controls (p < 0.0001). Compared with controls, children in the egg group were over nine times more likely to consume eggs at midline and endline. There was a comparable, but nonsignificant, greater total usual energy intake from complementary foods of 30 kcal/day at midline (p = 0.128) and 36 kcal/day at endline (p = 0.087). There also was a displacement of 7 kcal/day in legumes and nuts in children at endline (p = 0.059). At midline and endline, more than 80% of children in the egg group consumed a minimally diverse diet compared with 53% at midline and 60% at endline in the control group. This study illustrates that mothers in the egg group fed eggs to young children on a regular basis without substantial displacement of other complementary foods.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.

BackgroundVoluntarily fortified snack products are increasingly available but are not necessarily formulated to meet known dietary nutrient gaps, so potential impacts on population micronutrient intake adequacy are uncertain.ObjectivesWe modeled the impacts of hypothetical micronutrient-fortified biscuits on inadequate micronutrient intake in children and women of reproductive age (WRA) in Cameroon.MethodsIn a nationally representative survey stratified by macro-region (North, South, and Yaoundé/Douala), 24-h dietary recall data were collected from 883 children aged 12-59 mo and from 912 WRA. We estimated usual nutrient intake by the National Cancer Institute method for vitamin A, folate, vitamin B-12, zinc, and iron. We simulated the impact of biscuit fortification on prevalence of micronutrient intake below the estimated average requirement, given observed biscuit consumption, in the presence and absence of large-scale food fortification (LSFF) programs.ResultsBiscuit consumption in the prior 24-h by children and WRA, respectively, ranged from 4.5% and 1.5% in the South, to 20.7% and 5.9% in Yaoundé/Douala. In the absence of LSFF programs, biscuits fortified with retinol (600 μg/100 g), folic acid (300 μg/100 g), and zinc (8 mg/100 g) were predicted to reduce the prevalence of inadequacy among children by 10.3 ± 4.4, 13.2 ± 4.2, and 12.0 ± 6.1 percentage points, respectively, in Yaoundé/Douala. However, when existing vitamin A-fortified oil, and folic acid-fortified and zinc-fortified wheat flour programs were considered, the additional impacts of fortified biscuits were reduced substantially. Micronutrient-fortified biscuits were predicted to have minimal impact on dietary inadequacy in WRA, with or without LSFF programs.ConclusionsGiven observed patterns of biscuit consumption in Cameroon, biscuit fortification is unlikely to reduce dietary inadequacy of studied micronutrients, except possibly for selected nutrients in children in urban areas in the absence of LSFF programs. As voluntary fortification becomes increasingly common, modeling studies could help guide efforts to ensure that fortified products align with public health goals.

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4-6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4-6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children (n = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4-6 years. Trial registration: ClinicalTrials.gov Identifier NCT00970866.Lay SummaryThis study addressed a research gap about whether improved nutrition during pregnancy and early childhood impacts telomere length and cortisol in preschool children. There was no difference in child telomere length or cortisol between two trial arms of a nutritional supplementation trial that began during pregnancy. The research outcomes indicate lipid-based nutrient supplements, a relatively new form of supplementation, do not have an effect on markers of stress or cellular aging measured in later childhood.

BACKGROUND:Eggs are a rich source of nutrients important for brain development, including choline, riboflavin, vitamins B-6 and B-12, folate, zinc, protein, and DHA. OBJECTIVE:Our objective was to evaluate the effect of the consumption of 1 egg per day over a 6-mo period on child development. METHODS:In the Mazira Project randomized controlled trial, 660 children aged 6-9 mo were randomly allocated into an intervention or control group. Eggs were provided to intervention households during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. At enrollment, blinded assessors administered the Malawi Developmental Assessment Tool (MDAT), and 2 eye-tracking tasks using a Tobii-Pro X2-60 eye tracker: a visual paired comparison memory task and an Infant Orienting with Attention task. At endline, 6-mo later, blinded assessors administered the MDAT and eye-tracking tasks plus an additional elicited imitation memory task. RESULTS:At endline, intervention and control groups did not significantly differ in any developmental score, with the exception that a smaller percentage of children were delayed in fine motor development in the intervention group (10.6%) compared with the control group (16.5%; prevalence ratio: 0.59, 95% CI: 0.38-0.91). Among 10 prespecified effect modifiers for the 8 primary developmental outcomes, we found 7 significant interactions demonstrating a consistent pattern that children who were less vulnerable, for example, those with higher household wealth and maternal education, showed positive effects of the intervention. Given multiple hypothesis testing, some findings may have been due to chance. CONCLUSION:The provision of 1 egg per day had no overall effect on child development in this population of children, however, some benefits may be seen among children in less vulnerable circumstances. This trial was registered at clinicaltrials.gov as NCT03385252.

BackgroundDiarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment.MethodsChildren were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models.ResultsBaseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (18 months, TZ reduced diarrhea incidence by 24% vs MNP (P = 0.035), and 36% vs Control (P = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ (P = 0.03), and 16% vs Control (P = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P = 0.72).ConclusionsThere was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo.Trial registrationClinicalTrials.gov: NCT02428647.

Poor nutrition and hand hygiene are risk factors for acute respiratory infections (ARIs). Safe drinking water and sanitation can reduce exposure to pathogens and encourage healthy immune responses, reducing the risk of ARIs. Within a trial assessing impacts of water, sanitation, and handwashing (WASH), and nutritional interventions, we evaluated effects on ARIs. The WASH Benefits cluster-randomized trial enrolled pregnant women from Kenyan villages and evaluated health outcomes in children born to enrolled mothers 1 and 2 years after intervention delivery. Geographically adjacent clusters were block-randomized into a passive control (no promotional visits), a double-sized active control (monthly visits to measure mid-upper arm circumference), and six intervention groups: chlorinated drinking water (W), improved sanitation (S), handwashing with soap (H), combined WSH, improved nutrition (N) through counseling and lipid-based nutrient supplementation (LNS), and combined WSHN. The main outcome was the prevalence of ARI symptoms (cough, panting, wheezing, or difficulty breathing) in children younger than 3 years. Masking participants was not possible. Analyses were intention-to-treat. Between November 2012 and May 2014, 702 clusters were enrolled, including 6,960 (year 1) and 7,088 (year 2) children with ARI data. The cluster-level intra-cluster correlation coefficient for ARIs was 0.026 across both years. Water, sanitation, and handwashing interventions with behavior change messaging did not reduce ARIs. Nutrition counseling and LNS modestly reduced ARI symptoms compared with controls in year 1 [prevalence ratio (PR): 0.87, 95% confidence interval (CI): 0.77-0.99], but no effect in the combined WSHN group weakens this finding.

Moringa seeds have been used traditionally in the management of type 2 diabetes mellitus (T2DM) and contain potent bioactive isothiocyanates. This study evaluated the efficacy of an isothiocyanate-rich moringa seed extract in delaying the onset of T2DM in UC Davis T2DM rats, a well validated model which closely mimics T2DM in humans. Rats were separated into three groups; control, moringa seed extract at 0.4%, and a weight matched group. Rats were fed respective diets for 8 months, during which energy intake, body weight, the onset of diabetes circulating hormones, metabolites and markers of inflammation and liver function, and were monitored. The MS group had a significantly slower rate of diabetes onset p = 0.027), lower plasma glucose (p = 0.043), and lower HbA1c (p = 0.008) compared with CON animals. There were no significant differences in food intake and body weight between all groups. This study demonstrated MS can delay the onset of diabetes in the UC Davis T2DM rat model to a greater extent than moderate caloric restriction (by comparison to the WM group). The results support its documented traditional uses and a bioactive role of moringa isothiocyanates and suggest the potential efficacy for moringa supplementation for diabetes management in populations at risk for T2DM.

Few studies have evaluated the impact of nutritional supplementation among pregnant adolescents. We examined the effects of the Rang Din Nutrition Study (RDNS) interventions on children born to mothers

BackgroundDiet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated.ObjectiveWe evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA).MethodsWe enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6 mo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6 mo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18 mo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA).ResultsPrimary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFA + MMN). Mean ± SD α diversity was higher in the LNS group at 18 mo for Shannon index [3.01 ± 0.57 (LNS) compared with 2.91 ± 0.60 (IFA + MMN), P = 0.032] and Pielou's evenness index [0.61 ± 0.08 (LNS) compared with 0.60 ± 0.09 (IFA + MMN), P = 0.043]; no significant differences were observed at 1, 6, 12, or 30 mo. MAZ and β diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFA + MMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%.ConclusionsPrenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18 mo, after 12 mo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693.

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother's nutritional status at conception of the subsequent child and therefore that child's birth outcomes and growth. Using follow-up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small-quantity lipid-based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone.

IntroductionDiagnosis of infantile thiamine deficiency disorders (TDD) is challenging due to the non-specific, highly variable clinical presentation, often leading to misdiagnosis. Our primary objective is to develop a case definition for thiamine responsive disorders (TRD) to determine among hospitalised infants and young children, which clinical features and risk factors identify those who respond positively to thiamine administration.Methods and analysisThis prospective study will enrol 662 children (aged 21 days to

Environmental enteric dysfunction (EED) may be ameliorated by zinc supplementation. The objective of this study was to investigate the impact of different forms of zinc supplementation on biomarkers of EED (i.e., plasma citrulline, kynurenine, and tryptophan concentrations and the kynurenine:tryptophan [KT] ratio) among young Laotian children. In a double-blind randomized controlled trial, 3,407 children aged 6-23 months were randomized into one of four groups: daily preventive zinc dispersible tablets (PZ; 7 mg zinc), daily multiple micronutrient powders (MNP; 10 mg zinc, 6 mg iron, and 13 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/day for 10 days), or daily placebo powder, and followed up for ∼36 weeks. Plasma samples at baseline and endline for 359 children were analyzed for citrulline, kynurenine, and tryptophan concentrations. At baseline, the prevalence of stunting and zinc deficiency was 37% and 76.5%, respectively. The mean plasma citrulline, kynurenine, and tryptophan concentrations were 24.6 ± 5.4 µmol/L, 3.27 ± 0.83 µmol/L, and 72.3 ± 12.9 µmol/L, respectively; the mean KT ratio (×1,000) was 45.9 ± 12.0. At endline, neither plasma citrulline, kynurenine, or tryptophan concentrations, nor the KT ratio differed among intervention groups (P > 0.05). In this population, PZ, MNP, and TZ had no overall effect on plasma concentrations of citrulline, kynurenine, and tryptophan, or the KT ratio. The need remains to better understand the etiology of EED, and the development of biomarkers to diagnose EED and evaluate the impact of interventions.