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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.

Setting: Subnational, population-based birth cohort studies (n = 45) in 23 low-and middle-income countries (LMICs) spanning 2000–2021. Population: Liveborn infants. Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [

Objective: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low-and middle-income countries (LMICs). Design: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. Setting: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. Population: Live birth neonates. Methods: We categorically defined five vulnerable newborn types based on size (large-or appropriate-or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. Main Outcome Measures: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. Results: There were 238 143 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.8, interquartile range [IQR] 2.0–3.2), PT + LGA (median RR 7.3, IQR 2.3–10.4), PT + AGA (median RR 6.0, IQR 4.4–13.2) and PT + SGA (median RR 10.4, IQR 8.6–13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. Conclusions: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

Background 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. Methods 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. Results 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). Conclusions 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.

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.

Background: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. Objectives: We 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. Methods: We 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). Results: In 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). Conclusions: Child 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. publishedVersion

Additional file 1.

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.

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.

Prenatal nutritional supplements may improve birth outcomes. This study aims to examine the effect of prenatal lipid-based nutrient supplements (LNS), compared with iron and folic acid (IFA), on general newborn physical condition and feeding behaviours. We conducted a cluster-randomized effectiveness trial that enrolled 4,011 pregnant women at ≤20 gestational weeks. LNS and IFA were provided to women in 48 and 16 clusters, respectively, for daily consumption until delivery. We collected data on household socio-economic, food insecurity, and maternal characteristics during early pregnancy and on newborn condition and feeding within 72hr of delivery. We analysed intervention effects on these secondary outcomes using mixed models with analysis of covariance for continuous outcomes and logistic regression for dichotomous outcomes. Among 3,664 live births, intervention groups did not differ in newborn response, mother's rating of the general condition of her newborn, early initiation of breastfeeding (EIBF), suckling ability, or frequency and exclusivity of breastfeeding in the first 24hr. If the mother perceived her infant to be healthy, EIBF was more likely (OR [95% CI]: 2.08 [1.46, 2.97]) and frequency of breastfeeding in the first 24hr was greater (mean difference [95% CI]: 3.0 [1.91, 4.01]), but there was no difference in exclusive breastfeeding in the first 24hr. Newborn condition and early breastfeeding practices were not affected by giving mothers prenatal LNS versus IFA. However, early breastfeeding practices were related to maternal perception of her newborn's condition. Thus, interventions to improve breastfeeding practices for newborns with poorer perceived health status may be useful.

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering. Methods: The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6–24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105. Findings: Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score −1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01–0·25] in the nutrition group; 0·16 [0·05–0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth. Interpretation: Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence. Funding: Bill & Melinda Gates Foundation, United States Agency for International Development.

BackgroundTo estimate usual intake distributions of dietary components, collection of nonconsecutive repeated 24-h dietary recalls is recommended, but resource limitations sometimes restrict data collection to single-day dietary data per person.ObjectivesWe developed a new statistical method, the NCI 1-d method, which uses single-day dietary data and an external within-person to between-person variance ratio to estimate population distributions of usual intake of nearly-daily consumed foods and nutrients.MethodsWe used NHANES 2011-2014 data for men (n=4938 and n=4293 for the first and second 24-h recalls) to compare nutrient intake distributions of vitamin A, magnesium, folate, and vitamin E generated by the 1-d method (with use of only the first recall per person) with those from the NCI amount-only method (with use of all days of dietary intake per person). The within-person to between-person variance ratio from the amount-only model was used as the unbiased "external" estimate for the 1-d method. We also examined the effect of mis-specification of variance ratios on usual intake distributions.ResultsThe amount-only and 1-d methods estimated statistically equivalent median (25p, 75p): 647 (459, 890) compared with 648 (461, 886) µg retinol activity equivalents/d, 338 (268, 420) compared with 334 (266, 417) mg magnesium/d, 595 (458, 762) compared with 589 (456, 758) µg dietary folate equivalents/d, and 9.7 (7.3, 12.6) compared with 9.6 (7.3, 12.7) mg vitamin E/d. As the external variance ratios increased from 25% to 200% of the unbiased ratios, the prevalence of inadequate intake ranged from 53% to 43% for vitamin A, 57% to 55% for magnesium, 16% to 2% for folate, and 70% to 73% for vitamin E.ConclusionsThe 1-d method is a viable statistical method for estimating usual intakes of nearly-daily consumed dietary components when the variance ratio is unbiased. Results are sensitive to variance ratio selection, so researchers should still collect replicate data where possible.

BACKGROUND:The impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown. OBJECTIVE:We tested the hypothesis that the level of sucrose most preferred by 4-6-y-old children exposed to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not be higher than that of children never exposed to LNS. DESIGN:We followed up children born to women (n=1,320) who participated in a randomized trial in Ghana. In one group, LNS was provided to women on a daily basis during pregnancy and the first 6 mo postpartum and to their infants from age 6 to 18 mo (LNS group). The control groups received daily iron and folic acid or multiple micronutrients during pregnancy and the first 6 mo postpartum, with no infant supplementation (non-LNS group). At age 4-6 y, we randomly selected a subsample of children (n=775) to assess the concentration of sucrose most preferred using the Monell 2-series, forced-choice, paired-comparison tracking procedure. We compared LNS with non-LNS group differences using a noninferiority margin of 5% weight/volume (wt/vol). RESULTS:Of the 624 children tested, most (61%) provided reliable responses. Among all children, the mean±SD sucrose solution most preferred (% wt/vol) was 14.6±8.6 (LNS group 14.9±8.7; non-LNS group 14.2±8.4). However, among children with reliable responses, it was 17.0±10.2 (LNS group 17.5±10.4; non-LNS group 16.5±10.0). The upper level of the 95% CI of the difference between groups did not exceed the noninferiority margin in either the full sample or those with reliable responses, indicating that the LNS group did not have a higher sweet preference than the non-LNS group. CONCLUSION:Exposure to a slightly sweet nutrient supplement early in life did not increase the level of sweet taste most preferred during childhood. This trial was registered at clinicaltrials.gov as NCT00970866.

Background Whether consuming sweet foods early in life affects sweet food preferences and consumption later in childhood is unknown. Objective We tested the hypothesis that exposure to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not increase preference for or consumption of sweet items at preschool age. Methods We followed up children who had participated in a randomized trial in Ghana in which LNS was provided to 1 group of women during pregnancy and 6 mo postpartum and to their infants from ages 6–18 mo (LNS group). The control group (non-LNS group) received iron and folic acid during pregnancy or multiple micronutrients during pregnancy and 6 mo postpartum, with no infant supplementation. At 4–6 y, we obtained data from caregivers on children's food and beverage preferences and consumption (n = 985). For a randomly selected subsample (n = 624), we assessed preference for sweet items using a photo game (range in potential scores, 0–15). For the photo game and reported consumption of sweet items, we examined group differences using predetermined noninferiority margins equivalent to an effect size of 0.2. Results Median (quartile 1, quartile 3) reported consumption of sweet items (times in previous week) was 14 (8, 23) in the LNS group and 16 (9, 22) in the non-LNS group; in the photo game, the number of sweet items selected was 15 (11, 15) and 15 (11, 15), respectively. The upper level of the 95% CI of the mean difference between LNS and non-LNS groups did not exceed the noninferiority margins for these outcomes. Caregiver-reported preferences for sweet items also did not differ between groups (P = 0.9). Conclusion In this setting, where child consumption of sweet foods was common, exposure to a slightly sweet LNS early in life did not increase preference for or consumption of sweet foods and beverages at preschool age. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundAnemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene.ObjectiveWe evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh.DesignWe nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6-24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs.ResultsIn Kenya, 699 children were assessed at a mean±SD age of 22.1±1.8 mo, and in Bangladesh 1470 participants were measured at a mean±SD age of 28.0±1.9 mo. The control group anemia prevalences were 48.8% in Kenya and 17.4% in Bangladesh. There was a lower prevalence of anemia in the 2 N intervention groups in both Kenya [N: 36.2%; prevalence ratio (PR): 0.74; 95% CI: 0.58, 0.94; WSH+N: 27.3%; PR: 0.56; 95% CI: 0.42, 0.75] and Bangladesh (N: 8.7%; PR: 0.50; 95% CI: 0.32, 0.78; WSH+N: 7.9%, PR: 0.46; 95% CI: 0.29, 0.73). In both trials, the 2 N groups also had significantly lower prevalences of iron deficiency, iron deficiency anemia, and low vitamin B-12 and, in Kenya, a lower prevalence of folate and vitamin A deficiencies. In Bangladesh, the WSH group had a lower prevalence of anemia (12.8%; PR: 0.74; 95% CI: 0.54, 1.00) than the control group, whereas in Kenya, the WSH+N group had a lower prevalence of anemia than did the N group (PR: 0.75; 95% CI: 0.53, 1.07), but this was not significant (P=0.102).ConclusionsIYCF counseling with LNSs reduced the risks of anemia, iron deficiency, and low vitamin B-12. Effects on folate and vitamin A varied between studies. Improvements in WSH also reduced the risk of anemia in Bangladesh but did not provide added benefit over the nutrition-specific intervention. These trials were registered at clinicaltrials.gov as NCT01590095 (Bangladesh) and NCT01704105 (Kenya).

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol concentrations (HCC) in young Laotian children and examined risk factors associated with HCC. In a randomized double-blind controlled trial (NCT02428647), children aged 6&ndash, 23 mo were randomized to one of four intervention groups and followed for ~36 weeks: daily preventive zinc (PZ) tablets (7 mg/day), daily multiple micronutrient powder (MNP) sachets (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. HCC of 512 children was assessed at baseline and endline. ANCOVA and linear regression models were used to assess group differences in HCC and to examine the risk factors associated with HCC, respectively. At enrollment, mean HCC was 28.8 &plusmn, 43.9 pg/mg. In models adjusted for age at enrollment, health district, and baseline HCC there was no overall effect of the interventions on endline HCC and change in HCC. When controlling for additional predetermined covariates, there was a marginally significant effect on change in HCC (p = 0.075) with a slightly lower reduction of HCC in TZ compared to PZ (mean change (95% CI): &minus, 4.6 (&minus, 7.0, &minus, 2.3) vs. &minus, 9.4 (&minus, 11.7, 7.0) pg/mg, p = 0.053). At baseline, consumption of iron rich foods was negatively associated with HCC, whereas AGP (&alpha, 1-acid glycoprotein) levels, elevated AGP and C-reactive protein and high soluble transferrin receptor were positively associated with HCC. In young Laotian children, MNP, PZ and TZ had no impact on HCC. The marginal difference in change in HCC between the PZ and TZ groups was too small to be considered of health significance.

BackgroundPoor nutrition and infectious diseases can prevent children from reaching their developmental potential. We aimed to assess the effects of improvements in water, sanitation, handwashing, and nutrition on early child development in rural Kenya.MethodsIn this cluster-randomised controlled trial, we enrolled pregnant women in their second or third trimester from three counties (Kakamega, Bungoma, and Vihiga) in Kenya's western region, with an average of 12 households per cluster. Groups of nine geographically adjacent clusters were block-randomised, using a random number generator, into the six intervention groups (including monthly visits to promote target behaviours), a passive control group (no visits), or a double-sized active control group (monthly household visits to measure child mid-upper arm circumference). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at year 1, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at year 2. Masking of participants was not possible, but data assessors were masked. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.FindingsBetween Nov 27, 2012, and May 21, 2014, 8246 women residing in 702 clusters were enrolled. No clusters were lost to follow-up, but 2212 households with 2279 children were lost to follow-up by year 2. 5791 (69%) children were measured at year 1 and 6107 (73%) at year 2. At year 1, compared with the active control group, the combined water, sanitation, handwashing, and nutrition group had greater rates of attaining the standing with assistance milestone (hazard ratio 1·23, 95% CI 1·09-1·40) and the walking with assistance milestone (1·32, 1·17-1·50), and the handwashing group had a greater rate of attaining the standing alone milestone (1·15, 1·01-1·31). There were no differences when comparing the other intervention groups with the active control group on any of the motor milestone measures at year 1. At year 2, there were no differences among groups for the communication, gross motor, personal social, or combined EASQ scores.InterpretationThe handwashing and combined water, sanitation, handwashing, and nutrition interventions might have improved child motor development after 1 year, although after 2 years there were no other differences between groups. Future research should examine ways to make community health and nutrition programmes more effective at supporting child development.FundingBill & Melinda Gates Foundation.

Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation. Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial]. Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18–24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial). Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower (P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower (P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower (P = 0.02) at 6–24 mo postpartum in LNS households. Conclusions: The daily provision of LNSs to mothers and their children throughout much of the “first 1000 d” may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development. These trials were registered at clinicaltrials.gov as NCT00945698 (DOSE) NCT01239693 (DYAD-M), NCT00970866 (DYAD-G) and NCT01715038 (RDNS).

Background Zinc is an essential nutrient that is required for children’s normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10–14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea. Methods The present study is a community-based, randomized controlled trial in the Lao People’s Democratic Republic (PDR). Three thousand, four hundred children 6–23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA. Discussion Many countries are now rolling out large-scale programs to include therapeutic zinc supplementation in the treatment of childhood diarrhea, but few have established programs demonstrated to be effective in the prevention of zinc deficiency. This study will address how best to deliver supplemental zinc to prevent zinc deficiency and reduce the severity of diarrhea-related health complications. Trial registration Trial registration identifier (NCT02428647) ; Date of registration: April 29, 2015.

Objectives To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children. Study design In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression. Results At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P