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Background: Kwashiorkor is a major classification of severe acute malnutrition whose etiology remains elusive. It is estimated to affect hundreds of thousands of children annually, but no accurate global prevalence figures are available. Little is known how prevalence varies within populations, an important undocumented aspect of kwashiorkor obscured by the aggregation of prevalence or incidence of the condition across large populations and geographic areas.Objective: To estimate the prevalence of kwashiorkor in select neighboring villages of the eastern Democratic Republic of the Congo (DRC) and assess if prevalence can vary dramatically among neighboring villages.Methods: An anthropometric census survey evaluated 1328 children aged 12 to 59 months within all 19 villages in one health area of eastern DRC, recording all cases of kwashiorkor, diagnosed by bipedal pitting edema.Results: Village-level prevalence of kwashiorkor in the study area varied from 0% to 14.9%. Interviews with health services staff in the study area and across 2 provinces confirmed that current differences in prevalence reflect a long-term pattern and are a common feature of kwashiorkor throughout this region.Conclusions: Aggregation of kwashiorkor prevalence and incidence data across large populations or geographic regions poses several risks to understanding the epidemiology of kwashiorkor. If clustering of kwashiorkor is not taken into account, (1) nutritional crises in particular villages may go undetected; (2) the real effect of interventions may be underestimated; (3) interventions may be inappropriately targeted, leading to reduced coverage, efficacy, and cost-efficiency; and (4) important insights into the root causes of kwashiorkor may be lost. [ABSTRACT FROM AUTHOR]

(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I² and τ² statistic, stratified analyses, and meta-regression, and publication bias by Egger's and Begg's tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: -0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52-1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09-0.38), weight (WMD = 0.14 kg, 95%CI: 0.07-0.21), and weight-for-age Z-score (WMD = 0.04, 95%CI: 0.001-0.087), but not height-for-age Z-score (WMD = 0.02, 95%CI: -0.01-0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: -0.03-0.06). Child age at zinc supplementation appeared to modify the effects on height (P-interaction = 0.002) and HAZ (P-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50-2.25; WMD for HAZ = 0.12, 95%CI: 0.05-0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children. [ABSTRACT FROM AUTHOR]

Introduction As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam). [ABSTRACT FROM AUTHOR]

Background: LBW infants face increased risks for mortality, morbidity, neurodevelopmental impairments, growth faltering as well as challenges related to breastfeeding. Objectives: To describe the feeding profile of low birthweight infants in the first half of infancy and to examine growth patterns and early risk factors of poor growth outcomes at six months. Methods: The LIFE study was a multi-site, observational cohort study. Data were collected data from birth to six months for LBW infants recruited from health facilities in Dar es Salaam, Tanzania as well as India and Malawi. Results: In Tanzania, only 4.9% of LBW infants-initiated breastfeeding within the first hour of life and 52% were exclusively breastfed (EBF) to six months of age. Further, 57% of mothers of LBW infants reported feeding difficulties during the first 6 months and 80% reported having received breastfeeding counselling at the facility. In terms of growth of LBW infants in Tanzania, 15% did not regain their birthweight by two weeks of age; and at 6 months of age 35%, 21% and 7% were stunted, underweight, and wasted, respectively. Infants not regaining birthweight by two weeks had a greater risk for stunting at six months. Finally, there was no relationship between EBF duration to six months and growth outcomes at 6 months. Conclusion and recommendation: Breastfeeding initiation and duration of exclusive breastfeeding among LBW infants was suboptimal and their risk of poor growth was high. Given that regaining the birth weight by 2 weeks had a temporal relation to stunting, while no relationship between EBF with growth was found, interventions beyond promoting EBF alone in the earliest days of life are needed and breastfeeding behaviors (frequency and volume), milk quality, maternal nutrition, and other interventions should be evaluated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy of estimated fat mass and fat-free mass from bedside methods compared with reference methods in children with chronic illnesses.Study Design: Fat mass and fat-free mass values were obtained by skinfold, bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), and deuterium dilution method in children with spinal muscular atrophy, intestinal failure, and post hematopoietic stem cell transplantation (HSCT). Spearman's correlation and agreement analyses were performed between (1) fat mass values estimated by skinfold equations and by DXA and (2) fat-free mass values estimated by BIA equations and by DXA and deuterium dilution methods. Limits of agreement between estimating and reference methods within ±20% were deemed clinically acceptable.Results: Fat mass and fat-free mass values from 90 measurements in 56 patients, 55% male, and median age of 11.6 years were analyzed. Correlation coefficients between the skinfold-estimated fat mass values and DXA were 0.93-0.94 and between BIA-estimated fat-free mass values and DXA were 0.92-0.97. Limits of agreement between estimated and DXA values of fat mass and fat-free mass were greater than ±20% for all equations. Correlation coefficients between estimated fat-free mass values and deuterium dilution method in 35 encounters were 0.87-0.91, and limits of agreement were greater than ±20%.Conclusion: Estimated body composition values derived from skinfold and BIA may not be reliable in children with chronic illnesses. An accurate noninvasive method to estimate body composition in this cohort is desirable. [ABSTRACT FROM AUTHOR]

Background: Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children.Methods/design: The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2300 HIV-infected pregnant women receiving triple-drug ART under Option B+ in Dar es Salaam, Tanzania. HIV-infected pregnant women of 12-27 weeks gestation are randomized to either: 1) 3000 IU vitamin D3 taken daily from randomization in pregnancy until trial discharge at 12 months postpartum; or 2) a matching placebo regimen. Maternal participants are followed-up at monthly clinic visits during pregnancy, at delivery, and then with their children at monthly postpartum clinic visits. The primary efficacy outcomes of the trial are: 1) maternal HIV disease progression or death; 2) risk of small-for-gestational age (SGA) births; and 3) risk of infant stunting at 1 year of age. The primary safety outcome of the trial is incident maternal hypercalcemia. Secondary outcomes include a range of clinical and biological maternal and child health outcomes.Discussion: The ToV5 will provide causal evidence on the effect of vitamin D3 supplementation on HIV progression and death, SGA births, and infant stunting at 1 year of age. The results of the trial are likely generalizable to HIV-infected pregnant women and their children in similar resource-limited settings utilizing the Option B+ approach.Trial Registration: ClinicalTrials.gov identifier: NCT02305927 . Registered on 29 October 2014. [ABSTRACT FROM AUTHOR]

Background: Although vitamin A supplementation reduces child mortality, it remains unclear whether dosing frequency, total dose, or duration modifies effectiveness.Objective: Determine whether mortality effects of vitamin A vary by dosing frequency, total dose, or duration.Methods: Meta-analysis of randomized controlled trials, identified by systematic review and expert opinion, utilizing relatively standard World Health Organization doses in children <5 years. Meta-regression evaluated whether mortality effects varied by dosing frequency, total dose, or supplementation duration.Results: Identified 17 trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5 (15.4) months at baseline. Supplementation frequency ranged every 3 months-every 2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P = 0.002). This protective effect was not modified by increasing supplementation frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22), total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14). Multivariate meta-regression showed similar results. Sensitivity analyses excluding 1 controversial trial (Aswathi 2013) did not alter findings.Conclusion: Results confirm benefits of vitamin A supplementation in children <5 years in nations with vitamin A deficiency, without influence of frequency, total dose, or dosing duration within ranges evaluated. These findings inform design and efficiency of vitamin A supplementation policies. [ABSTRACT FROM AUTHOR]

This study assesses the impact of an integrated infant and young child feeding (IYCF) and micronutrient powder (MNP) intervention on children's risk of anemia and IYCF practices in Madagascar. Quantitative baseline and endline surveys were conducted in representative households with children 6-23 months from two districts, where an 18-month IYCF-MNP intervention was implemented. Relative risks comparing children's risk of anemia and maternal IYCF knowledge and practices at baseline versus endline, and also at endline among MNP-users versus non-users were estimated using log-binomial regression models. 372 and 475 children aged 6-23 months were assessed at baseline and endline respectively. Prevalence of anemia fell from 75.3% to 64.9% from baseline to endline (p = 0.002); the reduction in the risk of anemia remained significant in models adjusting for sociodemographic characteristics (ARR (95% CI): 0.86 (0.78, 0.95), p = 0.003). In endline assessments, 229 out of 474 (48.3%) of children had consumed MNPs. MNP-users had a lower risk of anemia (ARR (95% CI): 0.86 (0.74, 0.99), p = 0.04) than non-users, after controlling for child's dietary diversity and morbidity, maternal counseling by community-health-workers, and sociodemographic characteristics. Mothers interviewed at endline also had greater nutrition knowledge and were more likely to feed their children ≥4 food groups (ARR (95% CI): 2.92 (2.24, 3.80), p < 0.001), and the minimum acceptable diet (ARR (95% CI): 2.88 (2.17, 3.82), p < 0.001) than mothers interviewed at baseline. Integration of MNP into IYCF interventions is a viable strategy for improving children's consumption of micronutrients and reducing risk of anemia. The addition of MNP does not negatively impact, and may improve, IYCF practices. [ABSTRACT FROM AUTHOR]

Impaired childhood development has lifelong consequences for educational attainment and wage-earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B-complex) supplements on development among Tanzanian infants. In this randomized, 2 × 2 factorial, double-blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub-sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Mean BSID-III scores were compared using univariate and multivariate linear regression models adjusted for child's sex, post-conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID-III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID-III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID-III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B-complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID-III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations. © 2016 John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Introduction: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).