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Background: Children with underweight in the first 2 years have lower body mass index z-score (zBMI) and height-for-age z-score (HAZ) in later childhood. It is not known if underweight in the first 2 years is associated with nutrition risk in later childhood., Objective: (1) Determine the relationship between underweight (zBMI < -2) in the first 2 years and nutrition risk measured by the Nutrition Screening for Toddlers and Preschoolers (NutriSTEP) score from 18 months to 5 years. (2) Explore the relationship between underweight in the first 2 years and the NutriSTEP subscores for eating behaviours and dietary intake from 18 months to 5 years., Methods: This was a prospective study, including healthy full-term children in Canada aged 0-5 years. zBMI was calculated using measured heights and weights and the WHO growth standards. NutriSTEP score was measured using a parent-completed survey and ranged from 0 to 68. Nutrition risk was defined as a score ≥21. Linear mixed effects models were used., Results: Four thousand nine hundred twenty-nine children were included in this study. At enrolment, 51.9% of participants were male. The prevalence of underweight children was 8.8%. Underweight in the first 2 years was associated with higher NutriSTEP (0.79, 95% CI: 0.29,1.29), higher eating behaviour subscore (0.24, 95% CI: 0.03, 0.46) at 3 years and higher odds of nutrition risk (OR: 1.39, 95% CI: 1.07,1.82) at 5 years., Conclusions: Children with underweight in the first 2 years had higher nutrition risk in later childhood. Further research is needed to understand the factors which influence these relationships., (© 2023 The British Dietetic Association Ltd.)

Importance: Few studies have examined the association between underweight in the first 2 years and growth in later childhood in high-income countries., Objective: To evaluate the associations of underweight in the first 2 years of life with body mass index (calculated as weight in kilograms divided by height in meters squared) z score (zBMI), weight-for-age z score (WAZ), and height-for-age z score (HAZ) from ages 2 to 10 years., Design, Setting, and Participants: This prospective cohort study was conducted between February 2008 to September 2020 in The Applied Research Group for Kids! practice-based research network in Toronto, Canada. Participants included healthy children aged 0 to 10 years. Data were analyzed from October 2020 to December 2021., Exposures: Underweight (ie, zBMI less than -2, per the World Health Organization) in the first 2 years of life., Main Outcomes and Measures: The primary outcome was zBMI from ages 2 to 10 years. Linear mixed-effects models were used to account for multiple growth measures over time., Results: A total of 5803 children were included in the primary analysis. At baseline, the mean (SD) age was 4.07 (5.62) months, 2982 (52.2%) were boys, and 550 children (9.5%) were underweight. Underweight in the first 2 years was associated with lower zBMI (difference, -0.39 [95% CI, -0.48 to -0.31]) at 10 years and lower HAZ (difference, -0.24 [95% CI, -0.34 to -0.14]) at age 2 years. Stratified by sex, at age 10 years, girls and boys with underweight in the first 2 years both had lower zBMI (girls: difference, -0.47 [95% CI, -0.59 to -0.34]; boys: difference, -0.32 [95% CI, -0.44 to -0.20]). At age 10 years, children with underweight and a lower zBMI growth rate in the first 2 years had lower zBMI (difference, -0.64 [95% CI, -0.77 to -0.53) and HAZ (difference, -0.12 [-0.24 to -0.01]), while children with underweight and a higher zBMI growth rate in the first 2 years had similar zBMI (difference, -0.11 [95% CI, -0.22 to 0.001]) and higher HAZ (difference, 0.16 [95% CI, 0.05 to 0.27]) compared with children who did not have underweight in the first 2 years., Conclusions and Relevance: In this prospective cohort study, children with underweight in the first 2 years of life had lower zBMI and HAZ in later childhood. These associations were attenuated among children with a higher growth rate in the first 2 years.

Background: Iron deficiency is an important micronutrient deficiency contributing to the global burden of disease, and particularly affects children, premenopausal women, and people in low-resource settings. Anaemia is a possible consequence of iron deficiency, although clinical and functional manifestations of anemia can occur without iron deficiency (e.g. from other nutritional deficiencies, inflammation, and parasitic infections). Direct nutritional interventions, such as large-scale food fortification, can improve micronutrient status, especially in vulnerable populations. Given the highly successful delivery of iodine through salt iodisation, fortifying salt with iodine and iron has been proposed as a method for preventing iron deficiency anaemia. Further investigation of the effect of double-fortified salt (i.e. with iron and iodine) on iron deficiency and related outcomes is warranted.  OBJECTIVES: To assess the effect of double-fortified salt (DFS) compared to iodised salt (IS) on measures of iron and iodine status in all age groups., Search Methods: We searched CENTRAL, MEDLINE, Embase, five other databases, and two trial registries up to April 2021. We also searched relevant websites, reference lists, and contacted the authors of included studies., Selection Criteria: All prospective randomised controlled trials (RCTs), including cluster-randomised controlled trials (cRCTs), and controlled before-after (CBA) studies, comparing DFS with IS on measures of iron and iodine status were eligible, irrespective of language or publication status. Study reports published as abstracts were also eligible., Data Collection and Analysis: Three review authors applied the study selection criteria, extracted data, and assessed risk of bias. Two review authors rated the certainty of the evidence using GRADE. When necessary, we contacted study authors for additional information. We assessed RCTs, cRCTs and CBA studies using the Cochrane RoB 1 tool and Cochrane Effective Practice and Organisation of Care (EPOC) tool across the following domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and other potential sources of bias due to similar baseline characteristics, similar baseline outcome assessments, and declarations of conflicts of interest and funding sources. We also assessed cRCTs for recruitment bias, baseline imbalance, loss of clusters, incorrect analysis, and comparability with individually randomised studies. We assigned studies an overall risk of bias judgement (low risk, high risk, or unclear).  MAIN RESULTS: We included 18 studies (7 RCTs, 7 cRCTs, 4 CBA studies), involving over 8800 individuals from five countries. One study did not contribute to analyses. All studies used IS as the comparator and measured and reported outcomes at study endpoint.  With regards to risk of bias, five RCTs had unclear risk of bias, with some concerns in random sequence generation and allocation concealment, while we assessed two RCTs to have a high risk of bias overall, whereby high risk was noted in at least one or more domain(s). Of the seven cRCTs, we assessed six at high risk of bias overall, with one or more domain(s) judged as high risk and one cRCT had an unclear risk of bias with concerns around allocation and blinding. The four CBA studies had high or unclear risk of bias for most domains. The RCT evidence suggested that, compared to IS, DFS may slightly improve haemoglobin concentration (mean difference (MD) 0.43 g/dL, 95% confidence interval (CI) 0.23 to 0.63; 13 studies, 4564 participants; low-certainty evidence), but DFS may reduce urinary iodine concentration compared to IS (MD -96.86 μg/L, 95% CI -164.99 to -28.73; 7 studies, 1594 participants; low-certainty evidence), although both salts increased mean urinary iodine concentration above the cut-off deficiency. For CBA studies, we found DFS made no difference in haemoglobin concentration (MD 0.26 g/dL, 95% CI -0.10 to 0.63; 4 studies, 1397 participants) or urinary iodine concentration (MD -17.27 µg/L, 95% CI -49.27 to 14.73; 3 studies, 1127 participants). No studies measured blood pressure. For secondary outcomes reported in RCTs, DFS may result in little to no difference in ferritin concentration (MD -3.94 µg/L, 95% CI -20.65 to 12.77; 5 studies, 1419 participants; low-certainty evidence) or transferrin receptor concentration (MD -4.68 mg/L, 95% CI -11.67 to 2.31; 5 studies, 1256 participants; low-certainty evidence) compared to IS. However, DFS may reduce zinc protoporphyrin concentration (MD -27.26 µmol/mol, 95% CI -47.49 to -7.03; 3 studies, 921 participants; low-certainty evidence) and result in a slight increase in body iron stores (MD 1.77 mg/kg, 95% CI 0.79 to 2.74; 4 studies, 847 participants; low-certainty evidence). In terms of prevalence of anaemia, DFS may reduce the risk of anaemia by 21% (risk ratio (RR) 0.79, 95% CI 0.66 to 0.94; P = 0.007; 8 studies, 2593 participants; moderate-certainty evidence). Likewise, DFS may reduce the risk of iron deficiency anaemia by 65% (RR 0.35, 95% CI 0.24 to 0.52; 5 studies, 1209 participants; low-certainty evidence).  Four studies measured salt intake at endline, although only one study reported this for both groups. Two studies reported prevalence of goitre, while one CBA study measured and reported serum iron concentration. One study reported adverse effects. No studies measured hepcidin concentration., Authors' Conclusions: Our findings suggest DFS may have a small positive impact on haemoglobin concentration and the prevalence of anaemia compared to IS, particularly when considering efficacy studies. Future research should prioritise studies that incorporate robust study designs and outcome measures (e.g. anaemia, iron status measures) to better understand the effect of DFS provision to a free-living population (non-research population), where there could be an added cost to purchase double-fortified salt. Adequately measuring salt intake, both at baseline and endline, and adjusting for inflammation will be important to understanding the true effect on measures of iron status., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known., Methods: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling., Results: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons)., Conclusion: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015., (© 2022. The Author(s).)

Objective: To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency., Study Design: A blinded, placebo-controlled, randomized trial of children 1-3 years with nonanemic iron deficiency (hemoglobin ≥110 g/L, serum ferritin <14 μg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4 months; all parents received diet advice. The primary outcome was the Early Learning Composite (ELC) using the Mullen Scales of Early Learning (mean 100, SD 15). Secondary outcomes included serum ferritin. Measurements were obtained at baseline and 4 and 12 months. Sample size was calculated to detect a between-group difference of 6-7 points in ELC., Results: At enrollment (n = 60), mean age was 24.2 (SD 7.4) months and mean serum ferritin was 10.0 (SD 2.4) μg/L. For ELC, the mean between-group difference at 4 months was 1.1 (95% CI -4.2 to 6.5) and at 12 months was 4.1 (95% CI -1.9 to 10.1). For serum ferritin, at 4 months, the mean between-group difference was 16.9 μg/L (95% CI 6.5 to 27.2), and no child randomized to ferrous sulfate had a serum ferritin <14 μg/L (0% vs 31%, P = .003)., Conclusions: For young children with nonanemic iron deficiency, treatment options include oral iron and/or diet advice. We remain uncertain about which option is superior with respect to cognitive outcomes; however, adding ferrous sulfate to diet advice resulted in superior serum ferritin outcomes after 4 months. Shared decision-making between practitioners and parents may be considered when selecting either option., Trial Registration: Clinicaltrials.gov: NCT01481766., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Child growth standards are commonly used to derive age- and sex-standardized anthropometric indices but are often inappropriately applied to preterm-born children (<37 weeks of gestational age (GA)) in epidemiology studies. Using the 2004 Pelotas Birth Cohort, we examined the impact of correcting for GA in the application of child growth standards on the magnitude and direction of associations in 2 a priori-selected exposure-outcome scenarios: infant length-for-age z score (LAZ) and mid-childhood body mass index (scenario A), and infant LAZ and mid-childhood intelligence quotient (scenario B). GA was a confounder that had a strong (scenario A) or weak (scenario B) association with the outcome. Compared with uncorrected postnatal age, using GA-corrected postnatal age attenuated the magnitude of associations, particularly in early infancy, and changed inferences for associations at birth. Although differences in the magnitude of associations were small when GA was weakly associated with the outcome, model fit was meaningfully improved using corrected postnatal age. When estimating population-averaged associations with early childhood growth in studies where preterm- and term-born children are included, incorporating heterogeneity in GA at birth in the age scale used to standardize anthropometric indices postnatally provides a useful strategy to reduce standardization errors., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: Millions of children suffer from severe acute malnutrition (SAM) in low- and middle- income countries. Much is known about the effectiveness of community treatment programmes (CMAM) but little is known about post-discharge outcomes after successful treatment. The present study aimed to evaluate post-discharge outcomes of children cured of SAM., Design: Prospective, observational cohort study. Children with SAM who were discharged as cured were followed monthly for 6 months or until they experienced relapse to SAM. 'Cure' was defined as a child achieving a mid-upper arm circumference (MUAC) of ≥115 mm with ≥15 % weight gain after loss of oedema. Relapse was defined as a child with MUAC<115 mm and/or oedema at any monthly visit., Setting: Save the Children CMAM programme in Swabi, Pakistan, from January 2012 to December 2014., Subjects: Children aged 6-59 months (n 117) discharged as cured from the CMAM programme were eligible for the study and followed for 6 months., Results: One hundred children (92·6 %) remained free of SAM, eight (7·4 %) relapsed to SAM, nine (8·3 %) were lost to follow-up and none died. Most relapses occurred within 3 months of discharge (mean time to relapse 73·4 (sd 36·2) d). At enrolment, 90 % had moderate acute malnutrition (MAM) and 10 % were not malnourished. By the end of 6 months, 35 % persisted with MAM and the remaining were not malnourished., Conclusions: In rural Pakistan, fewer than 10 % of children cured of SAM relapsed. The first 3 months is the most vulnerable time.

Objectives: Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial., Design: Cluster-randomised controlled trial., Setting: Rural Ghana PARTICIPANTS: 1943 children (6-35 months of age) with geocoded compounds., Interventions: Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron., Primary and Secondary Outcome Measures: Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention., Results: The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined., Conclusion: In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres., Trial Registration Number: clinicaltrials.gov, NCT01001871., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Determining the spatial patterns of infection among young children living in a malaria-endemic area may provide a means of locating high-risk populations who could benefit from additional resources for treatment and improved access to healthcare. The objective of this secondary analysis of baseline data from a cluster-randomized trial among 1943 young Ghanaian children (6-35 months of age) was to determine the geo-spatial factors associated with malaria and non-malaria infection status., Methods: Spatial analyses were conducted using a generalized linear geostatistical model with a Matern spatial correlation function and four definitions of infection status using different combinations of inflammation (C-reactive protein, CRP > 5 mg/L) and malaria parasitaemia (with or without fever). Potentially informative variables were included in a final model through a series of modelling steps, including: individual-level variables (Model 1); household-level variables (Model 2); and, satellite-derived spatial variables (Model 3). A final (Model 4) and maximal model (Model 5) included a set of selected covariates from Models 1 to 3., Results: The final models indicated that children with inflammation (CRP > 5 mg/L) and/or any evidence of malaria parasitaemia at baseline were more likely to be under 2 years of age, stunted, wasted, live further from a health facility, live at a lower elevation, have less educated mothers, and higher ferritin concentrations (corrected for inflammation) compared to children without inflammation or parasitaemia. Similar results were found when infection was defined as clinical malaria or parasitaemia with/without fever (definitions 3 and 4). Conversely, when infection was defined using CRP only, all covariates were non-significant with the exception of baseline ferritin concentration. In Model 5, all infection definitions that included parasitaemia demonstrated a significant interaction between normalized difference vegetation index and land cover type. Maps of the predicted infection probabilities and spatial random effect showed defined high- and low-risk areas that tended to coincide with elevation and cluster around villages., Conclusions: The risk of infection among young children in a malaria-endemic area may have a predictable spatial pattern which is associated with geographical characteristics, such as elevation and distance to a health facility. Original trial registration clinicaltrials.gov (NCT01001871).

Background: The causes of stunting are complex but likely include prenatal effects, inadequate postnatal nutrient intake, and recurrent infections. Low-birth-weight (LBW) infants are at high risk of stunting. More than 25% of live births in low- and middle-income countries are at full term with low birth weight (FT-LBW). Evidence on the efficacy of specific interventions to enhance growth in this vulnerable group remains scant., Objective: We investigated the independent and combined effects of a directed use of a water-based hand sanitizer (HS) and a mineral- and vitamin-enhanced micronutrient powder (MNP) (22 minerals and vitamins) to prevent infections and improve nutrient intake to reduce stunting in FT-LBW infants., Design: The study was a prospective 2 × 2 factorial, cluster-randomized trial in 467 FT-LBW infants during 2 periods: from 0 to 5 mo postpartum (0-180 d postpartum) and from 6 to 12 mo postpartum (181-360 d postpartum) with the use of 48 clusters. All groups received the same general nutrition, health, and hygiene education (NHHE) at enrollment and throughout the 12 mo. Group assignments initially included the following 2 groups: no HS (control) group or HS from 0 to 5 mo postpartum. These assignments were followed by further divisions into the following 4 groups from 6 to 12 mo postpartum: 1) no HS and no MNP (control), 2) HS only, 3) MNP only, and 4) HS and MNP., Results: When delivered in combination with NHHE, the use of an HS showed no additional benefit in reducing indicators of infection in the first or second half of infancy or the likelihood of stunting at 12 mo postpartum. FT-LBW infants who received the MNP (with or without the HS) were significantly less likely to be stunted at 12 mo than were controls (OR: 0.35; 95% CI: 0.15, 0.84; P = 0.017)., Conclusions: The use of a mineral- and vitamin-enhanced MNP significantly reduced stunting in FT-LBW infants in this high-risk setting. The use of a water-based HS did not have an additive effect. This trial was registered at clinicaltrials.gov as NCT01455636., (© 2016 American Society for Nutrition.)

Background: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study., Methods: The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention., Conclusion: The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence., Trial Registration: ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).

Background: Vitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal., Methods/design: The Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17-24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes., Discussion: The role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens., Trial Registration: ClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013.

Background: Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA. There is little research regarding NAID, which may be associated with delayed development in young children. The aim of this study is to compare the effectiveness of four months of oral iron treatment plus dietary advice, with placebo plus dietary advice, in improving developmental outcomes in children with NAID and to conduct an internal pilot study., Methods/design: From a screening cohort, those identified with NAID (hemoglobin ≥110 g/L and serum ferritin <14 μg/L) are invited to participate in a pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority randomized trial. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children between 12 and 40 months of age and identified with NAID are randomized to receive four months of oral iron treatment at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per group). The primary outcome, child developmental score, is assessed using the Mullen Scales of Early Learning at baseline and at four months after randomization. Secondary outcomes include an age appropriate behavior measure (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and serum ferritin levels). Change in developmental and laboratory measures from baseline to the end of the four-month follow-up period will be analyzed using linear regression (analysis of covariance method)., Discussion: This trial will provide evidence regarding the association between child development and NAID, and the effectiveness of oral iron to improve developmental outcomes in children with NAID. The sample size of the trial will be recalculated using estimates taken from an internal pilot study., Trial Registration: This trial was registered with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.

Background: Prenatal calcium and iron supplements are recommended in settings of low dietary calcium intake and high prevalence of anemia. However, calcium administration may inhibit iron absorption. To overcome calcium-iron interactions, we developed a multi-micronutrient powder containing iron (60 mg), folic acid (400 μg), and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release., Objectives: We aimed to establish in vivo evidence that enteric-coated (EC) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption (FCA) in pregnancy., Design: This was a randomized crossover trial in pregnant women (26-28 wk of gestation) in Dhaka, Bangladesh. Participants were allocated to 1 of 3 dose groups (500, 1000, or 1500 mg elemental Ca). FCA was estimated in random order for EC and non-EC (control) granules by a dual-stable-isotope method ((44)Ca-labeled granules and intravenous (42)Ca) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h., Results: Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses. FCA geometric means were as follows: 21.8% (500 mg), 9.2% (1000 mg), and 11.7% (1500 mg) for non-EC granules compared with 3.3% (500 mg), 1.2% (1000 mg), and 2.1% for EC granules. Cumulative 48-h FCA of EC calcium was 85% lower (P < 0.001) than that of non-EC calcium, after adjustment for dose. In comparison to 500 mg, the FCA for the 1000-mg dose was 61% lower (P < 0.001) and was 42% lower (P = 0.002) for the 1500-mg dose, after adjustment for formulation., Conclusions: A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder. In its current formulation, this novel supplement is not suitable for clinical use. FCA was highly dose-dependent, such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose. This trial was registered at clinicaltrials.gov as NCT01678079., (© 2014 American Society for Nutrition.)

Background: Low-birth-weight children are known to be at risk of both anemia and cognitive/language deficits in their early years., Objective: The aim of the current study was to examine the effects of a 22-element multiple micronutrient powder (MNP) on the cognitive and language development of full-term low-birth-weight (LBW-T) children in Bangladesh., Methods: The current study was a follow-up of children who were enrolled in a randomized cluster trial at 7-12 mo of age. Children in 12 intervention clusters (communities) were administered a daily 22-element MNP sachet with their food for 5 mo, and both intervention and control groups (also 12 clusters) received nutrition, health, and hygiene education. The current study involved the assessment of children at 16-22 mo of age (22-element MNP group: n = 96; control group: n = 82) on 3 subtests of the Bayley Scales of Infant and Toddler Development III test to measure cognitive, receptive language, and expressive language development., Results: There was a significant effect of the 22-element MNP on children's expressive language scores (d = 0.39), and stunting moderated the effect on receptive language scores; there was no effect on cognitive development (d = 0.08)., Conclusion: An MNP may thus offer one feasible solution to improve language development of LBW-T children in low-resource community settings. This trial was registered at clinicaltrials.gov as NCT01455636., (© 2014 American Society for Nutrition.)

Background: Malnutrition among hospitalized children is known to negatively influence their response to therapy and to prolong their admission. It also has short- and long-term consequences for growth, development and well-being. It is commonly regarded as a condition affecting children in low-income countries; however, malnutrition has been found to be variably prevalent among hospitalized children in higher-income countries. At the time the present study was conducted, it had been >30 years since the nutritional status of Canadian hospitalized children was last published., Objectives: To determine and communicate the prevalence of malnutrition among children in a Canadian tertiary-care paediatric hospital at the time of their admission., Methods: In the present cross-sectional study, anthropometric measures were obtained from 322 children admitted to The Hospital for Sick Children in Toronto, Ontario. Nutritional indexes (BMI for age, weight for age, weight for length/height and length/height for age) were generated from anthropometric measures using the WHO igrowup software, and summarized according to WHO definitions., Results: The overall prevalence of malnutrition using BMI for age was 39.6% (95% CI 33% to 46%), of which 8.8% and 30.8% of participants were under- and overnourished, respectively. Furthermore, 6.9% (95% CI 3% to 13%) were determined to be acutely malnourished (weight for length/height <-2 SD) and 13.4% (95% CI 10% to 18%) chronically malnourished (length/height for age <-2 SD)., Conclusion: The high prevalence of overall malnutrition observed among study participants suggests that initial screening using simple anthropometric measures should be conducted on hospital admission so that patients can receive appropriate nutrition-specific care.

Objective: To investigate whether the recommended dietary intake of Ca in anaemic infants compromises the expected Hb response, via home fortification with a new Ca- and Fe-containing Sprinkles™ micronutrient powder (MNP)., Design: A double-blind, randomized controlled, 2-month trial was conducted in Bangladesh. Infants were randomized to one of two MNP intervention groups containing Fe and other micronutrients, with or without Ca. Hb, anthropometrics and dietary intake were measured pre- and post-intervention while family demographics were collected at baseline., Setting: Twenty-six rural villages in the Kaliganj sub-district of Gazipur, Bangladesh., Subjects: One hundred infants aged 6-11 months., Results: A significant increase in Hb (MNP, 13·3 (sd 12·6) g/l v. Ca-MNP, 7·6 (sd 11·6) g/l; P < 0·0001) was noted in infants from both groups. However, infants receiving MNP without Ca had a significantly higher end-point Hb concentration (P = 0·024) and rate of anaemia recovery (P = 0·008). Infants receiving MNP with Ca were more likely to remain anaemic (OR 3·2; 95 % CI 1·4, 7·5). Groups did not differ in dietary intake or demographic and anthropometric indicators., Conclusions: Although both groups showed significant improvement in Hb status, the nutrient-nutrient interaction between Fe and Ca may have diminished the Hb response in infants receiving the Ca-containing MNP.

Prenatal calcium supplementation is recommended by the WHO to decrease the risk of preeclampsia in women with low dietary calcium intake; yet, this recommendation has not been successfully implemented to date. One component of an effective population-based prenatal calcium intervention will be the selection of a widely accepted calcium vehicle to promote consistent, long-term consumption of the supplement. We aimed to evaluate preference and acceptability of 4 different options for delivering prenatal calcium (conventional tablets, chewable tablets, unflavored powder, and flavored powder) to pregnant women in urban Bangladesh. In a modified discrete-choice trial, pregnant women (n = 132) completed a 4-d "run-in period" in which each delivery vehicle was sampled once, followed by a 21-d "selection period" during which participants were instructed to freely select a single delivery vehicle of their choice each day. Preference was empirically defined as the probability that each delivery vehicle was selected on a given day, and measured from participants' daily delivery vehicle selections; acceptability was assessed by using mid- and post-trial questionnaires. Conventional tablets demonstrated the highest probability of selection (62%); the probability of selection of chewable tablets (19%), flavored powder (12%), and unflavored powder (5%) were all significantly lower than for conventional tablets (P < 0.001). The palatability and product characteristics of the conventional tablets were more acceptable than for the other 3 delivery vehicles. Our rigorous methodologic approach used both quantitative and self-reported measures that consistently identified the most preferred and accepted prenatal calcium delivery form. Through observation of pregnant women's actual supplement use, and perceptions of acceptability (i.e., ease of use, palatability), we demonstrated that conventional tablets are likely to be the most accepted and successful calcium delivery vehicle in future field studies and scale-up of the WHO recommendation in Bangladesh., (© 2014 American Society for Nutrition.)

Background: Hypertensive diseases of pregnancy are important causes of maternal and perinatal mortality. Based on meta-analyses of efficacy trials of prenatal calcium supplementation to reduce the risk of hypertensive diseases of pregnancy, the World Health Organization recommends 1.5 to 2.0 g of elemental calcium per day for pregnant women with low dietary calcium intakes (as well as 60 mg of iron and 400 microg of folic acid). However, implementation of this recommendation is challenged by the size and number of calcium tablets required and the need to avoid concurrent ingestion of calcium and iron due to intraintestinal interactions., Objective: We developed a novel micronutrient powder containing microencapsulated pH-sensitive calcium in addition to iron and folic acid, designed to facilitate early intestinal iron release and delayed calcium release., Methods: Two pharmaceutical companies were contracted to develop a prototype, one of which was chosen for clinical testing. Calcium carbonate granules were coated with a trilayer pH-sensitive enteric coating using a fluid-bed spray coater. Iron and folic acid granules were encapsulated with a time-release coating. Iron and calcium dissolution profiles were assessed during exposure to acidic (pH 1.2) and/or basic (pH 5.8) media using a modified USP apparatus 1 (basket) method., Results: At pH 1.2, calcium and iron release was < or = 10% and > 90% after 120 minutes, respectively. At pH 5.8, > 80% of total calcium was released after 90 minutes., Conclusions: Based on in vitro criteria, the supplement may be a promising approach for delivering calcium, iron, and folic acid as a single daily dose to pregnant women in settings of low dietary intake of calcium.

Background: Iron deficiency is a major cause of anemia and the most prevalent nutrient deficiency among pregnant women in developing countries. The use of iron and folic acid supplements to treat and prevent iron-deficiency anemia has limited effectiveness, mainly due to poor adherence. Home fortification with a micronutrient powder for pregnant women may be an effective and acceptable alternative to traditional drug models., Objective: To determine whether home fortification with micronutrient powders is at least as efficacious as iron and folic acid tablets for improving hemoglobin concentration in pregnant women., Methods: A cluster-randomized noninferiority trial was conducted in the rural subdistrict of Kaliganj in central Bangladesh. Pregnant women (gestational age 14-22 weeks, n=478), were recruited from 42 community-based Antenatal Care Centres. Each centre was randomly allocated to receive either a micronutrient powder (containing iron,folic acid, vitamin C, and zinc) or iron and folic acid tablets. Changes in hemoglobin from baseline were compared across groups using a linear mixed-effects regression model., Results: At enrolment, the overall prevalence of anemia was 45% (n = 213/478). After the intervention period, the mean hemoglobin concentrations among women receiving the micronutrient powder were not inferior to those among women receiving tablets (109.5 ± 12.9 vs. 112.0 ± 11.2 g/L; 95% CI, -0.757 to 5.716). Adherence to the micronutrient powder was lower than adherence to tablets (57.5 ± 22.5% vs. 76.0 ± 13.7%; 95% CI, -22.39 to -12.94); however, in both groups, increased adherence was positively correlated with hemoglobin concentration., Conclusions: The micronutrient powder was at least as efficacious as the iron and folic acid tablets in controlling moderate to severe anemia during pregnancy.

Background: Iron deficiency anemia (IDA) has been implicated in the etiology of transient ischemic attack and ischemic stroke. This study aimed to: 1) document IDA prevalence in patients ≥ 65 years of age admitted to hospital with transient ischemic attack or first ischemic stroke, and 2) investigate dietary intake as a predictor of iron status., Methods: Ninety-four patients were enrolled. An algorithm containing values for hemoglobin, ferritin, total iron binding capacity, transferrin saturation, and serum transferrin receptor measured at admission was used to identify IDA. Usual dietary intake was assessed with the Clue II food frequency questionnaire., Results: Prevalence estimates were 6.4% for IDA, 2.1% for iron deficiency without anemia, and 6.4% for anemia from other causes. IDA prevalence was significantly higher than published National Health and Nutrition Examination Survey III (NHANES III) estimates for gender-specific age groups ≥ 70 years (One-Sample Proportion Test; males p = 0.038 [n= 37]; females p = 0.002 [n=44]). A comparison of IDA prevalence against selected controls from the NHANES III database yielded an odds ratio (OR) of 6.3, 95% confidence interval (CI) 0.8 to 53.7, which was not statistically significant (Fisher's Exact Test; n=94; p = 0.118). Multivariate linear regression analysis of dietary intake with indicators of iron status (n=58) revealed only iron supplements (p = 0.013) and heme iron intake (p = 0.038) as negative predictors of total iron binding capacity (p<0.05)., Conclusions: These findings support the initiation of a prospective case control study to investigate IDA as a risk factor for ischemic stroke in elderly patients.

An international perspective of the magnitude of anemia in indigenous peoples is currently lacking. The present systematic review was performed to characterize the global prevalence, severity, and etiology of anemia in indigenous peoples by conducting a systematic search of original research published in English from 1996 to February 2010 using PubMed, Medline, and Embase. A total of 50 studies, representing the following 13 countries, met the inclusion criteria: Australia, Brazil, Canada, Guatemala, India, Kenya, Malaysia, Mexico, New Zealand, Sri Lanka, Tanzania, the United States, and Venezuela. Results indicate major deficiencies in the coverage and quality of anemia monitoring data for indigenous populations worldwide. The burden of anemia is overwhelmingly higher among indigenous groups compared to the general population and represents a moderate (20-39.9%) to severe (≥40%) public health problem. For the most part, the etiology of anemia is preventable and includes inadequate diet, poor living conditions, and high infection rates (i.e., malaria and intestinal parasites). A concerted global effort is needed to reduce the worldwide burden of anemia in these marginalized populations., (© 2011 International Life Sciences Institute.)

Background: A link between the provision of iron and infectious morbidity has been suggested, particularly in children with malnutrition. Two meta-analyses concluded that iron is not harmful, but malnourished children were underrepresented in most available studies., Objective: This study evaluated the effect of iron-containing micronutrient powder (iron MNP) on infectious morbidities when provided to children with moderate-to-severe malnutrition and anemia., Design: A randomized, double-blind, placebo-controlled, noninferiority safety trial using a 2-mo course of daily iron MNP or placebo powder (PP) was conducted in 268 Bangladeshi children aged 12-24 mo with moderate-to-severe malnutrition (weight-for-age z score ≤ -2) and a hemoglobin concentration between 70 and 110 g/L. The primary endpoint was a composite of diarrhea, dysentery, and lower respiratory tract infection episodes (DDL) recorded through home visits every 2 d during the intervention and then weekly for 4 mo. The noninferiority margin was 1.2. Secondary endpoints included hemoglobin and anthropometric changes at 2 and 6 mo. All deaths and hospitalizations were documented. To capture seasonal variation, the study was repeated in the winter and summer with 2 distinct groups. An intention-to-treat analysis of recurrent events was performed by using the univariate Anderson-Gill model., Results: The baseline characteristics of the subjects were similar. Analysis of phase-aggregated DDL data showed that iron MNP was not inferior to PP (relative risk: 0.81; 95% CI: 0.62, 1.04) and improved hemoglobin concentrations (P < 0.0001). We recorded no deaths, and hospitalizations were rare., Conclusion: Iron MNP is safe and efficacious when provided to children aged 12-24 mo with moderate-to-severe malnutrition and anemia. This trial is registered at clinicaltrials.gov as NCT00530374.

Objective: To determine the prevalence of anaemia and maternal and infant factors associated with Hb values in infants at 6 months of age in rural Bangladesh., Design: Infants (born to mothers supplemented with Fe-folic acid from mid-pregnancy) were visited at birth and 6 months of age. Mothers' anthropometric status, and infants' birth weight, gestational age at birth, weight and Hb concentration at 6 months were measured. Household socio-economic and demographic data, infant feeding practices and health status were collected using a pre-tested structured questionnaire., Setting: Rural Bangladesh., Subjects: Four hundred and two infants., Results: For the total cohort (n 402), the range of anaemia prevalence values was from 30.6 % using a cut-off value of Hb < 95 g/l to 71.9 % using a value of Hb < 110 g/l. Birth weight and month of birth were the only factors positively associated with infant Hb in a linear regression model (P = 0.008 and 0.011, respectively)., Conclusions: There was an unexpectedly high prevalence of anaemia in infants at 6 months of age, before the assumed period of vulnerability. Hb at this age tended to be higher in those with higher birth weight. We also found a season effect on Hb, as it tended to be higher as the study progressed. The high prevalence of anaemia at such an early age needs to be addressed to minimize the disease's long-term consequences.

Background: There is a growing interest in periconceptional iron supplementation in developing countries by researchers and policy makers; however, there are no randomized controlled trials that examine the effectiveness of this strategy in decreasing anemia during pregnancy., Objective: The aim was to determine whether periconceptional iron supplementation reduces anemia during pregnancy., Design: A randomized, double-blind, controlled trial was conducted in rural Bangladesh. Married, nulliparous women were randomly assigned to receive daily iron and folic acid (IFA; 60 mg ferrous fumarate and 400 microg folic acid) (n = 134) or folic acid (FA; 400 microg) (n = 138) in the form of a powdered supplement added to food. Women were followed until pregnancy or the end of 9 mo. Primary outcomes included hemoglobin, plasma ferritin, and plasma transferrin receptor concentrations., Results: Among 88 pregnant women, periconceptional IFA in comparison with FA did not affect anemia or iron status at 15 wk gestation. However, each 1% increase in adherence was associated with a 10-g/L increase in change in hemoglobin from baseline (P = 0.03), and those who initiated supplementation at a mean (+/-SD) time of 72.9 +/- 57.8 d before conception showed a 7.3-g/L increase in change in hemoglobin from baseline compared with those who initiated supplementation at 26.3 +/- 12.3 d after conception (P = 0.01). Among 146 nonpregnant women, IFA decreased anemia (odds ratio: 0.19; 95% CI: 0.04, 0.95) and improved iron stores (P = 0.001) more than did FA., Conclusion: Good adherence and initiation of supplementation before conception are needed to reduce anemia during early pregnancy. This trial was registered at www.clinicaltrials.gov as NCT00953134.

Background: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease., Objectives: To systematically review the efficacy and safety of n-3 for maintenance of remission in Crohn's disease (CD)., Search Strategy: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data., Selection Criteria: Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events., Data Collection and Analysis: Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. Meta-analyses were performed using RevMan 4.2 software weighted by the Mantel-Haenszel method. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed in an attempt to explore possible sources of heterogeneity., Main Results: Six studies were eligible for inclusion. There was a marginal significant benefit of n-3 therapy for maintaining remission (RR 0.77 0.; 95%CI 0.61 to 0.98; P = 0.03). However, the studies were both clinically and statistically heterogeneous (P = 0.03, I(2) = 58%). Two large studies showed negative results. When considering the estimated rather than the observed 1-year relapse rate of these two studies, the benefit was no longer statistically significant (RR 0.59; 95% CI 0.34 to 1.03; P=0.06). A funnel plot suggested publication bias. No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (RR 1.36 95% CI 1.01 to 1.84) and symptoms of the upper gastrointestinal tract (RR 1.98 95% CI 1.38 to 2.85) in the n-3 treatment group., Authors' Conclusions: Omega 3 fatty acids are safe but probably ineffective for maintenance of remission in CD. The existing data do not support routine maintenance treatment of Crohn's disease with omega 3 fatty acids.

Background & Aims: Congenital tufting enteropathy (CTE) is a rare autosomal recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia leading to severe malabsorption and significant morbidity and mortality. The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE., Methods: A family with 2 children affected with CTE was identified. The affected children are double second cousins providing significant statistical power for linkage. Using Affymetrix 50K single nucleotide polymorphism (SNP) chips, genotyping was performed on only 2 patients and 1 unaffected sibling. Direct DNA sequencing of candidate genes, reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blotting were performed on specimens from patients and controls., Results: SNP homozygosity mapping identified a unique 6.5-Mbp haplotype of homozygous SNPs on chromosome 2p21 where approximately 40 genes are located. Direct sequencing of genes in this region revealed homozygous G>A substitution at the donor splice site of exon 4 in epithelial cell adhesion molecule (EpCAM) of affected patients. Reverse-transcription polymerase chain reaction of duodenal tissue demonstrated a novel alternative splice form with deletion of exon 4 in affected patients. Immunohistochemistry and Western blot of patient intestinal tissue revealed decreased expression of EpCAM. Direct sequencing of EpCAM from 2 additional unrelated patients revealed novel mutations in the gene., Conclusions: Mutations in the gene for EpCAM are responsible for CTE. This information will be used to gain further insight into the molecular mechanisms of this disease.

Background: Home-fortification is a new strategy of adding micronutrients including zinc and iron to home-made foods. Zinc supplementation may prevent morbidity and mortality related to diarrheal illnesses, and iron supplementation may improve cognitive development, in children., Objectives: To project clinical and economic effects of home-fortification in children in an urban slum of Karachi, Pakistan., Methods: This is a cost benefit analysis of 5,000 simulated male and female infants (6-12 months) assigned to micronutrients or placebo for 4 months and followed for 55 years. We linked the effect of zinc on longitudinal prevalence of diarrhea to mortality, and the effect of iron on hemoglobin to IQ scores and lifetime earnings. Cost estimates were based on volumes of resource utilization from the Pakistan Sprinkles Diarrhea study. Main outcome was incremental benefit defined as the gain in lifetime earnings after accounting for the incremental costs of micronutrients over placebo (societal perspective)., Results: Our model projected that the reduction in diarrhea and improvement in hemoglobin concentrations through home-fortification was associated with reduced child mortality, higher IQ scores, and higher earnings. The present value of incremental benefit was $106 (95 percent probability interval = $17 to $193) U.S. dollars, which corresponds to $464.79 ($74.54 to $846.27) international dollars using a purchasing power parity exchange rate., Conclusions: Home-fortification appears to improve clinical outcomes at a reasonable cost, and may actually be cost beneficial when lifetime earnings are considered.

Background: Improving the nutritional status of an emergency-affected population is essential, because undernutrition increases infection risk and is linked to more than 50% of childhood deaths in developing countries. Emergency food aid addresses nutritional needs, including micronutrient deficiencies, but is provided only for a limited time and uses few items, so the needs of specific target groups are often not fully met., Objective: To describe the post-tsunami experience with distribution of Vitalita Sprinkles in Aceh and Nias and to analyze the monitoring data gathered for the emergency response., Methods: International agencies such as Helen Keller International and partners provided micronutrients in response to the tsunami emergency in Aceh and Nias and to analyze the monitoring data gathered for the emergency response., Results: In March and April 2006, the percentage of children aged 6 months to 59 months who had consumed Vitalita in the previous month was more than 70% in 5 of 11 districts evaluated, 40% to 70% in another five districts, and 32% in one district. An independent survey found 25% less anemia among recipients. Almost all mothers interviewed during March to April 2006 (96.3%) had heard about Vitalita and recognized its packaging, 69% said that Vitalita contained vitamins for under-fives, 86% knew the appropriate target group for Vitalita, and 83% said it had to be mixed with solid food. Of the 26% that reported not having given Vitalita to their child in the last month, 90.5% said that their child did not like it. CONCLUSIONS AND LESSONS LEARNED: Because the product, including its concept, was new, appropriate information and training was required as well as a thorough introduction to the beneficiaries, particularly on proper use, to ensure acceptance. This experience demonstrates that providing micronutrients as part of emergency relief and transition programming, as recently recommended by the World Health Organization/UNICEF/World Food Program, is feasible.

Background: The effectiveness of commonly suggested public health interventions to control childhood iron-deficiency anemia has been low., Objective: To determine whether iron provided in Sprinkles daily or in a higher dose once weekly affected hemoglobin, serum ferritin levels, and serum transferrin receptor levels, and to determine whether there were differences in the effects of the two regimens., Methods: In this cluster-randomized, community-based trial conducted in rural areas of Bangladesh, 136 children aged 12 to 24 months with mild to moderate anemia (hemoglobin 70-109 g/L) were randomly allocated to receive Sprinkles daily (12.5 mg of elemental iron, n = 79) or once weekly (30 mg of elemental iron, n = 73) for 8 weeks. Hemoglobin, serum ferritin, and serum transferrin receptor were assessed at the start and end of the intervention., Results: In both groups, there were significant increases in hemoglobin and serum ferritin and a significant decrease in serum transferrin receptor (p < .01). There were no significant differences between the groups in the increases in hemoglobin (16.1 +/- 13.2 g/L for the group receiving Sprinkles daily and 12.3 +/- 13.3 g/L for the group receiving Sprinkles once weekly) and serum ferritin (10.6 and 5.7 microg/L, respectively). The decrease in serum transferrin receptor also did not significantly differ between the groups (median, -2.5 and -1.8 mg/L, respectively). The prevalence rates of iron-deficiency anemia, depleted iron stores, and tissue iron deficiency decreased significantly within each group (p < .01), with no significant differences between the groups., Conclusions: Home fortification of complementary foods with Sprinkles given either daily or once weekly improved iron-deficiency anemia and iron status among young children.

To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

Nutrient-nutrient interactions are an important consideration for any multiple-micronutrient formulation, including Sprinkles, a home-fortification strategy to control anemia. The objectives of this randomized controlled trial were as follows: 1) to compare the absorption of zinc at 2 doses given as Sprinkles; and 2) to examine the effect of zinc and ascorbic acid (AA) on iron absorption from Sprinkles. Seventy-five children aged 12-24 mo were randomly assigned to the following groups: 1) 5 mg of labeled zinc (67Zn) with 50 mg AA (LoZn group); b) 10 mg of labeled zinc (67Zn) with 50 mg AA (HiZn group); or 3) 5 mg zinc with no AA (control). All groups contained 30 mg of labeled iron (57Fe). Intravenous infusions labeled with 70Zn (LoZn and HiZn groups) and 58Fe (control) were administered. Blood was drawn at baseline, 48 h and 14 d later. The percentage of zinc absorbed did not differ between LoZn (geometric mean = 6.4%; min-max: 1.7-14.6) and HiZn (geometric mean = 7.5%; min-max: 3.3-18.0) groups. However, total zinc absorbed was significantly different between the LoZn (geometric mean = 0.31 mg; min-max: 0.08-0.73) and HiZn (geometric mean = 0.82 mg; min-max: 0.33-1.82) groups (P = 0.0004). Geometric mean percentage iron absorption values did not differ between the LoZn (5.9%; min-max: 0.8-21) and HiZn (4.4%; min-max: 0.6-12.3) groups and between the LoZn and control groups (5.0%; min-max: 1.4-24). We conclude that zinc in the form of Sprinkles has a low bioavailability, yet provides adequate amounts of absorbed zinc in young children, and that there is no effect of zinc or AA on iron absorption from the given formulations of Sprinkles.

Despite current Canadian pre- and perinatal nutrition programs, the prevalence of both iron deficiency and iron deficiency anemia (IDA) is very high among young Aboriginal children from Canada's remote north. The major risk factors for IDA include prolonged consumption of evaporated cow's milk, chronic infection and prolonged exclusive breastfeeding. In the present article, the authors discuss IDA as a significant public health problem in Canadian Aboriginal communities. Whereas the prevalence of IDA in Canadian children is between 3.5% and 10.5% in the general population, in two Northern Ontario First Nations communities and one Inuit community, the anemia rate was 36%, with 56% having depleted iron stores. Traditional methods of preventing IDA, including targeted fortification, dietary diversification and supplementation, have not solved the problem. The authors' research group at The Hospital for Sick Children in Toronto, Ontario, conceived of the strategy of 'home fortification' with 'Sprinkles' - single-dose sachets containing micronutrients in a powder form, which are easily sprinkled onto any foods prepared in the household. In Sprinkles, the iron (ferrous fumarate) is encapsulated within a thin lipid layer to prevent the iron from interacting with food. Sprinkles have been shown to be efficacious in the treatment of anemia in many developing countries. Their use in Aboriginal communities to treat and prevent anemia is described in the present paper. The authors believe that children in Aboriginal communities across Canada would potentially benefit if Sprinkles were incorporated into Health Canada's current distribution system, in combination with a social marketing strategy to encourage their use.

Background: Anemia is common among children in Aboriginal communities in Canada. The objectives of this study were to determine the prevalence of anemia and to identify its associated risk factors among young children in Aboriginal communities in northern Ontario and Nunavut., Methods: 115 children from one Inuit and two Cree First Nations communities participated. We collected information on demographic and dietary factors and measured hemoglobin (Hb), ferritin (SF), serum transferrin receptor (sTfR) and Helicobacter pylori IgG antibodies. Odds ratios and 95% confidence intervals were determined to examine risk factors associated with anemia and iron deficiency (ID) and further analyzed using stepwise regression procedures., Results: Prevalence of anemia (Hb<110 g/L) was 36.0%. Iron deficiency (sTfR>8.5 mg/L) was present in 27.6% of the study population. Approximately 53.3% had depleted iron stores (SF<12 microg/L). Consumption of cow/evaporated milk was the only independent risk factor associated with anemia. Infection with H. pylori and prolonged consumption of breastmilk were also associated, although not independently, with anemia. Formula intake was negatively associated with ID., Interpretation: The prevalence of anemia in Aboriginal children was eight times higher than among similar populations in urban Canada and was especially high among Inuit children. ID was the major cause of anemia, but not the only one, since 10% of anemic children were not iron deficient. Given that the consumption of cow/evaporated milk was found to be a significant independent risk factor associated with anemia, public health strategies should include promotion of breastfeeding, combined with iron-rich complementary foods, while addressing socio-economic conditions that may be preventing these practices from being adopted. H. pylori may be a major contributing factor to anemia, thus improvements in water quality and sanitation also need to be considered.

Background: The use of microencapsulated ferrous fumarate sprinkles is a new approach for home fortification. Iron and hematologic status may affect the absorption of iron from sprinkles., Objective: The objective was to measure the absorption (corrected erythrocyte incorporation of (57)Fe) of 2 different doses of iron from sprinkles added to a maize-based complementary food provided to infants with different iron and hematologic status., Design: Infants aged 6-18 mo were randomly assigned to receive either 30 (n = 45) or 45 (n = 45) mg elemental Fe as (57)Fe-labeled sprinkles added to a maize-based porridge on 3 consecutive days. A (58)Fe tracer (0.2 mg as ferrous citrate) was also infused intravenously (n = 46). Blood was drawn at baseline and 14 d later to determine erythrocyte incorporation of (57)Fe and (58)Fe by using inductively coupled plasma mass spectrometry. On the basis of hemoglobin and soluble transferrin receptor concentrations, subjects were classified as having iron deficiency anemia (IDA), iron deficiency (ID), or sufficient iron status., Results: There was no significant effect of dose on iron absorption (P > 0.05). Geometric mean iron absorption was 8.25% (range: 2.9-17.8%) in infants with IDA (n = 32), 4.48% (range: 1.1-10.6%) in infants with ID (n = 20), and 4.65% (range: 1.5-12.3%) in iron-sufficient infants (n = 20). Geometric mean iron absorption was significantly higher in infants with IDA than in infants with ID or iron-sufficient infants (P = 0.0004); however, there were no significant differences between infants with ID and iron-sufficient infants., Conclusion: During infancy, iron absorption from sprinkles in a maize-based porridge meets and surpasses requirements for absorbed iron and is up-regulated in infants with IDA.

Iron deficiency anemia (IDA) is more common in South Asian countries including India, Bangladesh and Pakistan than anywhere else in the world. During infancy and early childhood, IDA is associated with impaired psycho-motor development and cognitive function that may be irreversible. As a consequence, there is a growing awareness that IDA is one of many factors impeding socio-economic prosperity of developing nations. The combination of unacceptably high prevalence rates and inadequate preventative programs highlights the need for new effective sustainable strategies to control IDA. The burden of iron deficiency can be reduced by taking a more holistic approach that would include promotion of healthy weaning practices and use of appropriate complementary foods, together with improving the nutritional value of such foods. There is an increasing body of peer-reviewed literature to support the contention that "micronutrient Sprinkles" is an effective strategy to improve the nutritional value of home-prepared complementary foods and thus to reduce the burden of iron deficiency among children. By combining data from recently conducted randomised control trials, Sprinkles were shown to be as efficacious as iron drops for treating childhood anemia. The iron in Sprinkles is well absorbed, and Sprinkles are easy to use and well accepted by young children and their caregivers. Integrated into existing public health programs, Sprinkles has the potential to improve the effectiveness of such programs.