Anemia design effects in cluster surveys of women and young children in refugee settings.

BACKGROUND: Nutrition surveys in many refugee settings routinely estimate anemia prevalence in high-risk population groups. Given the lack of information on anemia design effects (DEFF) observed in surveys in these settings, the goal of this paper is to better understand the magnitude and distribution of DEFFs and intracluster correlation coefficients (ICCs) in order to inform future survey design. METHODS: Two-stage cluster surveys conducted during 2013-2016 were included if they measured hemoglobin in refugee children aged 6-59 months and/or non-pregnant women aged 15-49 years. Prevalence of anemia, anemia DEFFs and ICCs, mean cluster size, number of clusters, and total sample size were calculated per-survey for non-pregnant women and children. Non-parametric tests were used to assess differences and correlations of ICC and DEFF between women and children and inter-regional differences. RESULTS: Eighty-seven unique cluster surveys from nine countries were included in this analysis. More than 90% of all surveys had ICC values for anemia below 0.10. Median ICC for children was 0.032 (IQR: 0.015-0.048), not significantly different from that observed for non-pregnant women for whom the median was 0.024 (IQR: -0.002-0.055). DEFFs were significantly higher for children [1.54 (IQR: 1.21-1.82)] versus women [1.20 (IQR: 0.99-1.46)]. Regional differences in DEFFs and ICCs were observed. CONCLUSIONS: Both ICCs and DEFF were relatively small for both non-pregnant women and preschool children and fall in a narrow range. Differences in ICCs between women and children were non-significant, suggesting similar inter-cluster distributions of anemia; significant differences in DEFF were likely attributable to differing cluster sizes. Given regional differences in both ICCs and DEFFs, location-specific values are preferred. However, in the absence of other context-specific information, we suggest using DEFFs of 1.4-1.8 if mean cluster size is around 20, and DEFFs of 1.2-1.4 if mean cluster size is around 10.

The burden of anaemia among displaced women and children in refugee settings worldwide, 2013-2016.

INTRODUCTION: Displaced persons have a unique risk for developing anaemia due to often limited diets, overcrowding, new infections and inadequate sanitation and hygiene. The lack of anaemia prevalence estimates among the displaced inhibit global planning for anaemia reduction. METHODS: We analysed population representative, cross-sectional nutrition surveys from 2013 to 2016 conducted by the United Nations High Commissioner for Refugees and partner agencies. Included surveys measured haemoglobin concentration among children 6-59 months, non-pregnant women 15-49 years, or both groups. For each survey, we calculated mean haemoglobin and prevalence of total anaemia (<110 g/L in children, <120 g/L in women), and classified public health severity following WHO guidelines. Pearson correlations between indicators from women and children surveys were calculated where both subpopulations were measured. RESULTS: Analysis included 196 surveys among children and 184 surveys among women from 121 unique refugee settings in 24 countries. The median prevalence of total anaemia in children and women was 44% and 28%, respectively. Sixty-one per cent of child surveys indicated a problem of severe public health importance compared with 25% of surveys in women. The prevalence of total anaemia in children and women was strongly correlated (ρ=0.80). Median prevalence of total anaemia was approximately 55% greater and mean haemoglobin was 6 g/L lower among children age 6-23 months compared with children 24-59 months. West and Central Africa region had the highest median prevalence of anaemia both in women and children. CONCLUSION: While the burden of anaemia is high among the displaced, it mirrors that of the general population. Haemoglobin should continue to be measured in nutrition surveys in refugee settings. Sustained, multisectoral efforts to reduce anaemia are needed, with specific focus on children under 2 years of age and refugee settings in the West and Central Africa region.

Enteral nutritional therapy for induction of remission in Crohn's disease.

BACKGROUND: Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts. SELECTION CRITERIA: Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review. DATA COLLECTION AND ANALYSIS: Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes. MAIN RESULTS: Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy.

Assessment of the effectiveness of a small quantity lipid-based nutrient supplement on reducing anaemia and stunting in refugee populations in the Horn of Africa: Secondary data analysis.

Stunting and micronutrient malnutrition are persistent public health problems in refugee populations. UNHCR and its partner organisations implement blanket supplementary feeding programmes using a range of special nutritional products as one approach to address these issues. The evidence base for the efficacy and effectiveness of a small quantity lipid-based nutrient supplement, Nutributter®, in reducing stunting and anaemia is limited. Secondary data analysis was used to assess the effectiveness of Nutributter® distribution on anaemia and stunting in children aged 6-23 months (programme target group) and 6-59 months (the standard age group sampled in routine nutrition surveys). Analysis was conducted using routine pre and post-intervention cross-sectional nutrition survey data collected between 2008-2011 in five refugee camps in Kenya and Djibouti. Changes in total anaemia (Haemoglobin<110g/L), anaemia categories (mild, moderate and severe), and stunting (height-for-age z-score <-2) were explored using available data on the Nutributter® programme and contextual factors. A significant reduction in the prevalence of anaemia in children aged 6-23 months and 6-59 months was seen in four of five, and in all five camps, respectively (p<0.05). Reductions ranged from 12.4 to 23.0, and 18.3 to 29.3 percentage points in each age group. Improvements were largely due to reductions in moderate and severe anaemia and occurred where the prevalence of acute malnutrition was stable or increasing. No change in stunting was observed in four of five camps. The replicability of findings across five sites strongly suggests that Nutributter® distribution was associated with a reduction in anaemia, but not stunting, among refugee children in the Horn of Africa. Benefits were not restricted to the 6-23 month target group targeted by the nutrition programme. However, even following this intervention anaemia remained a serious public health problem and additional work to define and evaluate an effective intervention package is warranted.

Rapid acceptability and adherence testing of a lipid-based nutrient supplement and a micronutrient powder among refugee children and pregnant and lactating women in Algeria.

OBJECTIVE: To assess the acceptability and adherence to daily doses of lipid-based nutrient supplement (LNS) among children and micronutrient powder (MNP) among children and pregnant and lactating women. DESIGN: Household interviews and sachet counting were conducted to measure acceptability and adherence, 15 and 30 d after product distribution. Qualitative information on product acceptability was collected using focus group discussions. SETTING: Saharawi refugee camps, Algeria, August-October 2009. SUBJECTS: LNS was distributed to 123 children aged 6-35 months (LNS-C), and MNP to 112 children aged 36-59 months (MNP-C) and 119 pregnant or lactating women (MNP-W). RESULTS: At the end of the test 98·4 % of LNS-C, 90·4 % of MNP-C and 75·5 % of MNP-W participants reported that they liked the product (P<0·05). Other measures of acceptability did not differ. Median consumption of sachets was highest in the LNS-C group (P<0·001). 'Good' adherence to the daily regimen (consumption of 75-125 % of recommended dose) was 89·1 % in the LNS-C, compared with 57·0 % in the MNP-C and 65·8 % in the MNP-W groups (P<0·001). Qualitative findings supported the quantitative measures and guided selection of local product names, packaging designs, distribution mechanisms, and the design of the information campaign in the subsequent programme scale-up. CONCLUSIONS: Acceptability, consumption and adherence were higher in participants receiving LNS compared with MNP. However, both products were found to be suitable when compared with predefined acceptability criteria. Acceptability studies are feasible and important in emergency nutrition programmes when the use of novel special nutritional products is considered.

Operational guidance on the use of special nutritional products in refugee populations.

BACKGROUND: Stunting, acute malnutrition, and micronutrient malnutrition are persistent public health problems in refugee populations worldwide. In recent years there has been an increase in the availability and use of special nutritional products in emergency and development contexts to help address inadequate nutrient intakes from low-diversity diets. The availability of new special nutritional products, and the decision by the United Nations High Commissioner for Refugees (UNHCR) to use blanket supplementary feeding programs to prevent stunting and anemia, raised new challenges for designing, monitoring, and evaluating nutritional programs. OBJECTIVE: To develop an Operational Guidance on the use of special nutritional products for the prevention of micronutrient malnutrition, stunting, and acute malnutrition in refugee populations. Methods. A literature review and a series of consultations with technical experts, operational organizations, and field staff were performed over a period of 2 years. The Operational Guidance was finalized and released in December 2011. RESULTS: The Operational Guidance describes six stages for defining nutritionalproblems and identifying possible solutions; assessing and managing risks; testing acceptability and adherence, program design and implementation; and monitoring and evaluation. Key performance indicators are defined and a working nomenclature for new special nutritional products is described. CONCLUSIONS: The UNHCR Operational Guidance has filled an important gap in helping field staff deal with the opportunities and challenges of preventing undernutrition through the use of new products in blanket supplementary feeding programs. The need for further integration of guidance on selective feeding programs is discussed.

The double burden of obesity and malnutrition in a protracted emergency setting: a cross-sectional study of Western Sahara refugees.

BACKGROUND: Households from vulnerable groups experiencing epidemiological transitions are known to be affected concomitantly by under-nutrition and obesity. Yet, it is unknown to what extent this double burden affects refugee populations dependent on food assistance. We assessed the double burden of malnutrition among Western Sahara refugees living in a protracted emergency. METHODS AND FINDINGS: We implemented a stratified nutrition survey in October-November 2010 in the four Western Sahara refugee camps in Algeria. We sampled 2,005 households, collecting anthropometric measurements (weight, height, and waist circumference) in 1,608 children (6-59 mo) and 1,781 women (15-49 y). We estimated the prevalence of global acute malnutrition (GAM), stunting, underweight, and overweight in children; and stunting, underweight, overweight, and central obesity in women. To assess the burden of malnutrition within households, households were first classified according to the presence of each type of malnutrition. Households were then classified as undernourished, overweight, or affected by the double burden if they presented members with under-nutrition, overweight, or both, respectively. The prevalence of GAM in children was 9.1%, 29.1% were stunted, 18.6% were underweight, and 2.4% were overweight; among the women, 14.8% were stunted, 53.7% were overweight or obese, and 71.4% had central obesity. Central obesity (47.2%) and overweight (38.8%) in women affected a higher proportion of households than did GAM (7.0%), stunting (19.5%), or underweight (13.3%) in children. Overall, households classified as overweight (31.5%) were most common, followed by undernourished (25.8%), and then double burden-affected (24.7%). CONCLUSIONS: The double burden of obesity and under-nutrition is highly prevalent in households among Western Sahara refugees. The results highlight the need to focus more attention on non-communicable diseases in this population and balance obesity prevention and management with interventions to tackle under-nutrition. Please see later in the article for the Editors' Summary.

Effect of daily versus once-weekly home fortification with micronutrient Sprinkles on hemoglobin and iron status among young children in rural Bangladesh.

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.

Demonstrating zinc and iron bioavailability from intrinsically labeled microencapsulated ferrous fumarate and zinc gluconate Sprinkles in young children.

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.

Physiologic mechanisms can predict hematologic responses to iron supplements in growing children: a computer simulation model.

BACKGROUND: Iron deficiency is the most common preventable nutrition problem in developing countries. Several randomized clinical trials (RCTs) have been conducted to determine the effectiveness of various iron dosing schemes in multiple settings. OBJECTIVE: The objective was to determine whether enough is known about iron metabolism to predict hemoglobin and serum ferritin (SF) concentrations with a computer model and whether the model could be used as a substitute for new RCTs. DESIGN: Guided by the physiology of iron absorption and regulation, we used data from RCTs that tested iron Sprinkles to develop a computer model. Of 2 RCTs in Ghana, we used 1 to compute the amount of iron absorbed from a given dose in anemic and nonanemic children and the other to compute the resulting change in hemoglobin concentrations. We used this model to predict hemoglobin and SF concentrations in a new RCT in China and compared model-predicted values with actual values by using summary statistics (means and medians) and quantile-quantile plots. RESULTS: The model-predicted hemoglobin means were within +/-2 g/L, and SF medians were within +/-3 microg/L of the corresponding means and medians of the actual values. On quantile-quantile plots, the predicted hemoglobin quantiles were within +/-5 g/L, and SF quantiles were within +/-10 microg/L of the corresponding quantiles of the actual values. CONCLUSION: Our model of iron metabolism can accurately predict hemoglobin and SF concentrations after iron supplementation with Sprinkles in children; the model can thus obviate the need for repeating RCTs in multiple settings.

Controlling iron deficiency anemia through the use of home-fortified complementary foods.

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.

Determination of iron absorption from intrinsically labeled microencapsulated ferrous fumarate (sprinkles) in infants with different iron and hematologic status by using a dual-stable-isotope method.

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.