Fabian Rohner

The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Côte d'Ivoire

BACKGROUND Iron is essential for the growth and virulence of many pathogenic enterobacteria, whereas beneficial barrier bacteria, such as lactobacilli, do not require iron. Thus, increasing colonic iron could select gut microbiota for humans that are unfavorable to the host. OBJECTIVE The objective was to determine the effect of iron fortification on gut microbiota and gut inflammation in African children. DESIGN In a 6-mo, randomized, double-blind, controlled trial, 6-14-y-old Ivorian children (n = 139) received iron-fortified biscuits, which contained 20 mg Fe/d, 4 times/wk as electrolytic iron or nonfortifoed biscuits. We measured changes in hemoglobin concentrations, inflammation, iron status, helminths, diarrhea, fecal calprotectin concentrations, and microbiota diversity and composition (n = 60) and the prevalence of selected enteropathogens. RESULTS At baseline, there were greater numbers of fecal enterobacteria than of lactobacilli and bifidobacteria (P < 0.02). Iron fortification was ineffective; there were no differences in iron status, anemia, or hookworm prevalence at 6 mo. The fecal microbiota was modified by iron fortification as shown by a significant increase in profile dissimilarity (P < 0.0001) in the iron group as compared with the control group. There was a significant increase in the number of enterobacteria (P < 0.005) and a decrease in lactobacilli (P < 0.0001) in the iron group after 6 mo. In the iron group, there was an increase in the mean fecal calprotectin concentration (P < 0.01), which is a marker of gut inflammation, that correlated with the increase in fecal enterobacteria (P < 0.05). CONCLUSIONS Anemic African children carry an unfavorable ratio of fecal enterobacteria to bifidobacteria and lactobacilli, which is increased by iron fortification. Thus, iron fortification in this population produces a potentially more pathogenic gut microbiota profile, and this profile is associated with increased gut inflammation. This trial was registered at controlled-trials.com as ISRCTN21782274.

Micronutrient Deficits Are Still Public Health Issues among Women and Young Children in Vietnam

Background The 2000 Vietnamese National Nutrition Survey showed that the populations dietary intake had improved since 1987. However, inequalities were found in food consumption between socioeconomic groups. As no national data exist on the prevalence of micronutrient deficiencies, a survey was conducted in 2010 to assess the micronutrient status of randomly selected 1526 women of reproductive age and 586 children aged 6–75 mo. Principal Findings In women, according to international thresholds, prevalence of zinc deficiency (ZnD, 67.2±2.6%) and vitamin B12 deficiency (11.7±1.7%) represented public health problems, whereas prevalence of anemia (11.6±1.0%) and iron deficiency (ID, 13.7±1.1%) were considered low, and folate (<3%) and vitamin A (VAD, <2%) deficiencies were considered negligible. However, many women had marginal folate (25.1%) and vitamin A status (13.6%). Moreover, overweight (BMI≥23 kg/m2 for Asian population) or underweight occurred in 20% of women respectively highlighting the double burden of malnutrition. In children, a similar pattern was observed for ZnD (51.9±3.5%), anemia (9.1±1.4%) and ID (12.9±1.5%) whereas prevalence of marginal vitamin A status was also high (47.3±2.2%). There was a significant effect of age on anemia and ID prevalence, with the youngest age group (6–17 mo) having the highest risk for anemia, ID, ZnD and marginal vitamin A status as compared to other groups. Moreover, the poorest groups of population had a higher risk for zinc, anemia and ID. Conclusion The prevalence of anemia and ID in Vietnam has been markedly reduced over the last decade, but a large part of the population is still at risk for other deficiencies such as zinc, vitamin A, folate and vitamin B12 especially the youngest children aged 6–17 mo. Consequently specific interventions to improve food diversity and quality should be implemented, among them food fortification of staple foods and condiments and improvement of complementary feeding.

Mapping malaria risk among children in Côte d’Ivoire using Bayesian geo-statistical models

BackgroundIn Côte d’Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria. Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged <16 years in Côte d’Ivoire at high spatial resolution.MethodsUsing different data sources, a systematic review was carried out to compile and geo-reference survey data on Plasmodium spp. infection prevalence in Côte d’Ivoire, focusing on children aged <16 years. The period from 1988 to 2007 was covered. A suite of Bayesian geo-statistical logistic regression models was fitted to analyse malaria risk. Non-spatial models with and without exchangeable random effect parameters were compared to stationary and non-stationary spatial models. Non-stationarity was modelled assuming that the underlying spatial process is a mixture of separate stationary processes in each ecological zone. The best fitting model based on the deviance information criterion was used to predict Plasmodium spp. infection risk for entire Côte d’Ivoire, including uncertainty.ResultsOverall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged <16 years were extracted. Most data points (n = 182, 77.4%) were collected between 2000 and 2007. A Bayesian non-stationary regression model showed the best fit with annualized rainfall and maximum land surface temperature identified as significant environmental covariates. This model was used to predict malaria infection risk at non-sampled locations. High-risk areas were mainly found in the north-central and western area, while relatively low-risk areas were located in the north at the country border, in the north-east, in the south-east around Abidjan, and in the central-west between two high prevalence areas.ConclusionThe malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Côte d’Ivoire. It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.

The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.

Vegetable oil of poor quality is limiting the success of fortification with vitamin A in Egypt.

Background Fortification of vegetable oil with vitamin A is considered a cost-effective and simple to implement strategy, but the stability of vitamin A remains a limiting factor. To account for losses of vitamin A, oil producers add an overage. Optimizing the amount of this overage can result in considerable savings for industry and government while ensuring a supply of adequately fortified oil to consumers. Objectives To estimate vitamin A losses in oil with different chemical characteristics. Methods Samples of fortified oils with different chemical characteristics were collected from two Egyp- tian companies (oil A and B) and stored for 1 month. Vitamin A levels were analyzed periodically during stor- age to determine losses over time, and peroxide values were determined. Results Fortified oil B, with a high peroxide value (5.8 mEq/kg), exposed to sunlight had significantly higher losses of vitamin A after 4 weeks than fortified oil A, with a low peroxide value (0.4 mEq/kg): 31.1% vs. 19.7% (p < .001), respectively. In semidark conditions, the vitamin A losses after 4 weeks in fortified oil B and fortified oil A were significantly different: 26.1% and 0.7% (p < .001), respectively. In an accelerated storage test, the vitamin A loss in 8 days was 48.3% for fortified oil B and 4.2% for fortified oil A (p < .001). Conclusions This study shows a significant effect of peroxide level (one indicator of the quality of oil) on the stability of vitamin A, regardless of storage conditions. To optimize and sustain vitamin A levels in fortified oil, governments and industries should minimize the perox- ide level to less than 2 mEq/kg at production.

Infant and Young Child Feeding Practices in Urban Philippines and Their Associations with Stunting, Anemia, and Deficiencies of Iron and Vitamin A

Background The prevalence of stunting, underweight, and micronutrient deficiencies are persistently high in young children in the Philippines, and among other factors, suboptimal infant and young child feeding behavior may contribute to these forms of malnutrition. Objective To improve the understanding of contributors associated with the nutritional status of children 6 to 23 months of age living in urban areas of the Philippines. Methods A cross-sectional survey was conducted covering five urban centers in the Philippines. Data on infant and young child feeding and nutritional status (including wasting, stunting, underweight, anemia, iron deficiency, and vitamin A deficiency) were collected for 1,784 children. Results Among children from urban and predominantly poor and very poor households, 26% were stunted, 18% were underweight, and 5% were wasted. Forty-two percent were anemic, 28% were iron deficient, and 3% were vitamin A deficient. About half of the children were breastfed within an hour after birth, were breastfed at the time of the survey, and had been continuously breastfed up to 1 year of age. Of the factors investigated, low socio-economic status, use of cheaper cooking fuel, and nonuse of multivitamins were all independently associated with stunting. The prevalence of anemia, iron deficiency, and vitamin A deficiency were independently associated with the same factors and poorer sanitation facilities, lower maternal education, current unemployment, and inflammation. Conclusions These factors merit attention in future programming, and interventions may include promotion of the timely introduction of appropriate fortified complementary foods, the use of affordable multiple micronutrient preparations, and measures to reduce infections.

Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation. Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration <12 μg/L in PSC and <15 μg/L in WRA) in inflammation and malaria settings as follows: 1) increase ferritin-concentration cutoff to <30 μg/L; 2) exclude individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3) apply arithmetic correction factors; and 4) use a regression correction approach. Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7–25 and 2–8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores. Conclusions: Our results lend support for the use of internal regression correction to estimate the prevalence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear relation of ferritin concentrations with acute-phase proteins. More research is warranted to validate the proposed approaches, but this study contributes to the evidence base to guide decisions about how and when to adjust ferritin for inflammation.

Vitamin A Supplementation Programs and Country-Level Evidence of Vitamin A Deficiency

Vitamin A supplementation (VAS) programs targeted at children aged 6–59 months are implemented in many countries. By improving immune function, vitamin A (VA) reduces mortality associated with measles, diarrhea, and other illnesses. There is currently a debate regarding the relevance of VAS, but amidst the debate, researchers acknowledge that the majority of nationally-representative data on VA status is outdated. To address this data gap and contribute to the debate, we examined data from 82 countries implementing VAS programs, identified other VA programs, and assessed the recentness of national VA deficiency (VAD) data. We found that two-thirds of the countries explored either have no VAD data or data that were >10 years old (i.e., measured before 2006), which included twenty countries with VAS coverage ≥70%. Fifty-one VAS programs were implemented in parallel with at least one other VA intervention, and of these, 27 countries either had no VAD data or data collected in 2005 or earlier. To fill these gaps in VAD data, countries implementing VAS and other VA interventions should measure VA status in children at least every 10 years. At the same time, the coverage of VA interventions can also be measured. We identified three countries that have scaled down VAS, but given the lack of VA deficiency data, this would be a premature undertaking in most countries without appropriate status assessment. While the global debate about VAS is important, more attention should be directed towards individual countries where programmatic decisions are made.

Improvement of the Vietnamese Diet for Women of Reproductive Age by Micronutrient Fortification of Staples Foods and Condiments

Background A micronutrient survey carried out in 2010 among randomly selected Vietnamese women in reproductive age indicated that anemia and micronutrient deficiencies are still prevalent. The objective of this study was thus to analyze the dietary micronutrient intakes of these women, to select the food vehicles to be fortified and to calculate their contributions to meet the recommended nutrient intake (RNI) for iron, zinc, vitamin A and folic acid. Main Findings Consumption data showed that the median intake was 38.4% of the RNI for iron, 61.1% for vitamin A and 91.8% for zinc. However, more than 50% of the women had daily zinc consumption below the RNI. Rice and vegetable oil were consumed daily in significant amounts (median: 320.4 g/capita/day and 8.6 g/capita/day respectively) by over 90% of the women, making them suitable vehicles for fortification. Based on consumption data, fortified vegetable oil could contribute to an additional vitamin A intake of 27.1% of the RNI and fortified rice could increase the intake of iron by 41.4% of the RNI, zinc by 15.5% and folate by 34.1%. Other food vehicles, such as fish and soy sauces and flavoring powders, consumed respectively by 63% and 90% of the population could contribute to increase micronutrient intakes if they are properly fortified and promoted. Wheat flower was consumed by 39% of the women and by less than 20% women from the lowest socioeconomic strata. Conclusion The fortification of edible vegetable oils with vitamin A and of rice with iron, zinc and folic acid are the most promising fortification strategies to increase micronutrient intakes of women in reproductive age in Vietnam. While rice fortification will be implemented, fortification of fish and soy sauces with iron, that has been proven to be effective, has to be supported and fortification of flavouring powders with micronutrients investigated.

Quantification of Vitamin A in Palm Oil Using a Fast and Simple Portable Device: Method Validation and Comparison to High-Performance Liquid Chromatography

Vitamin A deficiency continues to be a global public health problem. Fortification of oil with vitamin A is considered a cost-effective, feasible strategy to prevent this problem but quality control poses a challenge to program implementation. To overcome this, we have validated a newly developed device that quantitatively measures the content of retinyl palmitate in refined palm oil, is simple to use, and yields immediate results.Linearity of analysis ranged from 2.5 - 30 mg retinol equivalents (RE)/ kg of palm oil, with 2.5 mg RE/kg being the determination limit; inter- and intra-assay precision ranged from 1.4 - 7.1 %. Comparison with a high-performance liquid chromatography method showed high agreement between the methods (R(2) = 0.92; Limits of Agreement: -1.24 mg to 2.53 mg RE/kg), and further comparisons illustrate that the new device is useful in low-resource settings. This device offers a field- and user-friendly solution to quantifying the vitamin A content in refined palm oil.