Assessing Accuracy and Precision of Hemoglobin Determination in Venous, Capillary Pool, and Single-Drop Capillary Blood Specimens Using three Different HemoCue® Hb Models: The Multicountry Hemoglobin Measurement (HEME) Study.

BACKGROUND: Anemia prevalence estimates reported in population surveys can vary based on the blood specimen source (capillary or venous) and analytic device (hematology autoanalyzers or portable hemoglobinometers) used for hemoglobin (Hb) determination. OBJECTIVES: This study aimed to compare accuracy and precision of Hb measurement in three blood specimen types on three models of hemoglobinometers against the results from venous blood from the same individuals measured on automated analyzers (AAs). METHODS: This multisite (Cambodia, Ethiopia, Guatemala, Lebanon, Nigeria, and Tanzania) study assessed Hb measurements in paired venous and capillary blood specimens from apparently healthy women (aged 15-49 y) and children (aged 12-59 mo) using three HemoCue® Hb models (201+, 301, and 801). Measurements were compared against reference values: venous blood in hematology AA and adjusted via regression calibration or mean difference in HemoCue® Hb. Venous, capillary pool, and single-drop capillary blood specimens were assessed for accuracy and precision. RESULTS: Venous blood measured using HemoCue® Hb 301 exhibited a positive mean error, whereas responses in HemoCue® Hb 201+ and 801 were nondirectional compared with the reference. Adjustment with the reference harmonized mean errors for all devices across study sites to <1.0 g/L using venous blood. Precision was highest for venous blood (±5-16 g/L) in all sites, lowest for single-drop capillary (±9-37 g/L), and intermediate (±9-28 g/L) for capillary pool blood specimen. Imprecision differed across sites, especially with both capillary blood specimens, suggesting different levels of personnel skills. CONCLUSIONS: Findings suggest that venous blood is needed for accurate and precise Hb determination. Single-drop capillary blood use should be discouraged owing to high measurement variability. Further research should evaluate the viability and reliability of capillary pool blood for this purpose. Accuracy of HemoCue® Hb devices can be improved via standardization against results from venous blood assessed using AA.

Estimating minimum dietary diversity for children aged 6-23 months: a comparison of agreement and cost of two recall methods in Cambodia and Zambia.

OBJECTIVE: To compare the agreement and cost of two recall methods for estimating children's minimum dietary diversity (MDD). DESIGN: We assessed child's dietary intake on two consecutive days: an observation on day one, followed by two recall methods (list-based recall and multiple-pass recall) administered in random order by different enumerators at two different times on day two. We compared the estimated MDD prevalence using survey-weighted linear probability models following a two one-sided test equivalence testing approach. We also estimated the cost-effectiveness of the two methods. SETTING: Cambodia (Kampong Thom, Siem Reap, Battambang, and Pursat provinces) and Zambia (Chipata, Katete, Lundazi, Nyimba, and Petauke districts). PARTICIPANTS: Children aged 6-23 months: 636 in Cambodia and 608 in Zambia. RESULTS: MDD estimations from both recall methods were equivalent to the observation in Cambodia but not in Zambia. Both methods were equivalent to the observation in capturing most food groups. Both methods were highly sensitive although the multiple-pass method accurately classified a higher proportion of children meeting MDD than the list-based method in both countries. Both methods were highly specific in Cambodia but moderately so in Zambia. Cost-effectiveness was better for the list-based recall method in both countries. CONCLUSION: The two recall methods estimated MDD and most other infant and young child feeding indicators equivalently in Cambodia but not in Zambia, compared to the observation. The list-based method produced slightly more accurate estimates of MDD at the population level, took less time to administer and was less costly to implement.

Exploring the Anemia Ecology: A New Approach to an Old Problem.

Our ability to identify anemia and all its permutations demands an approach that integrates the key elements of a complex "ecology," which intertwines biology and mechanistic aspects of nutrients with both the health status and underlying factors-physical, economic, social, behavioral, demographic, and environmental. The complexity of anemia demands an ecologic approach that appreciates systems biology, translates sensitive and specific assessment methodologies and interventions, and ultimately improves clinical and public health outcomes. This series of technical papers on anemia by the U.S. Agency for International Development (USAID) Advancing Nutrition Anemia Task Force (ATF) is a first step in translating our ecologic approach to anemia with a view toward balancing research with its translation to effective programs, interventions, and policy. This introductory overview describes the components of our ecologic approach-linking the biology of anemia with its assessment and using the learning from that confluence to devise context-specific interventions. This introductory review briefly discusses the topics that underlie the biology and primary etiologies of anemia and presents a framework for public health assessment of anemia, leading to appropriate public health interventions. The other 3 manuscripts in the supplement provide the details of the arguments laid out in the introduction.

Approaches to Address the Anemia Challenge.

Anemia is a multifactorial condition; approaches to address it must recognize that the causal factors represent an ecology consisting of internal (biology, genetics, and health) and external (social/behavioral/demographic and physical) environments. In this paper, we present an approach for selecting interventions, followed by a description of key issues related to the multiple available interventions for prevention and reduction of anemia. We address interventions for anemia using the following 2 main categories: 1) those that address nutrients alone, and, 2) those that address nonnutritional causes of anemia. The emphasis will be on interventions of public health relevance, but we also consider the clinical context. We also focus on interventions at different stages of the life course, with a particular focus on women of reproductive age and preschool-age children, and present evidence on various factors to consider when selecting an intervention-inflammation, genetic mutations, nutrient delivery, bioavailability, and safety. Each section on an intervention domain concludes with a brief discussion of key research areas.

Assessing the performance of national sentinel food lists at subnational levels in six countries.

OBJECTIVE: To assess how well national sentinel lists of the most frequently consumed foods in each food group capture data at subnational levels to measure minimum diet diversity (MDD). DESIGN: We analysed data from seven surveys with 24-h open dietary recalls to evaluate: (1) the percentage of reported foods that were included in each sentinel food list; (2) whether these lists captured consumption of some food groups better than others and (3) differences between estimates of dietary diversity calculated from all food items mentioned in the open 24-h recall v. only food items included in the sentinel lists. SETTING: Seven subnational areas: Bangladesh (2), Benin, Colombia, Kenya, Malawi and Nepal. PARTICIPANTS: 8094 women 15-49 years; 4588 children 6-23 months. RESULTS: National sentinel food lists captured most foods reportedly consumed by women (84 %) and children (86 %). Food groups with the highest variability were 'other fruits' and 'other vegetables.' MDD calculated from the sentinel list was, on average, 6·5 (women) and 4·1 (children) percentage points lower than when calculated from open 24-h recalls, with a statistically significant difference in most subnational areas. CONCLUSION: National sentinel food lists can provide reliable data at subnational levels for most food groups, with some variability by country and sub-region. Assessing the accuracy of national sentinel food lists, especially for fruits and vegetables, before using them at the subnational level could avoid potentially underestimating dietary diversity and provide more accurate local information for programmes, policy and research.

Lower serum selenium concentration associated with anxiety in children.

PURPOSE: Few studies have examined the role of selenium in anxiety. This study aimed to evaluate the association between serum selenium concentrations and anxiety disorders and symptoms in children. DESIGN AND METHODS: This study utilized data from 831 children participating in the China Jintan Child Cohort Study (mean age = 12.67 years; 46.1% female). Serum selenium samples were collected and anxiety was assessed using the Chinese version of the Screen for Child Anxiety Related Disorders. Six types of anxiety scores were calculated, including total anxiety, panic/somatic, generalized anxiety, separation anxiety, social anxiety, and school phobia. RESULTS: Controlling for covariates, children with lower serum selenium concentrations were more likely to meet clinical cutoffs for total anxiety (OR = 0.992, p < 0.01), panic/somatic disorder (OR = 0.993, p < 0.05), generalized anxiety disorder (OR = 0.990, p < 0.05), social anxiety disorder (OR = 0.991, p < 0.01), and school phobia (OR = 0.989, p < 0.01), but not separation anxiety (OR = 1.000, p > 0.05). Controlling for covariates, lower serum selenium concentrations were also associated with higher continuous total anxiety, generalized anxiety, and school phobia scores (p < 0.05). CONCLUSIONS: Lower serum selenium concentrations were associated with higher anxiety. To our knowledge, this was the first study to examine the relationship between serum selenium and anxiety disorders in a sample of children. Results indicate an association between children's micronutrient levels and anxiety disorders. PRACTICE IMPLICATIONS: Improving child nutrition may be a promising strategy to help reduce childhood anxiety.

An Electronic Data Capture Framework (ConnEDCt) for Global and Public Health Research: Design and Implementation.

BACKGROUND: When we were unable to identify an electronic data capture (EDC) package that supported our requirements for clinical research in resource-limited regions, we set out to build our own reusable EDC framework. We needed to capture data when offline, synchronize data on demand, and enforce strict eligibility requirements and complex longitudinal protocols. Based on previous experience, the geographical areas in which we conduct our research often have unreliable, slow internet access that would make web-based EDC platforms impractical. We were unwilling to fall back on paper-based data capture as we wanted other benefits of EDC. Therefore, we decided to build our own reusable software platform. In this paper, we describe our customizable EDC framework and highlight how we have used it in our ongoing surveillance programs, clinic-based cross-sectional studies, and randomized controlled trials (RCTs) in various settings in India and Ecuador. OBJECTIVE: This paper describes the creation of a mobile framework to support complex clinical research protocols in a variety of settings including clinical, surveillance, and RCTs. METHODS: We developed ConnEDCt, a mobile EDC framework for iOS devices and personal computers, using Claris FileMaker software for electronic data capture and data storage. RESULTS: ConnEDCt was tested in the field in our clinical, surveillance, and clinical trial research contexts in India and Ecuador and continuously refined for ease of use and optimization, including specific user roles; simultaneous synchronization across multiple locations; complex randomization schemes and informed consent processes; and collecting diverse types of data (laboratory, growth measurements, sociodemographic, health history, dietary recall and feeding practices, environmental exposures, and biological specimen collection). CONCLUSIONS: ConnEDCt is customizable, with regulatory-compliant security, data synchronization, and other useful features for data collection in a variety of settings and study designs. Furthermore, ConnEDCt is user friendly and lowers the risks for errors in data entry because of real time error checking and protocol enforcement.

Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific.Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO4), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP).Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 µ/L) aged between 20 and 39 y with a normal body mass index (in kg/m2; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP (57FePP): 1) 1 meal without added zinc (57FePP-Zn), 2) 1 cofortified with ZnO (57FePP+ZnO), and 3) 1 cofortified with ZnSO4 (57FePP+ZnSO4). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate (58FeSO4) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57FePP-Zn, 57FePP+ZnO, and 57FePP+ZnSO4 expressed as a fraction of FeSO4 solubility.Results: Geometric mean fractional iron absorption (95% CI) from 57FePP+ZnSO4 was 4.5% (3.4%, 5.8%) and differed from 57FePP+ZnO (2.7%; 1.8%, 4.1%) (P < 0.03); both did not differ from 57FePP-Zn: 4.0% (2.8%, 5.6%). Relative iron bioavailabilities compared with 58FeSO4 were 62%, 57%, and 38% from 57FePP+ZnSO4, 57FePP-Zn, and 57FePP+ZnO, respectively. In vitro solubility from 57FePP+ZnSO4 differed from that of 57FePP-Zn (14.3%; P < 0.02) but not from that of 57FePP+ZnO (10.2% compared with 13.1%; P = 0.08).Conclusions: In iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at clinicaltrials.gov as NCT02255942.

Cold Extrusion but Not Coating Affects Iron Bioavailability from Fortified Rice in Young Women and Is Associated with Modifications in Starch Microstructure and Mineral Retention during Cooking.

Background: Rice can be fortified with the use of hot or cold extrusion or coating, but the nutritional qualities of the resulting rice grains have never been directly compared.Objective: Using fortified rice produced by coating or hot or cold extrusion, we compared 1) iron and zinc absorption with the use of stable isotopes, 2) iron and zinc retention during cooking, and 3) starch microstructure.Methods: We conducted 2 studies in young women: in study 1 [n = 19; mean ± SD age: 26.2 ± 3.4 y; body mass index (BMI; in kg/m2): 21.3 ± 1.6], we compared the fractional iron absorption (FAFe) from rice meals containing isotopically labeled ferric prophosphate (57FePP), zinc oxide (ZnO), citric acid, and micronutrients fortified through hot extrusion (HER1) with rice meals fortified through cold extrusion containing 57FePP, ZnO, citric acid, and micronutrients (CER); in study 2 (n = 22; age: 24 ± 4 y; BMI: 21.2 ± 1.3), we compared FAFe and fractional zinc absorption (FAZn) from rice meals fortified through hot extrusion (HER2) compared with rice meals fortified through coating containing 57FePP, ZnO, a citric acid and trisodium cirate mixture (CA/TSC), and micronutrients (COR) relative to rice meals extrinsically fortified with ferrous sulfate (reference). Rice types HER1 and CER contained citric acid, whereas types HER2 and COR contained CA/TSC. We assessed retention during standardized cooking experiments and characterized the rice starch microstructure.Results: FAFe (95% CI) was greater from CER [2.2% (1.4%, 3.4%)] than from HER1 [1.2% (0.7%, 2.0%)] (P = 0.036). There was no difference in FAFe between HER2 [5.1% (3.7%, 7.1%)] and COR [4.0% (2.9%, 5.4%)] (P = 0.14), but FAFe from COR was lower than that from the reference meal [6.6% (4.9%, 9.0%)] (P = 0.003), and the geometric mean FAZn (95% CI) did not differ between HER2 [9.5% (7.9%, 11.6%)] and COR [9.6% (8.7%, 10.7%)] (P = 0.92). Cooking in a rice-to-water ratio of 1:2 resulted in iron and zinc retentions >80%, and cooking in excess water did not affect iron retention from hot-extruded rice but caused iron losses of 25% from CER and COR. Distinct variations in starch microstructure were found in CER and HER1.Conclusions: Iron absorption was 64% higher from CER than from hot-extruded rice, with no difference between COR compared with hot-extruded rice. Lower extrusion temperatures may generate a more readily digestible starch structure, allowing for greater iron release in vivo but lower mineral retention during cooking. This trial was registered at clinicaltrials.gov as NCT02176759.

Iron biofortification interventions to improve iron status and functional outcomes.

This analysis was conducted to evaluate the evidence of the efficacy of iron biofortification interventions on iron status and functional outcomes. Iron deficiency is a major public health problem worldwide, with a disproportionate impact on women and young children, particularly those living in resource-limited settings. Biofortification, or the enhancing of micronutrient content in staple crops, is a promising and sustainable agriculture-based approach to improve nutritional status. Previous randomised efficacy trials and meta-analyses have demonstrated that iron-biofortification interventions improved iron biomarkers; however, no systematic reviews to date have examined the efficacy of biofortification interventions on health outcomes. We conducted a systematic review of the efficacy of iron-biofortified staple crops on iron status and functional outcomes: cognitive function (e.g. attention, memory) and physical performance. Five studies from three randomised efficacy trials (i.e. rice, pearl millet, beans) conducted in the Philippines, India and Rwanda were identified for inclusion in this review. Iron status (Hb, serum ferritin, soluble transferrin receptor, total body iron, α-1-acid glycoprotein) was measured at baseline and endline in each trial; two studies reported cognitive outcomes, and no studies reported other functional outcomes. Meta-analyses were conducted using DerSimonian and Laird random-effects methods. Iron-biofortified crop interventions significantly improved cognitive performance in attention and memory domains, compared with conventional crops. There were no significant effects on categorical outcomes such as iron deficiency or anaemia. Further studies are needed to determine the efficacy of iron-biofortified staple crops on human health, including additional functional outcomes and other high-risk populations.

Cofortification of ferric pyrophosphate and citric acid/trisodium citrate into extruded rice grains doubles iron bioavailability through in situ generation of soluble ferric pyrophosphate citrate complexes.

BACKGROUND: Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability. OBJECTIVE: We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains. DESIGN: We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios. RESULTS: Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice. CONCLUSIONS: Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759.