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.

The Value of an Ecological Approach to Improve the Precision of Nutritional Assessment: Addressing Contributors and Implications of the "Multiple Burdens of Malnutrition".

Globally, children are exposed to multiple health risks associated with diet and nutrition. Rather than simply being a condition of having too much or too little food, malnutrition is more a syndrome comprising multiple burdens of coexisting and reciprocal malnutrition, infection, or other conditions. Importantly, children with such syndromes (e.g., stunting and anemia, which are neither specific nor necessarily sensitive to nutritional status) are more likely to also have irreversible functional outcomes such as poor growth, impaired immune function, or cognitive delays. The global health community has identified nutrition-related targets (e.g., Sustainable Development Goals (SDGs) and World Health Organization (WHO) Global Nutrition Targets) that, for multiple reasons, are difficult to address. Moreover, as the complexity of the global health context increases with persistent pandemics of infectious diseases and the rising prevalence of noncommunicable diseases, there is a growing appreciation that conditions selected as nutrition/health targets indeed represent syndromes for which nutritional status serves as both an input and outcome. In recognition of the impact of these combined challenges and the role of the multiple manifestations of malnutrition, we suggest an approach to nutritional assessment that is intended to improve the precision of context-specific, equitable approaches to health promotion, disease prevention, and treatment.

Firm-Level and Public-Sector Costs Make Small-Scale Maize Flour Fortification Challenging in Uganda.

BACKGROUND: Maize flour in Uganda is milled by hundreds of enterprises, mostly small- (5-20 metric tons [MT]/day) and micro-scale (<5 MT/day) mills or firms. A mandatory maize flour fortification program exists for medium-scale mills (>20 MT/day) and policymakers are considering including smaller-scale millers. OBJECTIVE: We estimated the private and public costs of maize flour fortification at different scales and explored their implications for extending the mandatory fortification to include smaller-scale mills. METHODS: We used secondary data on the structure of the maize flour market and primary data on milling and fortification costs to estimate mill and regulatory costs at 3 scales of flour production: micro, small, and medium. RESULTS: For micro-, small-, and medium-size operations, respectively, operational costs of fortification were US$13, US$9, and US$7 per metric ton (MT) of maize flour, which represented 20%, 16%, and 16% of annual operating costs, and the ratio of fortification equipment cost to mill equipment costs was higher for micro-scale mills (2.7) than for small- (0.38) and medium-scale (0.54) maize mills. Governmental regulatory costs rise if smaller-scale mills are included due to the increased number of facility inspections. CONCLUSIONS: Fortification and regulatory costs increase as production scale decreases. Up-front capital costs of fortification would be daunting for micro- and small-scale mills. Medium-scale mills, which supply social protection programs, might be able to manage fortification costs and other challenges. Decision-makers should consider all costs and cost burdens, and the realities of enforcement capabilities before expanding fortification programs to include smaller-scale operations.

Plain language titleCosts of Small-scale Maize Flour Fortification in UgandaPlain language summaryA study of the costs of adding vitamins and minerals by small-scale maize flour millers in Uganda was undertaken to understand if it would be commercially beneficial from a business and operations perspective for them to do so, and if requiring them to do so would impose additional cost burdens on government to ensure that fortification standards were met.Why was the study done?Maize flour is consumed by the majority of Uganda's population, especially the rural poor. If the flour were fortified, it would reduce vitamin and mineral deficiencies among those at risk. The most important constraint to market-wide fortification is the presence of many small-scale mills or firms that neither have the resources nor the technology to adopt and sustain the fortification process. To date, no study has been done to calculate the costs that small-scale mills would have to face to fortify flour, or what the cost implications for government would be for including smaller-scale mills in a national fortification program, including the costs of enforcing regulations.What did the researchers do?The researchers interviewed millers of several scales of operation to collect cost information on their operations and interviewed representatives of government regulatory bodies to estimate the costs of testing maize flour to ensure compliance with regulations. Researchers estimated the cost to the mills of adding fortification to their business models, and the impacts on the government costs (eg, testing additional samples, etc.) of including smaller-scale mills in the fortification program.What did the researchers find?The researchers looked at 3 different types of mills based on their capacity to mill maize flour­micro-scale firms milled less than 5 metric tons (MT) a day, small-scale firms milled 5 to 20 MT per day, and medium-scale firms milled over 20 MT a day. For micro-, small-, and medium-size firms, respectively, fortification increased operational costs by US$13, US$9, and US$7 per MT of maize flour, which represented 20%, 16%, and 16% of annual operating costs. Similarly, governmental regulatory costs rose if smaller-scale mills were included because of the increased number of facility inspections required since the current legislation requires mandatory annual inspections.What do the findings mean?Fortification and regulatory costs increase as the scale of production by the millers decreases. If fortification by small- and micro-scale mills were made mandatory, up-front costs of fortification equipment and materials would be daunting for micro- and small-scale millers. Ugandan medium-scale millers might manage fortification costs and other challenges, but only if the social protection programs they supplied were of sufficient volume and regularity.

Validation of hemoglobin measurement in venous blood using HemoCue for the Ensanut 2022.

OBJECTIVE: To validate hemoglobin (Hb) concentration in venous blood (VB) using the HemoCue 201+ in a subsample of children and women from the Mexican National Health and Nutrition Survey 2022. MATERIALS AND METHODS: Prior to field work 50 HemoCue 201+ devices were verified using venous blood. During the field work 57 children (aged 1-11) and 62 women (aged 12-49) donated 3 mL of VB each. Hb was measured in each device of HemoCue 201+ and in a hematologic autoanalyzer for the validation. RESULTS: No significant bias was found in most of the devices. An adjustment criterion was used for 22 devices. Hb mean difference results were -0.049±0.578 g/dL in children and -0.098±0.628 g/dL in women. CONCLUSIONS: The HemoCue 201+ is a valid tool for estimating Hb concentration to produce reliable estimates of anemia prevalence when using venous blood.

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.

Improving Anemia Assessment in Clinical and Public Health Settings.

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

Diagnosing anemia: Challenges selecting methods, addressing underlying causes, and implementing actions at the public health level.

Accurate and affordable tools for diagnosing anemia and its main determinants are essential for understanding the magnitude and distribution of the problem and the appropriate interventions needed for its timely prevention and treatment. The objective of this review is to address methods, equipment, and sample-related and quality control aspects of hemoglobin measurement for anemia diagnosis. Also, other iron-, infectious-, and genetic-related causes of anemia are addressed in individuals and populations. The best practice for hemoglobin determination is the use of venous blood, analyzed on automated hematology analyzers, with high-quality control measures in place. The importance of a correct anemia diagnosis is highlighted by the cost of a misdiagnosis. A false-negative diagnosis may result in missing out and not treating anemia, its causes, and its adverse effects. On the other hand, a false-positive diagnosis may result in the provision of unneeded treatment or referral for expensive laboratory tests to determine a cause of anemia, wasting valuable resources and risking causing harm. At the individual level, clinicians must understand the causes of absolute and functional anemia to diagnose and treat anemia at the clinical level. Actions toward anemia diagnosis and control at public health levels require global, regional, and country actions that should cover general and context-specific characteristics.

Drops of Capillary Blood Are Not Appropriate for Hemoglobin Measurement with Point-of-Care Devices: A Comparative Study Using Drop Capillary, Pooled Capillary, and Venous Blood Samples.

Population-based surveys matched by time but using different methodologies for determining hemoglobin (Hb) concentration have shown inconsistencies in estimating anemia prevalence. This study aimed to estimate measurement errors in Hb quantification in HemoCue 201+ using venous blood (VB) and capillary blood both drops (DCB) and pools (PCB), and compare the results against those of a reference method (VB analyzed in hematology analyzers based on the cyanmethemoglobin method). Children (n = 49), adult females (n = 50), and older adults (n = 50) were randomly allocated to donate VB (4 mL) and either DCB (three drops) or PCB (350 µL). Results in HemoCue were analyzed through Bland Altman and Lyn's concordance against Hb concentration by the reference method. A positive average bias (systematic error) was found for the HemoCue (0.31 g/dL) using the same VB samples. This value was then subtracted from all readings carried out in the device. After this adjustment, DCB still produced a positive bias (0.42 ± 0.81 g/dL), and the variation of single results was ±1.6 g/dL (95% CI). PCB and VB performed similarly; the average bias was negligible (-0.02 ± 0.36 and 0.00 ± 0.33 g/dL, respectively) and the variation of the results (95% CI) was ±0.7 g/dL or lower. Lyn's concordance values were 0.86, 0.96, and 0.98 for DCB, PCB, and VB, respectively. Random variation using DCB is too large to approximate the true Hb values, and therefore DCB should be discontinued for diagnosing anemia both in individuals and in populations.

Systematic review of metrics used to characterise dietary nutrient supply from household consumption and expenditure surveys.

OBJECTIVE: To review existing publications using Household Consumption and Expenditure Survey (HCES) data to estimate household dietary nutrient supply to (1) describe scope of available literature, (2) identify the metrics reported and parameters used to construct these metrics, (3) summarise comparisons between estimates derived from HCES and individual dietary assessment data and (4) explore the demographic and socio-economic sub-groups used to characterise risks of nutrient inadequacy. DESIGN: This study is a systematic review of publications identified from online databases published between 2000 to 2019 that used HCES food consumption data to estimate household dietary nutrient supply. Further publications were identified by 'snowballing' the references of included database-identified publications. SETTING: Publications using data from low- and lower-middle income countries. RESULTS: In total, fifty-eight publications were included. Three metrics were reported that characterised household dietary nutrient supply: apparent nutrient intake per adult-male equivalent per day (n 35), apparent nutrient intake per capita per day (n 24) and nutrient density (n 5). Nutrient intakes were generally overestimated using HCES food consumption data, with several studies finding sizeable discrepancies compared with intake estimates based on individual dietary assessment methods. Sub-group analyses predominantly focused on measuring variation in household dietary nutrient supply according to socio-economic position and geography. CONCLUSION: HCES data are increasingly being used to assess diets across populations. More research is needed to inform the development of a framework to guide the use of and qualified interpretation of dietary assessments based on these data.

Seasonal effects on urinary iodine concentrations in women of reproductive age: An observational study in Tanzania and South Africa.

BACKGROUND: Iodine intake in populations is usually assessed by measuring urinary iodine concentrations (UICs) in spot samples. Hot climate conditions may reduce urine volume, thus leading to overestimations of UIC and thereby masking inadequate iodine intake. OBJECTIVES: We investigated the effects of season on UICs in 2 populations exposed to high-temperature climates. METHODS: In this observational study, we examined women (18-49 years) in Tanzania (ncold = 206; nhot = 179) and South Africa (ncold = 157; nhot = 126) during cold and hot seasons. From each woman in both seasons, we obtained two 24-hour urine collections and 2 spot urine samples, as well as salt, water, and cow's milk samples. We measured the urine volume, UIC, and urinary creatinine concentration (UCC). The 24-hour urinary iodine excretion (UIE) was calculated and used to estimate the iodine intake. We used linear mixed-effects models to test for differences between seasons. RESULTS: In Tanzanian women, we observed no seasonal effect on the urine volume, 24-hour UIE, 24-hour UIC, spot UIC, spot UIC:UCC ratio, or salt iodine concentration. In South African women, the median 24-hour urine volume was 1.40 L (IQR, 0.96-2.05 L) in the winter and 15% lower in the summer (P < 0.001). The median 24-hour UIE was 184 µg/day (IQR, 109-267 µg/day) in the winter and 34% lower in the summer (P < 0.001), indicating a lower iodine intake. As a result, UICs did not significantly differ between seasons in 24-hour collections and spot samples, whereas the spot UIC:UCC ratio differed by 21% (P < 0.001) and reflected the lower iodine intake. In both study populations, the within- and between-person variabilities in urine volume, 24-hour UICs, and spot UICs were higher than the variability between seasons. CONCLUSIONS: Spot UIC may slightly overestimate the iodine intake in hot temperatures due to concentrated urine, and methods to correct for urine volume may be considered. Local seasonal differences in iodine intakes may also occur in some populations. This trial was registered at http://www.clinicaltrials.gov as NCT03215680.

Modeling food fortification contributions to micronutrient requirements in Malawi using Household Consumption and Expenditure Surveys.

Large-scale food fortification may be a cost-effective intervention to increase micronutrient supplies in the food system when implemented under appropriate conditions, yet it is unclear if current strategies can equitably benefit populations with the greatest micronutrient needs. This study developed a mathematical modeling framework for comparing fortification scenarios across different contexts. It was applied to model the potential contributions of three fortification vehicles (oil, sugar, and wheat flour) toward meeting dietary micronutrient requirements in Malawi through secondary data analyses of a Household Consumption and Expenditure Survey. We estimated fortification vehicle coverage, micronutrient density of the diet, and apparent intake of nonpregnant, nonlactating women for nine different micronutrients, under three food fortification scenarios and stratified by subpopulations across seasons. Oil and sugar had high coverage and apparent consumption that, when combined, were predicted to improve the vitamin A adequacy of the diet. Wheat flour contributed little to estimated dietary micronutrient supplies due to low apparent consumption. Potential contributions of all fortification vehicles were low in rural populations of the lowest socioeconomic position. While the model predicted large-scale food fortification would contribute to reducing vitamin A inadequacies, other interventions are necessary to meet other micronutrient requirements, especially for the rural poor.

Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries.

OBJECTIVE: We explore factors such as the blood sampling site (capillary vs venous), the equipment (HemoCue vs automated haematology analyser) and the model of the HemoCue device (201+ vs 301) that may impact haemoglobin measurements in capillary and venous blood. METHODS: Eleven studies were identified, and bias, concordance and measures of diagnostic performance were assessed within each study. FINDINGS: Our analysis included 11 studies from seven countries (Cambodia, India, The Gambia, Ghana, Laos, Rwanda and USA). Samples came from children, men, non-pregnant women and pregnant women. Mean bias ranged from -8.7 to 2.5 g/L in Cambodian women, 6.2 g/L in Laotian children, 2.4 g/L in Ghanaian women, 0.8 g/L in Gambian children 6-23 months and 1.4 g/L in Rwandan children 6-59 months when comparing capillary blood on a HemoCue to venous blood on a haematology analyser. Bias was 8.3 g/L in Indian non-pregnant women and 2.6 g/L in Laotian children and women and 1.5 g/L in the US population when comparing capillary to venous blood using a HemoCue. For venous blood measured on the HemoCue compared with the automated haematology analyser, bias was 5.3 g/L in Gambian pregnant women 18-45 years and 11.3 g/L in Laotian children 6-59 months. CONCLUSION: Our analysis found large variability in haemoglobin concentration measured on capillary or venous blood and using HemoCue Hb 201+ or Hb 301 or automated haematology analyser. We cannot ascertain whether the variation is due to differences in the equipment, differences in capillary and venous blood, or factors affecting blood collection techniques.

Micronutrient status of Palestinian school children following salt and flour fortification: a cross-sectional study.

BACKGROUND: In 1996 and in 2006, Palestine initiated salt iodization and multiple micronutrient fortification of wheat flour, respectively as a strategy to prevent deficiencies of these nutrients. In 2009, we assessed the impact of these interventions on the health and nutritional status of schoolchildren residing in the West Bank. METHODS: We surveyed a sample of 22 schools run by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian Government. We randomly selected students from the first (mean age 6.7 years [SD 0.5]), sixth (11.8 years [0.6]), and ninth grades (14.8 years [0.6]). Data were obtained from 1484 (99%) of 1500 students planned for enrollment. RESULTS: Our results suggest that iodine intake appears adequate and there was essentially no iodine deficiency. As to the status of other micronutrients, the main nutritional micronutrient risks for schoolchildren in the West Bank continue to be low serum levels of iron, zinc, and vitamin B-12; folate levels were seemingly high. The overall prevalence of anemia was 9.6%, but there were pockets of anemia in certain districts. Almost 42% of the anemia in our sample was explained by iron deficiency. There were significant differences in iron deficiency between girls and boys, 29.5% vs. 15.7%, respectively (p = 0.0001). There were no cases of lead toxicity in the studied sample. CONCLUSIONS: Wheat flour and salt fortification has had a major influence on improving the micronutrient status of Palestinian children, for some but not all micronutrients. The recommended key blood and biochemical parameters to be incorporated in the surveillance system are iron, zinc, and vitamin B12.

Measurement and interpretation of hemoglobin concentration in clinical and field settings: a narrative review.

Anemia affects over 800 million women and children globally. Defined as a limited or insufficient functional red blood cell supply in peripheral blood, anemia causes a reduced oxygen supply to tissues and can have serious health consequences for women and children. Hemoglobin (Hb) concentration is most commonly measured for anemia diagnosis. Methods to measure Hb are usually invasive (requiring a blood sample); however, advances in diagnostic and clinical chemistry over the past decade have led to the development of new noninvasive methods. Accurate diagnosis at the individual level is important to identify individuals who require treatment. At the population level, anemia prevalence estimates are often the impetus for national nutrition policies or programs. Thus, it is essential that methods for Hb measurement are sensitive, specific, accurate, and reproducible. The objective of our narrative review is to describe the basic principles, advantages, limitations, and quality control issues related to methods of Hb measurement in clinical and field settings. We also discuss other biomarkers and tests that can help to determine the severity and underlying causes of anemia. In conclusion, there are many established and emerging methods to measure Hb concentration, each with their own advantages, limitations, and factors to consider before use.

Contemporary Dietary Intake: Too Much Sodium, Not Enough Potassium, yet Sufficient Iodine: The SALMEX Cohort Results.

Initiatives to reduce sodium intake are encouraged globally, yet there is concern about compromised iodine intake supplied through salt. The aim of the present study was to determine baseline sodium, potassium, and iodine intake in a sample of workers from our Institution in Mexico City (SALMEX Cohort). Methods. From a cohort of 1009 workers, appropriate 24-h urine and three-day dietary recall was collected in a sample of 727 adult subjects for assessment of urinary sodium, potassium, and iodine concentrations. Median urinary iodine excretion (UIE) was compared across categories of sodium intake of <2, 2⁻3.6, and ≥3.6 g/day. Results. Average sodium intake was 3.49 ± 1.38 g/day; higher in men than women (4.14 vs. 3.11 g/day, p ≤0.001). Only 10.6% of the population had sodium intake within the recommended range (<2 g/day); 45.4% had high (2⁻3.6 g/day) and 44% had excessive intake (>3.6 g/day). Average urinary Na/K ratio was 3.15 ± 1.22 (ideal < 1), higher in men (3.42 vs. 3.0, p ≤ 0.001). The multivariate analysis showed that sodium intake was associated with age (p = 0.03), male sex (p < 0.001), caloric intake (p = 0.002), UKE (p < 0.001) and BMI (p < 0.001). Median iodine intake was 286.7 µg/day (IQR 215⁻370 µg/day). Less than 2% of subjects had iodine intake lower than recommended for adults (95 µg/day); 1.3% of subjects in the recommended range of salt intake had low iodine intake. There is a direct relationship between iodine and sodium urinary excretion (r = 0.57, p < 0.0001). Conclusions. In the studied population, there was an excessive sodium intake and an imbalance between sodium and potassium intake. Only 10.6% of the population had sodium intake within the recommended values, but iodine intake in this group appears to be adequate.

Inventory on the dietary assessment tools available and needed in africa: a prerequisite for setting up a common methodological research infrastructure for nutritional surveillance, research, and prevention of diet-related non-communicable diseases.

OBJECTIVE: To carry out an inventory on the availability, challenges, and needs of dietary assessment (DA) methods in Africa as a pre-requisite to provide evidence, and set directions (strategies) for implementing common dietary methods and support web-research infrastructure across countries. METHODS: The inventory was performed within the framework of the "Africa's Study on Physical Activity and Dietary Assessment Methods" (AS-PADAM) project. It involves international institutional and African networks. An inventory questionnaire was developed and disseminated through the networks. Eighteen countries responded to the dietary inventory questionnaire. RESULTS: Various DA tools were reported in Africa; 24-Hour Dietary Recall and Food Frequency Questionnaire were the most commonly used tools. Few tools were validated and tested for reliability. Face-to-face interview was the common method of administration. No computerized software or other new (web) technologies were reported. No tools were standardized across countries. CONCLUSIONS: The lack of comparable DA methods across represented countries is a major obstacle to implement comprehensive and joint nutrition-related programmes for surveillance, programme evaluation, research, and prevention. There is a need to develop new or adapt existing DA methods across countries by employing related research infrastructure that has been validated and standardized in other settings, with the view to standardizing methods for wider use.

Global regulatory framework for production and marketing of crops biofortified with vitamins and minerals.

Biofortification of crops is being introduced in several countries as a strategy to reduce micronutrient deficiencies. Biofortified products, with increased contents of micronutrients, are currently produced by conventional plant breeding, genetic modification, or nutrient-enhanced fertilization. Corn, rice, wheat, beans, pearl millet, sweet potato, and cassava have been biofortified with increased contents of provitamin A carotenoids, iron, or zinc. However, regulatory considerations are rare or nonexistent. The objective of this paper is to review the regulatory framework for production and marketing of biofortified crops in countries that have adopted this strategy. The information was identified using Internet search engines and websites of health and nutrition organizations and nongovernmental organizations and by consulting scientists and government authorities. Thus far, biofortified products introduced in Latin America, Africa, and Asia have been produced only by conventional breeding. Cultivars using other techniques are still under testing. The production and marketing of these products have been conducted without regulatory framework and under limited government control or regulatory guidance. Nevertheless, some countries have integrated biofortified crops into their nutrition agendas. Although improvements by conventional breeding have not been subject to regulations, when biofortification becomes expanded by including other techniques, an appropriate regulatory framework will be necessary.