Comparison of Published Estimates of the National Prevalence of Iron, Vitamin A, and Zinc Deficiency and Sources of Inconsistencies.

Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency.

Aligning the Epidemiology of Malnutrition with Food Fortification: Grasp Versus Reach.

Large-scale food fortification (LSFF) has been recognized as one of the most cost-effective interventions to improve the intake of vitamins and minerals and decrease the burden of micronutrient deficiency. Indeed, the simple addition of micronutrients to staple foods, such as wheat, maize and rice, or condiments, including salt and bouillon, has tremendous potential to impact malnutrition. However, most LSFF programs have been poorly designed and have not taken into consideration critical inputs, including current levels of nutrient inadequacy and per capita consumption of different food vehicles when deciding which nutrients to add and at what concentrations. LSFF programs, like some other nutrition interventions, also tend to have low coverage and reach and lack monitoring to measure this and course correct. These program design flaws have resulted in limited effectiveness and have made it difficult to determine how best to harmonize LSFF with other interventions to reduce micronutrient deficiencies, including efforts to enhance dietary diversity, biofortification and supplementation. Furthermore, LSFF has often been touted as a population-based intervention, but in fact has heterogenous effects among sub-groups, particularly those with limited access to or inability to afford fortified foods, as well as those with higher physiological requirements, such as pregnant and lactating women. This article focuses on these limitations and the concerted efforts underway to improve the collection, analysis, and use of data to better plan LSFF programs, track implementation, and monitor coverage and impact. This includes a more sophisticated secondary analysis of existing data, innovations to increase the frequency of primary data collection and programmatically relevant visualizations of data of sub-national estimates. These improvements will enable better use of data to target resources and programmatic efforts to reach those who stand to benefit most from fortification.

Including calcium-fortified water or flour in modeled diets based on local foods could improve calcium intake for women, adolescent girls, and young children in Bangladesh, Uganda, and Guatemala.

Adequate calcium intake is essential for health, especially for infants, children, adolescents, and women, yet is difficult to achieve with local foods in many low- and middle-income countries. Previous analysis found it was not always possible to identify food-based recommendations (FBRs) that reached the calcium population recommended intake (PRI) for these groups in Bangladesh, Guatemala, and Uganda. We have modeled the potential contribution of calcium-fortified drinking water or wheat flour to FBR sets, to fill the remaining intake gaps. Optimized diets containing fortified products, with calcium-rich local foods, achieved the calcium PRI for all target groups. Combining fortified water or flour with FBRs met dietary intake targets for adolescent girls in all geographies and allowed a reduction from 3-4 to the more feasible 1-2 FBRs. Water with a calcium concentration of 100 mg/L with FBRs was sufficient to meet calcium targets in Uganda, but higher concentrations (400-500 mg/L) were mostly required in Guatemala and Bangladesh. Combining calcium-fortified wheat flour at 400 mg/100 g of flour and the FBR for small fish resulted in diets meeting the calcium PRI in Bangladesh. Calcium-fortified water or flour could improve calcium intake for vulnerable populations, especially when combined with FBRs based on locally available foods.

Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?

Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium-rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food-based approaches to promote dietary calcium adequacy were identified for 12- to 23-month-old breastfed children, 4- to 6-year-old children, 10- to 14-year-old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium-optimized diets achieved 75-253% of the Ca PRI, depending on the population, and were <100% for 4- to 6-year-olds in one region of each country and 10- to 14-year-old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime-treated) maize products, sesame seeds, and bean varieties, where consumed. Food-based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12- to 23-month-olds and NPNB women across geographic locations, and for 4- to 6-year-olds and 10-to 14-year-old girls in Uganda. However, for 4- to 6-year-olds and 10- to 14-year-old girls in Bangladesh and Guatemala, calcium-adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium-rich foods.

Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status.

Thiamine (vitamin B1) is an essential micronutrient required as a cofactor in many metabolic processes. Clinical symptoms of thiamine deficiency are poorly defined, hence biomarkers of thiamine status are important. The erythrocyte transketolase activity coefficient (ETKac) is a sensitive measure of thiamine status, but its interpretation may be confounded where the availability of the transketolase enzyme is limited. Basal ETK activity per gram of hemoglobin provides a complementary biomarker of thiamine status; however, its measurement and calculation are poorly described. Here, we describe in detail the assessment of basal ETK activity, including the calculation of path length in microplates and the molar absorption coefficient of NADH specific to the assay, and the measurement of hemoglobin in sample hemolysates. To illustrate the application of the methods, we present ETKac and basal ETK activity from women in The Gambia and UK. In conclusion, we present a clear protocol for the measurement of basal ETK activity that will permit the harmonization of methods to improve replication between laboratories.

Calcium status assessment at the population level: Candidate approaches and challenges.

Inadequate dietary calcium intake is a global public health problem that disproportionately affects low- and middle-income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high-risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium-rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population-level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population-based surveys.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

Nutrition modeling tools: a qualitative study of influence on policy decision making and determining factors.

Nutrition modeling tools (NMTs) generate evidence to inform policy and program decision making; however, the literature is generally limited to modeling methods and results, rather than use cases and their impacts. We aimed to document the policy influences of 12 NMTs and identify factors influencing them. We conducted semistructured interviews with 109 informants from 30 low- and middle-income country case studies and used thematic analysis to understand the data. NMTs were mostly applied by international organizations to inform national government decision making. NMT applications contributed to enabling environments for nutrition and influenced program design and policy in most cases; however, this influence could be strengthened. Influence was shaped by processes for applying the NMTs; ownership of the analysis and data inputs, and capacity building in NMT methods, encouraged uptake. Targeting evidence generation at specific policy cycle stages promoted uptake; however, where advocacy capacity allowed, modeling was embedded ad hoc into emerging policy discussions and had broader influence. Meanwhile, external factors, such as political change and resource constraints of local partner organizations, challenged NMT implementation. Importantly, policy uptake was never the result of NMTs exclusively, indicating they should be nested persistently and strategically within the wider evidence and advocacy continuum, rather than being stand-alone activities.

Calcium deficiency worldwide: prevalence of inadequate intakes and associated health outcomes.

Dietary calcium deficiency is considered to be widespread globally, with published estimates suggesting that approximately half of the world's population has inadequate access to dietary calcium. Calcium is essential for bone health, but inadequate intakes have also been linked to other health outcomes, including pregnancy complications, cancers, and cardiovascular disease. Populations in low- and middle-income countries (LMICs) are at greatest risk of low calcium intakes, although many individuals in high-income countries (HICs) also do not meet recommendations. Paradoxically, many LMICs with lower calcium intakes show lower rates of osteoporotic fracture as compared with HICs, though data are sparse. Calcium intake recommendations vary across agencies and may need to be customized based on other dietary factors, health-related behaviors, or the risk of calcium-related health outcomes. The lack of standard methods to assess the calcium status of an individual or population has challenged efforts to estimate the prevalence of calcium deficiency and the global burden of related adverse health consequences. This paper aims to consolidate available evidence related to the global prevalence of inadequate calcium intakes and associated health outcomes, with the goal of providing a foundation for developing policies and population-level interventions to safely improve calcium intake and status where necessary.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

Multiple micronutrient supplements versus iron-folic acid supplements and maternal anemia outcomes: an iron dose analysis.

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations.

Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5-2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.

Thiamine deficiency in Gambian women of reproductive age.

Thiamine deficiency disorders are associated with a variety of clinical symptoms affecting the nervous and cardiovascular systems. There is growing recognition that thiamine deficiency can occur in populations well beyond the classical region of South Asia, and at-risk populations include those who receive a large proportion of their energy from polished white rice (or other low-thiamine staple foods) and with low dietary diversity. Reports of thiamine deficiency in West Africa over the last century have suggested that this has historically been an issue in this population, but in more recent decades, these reports have been limited to prison populations. To understand if thiamine deficiency might be an unrecognized problem in the communities of this region, erythrocyte samples collected during the wet and dry seasons from 226 women of reproductive age (mean age = 28 years old) were assessed for thiamine status by measuring the erythrocyte transketolase activity coefficient (ETKac). Overall, 35.8% of the sample was at high risk of thiamine deficiency (ETKac ≥ 1.25). Risk of thiamine deficiency was significantly higher in the wet (47.9%) compared with the dry season (22.9%) (P < 0.001). To our knowledge, this is the first report of biochemical thiamine deficiency in a free-living population in West Africa in the 21st century and suggests that further investigation is warranted.

A fresh look at thiamine deficiency-new analyses by the global thiamine alliance.

Severe thiamine (vitamin B1 ) deficiency is generally regarded as a problem affecting mostly infants in low-income communities of Southeast Asia and adult alcoholics regardless of their location. However, recent scholarship shows that the disorders associated with thiamine deficiency may also affect heretofore unsuspected populations, and that the scope of disorders, including some long-lasting neurocognitive consequences, is broader than previously thought.

Thiamine deficiency unrelated to alcohol consumption in high-income countries: a literature review.

Thiamine deficiency has been typically associated with alcoholism or as a prevalent problem in low- and middle-income countries (LMICs) whose populations rely on staple foods with a low content of thiamine. We conducted a literature review of published and unpublished data to identify relevant adult cases with confirmed thiamine deficiency of nonalcoholic cause in developed countries. We selected 17 reports with 81 adult cases of confirmed thiamine deficiency affecting adult patients with a wide range of ages and underlying conditions (e.g., cancer, gastrointestinal diseases, heart failure, and obesity). Thiamine deficiency may have been caused by disease-related malnutrition, bariatric surgery, chronic use of diuretics, repeated vomiting, lack of thiamine in parenteral nutrition formulas, food insecurity, and reliance on monotonous or restrictive diets. Treatment with intravenous thiamine resulted in partial or complete recovery from the symptoms (cardiac, neurologic, and metabolic disorders) for most patients. The number and variety of symptomatic thiamine-deficient adults identified in this review demonstrates that thiamine deficiency is not exclusive to LMICs and, in high-income settings, is not exclusive to alcoholic patients. In developed countries, this serious but treatable condition can be expected in patients suffering from various medical conditions or following certain dietary patterns.

Interventions to increase adherence to micronutrient supplementation during pregnancy: a systematic review.

Prenatal micronutrient supplements are cost-effective in reducing nutritional deficiencies and adverse pregnancy and birth outcomes. However, poor adherence remains a potential barrier to the successful implementation of these supplementation programs. This systematic review assessed the effectiveness of interventions designed to increase adherence to prenatal micronutrient supplementation. Following the Cochrane Collaboration Methodology, literature searches were conducted in six electronic databases and gray literature (on July 24, 2020), and abstract screening, data extraction, and risk of bias assessment were conducted independently by two reviewers. We included 22 studies. Interventions that resulted in increased adherence were most of the education-based strategies, consumption monitoring by volunteer health workers or family members, SMS reminders, free provision of supplements, a multicomponent intervention with community mobilization, and a participatory action research intervention. In several studies, increased adherence was accompanied by beneficial effects on pregnancy and birth outcomes. Given the heterogeneity of study designs and methods used to define and measure adherence, a meta-analysis was not appropriate. We identified several potentially effective strategies to improve supplementation adherence, which may need to be adapted to specific contexts when considered for program implementation. However, additional high-quality studies are critically needed to effectively guide policies and programs.

Interventions to increase adherence to micronutrient supplementation during pregnancy: a protocol for a systematic review.

Micronutrient supplementation during pregnancy has been shown to be a cost-effective method to reduce the risk of adverse pregnancy and birth outcomes. However, one of the main barriers to the successful implementation of a micronutrient supplementation program in pregnancy is poor adherence. Our review will assess the effectiveness of interventions designed to increase adherence to micronutrient supplements in pregnancy. Following the Cochrane Collaboration Methodology, we will start by conducting the literature searches on Medline (via PubMed), Embase, Scopus, Web of Science, and Cochrane Library, in addition to sources of gray literature, to retrieve all the available relevant studies. We will include randomized controlled trials and nonrandomized studies with a control group, where participants are pregnant women taking any micronutrient supplements in the context of antenatal care globally. We will include studies with targeted interventions designed to improve adherence to micronutrient supplementation in pregnant women compared with (1) usual care or no intervention or (2) other targeted micronutrient adherence intervention. Abstract selection, data extraction, and risk of bias assessment (according to the type of studies) will be conducted by two independent reviewers. The pooled results will be reported using the standardized mean differences for continuous data, and odds ratio or risk ratio for dichotomous data. We will assess sources of heterogeneity and publication bias. By following this protocol, we will systematically assess and synthesize the existing evidence about interventions designed to increase adherence to micronutrient supplementation in pregnant women. Understanding which strategies are more effective to increase the consumption of micronutrient supplements during this critical stage of life will have significant implications for clinicians and policymakers involved in the delivery of prenatal micronutrient supplementation interventions.

Setting research priorities on multiple micronutrient supplementation in pregnancy.

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost-effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low- and middle-income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy-three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.