Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

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.

Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects.

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.

Salt-Containing Recipes in Popular Magazines with the Highest Circulation in the United States Do Not Specify Iodized Salt in the Ingredient List.

Iodine deficiency is a public health problem in the US, with the iodine status of women of reproductive age decreasing in recent years. This may be attributable to voluntary salt iodization in the US. Magazines, a common source of recipes and nutritional information, may influence salt use and iodine intake. The aim of this study is to assess whether the magazines with the highest circulation in the US include recipes that contain salt and, if so, whether they specify "iodized salt" in the recipes. Recipes in eight of the top ten magazines by circulation in the US were examined. Standardized information was collected on the presence and type of salt in recipes in the last 12 issues reviewed per magazine. About 73% of the 102 issues reviewed contained recipes. A total of 1026 recipes were surveyed for salt; 48% of the recipes listed salt as an ingredient. None of the 493 recipes containing salt specified iodized salt as the type of salt to be used. About half of the recipes in the last 12 issues of popular magazines published in the US included salt in the ingredient list; however, none recommend the use of iodized salt. There is potential for editorial changes among magazines to call for iodized salt in recipes, which may further prevent iodine deficiency in the US.

National Mandatory Grain Fortification Legislation Decreases Anemia Prevalence among Nonpregnant Women of Reproductive Age: Findings from Multiple Demographic and Health Surveys.

BACKGROUND: Two billion people are affected by anemia globally, mostly including women of reproductive age (WRA) and those residing in low- and middle-income countries (LMICs). Large national population-representative studies examining the impact of national grain fortification policies on the prevalence of anemia among WRA are lacking from recent years. OBJECTIVES: We aimed to determine whether mandatory national grain fortification policies reduce the prevalence of anemia among nonpregnant WRA. METHODS: We examined national food fortification policy characteristics from the Global Fortification Data Exchange (GFDx) database and anemia prevalence data from the Demographic and Health Surveys (DHSs). In total, 21 LMICs, with and without national grain fortification policies, completing ≥2 DHSs between 2000 and 2018, met study eligibility. We applied the difference-in-differences approach to compare changes in the prevalence of anemia among WRA in 10 countries with and 11 countries without fortification between each DHS year. Odds ratios (ORs) and average marginal effects, along with 95% confidence intervals (CIs) were calculated, adjusting for individual-, household-, and country-level factors. RESULTS: Our analytic study sample included 96,334 and 874,984 WRA in countries with and without fortification, respectively. Overall, countries with fortification showed 27% decreased odds of anemia (adjusted OR: 0.73; 95% CI: 0.63, 0.85) and a 7.47-percentage-point decrease in the mean anemia prevalence (average marginal effect: -7.47; 95% CI: -11.03, -3.92) from the pre- to the postfortification period, compared with countries without fortification, after controlling for selected individual-, household-, and country-level factors. CONCLUSIONS: Our findings, using nationally representative DHS data and applying a recommended analytic method to measure policy effectiveness, suggest significant reductions in anemia prevalence in WRA in countries with mandatory grain fortification compared with those without. Implementing national mandatory grain fortification in LMICs would effectively reduce anemia resulting from micronutrient deficiencies among WRA.

A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2020: 30-Year anniversary of gaining knowledge about folic acid's prevention potential for neural tube defects.

BACKGROUND: Spina bifida and anencephaly are major neural tube defects largely preventable through maternal periconceptional intake of folic acid. We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) prevented through mandatory folic acid fortification of cereal grains, including wheat flour, maize flour, and rice, at the end of year 2020, a time point marking the 30th anniversary of the publication of landmark British Medical Research Council (MRC) study providing unequivocal knowledge on folic acid's FAP SBA prevention potential. METHODS: The Food Fortification Initiative database was used to identify countries with mandatory fortification policies with folic acid added to cereal grains. We examined the status of FAP SBA prevention assuming mandatory folic acid fortification at 200 mcg/day of folic acid protects against FAP SBA and reduces their prevalence to a minimum achievable rate of 0.5 cases/1000 live births. RESULTS: Our analysis showed that 61,680 FAP SBA cases were prevented in the year 2020 through mandatory folic acid fortification of cereal grains in 58 countries, translating to 22% prevention of total possible FAP SBA prevention globally. Many countries in Africa, Asia, and Europe are yet to implement fortification. In 2020, 30 years after the MRC study was published, 218,270 preventable FAP SBA cases still occurred globally. CONCLUSION: Global prevention efforts for FAP SBA are inadequate even after three decades of knowledge on their prevention. Universal mandatory fortification of staples should be urgently implemented to prevent thousands of FAP SBA and associated elective terminations, stillbirths, and child mortality.

Comparison of Salt Iodization Requirements in National Standards with Global Guidelines.

Background: Food fortification is the addition of 1 or more micronutrients to commonly consumed foods and is utilized by many countries as a public health intervention to prevent and control micronutrient deficiencies. As iodine deficiency was a major public health issue globally, the WHO developed evidence-based guidelines for the fortification of salt with iodine. The implementation of salt iodization has been highly successful in reducing iodine deficiency disorders worldwide and is recommended as the main strategy to prevent iodine deficiency. Objectives: This analysis compared salt iodization requirements specified in countries' salt standards with WHO 2014 Guidelines on salt fortification. Methods: For countries with mandatory salt iodization legislation, data from the Global Fortification Data Exchange regarding iodine amounts and iodine compounds, to be added to salt per the country standard and corresponding national salt intake quantities, were compared with 2014 WHO Guidelines. Results: As of 4 September 2021, 110 countries with mandatory salt iodization legislation had national salt standards that specified iodine amounts and compounds and salt intake data. All but 1 specified at least 1 recommended iodine compound, but the majority specified higher iodine amounts in salt standards than indicated in the guidelines, taking salt consumption levels into account. Our analysis did not find excess iodine intake as a result; however, we did not have data on the extent of compliance with national salt standards. Conclusions: Existing iodization requirements in salt standards appear to be appropriate for most countries. Countries in which iodine amounts in salt standards are significantly higher than those recommended in the 2014 Guidelines, in particular those with low compliance with national standards or excess iodine intake, may wish to review program process and output indicators and assess whether current iodine amounts in standards would result in excessive intake if implementation was improved.

Systematic Process Framework for Conducting Implementation Science Research in Food Fortification Programs.

Food fortification has proven to be an effective approach for preventing micronutrient deficiencies in many settings. Factors that lead to successful fortification programs are well established. However, due to the multisectoral nature of fortification and the added complexities present in many settings, the barriers to success are not always evident and the strategies to address them are not always obvious. We developed a systematic process for identifying and addressing gaps in the implementation of a food fortification program. The framework is composed of 4 phases: (1) connect program theory of change to program implementation; (2) develop an implementation research agenda; (3) conduct implementation research; and (4) analyze findings and develop/disseminate recommendations for next steps. We detail steps in each phase to help guide teams through the process. To our knowledge, this is the first attempt to outline a systematic process for applying implementation science research to food fortification. The development of this framework is intended to promote implementation research in the field of food fortification, thus improving access to and effectiveness of this key public health intervention.

Food Fortification With Folic Acid for Prevention of Spina Bifida and Anencephaly: The Need for a Paradigm Shift in Evidence Evaluation for Policy-Making.

Context-specific evidence evaluation is advocated in modern epidemiology to support public health policy decisions, avoiding excessive reliance on experimental study designs. Here we present the rationale for a paradigm shift in evaluation of the evidence derived from independent studies, as well as systematic reviews and meta-analyses of observational studies, applying Hill's criteria (including coherence, plausibility, temporality, consistency, magnitude of effect, and dose-response) to evaluate food fortification as an effective public health intervention against folic acid-preventable (FAP) spina bifida and anencephaly (SBA). A critical appraisal of evidence published between 1983 and 2020 supports the conclusion that food fortification with folic acid prevents FAP SBA. Policy-makers should be confident that with mandatory legislation, effective implementation, and periodic evaluation, food fortification assures that women of reproductive age will safely receive daily folic acid to significantly reduce the risk of FAP SBA. Current evidence should suffice to generate the political will to implement programs that will save thousands of lives each year in over 100 countries.

The Potential Contribution of Fortified Maize Flour, Oil, Rice, Salt, and Wheat Flour to Estimated Average Requirements and Tolerable Upper Intake Levels for 15 Nutrients in 153 Countries.

Food fortification is designed to improve the nutritional profile of diets. The purpose of this research was to estimate the potential nutrient contribution of fortified maize flour, oil, rice, salt, and wheat flour in 153 countries, using the national intake (or availability) of the food and the nutrient levels required for fortification. This was done under two scenarios-maximum, where 100% of the food is assumed to be industrially processed and fortified, and realistic, where the maximum value is adjusted based on the percent of the food that is industrially processed and fortified. Under the maximum scenario, the median Estimated Average Requirements (EARs) met ranged from 22-75% for 14 nutrients (vitamins A, B1, B2, B3, B6, B12, D, E, folic acid and calcium, fluoride, iron, selenium and zinc), and 338% for iodine. In the realistic scenario, the median EARs met were 181% for iodine and <35% for the other nutrients. In both scenarios, the median Tolerable Upper Intake Levels (ULs) met were <55% for all nutrients. Under the realistic scenario, no country exceeded 100% of the UL for any nutrient. Current fortification practices of the five foods of interest have the global potential to contribute up to 15 nutrients to the diets of people, with minimal risk of exceeding ULs.

A 2019 global update on folic acid-preventable spina bifida and anencephaly.

BACKGROUND: Mandatory folic acid fortification of staples is a proven intervention to prevent spina bifida and anencephaly, two life-threatening and disabling neural tube defects. We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) prevented through mandatory folic acid fortification of wheat and/or maize flour in 2019. METHODS: Using data from the Global Fortification Data Exchange, we identified countries with mandatory fortification policies that required at least 1.0 ppm folic acid be added to wheat and/or maize flour and had information on percentage of industrially milled flour that is fortified. We built FAP SBA prevention models assuming mandatory folic acid fortification at 200 µg/day of folic acid fully protects against FAP SBA and would lower the prevalence neural tube defects to 0.5 per 1,000 live births. RESULTS: In 2019, 56 countries met our criteria for mandatory folic acid fortification of wheat (n = 56 countries) and/or maize (n = 15 countries) flour and with complete data for our modeling. Overall, our prevention model estimated that 65,380 FAP SBA cases were prevented in 2019 through folic acid fortification of wheat and/or maize flour. We estimated the current global prevention proportion of all preventable FAP SBA cases worldwide to be at 23% of total possible prevention. CONCLUSION: Global prevention efforts for FAP SBA are slow and have stalled. Mandatory fortification should be urgently implemented in all countries to prevent epidemics of FAP SBA, and to achieve health-related Sustainable Development Goals for year 2030 by reducing child mortality due to preventable FAP SBA.

Fortified Foods Are Major Contributors to Apparent Intakes of Vitamin A and Iodine, but Not Iron, in Diets of Women of Reproductive Age in 4 African Countries.

BACKGROUND: Food fortification is implemented to increase intakes of specific nutrients in the diet, but contributions of fortified foods to nutrient intakes are rarely quantified. OBJECTIVES: We quantified iron, vitamin A, and iodine intakes from fortified staple foods and condiments among women of reproductive age (WRA). METHODS: In subnational (Nigeria, South Africa) and national (Tanzania, Uganda) cross-sectional, clustered household surveys, we assessed fortifiable food consumption. We estimated daily nutrient intakes from fortified foods among WRA by multiplying the daily apparent fortifiable food consumption (by adult male equivalent method) by a fortification content for the food. Two fortification contents were used: measured, based on the median amount quantified from individual food samples collected from households; and potential, based on the targeted amount in national fortification standards. Results for both approaches are reported as percentages of the estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: Fortified foods made modest contributions to measured iron intakes (0%-13% RNI); potential intakes if standards are met were generally higher (0%-65% RNI). Fortified foods contributed substantially to measured vitamin A and iodine intakes (20%-125% and 88%-253% EAR, respectively); potential intakes were higher (53%-655% and 115%-377% EAR, respectively) and would exceed the tolerable upper intake level among 18%-56% of WRA for vitamin A in Nigeria and 1%-8% of WRA for iodine in Nigeria, Tanzania, and Uganda. CONCLUSIONS: Fortified foods are major contributors to apparent intakes of vitamin A and iodine, but not iron, among WRA. Contributions to vitamin A and iodine are observed despite fortification standards not consistently being met and, if constraints to meeting standards are addressed, there is risk of excessive intakes in some countries. For all programs assessed, nutrient intakes from all dietary sources and fortification standards should be reviewed to inform adjustments where needed to avoid risk of low or excessive intakes.

The Fallacy of Using Administrative Data in Assessing the Effectiveness of Food Fortification. Comment on: "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset. Nutrients 2020, 12, 247".

Our objective in this comment is to highlight several limitations in an ecological research study that was published in Nutrients by Murphy and Westmark (2020) in January 2020. The study used data from the Food Fortification Initiative (FFI) website, and applying an ecological study design, made an error of "ecologic fallacy" in concluding that "national fortification with folic acid is not associated with a significant decrease in the prevalence of neural tube defects (NTDs) at the population level". We list study limitations that led to their erroneous conclusions, stemming from incorrect considerations regarding NTD prevalence, the average grain availability for a country, the fortification coverage in a country, the population reach of fortified foods within a country, and the absence of the consideration of fortification type (voluntary vs. mandatory), country-specific policies on elective terminations for NTD-affected pregnancies, stillbirth proportions among those with NTDs, and fortification implementation. FFI data are derived from many sources and intended for fortification advocacy, not for hypothesis testing. The flawed study by Murphy & Westmark (2020) in Nutrients promotes a confusing and incorrect message to stakeholders, misguides policy makers, and hinders progress in global NTD prevention through a cost-effective, safe, and effective intervention: the mandatory large-scale folic acid fortification of staple foods.

Consumption of Fortified Wheat Flour and Associations with Anemia and Low Serum Ferritin in Colombia / Consumo de harina de trigo fortificada en Colombia y su asociación con anemia y ferritina sérica baja

Background: Colombia's mandatory wheat flour fortification program has yet to be evaluated. Objective: Examine associations between consumption of fortified wheat flour and low serum fer¬ritin (LSF) and anemia prevalence. Materials and Methods: A secondary analysis of the 2005 national nutrition survey (ENSIN) was completed for 3988 children 2-4 y, 5669 children 5-12 y and 2053 nonpregnant women 13-49 y. The relationship between consumption (quartiles) of wheat flour containing food (WFCF) and LSF and anemia was examined using chi-square analyses and logistic regression models. Results: In adjusted models, controlling for socio-economic status, intake of animal-origin foods, and supplement use in the last 24 hours, a correlation was found between WFCF and anemia in the preschool aged group, when comparing the quartile of highest WFCF consumption with the lowest quartile (OR: 0.7, 95 % CI: 0.6-0.9). The prevalence of LSF was similar across all quartiles of WFCF consumption in all age groups. The highest prevalence of anemia was observed in the lowest WFCF consumption quartiles in all age groups, but was not significantly different in non-pregnant women 13-49 y. No association between WFCF and LSF was observed in adjusted or unadjusted models. Conclusions: In Colombia, consumption of wheat flour containing foods is associated with lower levels of anemia in pre-school aged children.

Antecedentes: la fortificación obligatoria de harina de trigo en Colombia no se ha evaluado. Objetivo: examinar las asociaciones entre el consumo de harina y ferritina sérica baja (BSF) y la prevalencia de anemia. Materiales y métodos: se completó un análisis secundario de la Encuesta Nacional de la Situación Nutricional de 2005 (ENSIN) para 3988 niños de 2-4 años, 5669 escolares de 5-12 años y 2053 mujeres no embarazadas de 13-49 años. Se examinó la relación entre el consumo (cuartiles) de alimentos que contenían harina (ACHT) y la BSF y la anemia mediante análisis de ji al cuadrado y modelos de regresión logística. Resultados: en modelos ajustados, controlando por el estado socioeconómico, alimentos de origen animal y la ingesta de suplementos en las 24 horas anteriores, existía relación entre ACHT y la anemia en los preescolares, al comparar el cuartil más alto del consumo de ACHT con el cuartil más bajo (OR: 0,7; IC 95 %: 0,6-0,9). No se observó asociación entre ACHT y BFS en modelos ajustados. Conclusiones: en Colombia, el consumo de alimentos que contienen harina de trigo se asocia con niveles más bajos de anemia en preescolares.

Fortification of wheat and maize flour with folic acid for population health outcomes.

BACKGROUND: Folate is a B-vitamin required for DNA synthesis, methylation, and cellular division. Wheat and maize (corn) flour are staple crops consumed widely throughout the world and have been fortified with folic acid in over 80 countries to prevent neural tube defects. Folic acid fortification may be an effective strategy to improve folate status and other health outcomes in the overall population. OBJECTIVES: To evaluate the health benefits and safety of folic acid fortification of wheat and maize flour (i.e. alone or in combination with other micronutrients) on folate status and health outcomes in the overall population, compared to wheat or maize flour without folic acid (or no intervention). SEARCH METHODS: We searched the following databases in March and May 2018: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE In Process, Embase, CINAHL, Web of Science (SSCI, SCI), BIOSIS, Popline, Bibliomap, TRoPHI, ASSIA, IBECS, SCIELO, Global Index Medicus-AFRO and EMRO, LILACS, PAHO, WHOLIS, WPRO, IMSEAR, IndMED, and Native Health Research Database. We searched the International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing or planned studies in June 2018, and contacted authors for further information. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with randomisation at the individual or cluster level. We also included non-RCTs and prospective observational studies with a control group; these studies were not included in meta-analyses, although their characteristics and findings were described. Interventions included wheat or maize flour fortified with folic acid (i.e. alone or in combination with other micronutrients), compared to unfortified flour (or no intervention). Participants were individuals over two years of age (including pregnant and lactating women), from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed risk of bias. MAIN RESULTS: We included 10 studies: four provided data for quantitative analyses (437 participants); five studies were randomised trials (1182 participants); three studies were non-RCTs (1181 participants, 8037 live births); two studies were interrupted time series (ITS) studies (1 study population of 2,242,438, 1 study unreported). Six studies were conducted in upper-middle-income countries (China, Mexico, South Africa), one study was conducted in a lower-middle-income country (Bangladesh), and three studies were conducted in a high-income country (Canada). Seven studies examined wheat flour fortified with folic acid alone or with other micronutrients. Three studies included maize flour fortified with folic acid alone or with other micronutrients. The duration of interventions ranged from two weeks to 36 months, and the ITS studies included postfortification periods of up to seven years. Most studies had unclear risk of bias for randomisation, blinding, and reporting, and low/unclear risk of bias for attrition and contamination.Neural tube defects: none of the included RCTs reported neural tube defects as an outcome. In one non-RCT, wheat flour fortified with folic acid and other micronutrients was associated with significantly lower occurrence of total neural tube defects, spina bifida, and encephalocoele, but not anencephaly, compared to unfortified flour (total neural tube defects risk ratio (RR) 0.32, 95% confidence interval (CI) 0.21 to 0.48; 1 study, 8037 births; low-certainty evidence).Folate status: pregnant women who received folic acid-fortified maize porridge had significantly higher erythrocyte folate concentrations (mean difference (MD) 238.90 nmol/L, 95% CI 149.40 to 328.40); 1 study, 38 participants; very low-certainty evidence) and higher plasma folate (MD 14.98 nmol/L, 95% CI 9.63 to 20.33; 1 study, 38 participants; very low-certainty evidence), compared to no intervention. Women of reproductive age consuming maize flour fortified with folic acid and other micronutrients did not have higher erythrocyte folate (MD -61.80 nmol/L, 95% CI -152.98 to 29.38; 1 study, 35 participants; very low-certainty evidence) or plasma folate (MD 0.00 nmol/L, 95% CI -0.00 to 0.00; 1 study, 35 participants; very low-certainty evidence) concentrations, compared to women consuming unfortified maize flour. Adults consuming folic acid-fortified wheat flour bread rolls had higher erythrocyte folate (MD 0.66 nmol/L, 95% CI 0.13 to 1.19; 1 study, 30 participants; very low-certainty evidence) and plasma folate (MD 27.00 nmol/L, 95% CI 15.63 to 38.37; 1 study, 30 participants; very low-certainty evidence), versus unfortified flour. In two non-RCTs, serum folate concentrations were significantly higher among women who consumed flour fortified with folic acid and other micronutrients compared to women who consumed unfortified flour (MD 2.92 nmol/L, 95% CI 1.99 to 3.85; 2 studies, 657 participants; very low-certainty evidence).Haemoglobin or anaemia: in a cluster-randomised trial among children, there were no significant effects of fortified wheat flour flatbread on haemoglobin concentrations (MD 0.00 nmol/L, 95% CI -2.08 to 2.08; 1 study, 334 participants; low-certainty evidence) or anaemia (RR 1.07, 95% CI 0.74 to 1.55; 1 study, 334 participants; low-certainty evidence), compared to unfortified wheat flour flatbread. AUTHORS' CONCLUSIONS: Fortification of wheat flour with folic acid may reduce the risk of neural tube defects; however, this outcome was only reported in one non-RCT. Fortification of wheat or maize flour with folic acid (i.e. alone or with other micronutrients) may increase erythrocyte and serum/plasma folate concentrations. Evidence is limited for the effects of folic acid-fortified wheat or maize flour on haemoglobin levels or anaemia. The effects of folic acid fortification of wheat or maize flour on other primary outcomes assessed in this review is not known. No studies reported on the occurrence of adverse effects. Limitations of this review were the small number of studies and participants, limitations in study design, and low-certainty of evidence due to how included studies were designed and reported.

Potential Dietary Contributions From Rice and Wheat Flour Fortification in the Solomon Islands: Results From the 2012-2013 Household Income and Expenditure Survey.

BACKGROUND: Solomon Islands (SI) mandated wheat flour fortification in 2010. Rice is a key staple food in SI, and its fortification may provide an opportunity to deliver additional micronutrients to the population. OBJECTIVE: To determine whether fortified rice (proposed) and fortified wheat flour potentially benefit women of reproductive age (WRA). METHODS: We analyzed data from the 2012-2013 Household Income and Expenditure Survey to quantify food purchases, which served as a proxy for food consumption. We accounted for varied household composition by using adult male equivalent (AME) adjustments. RESULTS: Among 4478 households, 95.6% purchased rice and 86.6% purchased at least 1 food containing fortified wheat flour in the previous 14 days. Median apparent intake of rice among WRA was 205 g/d/AME. If fortified according to proposed standards, this apparent intake could result in the consumption of 12.3 mg iron/d, fulfilling 44% of the estimated average requirement (EAR), and 226 µg folic acid/d, satisfying 57% of World Health Organization's recommended intake of 400 µg/d. Overall, apparent rice consumption could fulfill 113%, 114%, and 131% of the EAR for WRA for zinc, thiamin, and niacin, respectively. Fortified wheat flour was consumed in much lower quantities, with an estimated apparent median intake of 22 g/d/AME among WRA and 78 g/d/AME among women in urban populations. CONCLUSIONS: The potential benefit of fortified wheat flour in SI is likely limited to urban populations. Apparent consumption of fortified rice in SI could contribute considerably to daily intake of iron, B vitamins including folic acid, and zinc among WRA.

Consumption of Fortified Wheat Flour and Associations with Anemia and Low Serum Ferritin in Colombia.

BACKGROUND: Colombia's mandatory wheat flour fortification program has yet to be evaluated. OBJECTIVE: Examine associations between consumption of fortified wheat flour and low serum ferritin (LSF) and anemia prevalence. MATERIALS AND METHODS: A secondary analysis of the 2005 national nutrition survey (ENSIN) was completed for 3988 children 2-4 y, 5669 children 5-12 y and 2053 non-pregnant women 13-49 y. The relationship between consumption (quartiles) of wheat flour containing food (WFCF) and LSF and anemia was examined using chi-square analyses and logistic regression models. RESULTS: In unadjusted analyses, the prevalence of LSF was similar across all quartiles of WFCF consumption in all age groups. The highest prevalence of anemia was observed in the lowest WFCF consumption quartiles in all age groups, but was not significantly different in non-pregnant women 13-49 y. In adjusted models this relationship between WFCF and anemia remained for children 2-4 y when comparing the highest WFCF intake quartile with the lowest quartile (OR: 0.7, 95 % Cl: 0.6-0.9). No association between WFCF and LSF was observed in adjusted (or unadjusted) models. CONCLUSIONS: In Colombia, consumption of wheat flour containing foods is associated with lower levels of anemia in pre-school children.

ANTECEDENTES: la fortificación obligatoria de harina de trigo en Colombia no se ha evaluado. OBJETIVO: examinar las asociaciones entre el consumo de harina y ferritina sérica baja (BSF) y la prevalencia de anemia. MATERIALES Y MÉTODOS: se completó un análisis secundario de la Encuesta Nacional de la Situacion Nutricional de 2005 (ENSIN) para 3988 niños de 2­4 años, 5669 escolares de 5­12 años y 2053 mujeres no embarazadas de 13­49 años, Se examino la relacion entre el consumo (cuartiles) de alimentos que contenían harina (ACHT) y la BSF y la anemia mediante análisis de ji al cuadrado y modelos ae regresión logística. RESULTADOS: en modelos ajustados, controlando por el estado socioeconomico, alimentos de origen animal y la ingesta de suplementos en las 24 horas anteriores, existía relacion entre ACHT y la anemia en los preescolares. al comparar el cuartil más alto del consumo de ACHT con el cuartil más bajo (OR: 0.7: IC 95 %: 0,6­0,9). No se observó asociación entre ACHT y BFS en modelos ajustados. CONCLUSIONES: en Colombia, el consumo de alimentos que contienen harina de trigo se asocia con niveles más bajos de anemia en preescolares.

Review of Grain Fortification Legislation, Standards, and Monitoring Documents.

OBJECTIVE: Analyze the content of documents used to guide mandatory fortification programs for cereal grains. METHODS: Legislation, standards, and monitoring documents, which are used to mandate, provide specifications for, and confirm fortification, respectively, were collected from countries with mandatory wheat flour (n=80), maize flour (n=11), and/or rice (n=6) fortification as of January 31, 2015, yielding 97 possible country-grain combinations (e.g., Philippines-wheat flour, Philippines-rice) for the analysis. After excluding countries with limited or no documentation, 72 reviews were completed, representing 84 country-grain combinations. Based on best practices, a criteria checklist was created with 44 items that should be included in fortification documents. Two reviewers independently scored each available document set for a given country and food vehicle (a country-grain combination) using the checklist, and then reached consensus on the scoring. We calculated the percentage of country-grain combinations containing each checklist item and examined differences in scores by grain, region, and income level. RESULTS: Of the 72 country-grain combinations, the majority of documentation came from countries in the Americas (46%) and Africa (32%), and most were from upper and lower middle-income countries (73%). The majority of country-grain combinations had documentation stating the food vehicle(s) to be fortified (97%) and the micronutrients (e.g., iron) (100%), fortificants (e.g., ferrous fumarate) (88%), and fortification levels required (96%). Most (78%) stated that labeling is required to indicate a product is fortified. Many country-grain combinations described systems for external (64%) monitoring, and stated that industry is required to follow quality assurance/quality control (64%), though detailed protocols (33%) and roles and responsibilities (45%) were frequently not described. CONCLUSIONS: Most country-grain combinations have systems in place for internal, external, and import monitoring. However, documentation of other important items that would influence product compliance to national standard, such as roles and responsibilities between agencies, the cost of regulating fortification, and enforcement strategies, are often lacking. Countries with existing mandatory fortification can improve upon these items in revisions to their documentation while countries that are beginning fortification can use the checklist to assist in developing new policies and programs.

Instant noodles made with fortified wheat flour to improve micronutrient intake in Asia: a review of simulation, nutrient retention and sensory studies.

BACKGROUND AND OBJECTIVES: Consumption of foods made with wheat flour, particularly instant noodles, is increasing in Asia. Given this trend, fortifying wheat flour with vitamins and minerals may improve micronutrient intake in the region. The objective of this review was to understand what is known about fortifying wheat flour used to make instant noodles. METHODS AND STUDY DESIGN: A literature review of seven databases was performed using the search terms "noodle" and ("Asian" or "instant"). Grey literature was requested through a food fortification listserv. Articles were title screened first for relevance and duplicity, with exclusion criteria applied during the second round of abstract-level screening. This review considered studies examining simulation, retention, sensory, bioavailability, efficacy, and effectiveness of instant noodles made with fortified wheat flour. RESULTS: Fourteen relevant documents were reviewed for simulation (n=1), retention (n=11), and sensory studies (n=3). The documents revealed that instant noodles produced from fortified wheat flour have potential to improve nutrient intakes, have high retention of most nutrients, and provoke no or minimal changes in sensory characteristics. CONCLUSIONS: The available literature indicates that using fortified wheat flour for instant noodle production results in retention of the added nutrients, except thiamin, with no significant sensory change to the final product. Given the rising consumption of instant noodles, production of this item with fortified wheat flour has potential to improve nutrient intakes in Asia. This review provides a resource for the design of a wheat flour fortification program in countries where a large proportion of wheat flour is consumed as instant noodles.

A 2015 global update on folic acid-preventable spina bifida and anencephaly.

BACKGROUND: Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward the total prevention of folic acid-preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015. METHODS: Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 µg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births. RESULTS: Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid. CONCLUSION: Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520-529, 2016. © 2016 Wiley Periodicals, Inc.