Iron Status, Anemia, and Iron Interventions and Their Associations with Cognitive and Academic Performance in Adolescents: A Systematic Review.

In adolescents, iron-deficiency anemia is the leading cause of disability-adjusted life years lost. The World Health Organization recommends delivering iron supplementation through school-based platforms, requiring partnerships with the education sector. This anemia-reduction intervention is valued for the perceived benefits of improved learning and school performance. This article aims to systematically review the available evidence on the relationship between iron status and anemia and impacts of iron interventions on cognitive and academic performance in adolescents. Fifty studies were included: n = 26 cross-sectional and n = 24 iron-containing interventions. Our review suggests that iron status and anemia may be associated with academic performance in some contexts and that iron supplementation during adolescence may improve school performance, attention, and concentration. However, nearly all supplementation trials were judged to have moderate or high risk of bias. We did not find evidence suggesting that iron status and anemia influenced or were associated with attention, intelligence, nor memory in adolescents. Further, iron supplementation did not improve memory and recall or intelligence. Overall, more high-quality research is needed to guide programmers and policy makers to understand the relationships between anemia and educational performance and the potential impacts of iron interventions, which effectively reduce anemia, on adolescents' learning and school performance.

The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia.

BACKGROUND: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anemia prevalence is ≥20%; however, it is unknown whether the inclusion of folic acid in weekly IFA supplements reduces anemia. OBJECTIVES: We examined whether the inclusion of folic acid in weekly IFA supplements conferred any benefit on hemoglobin (Hb) concentration, anemia reduction, or iron status [ferritin and soluble transferrin receptor (sTfR)], over iron alone. METHODS: In this secondary analysis of a randomized controlled trial in Malaysia, n = 311 nonpregnant women (18-45 y old) received 60 mg Fe with either 0, 0.4, or 2.8 mg folic acid once-weekly for 16 wk. Fasting blood was collected at baseline and 16 wk. A generalized linear model (normal distribution with identity link) was used to assess Hb concentration at 16 wk (primary outcome). RESULTS: At baseline, 84% of women had low folate status (plasma folate < 14 nmol/L). At 16 wk, marginal mean (95% CI) Hb was 131 (130, 133), 131 (129, 132), and 132 (130, 133) g/L; ferritin was 58.2 (53.9, 62.5), 56.5 (52.2, 60.9), and 58.0 (53.7, 62.3) µg/L; and sTfR was 5.8 (5.5, 6.1), 5.8 (5.5, 6.1), and 5.9 (5.6, 6.2) mg/L in the 0, 0.4, and 2.8 mg/wk groups, respectively, with no differences between groups (P > 0.05). Baseline plasma folate concentration did not modify the effect of treatment on Hb concentration at 16 wk. Among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P = 0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P < 0.001) were lower at 16 wk than at baseline. CONCLUSIONS: Despite the low folate status among these nonpregnant Malaysian women, the inclusion of folic acid in weekly IFA supplements did not reduce anemia or improve iron status, over iron alone. However, the benefits of folic acid for neural tube defect prevention still warrant its retention in weekly IFA supplements.This trial was registered at www.anzctr.org.au as ACTRN12619000818134.

Perspective: Weekly Iron and Folic Acid Supplementation (WIFAS): A Critical Review and Rationale for Inclusion in the Essential Medicines List to Accelerate Anemia and Neural Tube Defects Reduction.

Weekly iron and folic acid supplementation (WIFAS) is among the 8 key effective actions for improving adolescent nutrition included by the WHO in the 2018 guidelines. However, at present WIFAS in the WHO-recommended formulation is not included in the Model Essential Medicines List (MEML), limiting the potential for countries to import, produce, and prioritize this formulation as part of their national supply management and procurement plans for medicines. The WHO WIFAS guideline presents evidence that the formulation reduces anemia, but not that folic acid reduces neural tube defects (NTDs), because sufficient evidence was unavailable at the time of the last review. Recently, a 3-arm, parallel-group, randomized, double-blind, placebo-controlled folic acid efficacy trial on WIFAS was conducted to address this evidence gap. The study population included 331 women (18-45 y old), randomly assigned to 3 treatment groups, including a supplement with 60 mg Fe as ferrous fumarate and either 0 mg, 0.4 mg, or 2.8 mg of folic acid, to be consumed once weekly for 16 wk, followed by a 4-wk washout period. In this article we critically review how the outcomes of this folic acid efficacy trial, and how the evidence generated, could potentially be used to inform WHO WIFAS guidelines for the potential inclusion of this formulation on the MEML, and how this, in turn, may affect product availability. If the new evidence on weekly folic acid is assessed as adequately reducing the risk of NTDs, a guideline revision could be warranted and WIFAS could be presented to the MEML for the dual benefits of anemia reduction and NTD prevention. This inclusion could enable acceleration of implementing policies and programs to contribute to global anemia and NTD reduction efforts.

Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia.

INTRODUCTION: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk. METHODS: We conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks. RESULTS: At 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group. CONCLUSION: Weekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed. TRAIL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

Effect of once weekly folic acid supplementation on erythrocyte folate concentrations in women to determine potential to prevent neural tube defects: a randomised controlled dose-finding trial in Malaysia.

INTRODUCTION: Folic acid (0.4 mg) taken prior to and during early pregnancy reduces the risk of neural tube defects (NTDs). Because these birth defects occur early in pregnancy, before women may know they are pregnant, many countries have mandated the addition of folic acid to food staples. In countries where fortification is not possible, and weekly iron folic acid programmes exist to reduce anaemia, the WHO recommends that 2.8 mg (7×0.4 mg) folic acid be given instead of the current weekly practice of 0.4 mg. Currently, there is a lack of evidence to support if the 2.8 mg folic acid per week dose is sufficient to raise erythrocyte folate concentrations to a level associated with a reduced risk of a NTD-affected pregnancy. We aim to conduct a three-arm randomised controlled trial to determine the effect of weekly folic acid with iron on erythrocyte folate, a biomarker of NTD risk. METHODS AND ANALYSIS: We will recruit non-pregnant women (n=300; 18-45 years) from Selangor, Malaysia. Women will be randomised to receive either 2.8, 0.4 or 0.0 (placebo) mg folic acid with 60 mg iron weekly for 16 weeks, followed by a 4-week washout period. The primary outcome will be erythrocyte folate concentration at 16 weeks and the mean concentration will be compared between randomised treatment groups (intention-to-treat) using a linear regression model adjusting for the baseline measure. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of British Columbia (H18-00768) and Universiti Putra Malaysia (JKEUPM-2018-255). The results of this trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: ACTRN12619000818134 and NMRR-19-119-45736.

Mothers' groups enrich diet and culture through promoting traditional Quichua foods.

Indigenous Peoples in Latin America bear a disproportionate burden of undernutrition, yet traditional foods, including wild leafy greens, can contribute nutritional value to diets. As part of a community nutrition intervention using local foods in highland Tungurahua, Ecuador, mothers' groups promoted the consumption of wild leafy greens through community cooking clubs and recipe competitions at local fairs. The objective was to assess the social, cultural, and nutritional potential of a mothers' club intervention that promoted 2 indigenous greens (stinging nettle/Urtica dioica L. and round-leaved dock/Rumex obtusifolius L.) into children's diets. Key informant interviews and focus groups were conducted with 54 mothers and 16 elders to identify perceptions of the intervention and traditional foods. Social and cultural dimensions were identified through content analysis. The nutritional contribution of the leafy greens was estimated through semiquantitative food frequency questionnaires conducted with 160 participant mothers and 98 mothers living in comparison communities who had not been exposed to the intervention. The use of local foods generated pride for mothers and elders. Nonfood uses of the nettle proved an initial barrier to acceptance; however, peer support within mothers' groups enabled increased consumption. The greens were estimated to contribute an additional 8% vitamin A, 7% iron, 12% vitamin C, and 27% folate to children's recommended dietary intakes. By promoting wild leafy greens, mothers' groups improved food security and the cultural and nutritional value of their diets. Additionally, mothers' cooking clubs increased self-efficacy and cultural identity for Quichua women, offering a highly acceptable nutrition intervention model.

A Community-Based Positive Deviance/Hearth Infant and Young Child Nutrition Intervention in Ecuador Improved Diet and Reduced Underweight.

OBJECTIVE: Underweight and stunting are serious problems in Ecuador that require interventions in the first 2 years of life. The researchers assessed the effectiveness of a Positive Deviance (PD)/Hearth community-based intervention using local foods to improve infant and young children's nutrition. DESIGN: A quasi-experimental nonrandomized study was conducted between March and October, 2009. SETTING: The intervention and study were implemented in the Ecuadorian highlands provinces of Chimborazo and Tungurahua. PARTICIPANTS: Eighty mother-child pairs in 6 intervention communities and 184 mother-child pairs in 9 comparison communities. INTERVENTION: Mothers met in participatory peer-led PD/Hearth cooking and nutrition education sessions for 12 days. MAIN OUTCOME MEASURES: Dietary intake and nutritional status were collected at baseline and 6-month follow-up. ANALYSIS: Multiple linear and logistic regression were used for growth outcomes, and ANCOVA for mean dietary intakes. RESULTS: Mothers in the intervention were 1.3-5.7 times more likely to feed their children the promoted foods (P < .05). Children in the intervention consumed a higher percentage of recommended intakes for iron, zinc, vitamin A, protein, and energy (P < .05) at follow-up and had improvements in weight-for-age z-score (ß = .17; 95% confidence interval, 0.01-0.31). Likelihood of underweight was reduced for children in the intervention (odds ratio = 0.36; 95% confidence interval, 0.13-0.96) CONCLUSIONS AND IMPLICATIONS: The PD/Hearth interventions support mothers to improve infant and young children's nutrition practices and reduce underweight.

Infant and young child feeding practices and stunting in two highland provinces in Ecuador.

The first two years of life are critical for growth and development. Little is known about infant and young child feeding (IYCF) practices in the Ecuadorian highlands and how they contribute to stunting. With the objective of understanding nutritional status and the influencing factors to design an intervention, we assessed the nutritional status of 293 infants and children between 0 and 24 months of age, living in 14 communities in the provinces of Tungurahua and Chimborazo using a cross-sectional study design. We used the WHO IYCF indicators to assess feeding practices; estimated dietary intake with 24-h recalls; and identified nutritious local foods by food frequency questionnaires. Multiple regression modelling was performed to identify correlates of nutritional status. Stunting was found in 56.2% of children. Mean protein, vitamin A and vitamin C intakes were above recommendations for all ages. Only infants 6.0 to 8.9 months of age and non-breastfed children 12-23.9 months of age consumed energy intakes below recommendations. Younger age groups had below recommended intakes for iron and calcium. While mean complementary food densities met recommendations for protein, vitamin A, vitamin C and energy, those for zinc, iron and calcium were lower than recommended. Older age, respiratory infections and being male were predictors of lower HAZ, whereas early initiation of breastfeeding, higher socioeconomic status, consumption of iron-rich foods and higher dietary protein density were protective. Interventions that promote and support optimal breastfeeding practices and enable increased consumption of nutritious local foods have potential to contribute to reducing stunting in this vulnerable population. © 2016 John Wiley & Sons Ltd.

Community-based grain banks using local foods for improved infant and young child feeding in Ethiopia.

The first thousand days of a child's life are critical for ensuring adequate nutrition to enable optimal health, development and growth. Inadequate infant and young child feeding (IYCF) practices likely contribute to Ethiopia's concerning malnutrition situation. Development partners in four regions of Ethiopia implemented community production of complementary food with women's groups processing local grains and legumes at grain banks to improve availability, accessibility, dietary diversity and timely introduction of complementary foods. The objective of this study was to establish the acceptability, perceived impact, feasibility and required inputs to sustain local grain bank interventions to improve IYCF. A subsidized barter system was used by mothers in the rural communities, and flour was sold in the semi-urban context. Purposive sampling guided the qualitative study design and selection of project stakeholders. A total of 51 key informant interviews and 33 focus group discussions (n = 237) were conducted. The grain bank flour was valued for its perceived diverse local ingredients; while the project was perceived as creating labour savings for women. The grain bank flour offered the potential to contribute to improved IYCF; however, further dietary modification or fortification is needed to improve the micronutrient content. Dependence upon external inputs to subsidize the barter model and the reliance on volunteer labour from women's groups in the rural context are the greatest risks to sustainability. This intervention illustrates how integrated agricultural and health interventions leveraging local production can appeal to diverse stakeholders as an acceptable approach to improve IYCF.

Preconceptional Nutrition Interventions for Adolescent Girls and Adult Women: Global Guidelines and Gaps in Evidence and Policy with Emphasis on Micronutrients.

Much of the global nutrition efforts in recent years have been focused on improving the nutritional status of children during the window of the first 1000 d of life, from conception to 2 y of age. However, as the world transitions from the Millennium Development Goals to the Sustainable Development Goals, women's and adolescent girls' overall health and well-being are being placed at the center of the global agenda. It is also increasingly recognized that a woman's nutritional status before pregnancy affects maternal and child outcomes and thus needs to be improved to ensure optimal outcomes. This article reviews the global picture of preconception nutrition in women and girls, including some of the key factors that influence women's outcomes, as well as their children's outcomes, if they do become pregnant. This article describes the current global guidelines on preconceptional nutrition interventions for girls and women; highlights related gaps in evidence, guidelines, and policy; and discusses research to forward the agenda of improving women's and girls' preconceptional nutrition.

Behavioral Change Strategies for Improving Complementary Feeding and Breastfeeding.

Improving infant and young child feeding (IYCF) practices, including breastfeeding and complementary feeding, has been identified as one of the most effective interventions to improve child survival, stunting and wasting. Evidence from randomized controlled trials suggests that effective promotion of breastfeeding and complementary feeding, with or without food provision, has the potential to improve IYCF practices and child nutrition. However, in many countries, breastfeeding practices and complementary feeding practices are still far from optimal. The lack of implementation of available, effective, affordable interventions in scale-up programs is in part attributed to a lack of innovative, creative and effective behavioral change strategies that enable and encourage caregivers. Successful behavioral change strategies should be based on a rigorous situational analysis and formative research, and the findings and insights of formative research should be used to further design interventions that address the identified barriers and enablers, to select delivery channels, and to formulate appropriate and effective messages. In addition, successful behavioral change interventions should a priori define and investigate the program impact pathway to target behavioral change and should assess intermediary behavioral changes and indicators to learn why the expected outcome was achieved or not achieved by testing the program theory. The design of behavioral change communication must be flexible and responsive to shifts in societies and contexts. Performance of adequate IYCF also requires investments to generate community demand through social mobilization, relevant media and existing support systems. Applying these principles has been shown to be effective in improving IYCF practices in Vietnam, Bangladesh and Ethiopia and is recommended to be adopted by other programs and countries in order to accelerate progress in improving child nutrition.

Adjustments for weighing clothed babies at high altitude or in cold climates.

Public health nutritionists rely on anthropometry for nutritional assessment, program planning, and evaluation. Children are usually heavily clothed at high altitudes and in cold climates. Failing to adjust for clothing weight could underestimate malnutrition prevalence. The objective of this paper is to validate an adjustment process for estimating clothing weight and quantify potential misclassification error. In March and September 2009, 293 and 272 children under 2 years of age, respectively, were measured for weight and length in 14 highlands communities in Ecuador. Weight-for-age z-scores (WAZ) and weight-for-height z-scores (WHZ) were compared using clothing-unadjusted weights and two types of clothing-adjusted weights: individual clothing-weights and population-mean clothing-weights. Modelling showed up to 24% of children's nutritional status and degree of malnutrition were misclassified for WAZ, and 13% for WHZ, when clothing was not taken into account in this cold climate. Compared with the more time-intensive individual clothing-weight adjustment, the population-mean clothing-weight adjustments had high specificity and sensitivity for WAZ. In cold climates, adjusting for population mean clothing weight provides a better estimate of the prevalence of malnutrition to inform appropriate program decisions for addressing underweight. An individual clothing weight adjustment may also be essential to classify a specific child's nutritional status when acute malnutrition is a concern.

Infant and young child feeding in the Peruvian Amazon: the need to promote exclusive breastfeeding and nutrient-dense traditional complementary foods.

The study objective was to understand the role of traditional Awajún foods in dietary quality and the potential impacts on growth of Awajún infants and young children 0-23 months of age. Research took place in April and May of 2004, along the Cenepa River in six Awajún communities. Anthropometry estimated nutritional status for 32 infants (0-23 months). Repeat dietary recalls and infant feeding histories were completed with 32 mothers. Adequacy of the complementary foods was compared with World Health Organization guidelines. Anthropometry indicated a high prevalence of stunting (39.4% of infants and young children), with nutritional status declining with age. Half of the Awajún mothers practised exclusive breastfeeding. Dietary recalls and infant food histories suggested that many of the infants were getting adequate nutrition from complementary foods and breastfeeding; however, there was variation in breastfeeding and complementary feeding practices among the mothers. Complementary feeding for young children 12-23 months generally met nutrient recommendations, but mean intakes for iron, zinc, calcium and vitamin A were inadequate in infants 6-11 months. Traditional foods provided 85% of energy and were more nutrient dense than market foods. Appropriate infant and complementary feeding was found among some women; however, given the range of feeding practices and introduction of market foods, health promotion targeting infant and young child feeding is warranted.