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The field of nutrition has been investing in the development of many nutrition-specific and -sensitive policies and programs aimed at improving population-level malnutrition in all its forms. When there is a need to learn about a new system, programmatic context, or target population to understand how to effectively deploy an intervention to help improve nutrition, it is important to be able to ask a broad range of questions, both in topic and in scope. Our aim is to provide a simple and conceptually clear definition and principles to elaborate the science of implementation for nutrition to distinguish it from other ways of knowing and learning and to serve as a guide to the articulation of implementation science questions and methods. Implementation science is a body of systematized knowledge about how to improve implementation that 1) is distinguished by its aims to learn about the process of implementation, 2) uses methods that derive from and fit with the aims, and 3) is built with tacit (as well as expert) knowledge and experiential learning. Implementation science aims to generate the learning needed to improve implementation through facilitating collaboration among stakeholders to articulate and pursue the aims; capturing and using tacit knowledge and experiential learning from stakeholders, systems, providers, and recipients; and applying a mix of methods suited to the aims. This elaboration of the science provides a simple way to help those who already do, or want to do, implementation science understand and communicate how this science is unique and the value that it adds to the current landscape of nutrition priorities, innovations, and the attendant complex learning needs that follow. Implementation science encompasses both discovery- and mission-oriented research, and centers implementation as the object of study for the purposes of broad-based learning., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations. Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L): 1 ) the exclusion of individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2 ) the application of arithmetic correction factors, and 3 ) the use of regression approaches. Results: The prevalence of elevated sTfR concentrations incrementally decreased as CRP and AGP deciles decreased for PSC and WRA, but the effect was more pronounced for AGP than for CRP. Depending on the approach used to adjust for inflammation, the estimated prevalence of iron-deficient erythropoiesis decreased by 4.4-14.6 and 0.3-9.5 percentage points in PSC and WRA, respectively, compared with unadjusted values. The correction-factor approach yielded a more modest reduction in the estimated prevalence of iron-deficient erythropoiesis than did the regression approach. Mostly, adjustment for malaria in addition to AGP did not significantly change the estimated prevalence of iron-deficient erythropoiesis. Conclusions: sTfR may be useful to assess iron-deficient erythropoiesis, but inflammation influences its interpretation, and adjustment of sTfR for inflammation and malaria should be considered. More research is warranted to evaluate the proposed approaches in different settings, but this study contributes to the evidence on how and when to adjust sTfR for inflammation and malaria.

Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation. Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from 15 surveys for PSC ( n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration <12 μg/L in PSC and <15 μg/L in WRA) in inflammation and malaria settings as follows: 1 ) increase ferritin-concentration cutoff to <30 μg/L; 2 ) exclude individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3 ) apply arithmetic correction factors; and 4 ) use a regression correction approach. Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7-25 and 2-8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores. Conclusions: Our results lend support for the use of internal regression correction to estimate the prevalence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear relation of ferritin concentrations with acute-phase proteins. More research is warranted to validate the proposed approaches, but this study contributes to the evidence base to guide decisions about how and when to adjust ferritin for inflammation.

Background: Rigorous evaluations of health system-based interventions in large-scale programs to improve complementary feeding (CF) practices are limited. Alive & Thrive applied principles of social franchising within the government health system in Vietnam to improve the quality of interpersonal counseling (IPC) for infant and young child feeding combined with a national mass media (MM) campaign and community mobilization (CM). Objective: We evaluated the impact of enhanced IPC + MM + CM (intensive) compared with standard IPC + less-intensive MM and CM (nonintensive) on CF practices and anthropometric indicators. Methods: A cluster-randomized, nonblinded evaluation design with cross-sectional surveys ( n = ∼500 children aged 6-23.9 mo and ∼1000 children aged 24-59.9 mo/group) implemented at baseline (2010) and endline (2014) was used. Difference-in-difference estimates (DDEs) of impact were calculated for intent-to-treat (ITT) analyses and modified per-protocol analyses (MPAs; mothers who attended the social franchising at least once: 62%). Results: Groups were similar at baseline. In ITT analyses, there were no significant differences between groups in changes in CF practices over time. In the MPAs, greater improvements in the intensive than in the nonintensive group were seen for minimum dietary diversity [DDE: 6.4 percentage points (pps); P < 0.05] and minimum acceptable diet (8.0 pps; P < 0.05). Significant stunting declines occurred in both intensive (7.1 pps) and nonintensive (5.4 pps) groups among children aged 24-59.9 mo, with no differential decline. Conclusions: When combined with MM and CM, an at-scale social franchising approach to improve IPC, delivered through the existing health care system, significantly improved CF practices, but not child growth, among mothers who used counseling services at least once. A greater impact may be achieved with strategies designed to increase service utilization. This trial was registered at clinicaltrials.gov as NCT01676623.

Background: Child linear growth sometimes improves in both intervention and comparison groups in evaluations of nutrition interventions, possibly because of spillover intervention effects to nonintervention areas or improvements in underlying determinants of nutritional change in both areas. Objective: We aimed to understand what changes in underlying socioeconomic characteristics and behavioral factors are important in explaining improvements in child linear growth. Methods: Baseline (2010) and endline (2014) surveys from the Alive & Thrive impact evaluation were used to identify the underlying determinants of height-for-age z scores (HAZs) among children aged 24-48 mo in Bangladesh ( n = 4311) and 24-59 mo in Vietnam ( n = 4002). Oaxaca-Blinder regression decompositions were used to examine which underlying determinants contributed to HAZ changes over time. Results: HAZs improved significantly between 2010 and 2014 in Bangladesh (∼0.18 SDs) and Vietnam (0.25 SDs). Underlying determinants improved substantially over time and were larger in Vietnam than in Bangladesh. Multiple regression models revealed significant associations between changes in HAZs and socioeconomic status (SES), food security, maternal education, hygiene, and birth weight in both countries. Changes in HAZs were significantly associated with maternal nutrition knowledge and child dietary diversity in Bangladesh, and with prenatal visits in Vietnam. Improvements in maternal nutrition knowledge in Bangladesh accounted for 20% of the total HAZ change, followed by maternal education (13%), SES (12%), hygiene (10%), and food security (9%). HAZ improvements in Vietnam were accounted for by changes in SES (26%), prenatal visits (25%), hygiene (19%), child birth weight (10%), and maternal education (7%). The decomposition models in both countries performed well, explaining >75% of the HAZ changes. Conclusions: Decomposition is a useful and simple technique for analyzing nonintervention drivers of nutritional change in intervention and comparison areas. Improvements in underlying determinants explained rapid improvements in HAZs between 2010 and 2014 in Bangladesh and Vietnam.

Background: Promoting adequate nutrition through interventions to improve infant and young child feeding (IYCF) has the potential to contribute to child development., Objective: We examined whether an intensive intervention package that was aimed at improving IYCF at scale through the Alive & Thrive initiative in Bangladesh also advanced language and gross motor development, and whether advancements in language and gross motor development were explained through improved complementary feeding., Methods: A cluster-randomized design compared 2 intervention packages: intensive interpersonal counseling on IYCF, mass media campaign, and community mobilization (intensive) compared with usual nutrition counseling and mass media campaign (nonintensive). Twenty subdistricts were randomly assigned to receive either the intensive or the nonintensive intervention. Household surveys were conducted at baseline (2010) and at endline (2014) in the same communities (n = ∼4000 children aged 0-47.9 mo for each round). Child development was measured by asking mothers if their child had reached each of multiple milestones, with some observed. Linear regression accounting for clustering was used to derive difference-in-differences (DID) impact estimates, and path analysis was used to examine developmental advancement through indicators of improved IYCF and other factors., Results: The DID in language development between intensive and nonintensive groups was 1.05 milestones (P = 0.001) among children aged 6-23.9 mo and 0.76 milestones (P = 0.038) among children aged 24-47.9 mo. For gross motor development, the DID was 0.85 milestones (P = 0.035) among children aged 6-23.9 mo. The differences observed corresponded to age- and sex-adjusted effect sizes of 0.35 for language and 0.23 for gross motor development. Developmental advancement at 6-23.9 mo was partially explained through improved minimum dietary diversity and the consumption of iron-rich food., Conclusions: Intensive IYCF intervention differentially advanced language and gross motor development, which was partially explained through improved complementary feeding. Measuring a diverse set of child outcomes, including functional outcomes such as child development, is important when evaluating integrated nutrition programs. This trial was registered at clinicaltrials.gov as NCT01678716., (© 2017 American Society for Nutrition.)

Background: Complementary feeding (CF) contributes to child growth and development, but few CF programs are delivered at scale. Alive & Thrive addressed this in Bangladesh through intensified interpersonal counseling (IPC), mass media (MM), and community mobilization (CM)., Objective: The objective was to evaluate the impact of providing IPC + MM + CM (intensive) compared with standard nutrition counseling + less intensive MM + CM (nonintensive) on CF practices and anthropometric measurements., Methods: We used a cluster-randomized, nonblinded evaluation with cross-sectional surveys [n = ∼600 and 1090 children 6-23.9 mo and 24-47.9 mo/group, respectively, at baseline (2010) and n = ∼500 and 1100 children of the same age, respectively, at endline (2014)]. We derived difference-in-difference impact estimates (DDEs), adjusting for geographic clustering, infant age, sex, differences in baseline characteristics, and differential change in characteristics over time., Results: Groups were similar at baseline. CF improvements were significantly greater in the intensive than in the nonintensive group [DDEs: 16.3, 14.7, 22.0, and 24.6 percentage points (pp) for minimum dietary diversity, minimum meal frequency, minimum acceptable diet, and consumption of iron-rich foods, respectively]. In the intensive group, CF practices were high: 50.4% for minimum acceptable diet, 63.8% for minimum diet diversity, 75.1% for minimum meal frequency, and 78.5% for consumption of iron-rich foods. Timely introduction of foods improved. Significant, nondifferential stunting declines occurred in intensive (6.2 pp) and nonintensive (5.2 pp) groups in children 24-47.9 mo., Conclusions: The intensive program substantially improved CF practices compared with the nonintensive program. Large-scale program delivery was feasible and, with the use of multiple platforms, reached 1.7 million households. Nondifferential impacts on stunting were likely due to rapid positive secular trends in Bangladesh. Accelerating linear growth further could require accompanying interventions. This study establishes proof of concept for large-scale behavior change interventions to improve child feeding. This trial was registered at clinicaltrials.gov as NCT01678716., Competing Interests: 2 Author disclosures: T Sanghvi, J Baker, K Afsana, and R Haque were members of the program implementation team that designed and implemented the interventions studied and reported on in this manuscript. They reviewed the manuscript and provided contextual interpretation of the results, but final decisions for manuscript content lay with the primary authors from the evaluation team. P Menon, PH Nguyen, KK Saha, A Khaled, EA Frongillo, MT Reul, and R Rawat, no conflicts of interest. The Gates foundation and Alive & Thrive participated in the study design choices; neither participated in the data collection, or analysis. Alive & Thrive provided specific written input to the manuscript on intervention design and scale and provided feedback on interpretation of the results. Alive & Thrive and the Gates Foundation gave extensive feedback at all stages of the project, but freedom to publish the study findings was protected contractually in the agreement between the respective funding sources and the International Food Policy Research Institute. All final decisions on the manuscript were made by the researchers.

By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full intended impact., (© 2014 American Society for Nutrition.)

Household food insecurity (HFI) is a recognized underlying determinant of child undernutrition, but evidence of associations between HFI and child undernutrition is mixed. The purpose of this study was to investigate if HFI is associated with undernutrition in children aged 6-59.9 mo in Bangladesh (n = 2356), Ethiopia (n = 3422), and Vietnam (n = 3075) and if child dietary diversity (DD) mediated this effect. We used baseline survey data from the Alive & Thrive project. Logistic regression, adjusting for potential confounding factors, was used to determine the magnitude and significance of the association of HFI with stunting, underweight, and wasting. The mediating effect of child DD was tested by using a Sobel-Goodman mediation test. The prevalences of HFI were 66%, 40%, and 32% in Ethiopia, Vietnam, and Bangladesh, respectively. The prevalences of stunting, underweight, and wasting were higher in Bangladesh (47.1%, 43.7%, and 19.1%, respectively) and Ethiopia (50.7%, 27.5%, and 5.9%, respectively) than in Vietnam (20.7%, 15.8%, and 5%, respectively). In the adjusted models, the odds of being stunted or underweight were significantly higher for children in severely food-insecure households in Bangladesh (stunting OR: 1.36; 95% CI: 1.05, 1.76; underweight OR: 1.28; 95% CI: 0.99, 1.65) and Ethiopia (stunting OR: 1.48; 95% CI: 1.09, 2.00; underweight OR: 1.68; 95% CI: 1.22, 2.30) and in moderately food-insecure households in Vietnam (stunting OR: 1.39; 95% CI: 1.16, 1.65; underweight OR: 1.69; 95% CI: 1.28, 2.23). HFI was significantly associated with wasting in Bangladesh where close to 1 in 5 children demonstrated wasting. Child DD did not mediate the relation between HFI and undernutrition in any of the countries. Further research is recommended to investigate potential mediators in this pathway.

Dietary diversity (DD) reflects micronutrient adequacy of the diet and is associated with better child growth. Emerging evidence suggests that maternal and child DD are associated. This could have measurement and programmatic implications. Data on mother-child (6-24 mo) dyads in Bangladesh, Vietnam, and Ethiopia were used to examine agreement and association between maternal and child DD and identify determinants of maternal and child DD. The DD scores were derived from a 24-h recall of intake of foods from 7 groups. Multivariable regression was used to examine for the association, adjusting for covariates at child, maternal, and household levels. There was mother/child agreement for staple foods across the 3 countries but disagreement for flesh foods, dairy, fruits, and vegetables. A strong positive association was seen between maternal and child DD; a difference of one food group in mother's consumption was associated with a difference of 0.29, 033, and 0.24 groups in child's consumption in Bangladesh, Vietnam, and Ethiopia, respectively. The odds of achieving minimum DD (≥4 groups) were higher among children whose mother consumed 4 groups compared with ≤3 food groups [Bangladesh: OR = 2.73 (95% CI: 1.76, 4.25); Vietnam: OR = 2.30 (95% CI: 1.45, 3.43); Ethiopia: OR = 5.11 (95% CI: 2.36, 11.04)]. Maternal education was associated with both maternal and child DD; food security and socioeconomic status were associated only with maternal DD. Given the disagreements in mother/child intake for nutrient-rich foods, both maternal and child DD should be measured in surveys. Behavior change communications should focus on promoting both mother and child DD and encouraging mothers to feed young children all family foods, not just a subset.

This article reviews the potential of four broad types of platforms, health, agriculture, market-based, and social protection programs, to deliver multiple micronutrient (MMN) interventions (supplementation, fortification, and dietary modification). We assessed the platforms' potential based on seven performance criteria related to programs within these platforms: 1) targeting, 2) efficacy of interventions, 3) quality of implementation, 4) utilization, 5) impact, 6) coverage, and 7) sustainability. We highlight one type of program per platform to illustrate strengths and weaknesses for delivering MMN interventions, identify critical knowledge gaps, and highlight what is needed to increase effectiveness for delivering MMN interventions. We found that all four platforms have the potential to effectively deliver MMN interventions if the following key program elements are addressed: 1) strong behavior change communication strategies to increase demand and proper utilization of services/products; 2) supply side interventions to ensure consistent availability of high quality interventions, products, and well-trained staff; 3) rigorous evaluations of effectiveness, quality of delivery, and impact pathways to generate best practices for replication and scale-up; and 4) timely dissemination of evaluation results to ensure use by program implementers and policy makers. The diversification of delivery platforms, which simultaneously addresses multiple determinants of MMN deficiencies and expands coverage, is needed to accelerate progress in reducing MMN deficiencies.

Background: The World Health Organization and Centers for Disease Control and Prevention recommend the inclusion of indicators of iron status and inflammation in surveys assessing iron deficiency and/or anemia., Objective: We examined the associations between serum alpha(1)-acid glycoprotein (AGP), serum C-reactive protein (CRP), and urinary hepcidin and their relations with serum ferritin (SF), serum transferrin receptor (sTfR), and hemoglobin., Design: At enrollment, the measurements were made in randomly selected 7-12-y-old anemic children with documented Schistosoma haematobium infection (n = 224 for AGP, CRP, SF, sTfR, and hemoglobin; n = 61 for urinary hepcidin)., Results: The correlation between the conventional markers of inflammation, AGP and CRP, was positive (r = 0.40, P < 0.01), and the correlation between the unambiguous markers of iron nutrition, hemoglobin and s-TfR, was negative (r = -0.36, P < 0.01). None of the correlations (r < 0.08) between the above markers was statistically significant. Urinary hepcidin correlated positively with the 2 measured indicators of inflammation (r > or = 0.42, P < 0.01) but not with the 2 indicators of iron nutrition (r < 0.07). SF correlated positively with the 2 measured inflammation markers (r > or = 0.25, P < 0.01) and the 2 iron-nutrition indicators (r > 0.26, P < 0.01). Urinary hepcidin correlated positively with SF (r = 0.39, P < 0.01). Regression analyses suggested that CRP and AGP were significant predictors of SF (P < 0.001); however, CRP (R(2) = 0.38) explained more of SF's variance than did AGP (R(2) = 0.17)., Conclusions: Correlations between AGP, CRP, urinary hepcidin, and SF were statistically significant. CRP values explained SF's variance better than did the other markers of inflammation studied. We therefore recommend the measurement of both AGP and CRP in population surveys that include an assessment of iron deficiency in developing countries.