BACKGROUND: Hemoglobin and hematocrit are the two most common biomarkers used to identify anemia in clinical settings, but their results do not always agree. OBJECTIVE: To examine agreement between hemoglobin and hematocrit in identifying anemia among children aged 1-<5 years and pregnant persons. METHODS: Pregnant persons and children aged 1-<5 years with hemoglobin and hematocrit results from the same whole blood sample in National Health and Nutrition Examination Survey (NHANES,1999-2020) were included. We used the Centers for Disease Control and Prevention (CDC) anemia cutoff values for children, pregnancy status, trimester, and smoking adjustments. We examined concordance of anemia, sensitivity, and specificity among those with anemia based on at least one test overall and by race/ethnicity, sex, and income level. Cohen's kappa was used to measure concordance. RESULTS: Analytic samples included 7,052 children and 1,437 pregnant persons, of which 1,119 had trimester data. Among children, anemia prevalence was 3.7% (95% CI: 3.1-4.3) based on hemoglobin and 5.5% (95% CI: 4.7-6.3) based on hematocrit. Among pregnant persons, anemia prevalence based on hemoglobin was 7.7% (95% CI: 5.9-9.5) and 12.4% (95% CI: 10.1-14.6) based on hematocrit. Kappa scores overall and by sociodemographic characteristics ranged from 0.64-0.75 (moderate concordance) among children and 0.53-0.78 (weak to moderate concordance) among pregnant persons. Among those with anemia on at least one test, 53.5% of children and 61.5% of pregnant persons had anemia based on both tests. CONCLUSIONS: We found substantial discordance between the two biomarkers; about 50% of children and 40% of pregnant women were identified by only one of the two biomarkers. Because hemoglobin and hematocrit may be used interchangeably in the clinical setting, individuals with anemia may be missed, not receive treatment, and therefore be at higher risk of adverse pregnancy, birth, and developmental outcomes.

INTRODUCTION: Blood source is a known preanalytical factor affecting hemoglobin (Hb) concentrations, and there is evidence that capillary and venous blood may yield disparate Hb levels and anemia prevalence. However, data from adolescents are scarce. OBJECTIVE: To compare Hb and anemia prevalence measured by venous and individual pooled capillary blood among a sample of girls aged 10-19 years from 232 schools in four regions of Ghana in 2022. METHODS: Among girls who had venous blood draws, a random subsample was selected for capillary blood. Hb was measured using HemoCue® Hb-301. We used Lin's concordance correlation coefficient (CCC) to quantify the strength of the bivariate relationship between venous and capillary Hb and a paired t-test for difference in means. We used McNemar's test for discordance in anemia cases by blood source and weighted Kappa to quantify agreement by anemia severity. A multivariate generalized estimating equation was used to quantify adjusted population anemia prevalence and assess the association between blood source and predicted anemia risk. RESULTS: We found strong concordance between Hb measures (CCC = 0.86). The difference between mean venous Hb (12.8 g/dL, ± 1.1) and capillary Hb (12.9 g/dL, ± 1.2) was not significant (p = 0.26). Crude anemia prevalence by venous and capillary blood was 20.6% and 19.5%, respectively. Adjusted population anemia prevalence was 23.5% for venous blood and 22.5% for capillary (p = 0.45). Blood source was not associated with predicted anemia risk (risk ratio: 0.99, 95% CI: 0.96, 1.02). Discordance in anemia cases by blood source was not significant (McNemar p = 0.46). Weighted Kappa demonstrated moderate agreement by severity (ĸ = 0.67). Among those with anemia by either blood source (n = 111), 59% were identified by both sources. CONCLUSION: In Ghanaian adolescent girls, there was no difference in mean Hb, anemia prevalence, or predicted anemia risk by blood source. However, only 59% of girls with anemia by either blood source were identified as having anemia by both sources. These findings suggest that pooled capillary blood may be useful for estimating Hb and anemia at the population level, but that caution is needed when interpreting individual-level data.

BACKGROUND: Diversity is a key component of diet quality and health, but no indicator exists for adolescents under the age of 15 years. OBJECTIVE: To establish a dichotomous indicator for population-level assessment of adolescent dietary diversity as a proxy for micronutrient adequacy. METHODS: We used the probability approach to construct mean probability of adequacy (MPA) of 11 micronutrients from 2 days of 24-hour dietary recall data from NHANES, 2007-2018. For each micronutrient, probability of adequacy was calculated using the best linear unbiased predictor of usual intake. Adolescent dietary diversity score (ADDS) was derived with a maximum score of 10 food groups. Generalized linear mixed models were used to examine associations between ADDS and MPA. Receiver operating characteristic analysis was used to establish a cutoff for minimum dietary diversity for adolescents (MDD-A), using an energy-adjusted logistic model with ADDS predicting MPA > 0.6. RESULTS: Probability of adequacy was greater than 80% for all nutrients except vitamin C (42.1%), folate (65.7%), and calcium (23.8%). Population MPA was 79.4%, and nearly 92% of adolescents had an MPA > 0.6. ADDS was positively associated with MPA, and energy was a significant confounder. Area under the curve was > 0.8 on both days with sensitivity and specificity ranging from 0.71-0.80. The MDD-A cutoff was calculated as 5.12 and 5.10 food groups on day 1 and 2, respectively. CONCLUSIONS: In U.S. adolescents, the best cutoff for a dichotomous indicator of dietary diversity as a proxy for micronutrient adequacy is 6 food groups in a given day. Future research could validate MDD-A and its associated cutoff for use across country contexts.

Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the 1st trimester of pregnancy, based on expert opinion, and made no recommendations for the 2nd and 3rd trimesters. We examined the relationship of SF with two independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin (Hb) and soluble transferrin receptor 1 (sTfR1), in cross-sectional data from NHANES for 1999-2010 and 2015-2018. We included 1288 pregnant women 15-49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the 1st and lower during the 2nd and 3rd trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 (18.1, 28.5) µg/L during 1st trimester, <18.3 (16.3, 22.9) µg/L during 2nd trimester, and <19.0 (14.4, 26.1) µg/L during 3rd trimester. These SF threshold levels track concentrations of hepcidin, the iron regulatory hormone controlling the mobilization of iron stores. A SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional one of every ten pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of about 25 µg/L during the 1st and of about 20 µg/L during the 2nd and 3rd trimesters.

We agree that an open dialogue about modifying universal vitamin A supplementation (VAS) programs, suggested by researchers at Harvard (1) and supported by UNICEF (2), is needed. The goal of universal VAS programs is prevention of mortality and morbidity (3), given the role of vitamin A in immune functions (4). The Global Alliance for Vitamin A (GAVA) has a framework for evidence-based decision making to scale back universal VAS, and the decision tree outlined in the GAVA framework starts with a determination of the vitamin A status of a population using biochemical indicators (5). We recognize that the resource requirement, government commitment, and agency coordination required to collect and synthesize population-based vitamin A biochemical data are not trivial. Here, we describe the experience in Malawi by the government and partners to collect and analyze vitamin A biomarker data during the 2015–16 National Micronutrient Survey, as well as a pilot to test a new distribution model for VAS. | | The Government of Malawi regularly assesses their national vitamin A status, completing national surveys that collected vitamin A biomarker data in 2001, 2009, and 2015–16. In early 2019, planning discussions for the next national micronutrient survey were interrupted by the coronavirus disease 2019 pandemic. Survey planners anticipated low vitamin A deficiency (VAD) in 2015–16 (6), given the trend of decreasing VAD between 2001 and 2009 and the implementation of multiple, overlapping vitamin A interventions. Thus, survey planners decided a priori to collect sufficient serum for analyses of multiple vitamin A biomarkers. After the main vitamin A survey results of the modified-relative-dose response and retinol binding protein were disseminated, due to low levels of VAD a decision was made to also analyze retinyl esters, carotenoids, and retinol using back-up serum.

We read with interest the article by Kang et al. [1], “Hemoglobin distributions and prevalence of anemia in a multiethnic United States pregnant population,” as well as the accompanying Editorial by Merz and Achebe [2], “Iron deficiency in pregnancy: a health inequity [2].” Both Kang et al. [1] and Merz and Achebe [2] incorrectly stated that the Centers for Disease Control and Prevention (CDC) recommend use of lower race-adjusted thresholds to define anemia for Black individuals. The CDC does not recommend separate diagnostic thresholds to define anemia for Black individuals or any other race/ethnic group. Here, we clarify misinterpretations in recent American Journal of Clinical Nutrition publications regarding the CDC anemia threshold recommendations. | | The 1998 “Recommendations to prevent and control iron deficiency in the United States” [3], the most recent CDC publication providing guidance on thresholds to define anemia in individuals, did not recommend race-specific cutoff values for anemia. The 1998 recommendations included criteria for anemia threshold adjustments based on age, sex, pregnancy status, gestational age, altitude, and smoking status [3]. To guide the development of these 1998 CDC recommendations, the CDC requested that the Institute of Medicine (IOM) convene an expert committee to develop recommendations for preventing, detecting, and treating iron deficiency anemia among children and women of reproductive age in United States. The IOM report published in 1993 [4] is independent and not an official institutional CDC/federal recommendations publication. The 1998 CDC recommendations considered inputs from the IOM report [4], conclusions of a CDC expert panel convened in April 1994, and from other multidisciplinary subject matter experts [3].

Anemia remains a major public health problem, especially in low- and middle-income countries. The World Health Organization recommends several interventions to prevent and manage anemia in vulnerable population groups, including young children, menstruating adolescent girls and women, and pregnant and postpartum women. Daily iron supplementation reduces the risk of anemia in infants, children, and pregnant women, and intermittent iron supplementation reduces anemia risk in menstruating girls and women. Micronutrient powders reduce the risk of anemia in children. Fortifying wheat flour with iron reduces the risk of anemia in the overall population, whereas the effect of fortifying maize flour and rice is still uncertain. Regarding non-nutrition-related interventions, malaria treatment and deworming have been reported to decrease anemia prevalence. Promising interventions to prevent anemia include vitamin A supplementation, multiple micronutrient supplementation for pregnant women, small-quantity lipid-based supplements, and fortification of salt with iodine and iron. Future research could address the efficacy and safety of different iron supplementation formulations, identify the most bioavailable form of iron for fortification, examine adherence to supplementation regimens and fortification standards, and investigate the effectiveness of integrating micronutrient, helminth, and malaria control programs.

Accurate and precise measurement of hemoglobin concentration is critical for reliable estimations of anemia prevalence at the population-level. When systematic and/or random error are introduced in hemoglobin measurement, estimates of anemia prevalence might be significantly erroneous and, hence, limit their usefulness. For decades, single-drop capillary blood has been the most common blood source used for the measurement of hemoglobin concentration in surveys, especially in low- and middle-income countries. Here, we highlight historical and emerging evidence that single-drop capillary blood introduces a high degree of random error (variability) to hemoglobin estimates, leading to less reliable estimates of anemia prevalence at the population-level. At present, the best practice is to collect and use venous blood for measurement of hemoglobin with an automated hematology analyzer, following standard operating procedures and quality assurance measures. Where use of an automated analyzer is not possible, the analysis of venous blood in a point-of-care hemoglobinometer by trained phlebotomists or specimen collectors should be considered. A forthcoming systematic review will provide additional evidence on the accuracy and precision of single-drop capillary blood for hemoglobin assessment. In the meantime, we raise caution when using single-drop capillary blood for hemoglobin measurement as it can result in inaccurate hemoglobin estimates and less reliable anemia prevalence estimates.

Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 1549 y [women of reproductive age (WRA)] and children 659 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 20172019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. 2023

Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 15–49 y [women of reproductive age (WRA)] and children 6–59 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 2017–2019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. © 2023

BACKGROUND: Although the importance of adolescent nutrition has gained attention in the global nutrition community, there is a gap in research focused on adolescent dietary diversity and food group consumption. OBJECTIVES: This study aimed to characterize population-level food group consumption patterns and quantify the extent of dietary diversity among United States adolescents using a large nationally representative sample of adolescents aged 10-19 y. METHODS: We used 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 to construct the 10 food groups comprising the minimum dietary diversity for women (MDD-W) indicator and estimated the prevalence of intake of each food group. A composite metric adolescent dietary diversity score (ADDS) was derived for each adolescent where 1 point was awarded per food group. Both population scores and the distribution of individual scores were estimated. Differences in proportions of food groups consumed across sociodemographic categories were tested using the Rao-Scott χ(2) test, and pairwise comparisons were expressed as population prevalence differences and prevalence ratios. RESULTS: Food group consumption patterns were very similar across 2 d of dietary recall but varied significantly by sex, race/ethnicity, and income status. The food groups with the highest prevalence of consumption were grains, white, roots, and tubers (∼99%), milk products (∼92%), and meat, poultry, and fish (∼85%), whereas <15% of adolescents consumed key micronutrient-dense foods, such as vitamin A-rich fruits and vegetables and dark green vegetables. The mean ADDS was 4.69, with modest variation across strata. CONCLUSIONS: On average, United States youth consumed fewer than 5 food groups on a given day. The lack of dietary variety and relatively low prevalence of consumption of several micronutrient-rich plant-based foods could pose a risk for adolescents' ability to achieve micronutrient adequacy in the United States.

Anemia is a major global public health concern with a complex etiology. The main determinants are nutritional factors, infection and inflammation, inherited blood disorders, and women's reproductive biology, but the relative role of each varies between settings. Effective anemia programming, therefore, requires evidence-based, data-driven, contextualized multisectoral strategies, with coordinated implementation. Priority population groups are preschool children, adolescent girls, and pregnant and nonpregnant women of reproductive age. Opportunities for comprehensive anemia programming include: (i) bundling interventions through shared delivery platforms, including antenatal care, community-based platforms, schools, and workplaces; (ii) integrating delivery platforms to extend reach; (iii) integrating anemia and malaria programs in endemic areas; and (iv) integrating anemia programming across the life course. Major barriers to effective anemia programming include weak delivery systems, lack of data or poor use of data, lack of financial and human resources, and poor coordination. Systems strengthening and implementation research approaches are needed to address critical gaps, explore promising platforms, and identify solutions to persistent barriers to high intervention coverage. Immediate priorities are to close the gap between access to service delivery platforms and coverage of anemia interventions, reduce subnational coverage disparities, and improve the collection and use of data to inform anemia strategies and programming.

We agree with Tamohiko Sato and colleagues that a paucity of ferritin measurements to detect iron deficiency in high-income, middle-income, and low-income countries restricts how well research can quantify the magnitude of the disease burden and prevent and treat the disease. Following Sato and colleagues’ suggestions, we reanalysed ferritin concentration data from the US National Health and Nutrition Examination Survey (NHANES) by age, body-mass index, and income and found no meaningful correlations. In our Article,1 we proposed a method to derive physiologically based ferritin thresholds for iron deficiency among apparently healthy young children and non-pregnant women. We concluded that this approach needs validation in non-US populations before specific threshold values are adopted. Although Sato and colleagues highlight the scarcity of ferritin data for Japan, there is also a paucity of data in the USA for populations at high risk of iron deficiency, hindering surveillance and clinical practice. NHANES measures ferritin but does not collect blood among infants younger than 12 months. Ferritin is an acute phase protein and should be adjusted for inflammation, but NHANES does not measure inflammation in all age groups consistently. Sample sizes for pregnant women are small, requiring the combining of data from approximately 10 years for dependable estimates; after 2013, NHANES stopped recording the trimester of pregnancy. The US Public Health Task Force has also emphasised the paucity of prevalence data for iron deficiency anaemia among pregnant women.2 Analysis of electronic health records for first-trimester pregnancies found that anaemia screening is virtually universal, but ferritin screening for iron deficiency is not,3 despite recommendations by the American College of Obstetrics and Gynecologists.4 We continue to search for suitable anonymised databases to examine the proposed method for deriving physiologically based thresholds for serum ferritin concentration for iron deficiency among apparently healthy individuals. Having found that some national datasets from other countries have prohibitive restrictions on their use, we welcome any suggestions of publicly available and representative ferritin data.

Background: Analyses of predictors of anemia or malnutrition often pool national or regional data, which may hide variability at subnational levels. Objectives: We sought to identify the risk factors for anemia in young Nepali children aged 6–23 mo in 2 districts: Kapilvastu and Achham. Methods: This is an analysis of two cross-sectional surveys that were conducted as part of a program evaluation of an infant and young child feeding and micronutrient powder intervention that included anemia as a primary outcome. Baseline and endline surveys in each district (in 2013 and 2016) included hemoglobin assessments in n = 4709 children who were representative of children 6–23 mo in each district. Log-binomial regression models accounting for the survey design were used to estimate univariable and multivariable prevalence ratios for risk factors at multiple levels—underlying, direct, and biological causes. Average attributable fractions (AFs) for the population were calculated for significant predictor biomarkers of anemia in multivariable models. Results: In Accham, the prevalence of anemia was 31.4%; significant predictors included child's age, household asset ownership, length-for-age z-score, inflammation (CRP concentration > 0.5 mg/L; α-1 acid glycoprotein concentration > 1 mg/mL), and iron deficiency (serum ferritin concentration < 12 μg/L with BRINDA-inflammation adjustment). In Kapilvastu, the prevalence of anemia was 48.1%; significant predictors included child's sex and ethnicity, wasting and weight-for-length z-score, any morbidity in the previous 2 wk, consumption of fortified foods, receipt of multiple micronutrient powder distributions, iron deficiency, zinc deficiency (nonfasting serum zinc concentration of <65 μg/dL in the morning and that of <57 μg/dL in the afternoon), and inflammation. In Achham, average AFs were 28.2% and 19.8% for iron deficiency and inflammation, respectively. Average AFs for anemia in Kapilvastu were 32.1%, 4.2%, and 4.9% for iron deficiency, zinc deficiency, and inflammation, respectively. Conclusions: The prevalence of anemia and its risk factors varied between districts, with inflammation contributing to a greater share of anemia in Achham than in Kapilvastu. The estimated AF for iron deficiency was around 30% in both districts; iron-delivering interventions and multisectoral approaches to anemia are warranted. © 2023

Background: The School Nutrition for Adolescents Project (SNAP) provided weekly iron and folic acid (WIFA) supplementation and menstrual hygiene management (MHM) support for girls; actions to improve water, sanitation, and hygiene (WASH) practices; and behavior change interventions to adolescents aged 10–19 y in 65 intervention schools in 2 districts of Bangladesh. Objectives: We aimed to describe the project design and select baseline results of students and school project implementers. Methods: Girls (n = 2244) and boys (n = 773) in 74 schools (clusters) and project implementers [headteachers (n = 74), teachers (n = 96), and student leaders (n = 91)] participated in a survey assessing nutrition, MHM, and WASH knowledge and experience. Hemoglobin, inflammation-adjusted ferritin, retinol-binding protein, and serum and RBC folate (RBCF) levels in girls were measured. School WASH infrastructure was observed and drinking water was tested for E. coli. Results: IFA and deworming tablet intake in the last 1 and 6 mo were 4% and 81% for girls and 1% and 86%, respectively. Applying the Minimum Dietary Diversity for Women (MDD-W) tool, most (63%–68%) girls and boys achieved minimum dietary diversity. Fewer adolescents (14%–52%) had ever heard of anemia, IFA tablets, or worm infestation than project implementers (47%–100%). Girls (35%) missed school during menstruation; 39% reported of ever leaving school due to unexpected menstruation. The micronutrient status and deficiency severity varied: anemia (25%), RBCF insufficiency (76%), risk of serum folate deficiency (10%), deficiencies of iron (9%), and vitamin A (3%). WASH in school sustainable development goal (SDG) indicators achievement varied: basic drinking water service (70%), basic sanitation service (42%), and basic hygiene service (3%); 59% of sampled drinking water access points complied with WHO E. coli standards. Conclusions: There is room for improvement of nutrition and health awareness, practices, micronutrient status, SDG basic WASH in-school services, and E coli contamination in school drinking water. This trial was registered in clinicaltrials.gov as NCT05455073. © 2023 The Author(s)

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

Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil-transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low- and middle-income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated approach across various expert groups and programs could make the best use of existing data or could help to determine when newer and more relevant data may need to be collected, especially in countries with a high anemia burden and limited information on the etiology of anemia.

Interventions distributing micronutrient powders (MNPs) and small-quantity lipid-based nutrient supplements (SQ-LNS), or home fortification products (HFPs), have the potential to improve infant and young child feeding (IYCF) practices and children's nutrition. We systematically searched for studies on the effect of interventions distributing HFP on IYCF practices. We identified 12 (8 MNP, 4 SQ-LNS) studies: seven programmes with IYCF behaviour change communications (BCC) and MNP (IYCF-MNP) and one provided MNP without IYCF BCC (MNP only). Three SQ-LNS studies came from randomised trials without an IYCF component (SQ-LNS only) and one from a programme with both IYCF BCC and SfQ-LNS (IYCF-SQ-LNS). Five IYCF-MNP programmes reported positive associations with some IYCF practices-four with minimum dietary diversity, two with minimum meal frequency, four with minimum acceptable diet, and three with the initiation of complementary foods at 6 months. Two reported no association between MNP and IYCF indicators, and one reported a decline in IYCF practices during the intervention, although it also reported significant changes to the IYCF programme during the evaluation period. Two studies from interventions that distributed SQ-LNS (one from a related set of randomised controlled trials and the sole IYCF-SQ-LNS programme) reported a positive association with IYCF practices; one trial reported no change in breast milk intake with the provision of SQ-LNS and one found no association with IYCF practices. SQ-LNS and MNP can address nutrient gaps for young children in low-resource settings; our findings indicate that programmes that combine HFP with IYCF interventions may also contribute to improved IYCF practices in some settings.

BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 μg/L) and women (<15 μg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 μg/L; women, <25 μg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 μg/L (95% confidence interval: 18.5, 26.5) and 18.7 μg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 μg/L (23.4, 26.9) and 22.5 μg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines. Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia's low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening. To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826-S835. https://doi.org/10.2105/AJPH.2022.306998).

The first 1000 days begins with pregnancy and ends at the child's second birthday. Nutrition throughout the life course, and especially during the first 1000 days, supports maternal health and optimal growth and development for children. We give a high-level summary of the state of nutrition in the first 1000 days in the United States. We provide examples where continued efforts are needed. We then discus select opportunities to strengthen federal research and surveillance, programs, and communication and dissemination efforts aimed at improving nutrition and positively, and equitably, influencing the health and well-being of mothers and children. (Am J Public Health. Published online ahead of print September 19, 2022::e1-e9. https://doi.org/10.2105/AJPH.2022.307028).

BACKGROUND: An efficacy evaluation of the AutoAnthro system to measure child (0-59 months) anthropometry in the United States found 3D imaging performed as well as gold-standard manual measurements for biological plausibility and precision. OBJECTIVES: We conducted an effectiveness evaluation of the accuracy of the AutoAnthro system to measure 0- to 59-month-old children's anthropometry in population-based surveys and surveillance systems in households in Guatemala and Kenya and in hospitals in China. METHODS: The evaluation was done using health or nutrition surveillance system platforms among 600 children aged 0-59 months (Guatemala and Kenya) and 300 children aged 0-23 months (China). Field team anthropometrists and their assistants collected manual and scan anthropometric measurements, including length or height, midupper arm circumference (MUAC), and head circumference (HC; China only), from each child. An anthropometry expert and assistant later collected both manual and scan anthropometric measurements on the same child. The expert manual measurements were considered the standard compared to field team scans. RESULTS: Overall, in Guatemala, Kenya, and China, for interrater accuracy, the average biases for length or height were -0.3cm, -1.9cm, and -6.2cm, respectively; for MUAC were 0.9cm, 1.2cm, and -0.8cm, respectively; and for HC was 2.4cm in China. The inter-technical errors of measurement (inter-TEMs) for length or height were 2.8cm, 3.4cm, 5.5cm, respectively; for MUAC were 1.1cm, 1.5cm, and 1.0cm, respectively; and for HC was 2.8cm in China. For intrarater precision, the absolute mean difference and intra-TEM (interrater, intramethod TEM) were 0.1cm for all countries for all manual measurements. For scans, overall, absolute mean differences for length or height were 0.4-0.6cm; for MUAC were 0.1-0.1cm; and for HC was 0.4cm. For the intra-TEM, length or height was 0.5cm in Guatemala and China and 0.7cm in Kenya, and other measurements were0.3cm. CONCLUSIONS: Understanding the factors that cause the many poor scan results and how to correct them will be needed prior to using this instrument in routine, population-based survey and surveillance systems.

BACKGROUND: Portable systems using three-dimensional (3D) scan data to calculate young child anthropometry measurements in population-based surveys and surveillance systems lack acceptability data from field workers and caregivers. OBJECTIVE: The aim was to assess acceptability and experiences with 3D scans measuring child aged 0-59 mo anthropometry in population-based surveys and surveillance systems in Guatemala, Kenya, and China (0-23 mo only) among field teams and caregivers of young children as secondary objectives of an external effectiveness evaluation. METHODS: Manual data were collected twice and 12 images captured per child by anthropometrist/expert and assistant (AEA) field teams (individuals/country, n = 15/Guatemala, n = 8/Kenya, n = 6/China). Caregivers were interviewed after observing their child's manual and scan data collection. Mixed methods included an administered caregiver interview (Guatemala, n = 465; Kenya, n = 496; China, n = 297) and self-administered AEA questionnaire both with closed- and open-ended questions, and 6 field team focus group discussions (FGDs; Guatemala, n = 2; Kenya, n = 3; China, n = 1). Qualitative data were coded by 2 authors and quantitative data produced descriptive statistics. Mixed-method results were compared and triangulated. RESULTS: Most AEAs were female with secondary or higher education. Approximately 80-90% of caregivers were the child's mother. To collect all anthropometry data, 62.1% of the 29 AEAs preferred scan, while 31% preferred manual methods. In FGDs, a key barrier for manual and scan methods was lack of child cooperation. Across countries, approximately 30% to almost 50% of caregivers said their child was bothered by each manual and scan method, while 95% of caregivers were willing to have their child measured by scans in the future. CONCLUSIONS: Use of 3D scans to calculate anthropometry measurements was generally at least as acceptable as manual anthropometry measurement among AEA field workers and caregivers of young children aged <60 mo, and in some cases preferred.

BACKGROUND: Practice-based experiences documenting development and implementation of nutrition and health surveillance systems are needed. OBJECTIVES: To describe processes, methods, and lessons learned from developing and implementing a population-based household nutrition and health surveillance system in Guatemala. METHODS: The phases and methods for the design and implementation of the surveillance system are described. Efforts to institutionalize the system in government institutions are described, and illustrative examples describing different data uses, and lessons learned are provided. RESULTS: After initial assessments of data needs and consultations with officials in government institutions and partners in the country, a population-based nutrition surveillance system prototype with complex sampling was designed and tested in 5 Guatemalan Highland departments in 2011. After dissemination of the prototype, government and partners expanded the content, and multitopic nutrition and health surveillance cycles were collected in 2013, 2015, 2016, 2017/18, and 2018/19 providing nationally representative data for households, women of reproductive age (15-49 y), and children aged 0-59 mo. For each cycle, data were to be collected from 100 clusters, 30 households in each, and 1 woman and 1 child per household. Content covered ∼25 health and nutrition topics, including coverage of all large-scale nutrition-specific interventions; the micronutrient content of fortifiable sugar, salt, and bread samples; anthropometry; and biomarkers to assess annually, or at least once, ∼25 indicators of micronutrient status and chronic disease. Data were collected by 3-5 highly trained field teams. The design was flexible and revised each cycle allowing potential changes to questionnaires, population groups, biomarkers, survey design, or other changes. Data were used to change national guidelines for vitamin A and B-12 interventions, among others, and evaluate interventions. Barriers included frequent changes of high-level government officials and heavy dependence on US funding. CONCLUSIONS: This system provides high-quality data, fills critical data gaps, and can serve as a useful model for others.

Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and two independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20-49 years, who were first-time or reactivated donors in the REDS-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin <25.4 µg/L) and by hemoglobin (serum ferritin <25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin <25.5 µg/L) and hemoglobin (serum ferritin <26.6 µg/L) in a previous study of 5,442 women, 20-49 years, in the U.S. National Health and Nutrition Examination Survey 2003-2018 (NHANES) (p=0.98 and 0.83, respectively). While international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

BACKGROUND: Standardized practices are needed in the analysis of inflammation biomarker values outside limits of detection (LOD) when used for inflammation correction of nutritional biomarkers. OBJECTIVE: We assessed the direction and extent to which serum C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP) values outside LODs (<0.05 mg/L and >4.0 g/L, respectively) affect inflammation regression correction of serum ferritin and compared approaches to addressing such values when estimating inflammation-adjusted ferritin and iron deficiency (ID). METHODS: Examined 29 cross-sectional datasets from 7 countries with reproductive-age women (15-49y) (n = 12,944), preschool-age children (6-59m) (n = 18,208) and school-age children (6-14y) (n = 4,625). For each dataset, we compared 6 analytic approaches for addressing CRP <LOD: listwise deletion, single imputation (lower, middle, or upper bound; LOD/√2; random number), with multiple imputation (MI). For each approach, inflammation-adjusted ferritin and ID using BRINDA regression correction were estimated. We calculated deviance of each estimate from that given by MI within each dataset and performed fixed effects multivariate meta-regression with analytic approach as moderator to compare the reliability of each approach to MI. RESULTS: Across datasets, observations outside LOD ranged from 0.0 to 35.0% of CRP values and 0.0 to 2.5% of AGP values. Pooled deviance estimates for mean ferritin (µg/L) and ID (percentage points) were: listwise deletion -0.46 (95%CI: -0.76, -0.16) and 0.14 (-0.43, 0.72), lower bound 0.45 (0.14, 0.76) and -0.36 (-0.91, 0.20), middle bound -0.21 (-0.51, 0.09) and 0.22 (-0.34, 0.79), LOD/√(2) -0.26 (-0.57, 0.04) and 0.25 (-0.31, 0.81), upper bound -0.31 (-0.61, -0.01) and 0.30 (-0.27, 0.86), and random number -0.08 (-0.38, 0.22) and 0.11 (-0.46, 0.67). There was moderation by approach in the ferritin model (p<0.001). CONCLUSIONS: Findings demonstrate the need for standardized analyses of inflammation biomarker values outside LODs and suggest that random number single imputation may be a reliable and feasible alternative to MI for CRP <LOD.

We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (μg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (μmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [μmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.

BACKGROUND: The low cost and small specimen volume of the VitMin Lab ELISA assays for serum ferritin (Fer), soluble transferrin receptor (sTfR), C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) allowed their application to micronutrient surveys conducted in low-resource countries for ∼2 decades. OBJECTIVE: We conducted a comparison between the ELISA and reference-type assays used in the US National Health and Nutrition Examination Survey. METHODS: Using the Roche clinical analyzer as a reference, we measured random subsets of the 2016 Nepal National Micronutrient Status Survey (200 serum samples from children 6-59 mo; 100 serum samples from non-pregnant women) for Fer, sTfR, CRP, and AGP. We compared the combined data sets to the ELISA survey results using descriptive analyses. RESULTS: The Lin's concordance coefficients between the 2 assays were ≥ 0.89 except for sTfR (Lin's rho = 0.58). The median relative difference to the reference was: Fer -8.5%, sTfR 71.2%, CRP -19.5%, and AGP -8.2%. The percentage of VitMin samples agreeing within ± 30% of the reference was: Fer 88.5%, sTfR 1.70%, CRP 74.9%, and AGP 92.9%. The prevalence of abnormal results was comparable between the 2 assays for Fer, CRP, and AGP, and for sTfR after adjusting to the Roche assay. Continued biannual performance (2007-2019) of the VitMin assays in CDC's external quality assessment program (6 samples/y) demonstrated generally acceptable performance. CONCLUSION: Using samples from the Nepal survey, the VitMin ELISA assays produced mostly comparable results to the Roche reference-type assays for Fer, CRP, and AGP. The lack of sTfR assay standardization to a common reference material explains the large systematic difference observed for sTfR, which could be corrected by an adjustment equation pending further validation. This snapshot comparison together with the long-term external quality assessment links the survey data generated by the VitMin Lab to the Roche assays used in NHANES.

IMPORTANCE: Anemia, defined as low hemoglobin (Hb) concentration insufficient to meet an individual's physiological needs, is the most common blood condition worldwide. OBJECTIVE: To evaluate the current World Health Organization (WHO) Hb cutoffs for defining anemia among persons who are apparently healthy and to assess threshold validity with a biomarker of tissue iron deficiency and physiological indicator of erythropoiesis (soluble transferrin receptor [sTfR]) using multinational data. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, data were collected and evaluated from 30 household, population-based nutrition surveys of preschool children aged 6 to 59 months and nonpregnant women aged 15 to 49 years during 2005 to 2016 across 25 countries. Data analysis was performed from March 2020 to April 2021. EXPOSURE: Anemia defined according to WHO Hb cutoffs. MAIN OUTCOMES AND MEASURES: To define the healthy population, persons with iron deficiency (ferritin <12 ng/mL for children or <15 ng/mL for women), vitamin A deficiency (retinol-binding protein or retinol <20.1 μg/dL), inflammation (C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L), or known malaria were excluded. Survey-specific, pooled Hb fifth percentile cutoffs were estimated. Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia. RESULTS: A total of 79 950 individuals were included in the original surveys. The final healthy sample was 13 445 children (39.9% of the original sample of 33 699 children; 6750 boys [50.2%]; mean [SD] age 32.9 [16.0] months) and 25 880 women (56.0% of the original sample of 46 251 women; mean [SD] age, 31.0 [9.5] years). Survey-specific Hb fifth percentile among children ranged from 7.90 g/dL (95% CI, 7.54-8.26 g/dL in Pakistan) to 11.23 g/dL (95% CI, 11.14-11.33 g/dL in the US), and among women from 8.83 g/dL (95% CI, 7.77-9.88 g/dL in Gujarat, India) to 12.09 g/dL (95% CI, 12.00-12.17 g/dL in the US). Intersurvey variance around the Hb fifth percentile was low (3.5% for women and 3.6% for children). Pooled fifth percentile estimates were 9.65 g/dL (95% CI, 9.26-10.04 g/dL) for children and 10.81 g/dL (95% CI, 10.35-11.27 g/dL) for women. The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at Hb of 9.61 g/dL (95% CI, 9.55-9.67 g/dL) among children and 11.01 g/dL (95% CI, 10.95-11.09 g/dL) among women. CONCLUSIONS AND RELEVANCE: Current WHO cutoffs to define anemia are higher than the pooled fifth percentile of Hb among persons who are outwardly healthy and from nearly all survey-specific estimates. The lower proposed Hb cutoffs are statistically significant but also reflect compensatory increased erythropoiesis. More studies based on clinical outcomes could further confirm the validity of these Hb cutoffs for anemia.

BACKGROUND: To address the burden of anemia in adolescent girls in Ghana, the Girls' Iron-Folate Tablet Supplementation (GIFTS) program was established in 2017. An evaluation found that although iron and folic acid (IFA) supplementation reached nearly all adolescent girls in schools during year 1, most girls received fewer than the minimum effective number of tablets over the school year. Barrier analyses highlighted schools as drivers of adherence, though information was incomplete on the reasons for the disparities among schools. Information was also lacking on the implementation of health and nutrition education. OBJECTIVES: At the start of year 3 of an integrated adolescent anemia prevention program with IFA supplementation, the present study sought to illuminate differences in program fidelity among schools and across time and potential factors that drive such differences. METHODS: After stratifying by school level, size, geographic location, and intake adherence during year 1, 16 schools were purposively selected. For each school, semistructured key informant interviews were conducted with 1 coordinator at the district level, 3 educators at the school level, and 1 parent leader. Following thematic analysis methods, recorded and transcribed interviews were coded and organized into deductive and inductive themes. RESULTS: Limited training, challenges during distribution of IFA, lack of incentives, and inconsistent health and nutrition education diminished program fidelity. Strong supply chain, widespread awareness promotion, improved acceptability, and intrinsically motivated educators improved program fidelity. After 2 y of implementation, schools had made program adaptations, and widespread changes in attitudes and beliefs about the IFA tablets had improved their acceptability. However, limitations remained related to supply chain, program ownership, communication between health and education sectors, training, motivation, and resources. CONCLUSIONS: The fidelity of Ghana's GIFTS program is strengthened by its supply chain, acceptability, and motivated stakeholders; however, training, curricula, clear communication, and incentives could improve it.