Physiologically Based Trimester-Specific Serum Ferritin Thresholds for Iron Deficiency in US Pregnant Women.

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.

Review of intervention products for use in the prevention and control of anemia.

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.

Trends in Micronutrient Interventions, Anemia, and Iron Deficiency among Women and Children in Guatemala, 2009-2019.

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.

What Do United States Adolescents Eat? Food Group Consumption Patterns and Dietary Diversity from a Decade of Nationally Representative Data.

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 χ2 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.

Design, Methods, and Select Baseline Results from a School Nutrition Project for Adolescents in Bangladesh.

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.

The Prevalence of Anemia in Children Aged 6-23 Months and its Correlates Differ by District in Kapilvastu and Achham Districts in Nepal.

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.

Integrating and coordinating programs for the management of anemia across the life course.

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.

Association between Hemoglobin and Elevation among School-aged Children: A Verification of Proposed Adjustments.

BACKGROUND: Anemia is defined by a hemoglobin (Hb) concentration lower than normal based on cutoffs specific to age, sex, and pregnancy status. Hb increases with elevation as an adaptive response to lower blood oxygen saturation, thus, adjusting Hb concentrations for elevation is necessary before applying cutoffs. OBJECTIVES: Recent evidence among preschool-aged children (PSC) and nonpregnant reproductive-aged women (WRA) suggests that current World Health Organization (WHO)-recommended Hb adjustments for elevation need updating. To confirm these findings, we examined the cross-sectional association between Hb and elevation among school-aged children (SAC). METHODS: Using data from 9 population-based surveys, we examined 26,518 SAC aged 5-14 y (54.5% female) with data on Hb and elevation (-6 to 3834 m). We used generalized linear models to assess the association between Hb and elevation under varying conditions, including controlling for inflammation-corrected iron and vitamin A deficiency (VAD). Hb adjustments for each 500-m increase in elevation were estimated for SAC and compared with existing adjustments and those estimated for PSC and WRA. We evaluated the impact of these adjustments on anemia prevalence. RESULTS: Hb concentration (g/L) was positively associated with elevation (m). The SAC-elevation adjustments were consistent with those reported among PSC and WRA and suggest current recommendations may under-adjust Hb for those residing at lower elevations (<3000 m) and over-adjust Hb for those residing at higher elevations (>3000 m). Among the surveys included, the proposed elevation adjustments increased anemia prevalence among SAC by 0% (Ghana and United Kingdom) to 15% (Malawi) relative to current elevation adjustments. CONCLUSION: Results confirm that current recommended Hb adjustments for elevation may need updating, and anemia prevalence among SAC may be higher than currently estimated. Findings will inform the WHO's reexamination of global guidelines on the use of Hb adjustments for anemia assessment and may result in improved identification and treatment of anemia.

Accelerating action to reduce anemia: Review of causes and risk factors and related data needs.

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.

Comparison of Current World Health Organization Guidelines with Physiologically Based Serum Ferritin Thresholds for Iron Deficiency in Healthy Young Children and Nonpregnant Women Using Data from the Third National Health and Nutrition Examination Survey.

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.

The effect of interventions distributing home fortification products on infant and young child feeding (IYCF) practices: A systematic narrative review.

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.

Iron Deficiency in the United States: Limitations in Guidelines, Data, and Monitoring of Disparities.

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).

Improving Nutrition in the First 1000 Days in the United States: A Federal Perspective.

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 discuss 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. 2022;112(S8):S817-S825. https://doi.org/10.2105/AJPH.2022.307028).

Acceptability and Experiences with the Use of 3D Scans to Measure Anthropometry of Young Children in Surveys and Surveillance Systems from the Perspective of Field Teams and Caregivers.

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.

Experiences and Lessons Learned in Developing and Implementing a Population-Based Nutrition and Health Surveillance System in Guatemala 2011-2021.

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.

Evaluation of Hemoglobin Cutoff Levels to Define Anemia Among Healthy Individuals.

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.

Relation between Timing of High-Dose Vitamin A Supplementation and Modified-Relative-Dose-Response Values in Children 12-23 Months in Uganda.

BACKGROUND: High-dose vitamin A (VA) supplements (VAS) can temporarily affect VA status. Hence, micronutrient surveys might need to be timed around VAS campaigns to accurately estimate VA deficiency (VAD) prevalence. Little is known about optimal timing of micronutrient surveys when the modified-relative-dose-response (MRDR) is used as a VA indicator. OBJECTIVES: We evaluated the association between days since the end of a VAS campaign and MRDR values in children aged 12-23 mo in Uganda. METHODS: We pooled data from 2 cross-sectional, population-based surveys in eastern Uganda conducted in 2015-2016 (n = 118 children). We estimated the prevalence of VAD (MRDR ≥0.060). Days since the end of a VAS campaign ("days since VAS") was calculated as the interview date minus the end date of the VAS campaign. The MRDR value was assessed using HPLC. We excluded children whose MRDR values were below the limit of detection (<0.007). We used linear regression to evaluate the association between days since VAS and log-transformed MRDR. In adjusted analyses, we controlled for potential confounders. Statistical analyses accounted for the surveys' complex design. RESULTS: The prevalence of VAD was 5.2% (95% CI: 1.1%, 9.3%). Mean days since VAS was 54.1 d (range 39-68 d). Days since VAS was not associated with log-transformed MRDR in unadjusted analyses ($\hat{\beta } = \ $0.0055; 95% CI: -0.009, 0.020; P = 0.45) or adjusted analyses ($\hat{\beta } = $ -0.0073; 95% CI: -0.024, 0.010; P = 0.39). CONCLUSIONS: MRDR measurement through a nutrition survey began as early as 1.3 mo after the end of a VAS campaign in eastern Uganda. Days since the end of a VAS campaign was not associated with MRDR in Ugandan children aged 12-23 mo. Future studies should consider longitudinal designs and evaluate time since VAS and MRDR in children of different ages and in regions with higher VAD prevalence.

Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12-23 months and their non-pregnant caregivers.

Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12-23 months and 28 non-pregnant mothers aged 15-49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were -0.19 µmol/L (95% limits of agreement [LOA] 0.62, -0.99) for children and -0.01 µmol/L (95% LOA -1.11, -1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA -0.37, 1.03) for children, and 0.29 µmol/L (95% LOA -0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA -0.23, 0.49) for children and 0.18 µmol/L (95% LOA -0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.

Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age.

BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin A, and zinc, affect more than two billion people worldwide. Young children are highly vulnerable because of rapid growth and inadequate dietary practices. Multiple micronutrient powders (MNPs) are single-dose packets containing multiple vitamins and minerals in powder form, which are mixed into any semi-solid food for children six months of age or older. The use of MNPs for home or point-of-use fortification of complementary foods has been proposed as an intervention for improving micronutrient intake in children under two years of age. In 2014, MNP interventions were implemented in 43 countries and reached over three million children. This review updates a previous Cochrane Review, which has become out-of-date. OBJECTIVES: To assess the effects and safety of home (point-of-use) fortification of foods with MNPs on nutrition, health, and developmental outcomes in children under two years of age. For the purposes of this review, home fortification with MNP refers to the addition of powders containing vitamins and minerals to semi-solid foods immediately before consumption. This can be done at home or at any other place that meals are consumed (e.g. schools, refugee camps). For this reason, MNPs are also referred to as point-of-use fortification. SEARCH METHODS: We searched the following databases up to July 2019: CENTRAL, MEDLINE, Embase, and eight other databases. We also searched four trials registers, contacted relevant organisations and authors of included studies to identify any ongoing or unpublished studies, and searched the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with individual randomisation or cluster-randomisation. Participants were infants and young children aged 6 to 23 months at the time of intervention, with no identified specific health problems. The intervention consisted of consumption of food fortified at the point of use with MNP formulated with at least iron, zinc, and vitamin A, compared with placebo, no intervention, or use of iron-containing supplements, which is standard practice. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, and assessed the risk of bias of included studies. We reported categorical outcomes as risk ratios (RRs) or odds ratios (ORs), with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) and 95% CIs. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 29 studies (33,147 children) conducted in low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean, where anaemia is a public health problem. Twenty-six studies with 27,051 children contributed data. The interventions lasted between 2 and 44 months, and the powder formulations contained between 5 and 22 nutrients. Among the 26 studies contributing data, 24 studies (26,486 children) compared the use of MNP versus no intervention or placebo; the two remaining studies compared the use of MNP versus an iron-only supplement (iron drops) given daily. The main outcomes of interest were related to anaemia and iron status. We assessed most of the included studies at low risk of selection and attrition bias. We considered some studies to be at high risk of performance and detection bias due to lack of blinding. Most studies were funded by government programmes or foundations; only two were funded by industry. Home fortification with MNP, compared with no intervention or placebo, reduced the risk of anaemia in infants and young children by 18% (RR 0.82, 95% CI 0.76 to 0.90; 16 studies; 9927 children; moderate-certainty evidence) and iron deficiency by 53% (RR 0.47, 95% CI 0.39 to 0.56; 7 studies; 1634 children; high-certainty evidence). Children receiving MNP had higher haemoglobin concentrations (MD 2.74 g/L, 95% CI 1.95 to 3.53; 20 studies; 10,509 children; low-certainty evidence) and higher iron status (MD 12.93 µg/L, 95% CI 7.41 to 18.45; 7 studies; 2612 children; moderate-certainty evidence) at follow-up compared with children receiving the control intervention. We did not find an effect on weight-for-age (MD 0.02, 95% CI -0.03 to 0.07; 10 studies; 9287 children; moderate-certainty evidence). Few studies reported morbidity outcomes (three to five studies each outcome) and definitions varied, but MNP did not increase diarrhoea, upper respiratory infection, malaria, or all-cause morbidity. In comparison with daily iron supplementation, the use of MNP produced similar results for anaemia (RR 0.89, 95% CI 0.58 to 1.39; 1 study; 145 children; low-certainty evidence) and haemoglobin concentrations (MD -2.81 g/L, 95% CI -10.84 to 5.22; 2 studies; 278 children; very low-certainty evidence) but less diarrhoea (RR 0.52, 95% CI 0.38 to 0.72; 1 study; 262 children; low-certainty of evidence). However, given the limited quantity of data, these results should be interpreted cautiously. Reporting of death was infrequent, although no trials reported deaths attributable to the intervention. Information on side effects and morbidity, including malaria and diarrhoea, was scarce. It appears that use of MNP is efficacious among infants and young children aged 6 to 23 months who are living in settings with different prevalences of anaemia and malaria endemicity, regardless of intervention duration. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. AUTHORS' CONCLUSIONS: Home fortification of foods with MNP is an effective intervention for reducing anaemia and iron deficiency in children younger than two years of age. Providing MNP is better than providing no intervention or placebo and may be comparable to using daily iron supplementation. The benefits of this intervention as a child survival strategy or for developmental outcomes are unclear. Further investigation of morbidity outcomes, including malaria and diarrhoea, is needed. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups.