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Background: There is a lack of peer-reviewed literature describing in detail the formative research to develop Sprinkles interventions.Objective: To describe community members' reactions to and experiences using Sprinkles, with an emphasis on acceptability, utilization, and promotion.Methods: Fourteen initial focus group discussions on Sprinkles and a 25-family home study were conducted. For the home study, each child 6 to 59 months of age in the household received 30 sachets (1 per day). The initial 14 focus group discussions included mothers, grandmothers, vendors, women who purchased from vendors, and adults in the general population. Home study families were recruited from participants in the initial 14 focus group discussions who had at least one child 6 to 59 months of age.Results: Sprinkles were highly acceptable to adults and most children; some children thought Sprinkles were sugar. Most home study families prepared and used Sprinkles correctly. All families reported positive effects, particularly increased appetite, and recommended Sprinkles; none experienced major problems. Potential barriers identified were lack of knowledge of and experience with Sprinkles, availability of Sprinkles, and cost. Promotional messages targeted to mothers, fathers, all child-care providers, and doctors focused on the positive health effects of Sprinkles.Conclusions: Issues related to Sprinkles preparation, use, and barriers required attention before implementation. Locally appropriate visual and written instructions were developed for dissemination. Intervention training sessions and promotions were tailored to answer frequently asked questions, increase knowledge of Sprinkles, and provide tangible evidence of health benefits. Information needs and perceptions changed quickly after use of Sprinkles. Existing levels of Sprinkles awareness and knowledge should be considered when designing interventions. [ABSTRACT FROM AUTHOR]

Background: In 2007, the US Centers for Disease Control and Prevention partnered with local Kenyan institutions to implement the Nyando Integrated Child Health and Education Project, an effectiveness study that used social marketing and a community-based distribution program to promote the sale of Sprinkles and other health products.Objective: To describe monitoring of wholesale sales, household demand, promotional strategies, and perceived factors influencing Sprinkles sales among vendors.Methods: Ongoing quantitative and qualitative monitoring of Sprinkles sales began in May 2007 in 30 intervention villages. Data sources included baseline and follow-up cross-sectional surveys; office records of Sprinkles sales to vendors; biweekly household monitoring of Sprinkles use; and qualitative data collection, including vendor focus groups and key informant interviews.Results: A total of 550 children aged 6 to 35 months were enrolled at baseline, and 451 were available at 12-month follow-up. During this period, nearly 160,000 sachets were sold wholesale to vendors, with variability in sales influenced by the social, political, and economic context. Vendors living closer to the wholesale office purchased more Sprinkles, so a second office was opened closer to remote vendors. On average, 33% of households purchased Sprinkles during household monitoring visits. Training sessions and community launches were important for community support and raising awareness about Sprinkles. Vendor incentives motivated vendors to sell Sprinkles, and consumer incentives promoted purchases.Conclusions: Sprinkles program monitoring in Kenya was critically important for understanding sales and distribution trends and vendor perceptions. Understanding these trends led to strategic changes to the intervention over time. [ABSTRACT FROM AUTHOR]

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% ( n = 880) of the study participants were seropositive for anti-spike protein antibodies. Significant factors associated with infection included younger age; living within the central, more populated zone of the country; living in a larger household (≥7 members); household members with COVID-19 or compatible symptoms; and those who worked in auxiliary services (i.e., housekeeping and food services). These findings provide insight into opportunities to mitigate SARS-CoV-2 risk and other emerging respiratory pathogens in HCP in El Salvador.

Objectives: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD)., Study Design: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 μmol/g, >0.1 to <0.7 μmol/g, ≥0.7 to <1.0 μmol/g, and ≥1.0 μmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review., Results: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013)., Conclusions: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries., Competing Interests: Declaration of Competing Interest This work was funded by grant OPP1126780 from the Bill & Melinda Gates Foundation and a seed grant from the Global Health Institute at University of Wisconsin-Madison. The funders participated in discussions of study design and data collection. They did not participate in the conduct of the study; the management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors declare no conflicts of interest., (Published by Elsevier Inc.)

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B 12 , or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries., Objective: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site., Design: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software., Results: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements., Conclusions: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eugene Alexander holds an ownership position in Body Surface Translations and therefore has a financial interest in the success of the 3D testing device described in this study. Data were blinded and not shared with Mr. Alexander until completion of draft manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Additional disclosure: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Competing Interests: We declare no competing interests. This work was supported by the Bill & Melinda Gates Foundation (INV-010744), Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, HarvestPlus, and the United States Agency for International Development. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Micronutrient deficiency is a common global health problem, and accurately assessing micronutrient biomarkers is crucial for planning and managing effective intervention programs. However, analyzing micronutrient data and applying appropriate cutoffs to define deficiencies can be challenging, particularly when considering the confounding effects of inflammation on certain micronutrient biomarkers. To address this challenge, we developed the Statistical Apparatus of Micronutrient Biomarker Analysis (SAMBA) R package, a new tool that increases ease and accessibility of population-based micronutrient biomarker analysis. The SAMBA package can analyze various micronutrient biomarkers to assess status of iron, vitamin A, zinc, and B vitamins; adjust for inflammation; account for complex survey design when appropriate; and produce reports of summary statistics and prevalence estimates of micronutrient deficiencies using recommended age-specific and sex-specific cutoffs. In this study, we aimed to provide a step-by-step procedure for how to use the SAMBA R package, including how to customize it for broader use, and made both the package and user manual publicly available on GitHub. SAMBA was validated by comparing results by analyzing 24 data sets on nonpregnant women of reproductive age from 23 countries and 30 data sets on preschool-aged children from 26 countries with those obtained by an independent analyst. SAMBA generated identical means, percentiles, and prevalence of micronutrient deficiencies to those calculated by the independent analyst. In conclusion, SAMBA simplifies and standardizes the process for deriving survey-weighted and inflammation-adjusted (when appropriate) estimates of the prevalence of micronutrient deficiencies, reducing the time from data cleaning to result generation. SAMBA is a valuable tool that facilitates the accurate and rapid analysis of population-based micronutrient biomarker data, which can inform public health research, programs, and policy across contexts., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia., Methods: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site., Findings: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site., Interpretation: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SEA reports grants from Emory University, during the conduct of the study. JAGS reports grants from the Wellcome Trust, the National Institute for Health and Care Research, Gavi, the Foreign Commonwealth and Development Office (UK), the European and Developing Countries Clinical Trials Partnership, the Medical Research Council, and the Bill & Melinda Gates Foundation whose payments were direct to his institution. LM reports grants from the Bill & Melinda Gates Foundation via Emory, whose payments were made direct to her institution. KLK reports grants from the Bill & Melinda Gates Foundation, whose payments were made direct to her institution and support attending meetings. KLK, SOS, and AMK report the provision of study materials and funding to their institution for this study from the Bill & Melinda Gates Foundation. AW reports a stipend for participating in the CHAMPS research and payment for travel to the High Horizons meeting in Belgium from the University of Witwatersrand; honoraria for lectures from Sanofi; and being a council member of The South African Society of Obstetricians and Gynaecologists. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) research group was formed over a decade ago to improve the interpretation of micronutrient biomarkers in settings with inflammation. The BRINDA inflammation adjustment method uses regression correction to adjust for the confounding effects of inflammation on select micronutrient biomarkers and has provided important insights to micronutrient research, policy, and programming. However, users may face challenges when applying the BRINDA inflammation adjustment methods to their own data due to varying guidance on the adjustment approach for different biomarkers and the need to develop statistical programming to conduct these analyses. This may result in lost opportunities to have results of micronutrient data readily available during critical decision-making periods. Our research objectives are to 1) provide an all-in-one summary of the BRINDA method in adjusting multiple micronutrient biomarkers for inflammation, 2) evaluate whether malaria as a binary variable should be included in the BRINDA inflammation adjustment method, and 3) present standardized and user-friendly BRINDA adjustment R package and SAS macro. This paper serves as a practical guidebook for the BRINDA inflammation adjustment approach and aids users to use the BRINDA R package and SAS to streamline their analyses., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Republic of Guatemala's reported COVID-19 vaccination coverage is among the lowest in the Americas and there are limited studies describing the disparities in vaccine uptake within the country. We performed a cross-sectional ecological analysis using multi-level modeling to identify sociodemographic characteristics that were associated with low COVID-19 vaccination coverage among Guatemalan municipalities as of 30 November 2022. Municipalities with a higher proportion of people experiencing poverty (β = -0.25, 95% CI: -0.43--0.07) had lower vaccination coverage. Municipalities with a higher proportion of people who had received at least a primary education (β = 0.74, 95% CI: 0.38-1.08), children (β = 1.07, 95% CI: 0.36-1.77), people aged 60 years and older (β = 2.94, 95% CI: 1.70-4.12), and testing for SARS-CoV-2 infection (β = 0.25, 95% CI: 0.14-0.36) had higher vaccination coverage. In the simplified multivariable model, these factors explained 59.4% of the variation in COVID-19 vaccination coverage. Poverty remained significantly associated with low COVID-19 vaccination coverage in two subanalyses restricting the data to the time period of the highest national COVID-19-related death rate and to COVID-19 vaccination coverage only among those aged 60 years or older. Poverty is a key factor associated with low COVID-19 vaccination and focusing public health interventions in municipalities most affected by poverty may help address COVID-19 vaccination and health disparities in Guatemala.

Background: Vitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear., Objective: We determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania., Methods: Five studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13 C-RID and measurement of inflammation markers, CRP, and α 1 -acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal-Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]., Results: Complete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) μmol/g in Ethiopia to 1.10 (0.88, 1.38) μmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = -0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant., Conclusions: No indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity., (Copyright © 2022. Published by Elsevier Inc.)

Background: It is unclear whether 25(OH)D concentrations in children and female adults may be influenced by inflammation and thus require adjustment when estimating the population prevalence of vitamin D deficiency., Objectives: We examined correlations between inflammation biomarkers, CRP or alpha-1-acid glycoprotein (AGP), and serum 25(OH)D concentrations among preschool children (PSC; 6-59 mo) and nonpregnant females of reproductive age (FRA; 15-49 y)., Methods: We analyzed cross-sectional data from 6 nationally representative nutrition surveys (Afghanistan, Cambodia, Pakistan, UK, USA, and Vietnam) conducted among PSC (n = 9880) and FRA (n = 14,749) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Rank correlations between CRP or AGP and 25(OH)D concentrations were examined while taking into account complex survey design effects., Results: Among both PSC and FRA, correlations between inflammation and vitamin D biomarkers were weak and inconsistent across surveys. For PSC, correlation coefficients between CRP and 25(OH)D concentrations ranged from -0.04 to 0.08, and correlations between AGP and 25(OH)D ranged from 0.01 to 0.05. Correlation coefficients between CRP and 25(OH)D for FRA ranged from -0.11 to 0.14, and correlations between AGP and 25(OH)D concentrations ranged from -0.05 to 0.01., Conclusions: Based on the weak and inconsistent correlations between CRP or AGP and 25(OH)D, there is no rationale to adjust for these inflammation biomarkers when estimating population prevalence of vitamin D deficiency in PSC or FRA., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Attributable fractions (AF) of anemia are often used to understand the multifactorial etiologies of anemia, despite challenges interpreting them in cross-sectional studies. We aimed to compare different statistical approaches for estimating AF for anemia due to inflammation, malaria, and micronutrient deficiencies including iron, vitamin A, vitamin B12, and folate., Methods: AF were calculated using nationally representative survey data among preschool children (10 countries, total N = 7,973) and nonpregnant women of reproductive age (11 countries, total N = 15,141) from the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project. We used the following strategies to calculate AF: 1) Levin's formula with prevalence ratio (PR) in place of relative risk (RR), 2) Levin's formula with odds ratio (OR) in place of RR, and 3) average (sequential) AF considering all possible removal sequences of risk factors. PR was obtained by 1) modified Poisson regression with robust variance estimation, 2) Kleinman-Norton's approach, and 3) estimation from OR using Zhang-Yu's approach. Survey weighted country-specific analysis was performed with and without adjustment for age, sex, socioeconomic status, and other risk factors., Results: About 20-70% of children and 20-50% of women suffered from anemia, depending on the survey. Using OR yielded the highest and potentially biased AF, in some cases double those using PR. Adjusted AF using different PR estimations (Poisson regression, Kleinman-Norton, Zhang-Yu) were nearly identical. Average AF estimates were similar to those using Levin's formula with PR. Estimated anemia AF for children and women were 2-36% and 3-46% for iron deficiency, <24% and <12% for inflammation, and 2-36% and 1-16% for malaria. Unadjusted AF substantially differed from adjusted AF in most countries., Conclusion: AF of anemia can be estimated from survey data using Levin's formula or average AF. While different approaches exist to estimate adjusted PR, Poisson regression is likely the easiest to implement. AF are a useful metric to prioritize interventions to reduce anemia prevalence, and the similarity across methods provides researchers flexibility in selecting AF approaches., Competing Interests: The authors have read the journal’s policy and have the following competing interests: JPW is an employee of GroundWork LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: In the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain., Objectives: We describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings., Methods: Cross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications., Results: In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines., Conclusions: Where having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Standardized practices are needed in the analysis of inflammation biomarker values outside limits of detection (LODs) when used for inflammation correction of nutritional biomarkers., Objective: We assessed the direction and extent to which serum C-reactive protein (CRP) and α-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: We examined 29 cross-sectional datasets from 7 countries with reproductive-age women (age 15-49 y) (n = 12,944), preschool-age children (age 6-59 mo) (n = 18,208), and school-age children (age 6-14 y) (n = 4625). For each dataset, we compared 6 analytic approaches for addressing CRP

Aim: To assess correlation between successful Helicobacter pylori (HP) eradication and resolution of iron deficiency in children, without iron supplementation., Methods: Medical records of children diagnosed with HP infection based on endoscopy were retrospectively reviewed. Among those with non-anaemic iron deficiency (NAID) or iron deficiency anaemia (IDA), haemoglobin, ferritin and CRP levels were compared prior and 6-9 months' post-successful HP eradication. Predictors of resolution of iron deficiency following HP eradication were assessed., Results: Among 60 included children (median age 14.8, IQR12.3-16 years; 62% males), 35% had IDA while the remaining 65% had NAID. Following successful HP eradication, iron normalised in 60% of patients with iron deficiency (ID), without iron supplementation. There were significant improvements in haemoglobin and ferritin concentrations following HP eradication with haemoglobin increasing from 12.3 g/dL to 13.0 g/dL and ferritin increasing from 6.3 μg/L to 15.1 μg/L (p < 0.001). In multiple logistic regression, older age was the only factor associated with resolution of anaemia following HP eradication (OR 1.65, 95% CI 1.16-2.35, p = 0.005)., Conclusion: Successful HP eradication could be helpful in improving iron status among children with refractory NAID or IDA. Older age may predict this outcome. Screening for HP might be considered in the workup of refractory IDA or ID., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Anaemia causes health and economic harms. The prevalence of anaemia in women aged 15-49 years, by pregnancy status, is indicator 2.2.3 of the UN Sustainable Development Goals, and the aim of halving the anaemia prevalence in women of reproductive age by 2030 is an extension of the 2025 global nutrition targets endorsed by the World Health Assembly (WHA). We aimed to estimate the prevalence of anaemia by severity for children aged 6-59 months, non-pregnant women aged 15-49 years, and pregnant women aged 15-49 years in 197 countries and territories and globally for the period 2000-19., Methods: For this pooled analysis of population-representative data, we collated 489 data sources on haemoglobin distribution in children and women from 133 countries, including 4·5 million haemoglobin measurements. Our data sources comprised health examination, nutrition, and household surveys, accessed as anonymised individual records or as summary statistics such as mean haemoglobin and anaemia prevalence. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions in each population and country-year. This model allowed for coherent estimation of mean haemoglobin and prevalence of anaemia by severity., Findings: Globally, in 2019, 40% (95% uncertainty interval [UI] 36-44) of children aged 6-59 months were anaemic, compared to 48% (45-51) in 2000. Globally, the prevalence of anaemia in non-pregnant women aged 15-49 years changed little between 2000 and 2019, from 31% (95% UI 28-34) to 30% (27-33), while in pregnant women aged 15-49 years it decreased from 41% (39-43) to 36% (34-39). In 2019, the prevalence of anaemia in children aged 6-59 months exceeded 70% in 11 countries and exceeded 50% in all women aged 15-49 years in ten countries. Globally in all populations and in most countries and regions, the prevalence of mild anaemia changed little, while moderate and severe anaemia declined in most populations and geographical locations, indicating a shift towards mild anaemia., Interpretation: Globally, regionally, and in nearly all countries, progress on anaemia in women aged 15-49 years is insufficient to meet the WHA global nutrition target to halve anaemia prevalence by 2030, and the prevalence of anaemia in children also remains high. A better understanding of the context-specific causes of anaemia and quality implementation of effective multisectoral actions to address these causes are needed., Funding: USAID, US Centers for Disease Control and Prevention, and Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests GAS and CJP report consulting contracts from WHO supporting this work. ME reports receiving a charitable grant from the AstraZeneca Young Health Programme. GAS, FR, and JPW report contracts with the Global Alliance for Improved Nutrition, WHO, and UNICEF. FR and JPW report contracts with Harvest Plus. GAS reports a contract with the World Bank and travel support from UNICEF. PSS reports contracts with the US Centers for Disease Control and Prevention and the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Minimally invasive tissue sampling (MITS) is increasingly being used to better understand causes of death in low-resource settings. Undernutrition (eg, wasting, stunting) is prevalent among children globally and yet not consistently coded or uniformly included on death certificates in MITS studies when present. Consistent and accurate attribution of undernutrition is fundamental to understanding its contribution to child deaths. In May 2020, members of the MITS Alliance Cause of Death Technical Working Group convened a panel of experts in public health, child health, nutrition, infectious diseases, and MITS to develop guidance for systematic integration of undernutrition, as assessed by anthropometry, in cause of death coding, including as part of the causal chain or as a contributing condition, in children <5 years of age. The guidance presented here will support MITS and other researchers, public health practitioners, and clinicians with a systematic approach to assigning and interpreting undernutrition in death certification., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: In the management of pediatric osteomyelitis or septic arthritis, delay in treatment may affect outcome, while receipt of antibiotics prior to culture may affect culture results. We aimed to determine if pathogen identification decreased in cultures that were pretreated with antibiotics., Methods: We conducted a retrospective cohort study of 584 hospitalized children between 30 days and 18 years of age admitted to two tertiary children's hospitals. Logistic regression assessed the effect of antibiotic duration on blood, bone, joint aspirate, and "other" culture positivity., Results: Overall, 42% of blood cultures, 70% of bone cultures, 39% of joint cultures, and 70% of "other" cultures were positive. Compared with children who did not receive antibiotics prior to culture, there were no significant differences in odds of a positive culture in children whose cultures were pretreated with antibiotics for any of the culture types [OR (95% CI) 0.90 (0.56-1.44) for blood cultures, 0.77 (0.25-2.34) for bone cultures, 0.71 (0.39-1.28) for joint cultures, 1.18 (0.58-2.41) "for other" cultures; all p > 0.05]. Furthermore, the duration (hours) of antibiotics in the pretreated cultures was also not a significant predictor of culture positivity (OR ranged from 0.99-1.00 for all cultures, p > 0.05)., Conclusions: Culture positivity was not associated with antibiotic pretreatment in any of the samples, even for longer duration of antibiotics prior to culture, though the small sample size of subgroups is an important limitation. In pediatric patients hospitalized with osteomyelitis and/or septic arthritis, early initiation of antibiotics may not affect culture positivity., (© 2021. The Author(s).)

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.

Anemia remains an important global health problem. Inexpensive, accurate, and noninvasive solutions are needed to monitor and evaluate anemia in resource-limited settings. We evaluated the performance of multiple point-of-care hemoglobin devices, including a novel noninvasive smartphone application tested on Apple® and Android® cell phones, Masimo Pronto®, and HemoCue® Hb-301 and Hb-801, against a gold-standard hematology analyzer (reference hemoglobin) using venous blood. We examined correlations between hemoglobin devices and reference hemoglobin, device accuracy (average bias, Bland-Altman plots, clinical performance) and classification bias (sensitivity, specificity) among 299 refugees (10mo-65y) in Atlanta, GA. Semi-structured interviews (n = 19) with participants and staff assessed usability and acceptability. Mean reference hemoglobin was 13.7 g/dL (SD:1.8) with 12.5% anemia. Noninvasive hemoglobin devices were not well correlated with reference hemoglobin (Apple® R2 = 0.08, Android® R2 = 0.11, Masimo Pronto® R2 = 0.29), but stronger correlations were reported with HemoCue® Hb-301 (R2 = 0.87) and Hb-801 (R2 = 0.88). Bias (SD) varied across each device: Apple®: -1.6 g/dL (2.0), Android®: -0.7 g/dL (2.0), Masimo Pronto®: -0.4 g/dL (1.6), HemoCue® Hb-301: +0.4 g/dL (0.7) and HemoCue® Hb-801: +0.2 g/dL (0.6). Clinically acceptable performance (within ± 1 g/dL of reference hemoglobin) was higher for the invasive devices (HemoCue® Hb-301: 90.3%; HemoCue® Hb-801: 93.4%) compared to noninvasive devices (Apple®: 31.5%; Android®: 34.6%; Masimo Pronto®: 49.5%). Sensitivity and specificity were 63.9% and 48.2% for Apple®, 36.1% and 67.6% for Android®, 45.7% and 85.3% for Masimo Pronto®, 54.3% and 97.6% for HemoCue® Hb-301, and 66.7% and 97.6% for HemoCue® Hb-801. Noninvasive devices were considered easy to use and were the preferred method by participants. Among the only studies to compare multiple point-of-care approaches to hemoglobin testing, the diagnostic ability of HemoCue® was comparable to reference hemoglobin, while noninvasive devices had high user acceptability but considerable biases. Improvements in noninvasive device performance and further testing in anemic populations are recommended before broader use., Competing Interests: The authors have declared that no competing interest exists.

Background: Anemia is a worldwide concern. Nutritional deficiencies and inflammation are considered main contributors, but zinc deficiency has only recently been associated with anemia., Objectives: In this study we assessed associations between zinc status and hemoglobin (Hb) concentrations and anemia in preschool children 6-59 mo old (PSC) and nonpregnant women of reproductive age 15-49 y old (WRA) in population-based nutrition surveys., Methods: Cross-sectional data from 13 (PSC) and 12 (WRA) countries within the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were used. Multivariable linear models were constructed that included zinc status (plasma/serum zinc concentrations), Hb concentrations and anemia, iron status, age, sex, and inflammation (C-reactive protein and α-1-acid glycoprotein). Zinc was adjusted for inflammation in PSC according to the BRINDA algorithm., Results: Data were available for 18,658 PSC and 22,633 WRA. Prevalence of anemia ranged from 7.5% to 73.7% and from 11.5% to 94.7% in PSC and WRA, respectively. Prevalence of zinc deficiency ranged from 9.2% to 78.4% in PSC and from 9.8% to 84.7% in WRA, with prevalence of zinc deficiency >20% in all countries except Azerbaijan (PSC), Ecuador (PSC), and the United Kingdom (WRA). Multivariable linear regression models showed that zinc concentrations were independently and positively associated with Hb concentrations in 7 of 13 countries for PSC and 5 of 12 countries for WRA. In the same models, ferritin concentration was also significantly associated with Hb among PSC and WRA in 9 and 10 countries, respectively. Zinc deficiency was significantly associated with anemia in PSC and WRA in 5 and 4 countries respectively., Conclusions: Zinc deficiency was prevalent in most countries and associations between zinc and Hb in roughly half of the countries examined suggesting that strategies to combat zinc deficiency may help reduce anemia prevalence. More research on mechanisms by which zinc deficiency is associated with anemia and the reasons for the heterogeneity among countries is warranted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS)., Objective: We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey., Methods: Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design., Results: We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables., Conclusions: Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification., (© Crown copyright 2021.)

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID 1 . To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria 2 , as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

Zinc (Zn) is an essential micronutrient, and Zn deficiency remains a major global public health challenge. Recognised biomarkers of population Zn status include blood plasma or serum Zn concentration and proxy data such as dietary Zn intake and prevalence of stunting. Urine Zn concentration is rarely used to assess population Zn status. This study assessed the value of urine Zn concentration as a biomarker of population Zn status using a nationally representative sample of non-pregnant women of reproductive age (WRA) and school-aged children (SAC) in Malawi. Spot (casual) urine samples were collected from 741 WRA and 665 SAC. Urine Zn concentration was measured by inductively coupled plasma mass spectrometry with specific gravity adjustment for hydration status. Data were analysed using a linear mixed model with a spatially correlated random effect for between-cluster variation. The effect of time of sample collection (morning or afternoon), and gender (for SAC), on urine Zn concentration were examined. There was spatial dependence in urine Zn concentration between clusters among SAC but not WRA, which indicates that food system or environmental factors can influence urine Zn concentration. Mapping urine Zn concentration could potentially identify areas where the prevalence of Zn deficiency is greater and thus where further sampling or interventions might be targeted. There was no evidence for differences in urine Zn concentration between gender (P = 0.69) or time of sample collection (P = 0.85) in SAC. Urine Zn concentration was greater in afternoon samples for WRA (P = 0.003). Relationships between urine Zn concentration, serum Zn concentration, dietary Zn intake, and potential food systems covariates warrant further study.

Anaemia is a public health problem in Ghana. We sought to identify factors associated with haemoglobin concentration (Hb) and anaemia among school-attending adolescents. We analysed data from 2948 adolescent girls and 609 boys (10-19 years) selected from 115 schools from regions of Ghana as a secondary analysis of baseline surveys conducted at two time-points. We measured Hb, malaria from capillary blood, anthropometry and used a modified food frequency questionnaire to assess diet. Multivariable linear and Poisson regression models were used to identify predictors of Hb and anaemia. The prevalence of anaemia, malaria and geophagy were 24, 25, and 24 %, respectively, among girls and 13, 27 and 6 %, respectively, among boys. Girls engaging in geophagy had a 53 % higher adjusted prevalence of anaemia and 0⋅39 g/dl lower Hb. There were similar results among those who tested positive for malaria (+52 % anaemia; -0⋅42 g/dl Hb). Among girls, lower anaemia prevalence and higher Hb were associated with consumption of foods rich in haeme iron (-22 %; +0⋅18 g/dl), consumption of iron-fortified cereal/beverages consumed with citrus (-50 %; +0⋅37 g/dl) and being overweight (-22 %; +0⋅22 g/dl). Age was positively associated with anaemia among girls, but negatively associated among boys. Boys who tested positive for malaria had 0⋅31 g/dl lower Hb. Boys who were overweight or had obesity and consumed flour products were also more likely to be anaemic (119 and 56 %, respectively). Factors associated with Hb and anaemia may inform anaemia reduction interventions among school-going adolescents and suggest the need to tailor them uniquely for boys and girls., (© The Author(s) 2020.)

Background: Accurate anthropometric measurements are essential for assessing nutritional status, monitoring child growth, and informing clinical care. We aimed to improve height measurements of hospitalized pediatrics patients through implementation of gold standard measurement techniques., Methods: A quality improvement project implemented computerized training modules on anthropometry and standardized wooden boards for height measurements in a tertiary children's hospital. Heights were collected pre- and post-intervention on general pediatric inpatients under 5 years of age. Accuracy of height measurements was determined by analyzing the variance and by comparing to World Health Organization's defined biologically plausible height-for-age z-scores. Qualitative interviews assessed staff attitudes., Results: Ninety-six hospital staff completed the anthropometry training. Data were available on 632 children pre- and 933 post-intervention. Training did not increase the proportion of patients measured for height (78.6% pre-intervention vs. 75.8% post-intervention, p = 0.19). Post-intervention, wooden height boards were used to measure height of 34.8% patients, while tape measures and wingspan accounted for 42.0% and 3.5% of measurements, respectively. There was no improvement in the quality of height measurements based on plausibility (approximately 3% height-for-age z-scores measurements flagged out of range pre- and post-intervention), digit preference (13.4% of digits pre- and 12.3% post-intervention requiring reclassification), or dispersion of measurements (height-for-age z-scores standard deviation 1.9 pre- and post-intervention). Staff reported that using the wooden board was too labor consuming and cumbersome., Conclusions: Our findings suggest that efforts to improve anthropometric measurements of hospitalized children have multiple obstacles, and further investigation of less cumbersome methods of measurements may be warranted.

Background: Universal home fortification of complementary foods with iron-containing multiple micronutrient powders (MNPs) is a key intervention to prevent anaemia in young children in low-income and middle-income countries. However, evidence that MNPs might promote infection raises uncertainty about whether MNPs give net health benefits and are cost-effective. We aimed to determined country-specific net benefit or harm and cost-effectiveness of universal provision of MNPs to children aged 6 months., Methods: We developed a microsimulation model to estimate net country-specific disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to anaemia, malaria, and diarrhoea averted (or increased) by provision of a 6-month course of MNPs to children aged 6 months, compared with no intervention, who would be followed up for an additional 6 months (ie, to age 18 months). Anaemia prevalence was derived from Demographic and Health Surveys or similar national surveys, and malaria and diarrhoea incidence were sourced from the Global Burden of Disease Study. Programme and health-care costs were modelled to determine cost per DALY averted (US$). Additionally, we explored the effects of reduced MNP coverage in a sensitivity analysis., Findings: 78 countries (46 countries in Africa, 20 in Asia or the Middle East, and 12 in Latin America) were included in the analysis, and we simulated 5 million children per country. 6 months of universal distribution of daily MNPs, assuming 100% coverage, produced a net benefit (DALYs averted) in 54 countries (24 in Africa, 19 in Asia and the Middle East, 11 in Latin America) and net harm in 24 countries (22 in Africa, one in Asia, and one in Latin America). MNP intervention provided a benefit on YLDs associated with anaemia, but these gains were attenuated and sometimes reversed by increases in YLLs associated with malaria and diarrhoea, reducing the benefits seen for DALYs. In the 54 countries where MNP provision was beneficial, the median benefit was 28·1 DALYs averted per 10 000 children receiving MNPs (IQR 20·6-40·4), and median cost per DALY averted was $3576 (IQR 2474-4918). DALY effects positively correlated with moderate and severe anaemia prevalence in Asia, the Middle East, and Latin America, but correlated inversely in Africa. Suboptimal coverage markedly reduced DALYs averted and cost-effectiveness., Interpretation: Net health benefits of MNPs vary between countries, are highest where prevalence of moderate and severe anaemia is greatest but infection prevalence is smallest, and are ameliorated when coverage of the intervention is poor. Our data provide country-specific guidance to national policy makers., Funding: International Union of Nutrition Sciences., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In low-resource settings, urbanization may contribute to the individual-level double burden of malnutrition (DBM), whereby under- and overnutrition co-occur within the same individuals., Objective: We described DBM prevalence among Malawian women by urban-rural residence, examined whether urban residence was associated with DBM, and assessed whether DBM prevalence was greater than the prevalence expected by chance given population levels of under- and overnutrition, which would suggest DBM is a distinct phenomenon associated with specific factors., Methods: We analyzed nationally representative data of 723 nonpregnant women aged 15-49 y from the 2015-2016 Malawi Micronutrient Survey. DBM was defined as co-occurring overweight or obesity (OWOB) and ≥1 micronutrient deficiency or anemia. We used Poisson regression models to examine the association between urban residence and DBM and its components. The Rao-Scott modified chi-square test compared the observed and expected DBM prevalence., Results: Nationally, 10.8% (95% CI: 7.0, 14.5) of women had co-occurring OWOB and any micronutrient deficiency and 3.4% (95% CI: 1.3, 5.5) had co-occurring OWOB and anemia. The prevalence of co-occurring OWOB and any micronutrient deficiency was 2 times higher among urban women than rural women [urban 32.6 (24.1, 41.2) compared with rural 8.6 (5.2, 11.9), adjusted prevalence ratio: 2.0 (1.1, 3.5)]. Co-occurring OWOB and anemia prevalence did not significantly differ by residence [urban 6.9 (0.6, 13.2) compared with rural 3.0 (0.8, 5.3)]. There were no statistically significant differences in observed and expected prevalence estimates of DBM., Conclusions: This analysis shows that co-occurring OWOB and any micronutrient deficiency was higher among women in urban Malawi compared with rural areas. However, our finding that co-occurring OWOB and any micronutrient deficiency or anemia may be due to chance suggests that there may not be common causes driving DBM in Malawian women. Thus, there may not be a need to design and target interventions specifically for women with DBM., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation., Objectives: We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted., Methods: Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or α-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRP > 5 mg/L or AGP > 1 g/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach., Results: In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence., Conclusions: Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA., (Copyright © The Author(s) 2020.)

Background: Vitamin B-12 and folate deficiencies in women and children have important public health implications. However, the evidence is conflicting and limited on whether the influence of inflammation on biomarker concentrations may be sufficiently and consistently influenced by inflammation to require adjustment for interpreting concentrations or estimating population prevalence of deficiencies., Objective: We examined correlations between concentrations of the inflammation biomarkers C-reactive protein (CRP) and α1-acid glycoprotein (AGP) and serum vitamin B-12 and serum and RBC folate among nonpregnant women of reproductive age (WRA; 15-49 yr) and preschool children (PSC; 6-59 mo)., Methods: We analyzed cross-sectional data from 16 nationally representative nutrition surveys conducted in WRA (n = 32,588) and PSC (n = 8,256) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Spearman correlations between CRP or AGP and vitamin B-12 or folate concentrations were examined, taking into account complex survey design effects., Results: Correlations between inflammation and vitamin B-12 or folate were weak, with no clear pattern of association in either WRA or PSC. Correlation coefficients between CRP and vitamin B-12 for WRA and PSC ranged from -0.25 to 0.16, and correlations between AGP and vitamin B-12 ranged between -0.07 and 0.14. Similarly, correlations between CRP and serum folate ranged from -0.13 to 0.08, and correlations between AGP and serum folate between -0.21 and 0.02. Only 3 surveys measured RBC folate, and among them, correlations for WRA ranged from -0.07 to 0.08 for CRP and -0.04 for AGP (1 country)., Conclusions: Based on the weak and inconsistent correlations between CRP or AGP and vitamin B-12 or folate biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence of vitamin B-12 or folate deficiencies in WRA or PSC., (Copyright © The Author(s) 2020.)

Background: Valid measurement of hemoglobin is important for tracking and targeting interventions. This study compares hemoglobin distributions between surveys matched by country and time from The Demographic and Health Survey (DHS) Program and the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project., Methods: Four pairs of nationally representative surveys measuring hemoglobin using HemoCue® with capillary (DHS) or venous (BRINDA) blood were matched by country and time. Data included 17,719 children (6-59 months) and 21,594 non-pregnant women (15-49 y). Across paired surveys, we compared distributional statistics and anemia prevalence., Results: Surveys from three of the four countries showed substantial differences in anemia estimates (9 to 31 percentage point differences) which were consistently lower in BRINDA compared to DHS (2 to 31 points for children, 1 to 16 points for women)., Conclusion: We identify substantial differences in anemia estimates from surveys of similar populations. Further work is needed to identify the cause of these differences to improve the robustness of anemia estimates for comparing populations and tracking improvements over time.

An ongoing challenge to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance that are safe, efficacious, and avoid unintended consequences. The integration to effective implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the generation, translation, and implementation of evidence to public health guidance/programs. The I-to-I approach was developed under the auspices of the Micronutrient Forum and has been previously applied to the question of safety and effectiveness of interventions to prevent and treat nutritional iron deficiency. The present article applies the I-to-I approach to questions regarding the safety and utility of large-dose vitamin A supplementation programs, and presents the authors' perspective on key aspects of the topic, including coverage of the basic and applied biology of vitamin A nutrition and assessment, clinical implications, and an overview of the extant data with regard to both the justification for and utility of available intervention strategies. The article includes some practical considerations based on specific country experiences regarding the challenges of implementing vitamin A-related programs. This is followed by an overview of some challenges associated with engagement of the enabling communities that play a critical role in the implementation of these types of public health interventions. The article concludes with suggestions for potential approaches to move this important agenda forward., (Copyright © American Society for Nutrition 2019.)

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., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

This study sought to assess clinical characteristics and differences in outcomes between children with Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) osteomyelitis or septic arthritis and whether initial antibiotic regimen affects patient outcomes. We analyzed records of children ages 15 days to 18 years admitted between 2009 and 2016 to two tertiary children's hospitals who were diagnosed with an osteoarticular infection and had a microorganism identified. A total of 584 patients met inclusion criteria, of which 365 (62.5%) had a microbiological diagnosis. MSSA was the most common pathogen identified (45.5%), followed by MRSA (31.2%). Compared to MSSA, patients with MRSA had a higher initial C-reactive protein and longer hospitalization. Patients whose initial antibiotic regimens included vancomycin had a longer hospitalization than those initiated on clindamycin without vancomycin, even after removing sicker patients admitted to the pediatric intensive care unit. While MRSA was associated with increased severity of osteoarticular infections compared to MSSA, the incidence of MRSA has been declining at our institution. Patients with longer lengths of stay were more likely to be on vancomycin. Clindamycin should be considered in the initial antibiotic regimen for osteomyelitis and septic arthritis with ongoing surveillance of local microbiology and outcomes., Competing Interests: The authors declare no conflict of interest

Background: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children., Methods: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard., Results: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard., Conclusions: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Background: To accurately assess micronutrient status, it is necessary to characterize the effects of inflammation and the acute-phase response on nutrient biomarkers., Objective: Within a norovirus human challenge study, we aimed to model the inflammatory response of C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) by infection status, model kinetics of micronutrient biomarkers by inflammation status, and evaluate associations between inflammation and micronutrient biomarkers from 0 to 35 d post-norovirus exposure., Methods: Fifty-two healthy adults were enrolled into challenge studies in a hospital setting and followed longitudinally; all were exposed to norovirus, half were infected. Post hoc analysis of inflammatory and nutritional biomarkers was performed. Subjects were stratified by inflammation resulting from norovirus exposure. Smoothed regression models analyzed the kinetics of CRP and AGP by infection status, and nutritional biomarkers by inflammation. Linear mixed-effects models were used to analyze the independent relations between CRP, AGP, and biomarkers for iron, vitamin A, vitamin D, vitamin B-12, and folate from 0 to 35 d post-norovirus exposure., Results: Norovirus-infected subjects had median (IQR) peak concentrations for CRP [16.0 (7.9-29.5) mg/L] and AGP [0.9 (0.8-1.2) g/L] on day 3 and day 4 postexposure, respectively. Nutritional biomarkers that differed (P < 0.05) from baseline within the inflamed group were ferritin (elevated day 3), hepcidin (elevated days 2, 3), serum iron (depressed days 2-4), transferrin saturation (depressed days 2-4), and retinol (depressed days 3, 4, and 7). Nutritional biomarker concentrations did not differ over time within the uninflamed group. In mixed models, CRP was associated with ferritin (positive) and serum iron and retinol (negative, P < 0.05)., Conclusion: Using an experimental infectious challenge model in healthy adults, norovirus infection elicited a time-limited inflammatory response associated with altered serum concentrations of certain iron and vitamin A biomarkers, confirming the need to consider adjustments of these biomarkers to account for inflammation when assessing nutritional status. These trials were registered at clinicaltrials.gov as NCT00313404 and NCT00674336., (Copyright © American Society for Nutrition 2019.)

Leprosy reactions are immune-mediated complications occurring in up to 50% of patients. The immune consequences of helminth infections and micronutrient deficiencies suggest a potential role in type 1 reactions (T1R) or type 2 reactions (T2R). We conducted a case-control study in Minas Gerais, Brazil, to evaluate whether comorbidities and other factors are associated with reactions in patients with multibacillary leprosy. Stool and serum were tested for helminth infections. Deficiencies of vitamin A, D, and iron were measured using serum retinol, 25-hydroxyvitamin D, and ferritin, respectively. Logistic regression models identified associations between reactions and helminth infections, micronutrient deficiencies, and other variables. Seventy-three patients were enrolled, 24 (33%) with T1R, 21 (29%) with T2R, 8 (15%) with mixed T1R/T2R, and 20 (27%) without reactions. Evidence of helminth infections were found in 11 participants (15%) and included IgG4 reactivity against Schistosoma mansoni , Strongyloides , and Ascaris antigens. Thirty-eight (52%) had vitamin D deficiency, eight (11%) had vitamin A insufficiency, 21 (29%) had anemia, and one (1.4%) had iron deficiency. Multivariable logistic regression showed no statistically significant associations between helminth coinfections and total reactions (adjusted odds ratios [aOR]: 1.36, 95% CI: 0.22, 8.33), T1R (aOR: 0.85, 95% CI: 0.17, 4.17), or T2R (aOR: 2.41, 95% CI: 0.29, 20.0). Vitamin D deficiency and vitamin A insufficiency were also not statistically associated with reactions. However, vitamin deficiencies and helminth infections were prevalent in these patients, suggesting a potential role for additional treatment interventions. Studying reactions prospectively may further clarify the role of comorbidities in the clinical presentation of leprosy.

Background: The associations between anemia and household water source and sanitation remain unclear., Objectives: We aimed to assess the associations between anemia and household water source or sanitation in preschool children (PSC; age 6-59 mo) using population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project., Methods: We analyzed national and subnational data from 21 surveys, representing 19 countries (n = 35,963). Observations with hemoglobin (Hb) and ≥1 variable reflecting household water source or sanitation were included. Anemia was defined as an altitude-adjusted Hb concentration <110 g/L. Household water source and sanitation variables were dichotomized as "improved" or "unimproved." Poisson regressions with robust variance estimates were conducted for each survey, adjusting for child sex, age, household socioeconomic status, maternal education, and type of residence., Results: Access to an improved water source and improved sanitation ranged from 29.9% (Burkina Faso) to 98.4% (Bangladesh, 2012), and from 0.2% (Kenya, 2007) to 97.4% (Philippines), respectively. Prevalence of anemia ranged from 20.1% (Nicaragua) to 83.5% (Bangladesh, 2010). Seven surveys showed negative associations between anemia and improved sanitation. Three surveys showed association between anemia and improved water, with mixed directions. Meta-analyses suggested a protective association between improved household sanitation and anemia [adjusted prevalence ratio (aPR) = 0.88; 95% CI: 0.79, 0.98], and no association between improved household water and anemia (aPR = 1.00; 95% CI: 0.91, 1.10). There was heterogeneity across surveys for sanitation (P < 0.01; I2 = 66.3%) and water (P < 0.01; I2 = 55.8%)., Conclusions: Although improved household sanitation was associated with reduced anemia prevalence in PSC in some surveys, this association was not consistent. Access to an improved water source in general had no association with anemia across surveys. Additional research could help clarify the heterogeneity between these conditions across countries to inform anemia reduction programs., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

The correct interpretation of hemoglobin (Hb) to identify anemia requires adjusting for altitude and smoking. Current adjustments were derived using data collected before 1985, from low-income preschool-aged children (PSC) in the United States and indigenous men in Peru for altitude, and from White women of reproductive age (WRA) in the United States for smoking. Given the oldness and limited representativeness of these data, we reexamined associations between Hb and altitude and/or smoking using 13 population-based surveys and 1 cohort study each conducted after 2000. All WHO regions except South-East Asia were represented. The dataset included 68,193 observations among PSC (6-59 months) and nonpregnant WRA (15-49 years) with data on Hb and altitude (-28 to 4000 m), and 19,826 observations among WRA with data on Hb and smoking (status or daily cigarette quantity). Generalized linear models were used to assess the robustness of associations under varying conditions, including controlling for inflammation-corrected iron and vitamin A deficiency. Our study confirms that Hb should be adjusted for altitude and/or smoking; these adjustments are additive. However, recommendations for Hb adjustment likely need updating. Notably, current recommendations may underadjust Hb for light smokers and for those residing at lower altitudes and overadjust Hb for those residing at higher altitudes., (© 2019 New York Academy of Sciences.)

Background: Child overweight prevalence is increasing globally, but micronutrient deficiencies persist., Objectives: We aimed to 1) describe the prevalence and distribution of intraindividual double burden of malnutrition (DBM), defined as coexistence of overweight or obesity (OWOB) and either micronutrient deficiencies or anemia, among preschool children; 2) assess the independence of DBM components, e.g., whether the prevalence of DBM is greater than what would be expected by chance; and 3) identify predictors of intraindividual DBM, to guide intervention targeting., Methods: We analyzed data from 24 population-based surveys from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (separately by survey; n = 226 to n = 7166). We defined intraindividual DBM as coexisting OWOB and ≥1 micronutrient deficiency [e.g., Micronutrient Deficiency Index (MDI) > 0; DBM-MDI] or anemia (DBM-Anemia). We assessed independence of DBM components with the Rao-Scott chi-square test and examined predictors of DBM and its components with logistic regression., Results: DBM prevalence ranged from 0% to 9.7% (median: 2.5%, DBM-MDI; 1.4%, DBM-Anemia), reflecting a lower prevalence of OWOB (range: 0%-19.5%) than of micronutrient deficiencies and anemia, which exceeded 20% in most surveys. OWOB was generally not significantly associated with micronutrient deficiencies or anemia. In more than half of surveys, children 6-23 mo of age, compared with ≥24 mo, had greater adjusted odds of DBM-Anemia, anemia, and micronutrient deficiencies. Child sex and household socioeconomic status, urban location, and caregiver education did not consistently predict DBM or its components., Conclusions: Intraindividual DBM among preschool children was low but might increase as child OWOB increases. The analysis does not support the hypothesis that DBM components cluster within individuals, suggesting that population-level DBM may be addressed by programs to reduce DBM components without targeting individuals with DBM., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Accurate assessment of iron and vitamin A status is needed to inform public health decisions, but most population-level iron and vitamin A biomarkers are independently influenced by inflammation., Objectives: We aimed to assess the reproducibility of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) regression approach to adjust iron [ferritin, soluble transferrin receptor (sTfR)] and vitamin A [retinol-binding protein (RBP), retinol] biomarkers for inflammation (α-1-acid glycoprotein and C-reactive protein)., Methods: We conducted a sensitivity analysis comparing unadjusted and adjusted estimates of iron and vitamin A deficiency using the internal-survey regression approach from BRINDA phase 1 (16 surveys in children, 10 surveys in women) and 13 additional surveys for children and women (BRINDA phase 2)., Results: The relations between inflammation and iron or vitamin A biomarkers were statistically significant except for vitamin A biomarkers in women. Heterogeneity of the regression coefficients across surveys was high. Among children, internal-survey adjustments increased the estimated prevalence of depleted iron stores (ferritin <12 µg/L) by a median of 11 percentage points (pp) (24 pp and 9 pp in BRINDA phase 1 and phase 2, respectively), whereas estimates of iron-deficient erythropoiesis (sTfR >8.3 mg/L) decreased by a median of 15 pp (15 pp and 20 pp in BRINDA phase 1 and phase 2, respectively). Vitamin A deficiency (RBP <0.7 µmol/L or retinol <0.7 µmol/L) decreased by a median of 14 pp (18 pp and 8 pp in BRINDA phase 1 and phase 2, respectively) in children. Adjustment for inflammation in women resulted in smaller differences in estimated iron deficiency than in children., Conclusions: Our findings are consistent with previous BRINDA conclusions that not accounting for inflammation may result in an underestimation of iron deficiency and overestimation of vitamin A deficiency. Research is needed to understand the etiology of the heterogeneity in the regression coefficients before a meta-analyzed regression correction can be considered., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)