Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs

Supporting Global Health at the Pediatric Department Level: Why and How

Over the past 20 years, involvement in pediatric global health (GH), the study and practice of improving the health of children worldwide, has evolved from an extracurricular activity to a robust academic pursuit that enhances the clinical, educational, and research missions of academic health centers (Fig 1). As evidenced by the paradigm shift laid out in the United Nations Sustainable Development Goals, which focus on the health of all people worldwide, GH is no longer a field constrained by arbitrary borders.1 Likewise, pediatric departments seeking to expand knowledge, train pediatricians, or improve care for children through research and innovation must be concerned with the health of all children and addressing health equity, which by definition, implies GH work.2 This article aims to provide pediatric department leadership with the background and action steps necessary to respond to the call that support for GH should not be a luxury limited to a few elite institutions but a core part of pediatric education and research across the country.

National, regional, and global estimates of anaemia by severity in women and children for 2000-19: a pooled analysis of population-representative data

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

Intraindividual double burden of overweight and micronutrient deficiencies or anemia among preschool children

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) \u3e 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

Estimating the burden of iron deficiency among African children

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

Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation

Urine selenium concentration is a useful biomarker for assessing population level selenium status

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

Estimating the burden of iron deficiency among African children.

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??g/L or <?30??g/L in the presence of inflammation in children <?5?years old or <?15??g/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

Spatial analysis of urine zinc (Zn) concentration for women of reproductive age and school age children in Malawi

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

Intraindividual double burden of overweight or obesity and micronutrient deficiencies or anemia among women of reproductive age in 17 population-based surveys

Background: Rising prevalence of overweight/obesity (OWOB) alongside persistent micronutrient deficiencies suggests many women face concomitant OWOB and undernutrition. Objectives: We aimed to 1) describe the prevalence of the double burden of malnutrition (DBM) among nonpregnant women of reproductive age, defined as intraindividual OWOB and either ≥1 micronutrient deficiency [micronutrient deficiency index (MDI) \u3e 0; DBM-MDI] or anemia (DBM-anemia); 2) test whether the components of the DBM were independent; and 3) identify factors associated with DBM-MDI and DBM-anemia. Methods: With data from 17 national surveys spanning low- and middle-income countries (LMICs) and high-income countries from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project (n = 419 to n = 9029), we tested independence of over- and undernutrition using the Rao–Scott chi-square test and examined predictors of the DBM and its components using logistic regression for each survey. Results: Median DBM-MDI was 21.9% (range: 1.6%–39.2%); median DBM-anemia was 8.6% (range: 1.0%–18.6%). OWOB and micronutrient deficiencies or anemia were independent in most surveys. Where associations existed, OWOB was negatively associated with micronutrient deficiencies and anemia in LMICs. In 1 high-income country, OWOB women were more likely to experience micronutrient deficiencies and anemia. Age was consistently positively associated with OWOB and the DBM, whereas the associations with other sociodemographic characteristics varied. Higher socioeconomic status tended to be positively associated with OWOB and the DBM in LMICs, whereas in higher-income countries the association was reversed. Conclusions: The independence of OWOB and micronutrient deficiencies or anemia within individuals suggests that these forms of over- and undernutrition may have unique etiologies. Decision-makers should still consider the prevalence, consequences, and etiology of the individual components of the DBM as programs move towards double-duty interventions aimed at addressing OWOB and undernutrition simultaneously