Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-30 (of 50 Records) |
Query Trace: Flores-Ayala R[original query] |
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Physiologically based trimester-specific serum ferritin thresholds for iron deficiency in US pregnant women
Mei Z , Addo YPhD , Jefferds MEDPhD , Flores-Ayala R , Brittenham GM . Blood Adv 2024 Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the 1st trimester of pregnancy, based on expert opinion, and made no recommendations for the 2nd and 3rd trimesters. We examined the relationship of SF with two independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin (Hb) and soluble transferrin receptor 1 (sTfR1), in cross-sectional data from NHANES for 1999-2010 and 2015-2018. We included 1288 pregnant women 15-49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the 1st and lower during the 2nd and 3rd trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 (18.1, 28.5) µg/L during 1st trimester, <18.3 (16.3, 22.9) µg/L during 2nd trimester, and <19.0 (14.4, 26.1) µg/L during 3rd trimester. These SF threshold levels track concentrations of hepcidin, the iron regulatory hormone controlling the mobilization of iron stores. A SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional one of every ten pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of about 25 µg/L during the 1st and of about 20 µg/L during the 2nd and 3rd trimesters. |
Trends in micronutrient interventions, anemia, and iron deficiency among women and children in Guatemala, 2009-2019
Gosdin L , Addo OY , Palmieri M , Mesarina K , Mazariegos DI , Martnez C , Santizo MC , Guzmn L , Alfaro Y , Flores-Ayala R , Jefferds MED . Curr Dev Nutr 2023 7 (8) Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 1549 y [women of reproductive age (WRA)] and children 659 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 20172019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. 2023 |
Trends in micronutrient interventions, anemia, and iron deficiency among women and children in Guatemala, 2009–2019
Gosdin L , Addo OY , Palmieri M , Mesarina K , Mazariegos DI , Martínez C , Santizo MC , Guzmán L , Alfaro Y , Flores-Ayala R , Jefferds MED . Curr Dev Nutr 2023 7 (8) 101970 Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 15–49 y [women of reproductive age (WRA)] and children 6–59 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 2017–2019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. © 2023 |
Under-recognition of measurement and management of serum ferritin among populations at high risk of iron deficiency - Authors' reply
Jefferds ME , Mei Z , Addo OY , Sharma AJ , Flores-Ayala RC , Brittenham GM . Lancet Haematol 2021 8 (11) e787-e788 We agree with Tamohiko Sato and colleagues that a paucity of ferritin measurements to detect iron deficiency in high-income, middle-income, and low-income countries restricts how well research can quantify the magnitude of the disease burden and prevent and treat the disease. Following Sato and colleagues’ suggestions, we reanalysed ferritin concentration data from the US National Health and Nutrition Examination Survey (NHANES) by age, body-mass index, and income and found no meaningful correlations. In our Article,1 we proposed a method to derive physiologically based ferritin thresholds for iron deficiency among apparently healthy young children and non-pregnant women. We concluded that this approach needs validation in non-US populations before specific threshold values are adopted. Although Sato and colleagues highlight the scarcity of ferritin data for Japan, there is also a paucity of data in the USA for populations at high risk of iron deficiency, hindering surveillance and clinical practice. NHANES measures ferritin but does not collect blood among infants younger than 12 months. Ferritin is an acute phase protein and should be adjusted for inflammation, but NHANES does not measure inflammation in all age groups consistently. Sample sizes for pregnant women are small, requiring the combining of data from approximately 10 years for dependable estimates; after 2013, NHANES stopped recording the trimester of pregnancy. The US Public Health Task Force has also emphasised the paucity of prevalence data for iron deficiency anaemia among pregnant women.2 Analysis of electronic health records for first-trimester pregnancies found that anaemia screening is virtually universal, but ferritin screening for iron deficiency is not,3 despite recommendations by the American College of Obstetrics and Gynecologists.4 We continue to search for suitable anonymised databases to examine the proposed method for deriving physiologically based thresholds for serum ferritin concentration for iron deficiency among apparently healthy individuals. Having found that some national datasets from other countries have prohibitive restrictions on their use, we welcome any suggestions of publicly available and representative ferritin data. |
Fruit, vegetable, and sugar-sweetened beverage intake among young children, by state - United States, 2021
Hamner HC , Dooyema CA , Blanck HM , Flores-Ayala R , Jones JR , Ghandour RM , Petersen R . MMWR Morb Mortal Wkly Rep 2023 72 (7) 165-170 Good nutrition in early childhood supports optimal growth, development, and health (1). Federal guidelines support a dietary pattern with daily fruit and vegetable consumption and limited added sugars, including limited consumption of sugar-sweetened beverages (1). Government-published dietary intake estimates for young children are outdated at the national level and unavailable at the state level. CDC analyzed data from the 2021 National Survey of Children's Health (NSCH)* to describe how frequently, according to parent report, children aged 1-5 years (18,386) consumed fruits, vegetables, and sugar-sweetened beverages, nationally and by state. During the preceding week, approximately one in three (32.1%) children did not eat a daily fruit, nearly one half (49.1%) did not eat a daily vegetable, and more than one half (57.1%) drank a sugar-sweetened beverage at least once. Estimates of consumption varied by state. In 20 states, more than one half of children did not eat a vegetable daily during the preceding week. In Vermont, 30.4% of children did not eat a daily vegetable during the preceding week, compared with 64.3% in Louisiana. In 40 states and the District of Columbia, more than one half of children drank a sugar-sweetened beverage at least once during the preceding week. The percentage of children drinking sugar-sweetened beverages at least once during the preceding week ranged from 38.6% in Maine to 79.3% in Mississippi. Many young children are not consuming fruits and vegetables daily and are regularly consuming sugar-sweetened beverages. Federal nutrition programs and state policies and programs can support improvements in diet quality by increasing access to and availability of fruits and vegetables and healthy beverages in places where young children live, learn, and play. |
Comparison of current World Health Organization guidelines with physiologically based serum ferritin thresholds for iron deficiency in healthy young children and nonpregnant women using data from the third National Health and Nutrition Examination Survey
Mei Z , Addo OY , Jefferds MED , Sharma AJ , Flores-Ayala RC , Pfeiffer CM , Brittenham GM . J Nutr 2023 153 (3) 771-780 BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 μg/L) and women (<15 μg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 μg/L; women, <25 μg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 μg/L (95% confidence interval: 18.5, 26.5) and 18.7 μg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 μg/L (23.4, 26.9) and 22.5 μg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID. |
Approaches to quantify the contribution of multiple anemia risk factors in children and women from cross-sectional national surveys
Ko YiAn , Williams AM , Peerson JM , Luo HanQi , Flores-Ayala R , Wirth JP , Engle-Stone R , Young MF , Suchdev PS . PLoS Glob Public Health 2022 2 (10) e0001071 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. |
The relationship between ferritin and BMI is mediated by inflammation among women in higher-income countries, but not in most lower-income countries nor among young children: A multi-country analysis
Davis JN , Williams A , Arnold CD , Rohner F , Wirth JP , Addo Y , Flores-Ayala RC , Oaks BM , Young MF , Suchdev PS , Engle-Stone R . Curr Dev Nutr 2022 6 (10) nzac139 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. |
Five priority public health actions to reduce chronic disease through improved nutrition and physical activity
O'Toole TP , Blanck HM , Flores-Ayala R , Rose K , Galuska DA , Gunn J , O'Connor A , Petersen R , Hacker K . Health Promot Pract 2022 23 5s-11s Welcome to this supplemental issue of Health Promotion Practice (HPP), “Reducing Chronic Disease through Physical Activity and Nutrition: Public Health Practice in the Field” (https://journals.sagepub.com/toc/hppa/23/1_suppl), which is entirely devoted to practice-based wisdom from the field of nutrition, physical activity, and obesity programs. The specific aims of this supplement are to advance public health research and practice by showcasing innovative community-centered interventions, implementation, adaptations, and evaluations employed by the Centers for Disease Control and Prevention (CDC), Division of Nutrition, Physical Activity, and Obesity (DNPAO) (www.cdc.gov/nccdphpd/dnpao/index.html) cooperative agreement recipients: State Physical Activity and Nutrition Program (SPAN, DP18-1807) (www.cdc.gov/nccdphp/dnpao/state-local-programs/span-1807/index.html), Racial and Ethnic Approaches to Community Health (REACH, DP18-1813) (www.cdc.gov/nccdphp/dnpao/state-local-programs/reach/index.htm), and the High Obesity Programs (HOP, DP18-1809) (www.cdc.gov/nccdphp/dnpao/state-local-programs/hop-1809/high-obesity-program-1809.html). |
Iron deficiency in the United States: Limitations in guidelines, data, and monitoring of disparities
Jefferds MED , Mei Z , Addo Y , Hamner HC , Perrine CG , Flores-Ayala R , Pfeiffer CM , Sharma AJ . Am J Public Health 2022 112 S826-s835 Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines. Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia's low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening. To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826-S835. https://doi.org/10.2105/AJPH.2022.306998). |
Improving nutrition in the first 1000 days in the United States: A federal perspective
Hamner HC , Nelson JM , Sharma AJ , Jefferds MED , Dooyema C , Flores-Ayala R , Bremer AA , Vargas AJ , Casavale KO , de Jesus JM , Stoody EE , Scanlon KS , Perrine CG . Am J Public Health 2022 112 e1-e9 The first 1000 days begins with pregnancy and ends at the child's second birthday. Nutrition throughout the life course, and especially during the first 1000 days, supports maternal health and optimal growth and development for children. We give a high-level summary of the state of nutrition in the first 1000 days in the United States. We provide examples where continued efforts are needed. We then discus select opportunities to strengthen federal research and surveillance, programs, and communication and dissemination efforts aimed at improving nutrition and positively, and equitably, influencing the health and well-being of mothers and children. (Am J Public Health. Published online ahead of print September 19, 2022::e1-e9. https://doi.org/10.2105/AJPH.2022.307028). |
Experiences and lessons learned in developing and implementing a population-based nutrition and health surveillance system in Guatemala 2011-2021
Palmieri M , Flores-Ayala R , Mesarina K , Mazariegos DI , Martínez C , López B , Santizo MC , Whitehead RDJr , Addo OY , Aponte J , Quiñónez EL , Sagastume MJ , Jefferds MED . Curr Dev Nutr 2022 6 (4) nzac027 BACKGROUND: Practice-based experiences documenting development and implementation of nutrition and health surveillance systems are needed. OBJECTIVES: To describe processes, methods, and lessons learned from developing and implementing a population-based household nutrition and health surveillance system in Guatemala. METHODS: The phases and methods for the design and implementation of the surveillance system are described. Efforts to institutionalize the system in government institutions are described, and illustrative examples describing different data uses, and lessons learned are provided. RESULTS: After initial assessments of data needs and consultations with officials in government institutions and partners in the country, a population-based nutrition surveillance system prototype with complex sampling was designed and tested in 5 Guatemalan Highland departments in 2011. After dissemination of the prototype, government and partners expanded the content, and multitopic nutrition and health surveillance cycles were collected in 2013, 2015, 2016, 2017/18, and 2018/19 providing nationally representative data for households, women of reproductive age (15-49 y), and children aged 0-59 mo. For each cycle, data were to be collected from 100 clusters, 30 households in each, and 1 woman and 1 child per household. Content covered ∼25 health and nutrition topics, including coverage of all large-scale nutrition-specific interventions; the micronutrient content of fortifiable sugar, salt, and bread samples; anthropometry; and biomarkers to assess annually, or at least once, ∼25 indicators of micronutrient status and chronic disease. Data were collected by 3-5 highly trained field teams. The design was flexible and revised each cycle allowing potential changes to questionnaires, population groups, biomarkers, survey design, or other changes. Data were used to change national guidelines for vitamin A and B-12 interventions, among others, and evaluate interventions. Barriers included frequent changes of high-level government officials and heavy dependence on US funding. CONCLUSIONS: This system provides high-quality data, fills critical data gaps, and can serve as a useful model for others. |
Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors
Addo OY , Mei Z , Hod EA , Jefferds MED , Sharma AJ , Flores-Ayala RC , Spitalnik SL , Brittenham GM . Blood Adv 2022 6 (12) 3661-3665 Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and two independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20-49 years, who were first-time or reactivated donors in the REDS-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin <25.4 µg/L) and by hemoglobin (serum ferritin <25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin <25.5 µg/L) and hemoglobin (serum ferritin <26.6 µg/L) in a previous study of 5,442 women, 20-49 years, in the U.S. National Health and Nutrition Examination Survey 2003-2018 (NHANES) (p=0.98 and 0.83, respectively). While international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency. |
Factors associated with anaemia among adolescent boys and girls 10-19 years old in Nepal
Ford ND , Bichha RP , Parajuli KR , Paudyal N , Joshi N , Whitehead RDJr , Chitekwe S , Mei Z , Flores-Ayala R , Adhikari DP , Rijal S , Jefferds ME . Matern Child Nutr 2022 18 Suppl 1 e13013 We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (μg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (μmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [μmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation. |
Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: A US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study
Mei Z , Addo OY , Jefferds ME , Sharma AJ , Flores-Ayala RC , Brittenham GM . Lancet Haematol 2021 8 (8) e572-e582 BACKGROUND: Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). METHODS: In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×10(9)/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. FINDINGS: 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05). INTERPRETATION: The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. FUNDING: None. |
Relation between timing of high-dose vitamin A supplementation and modified-relative-dose-response values in children 12-23 months in Uganda
Pickens CM , Flores-Ayala R , Ford ND , Whitehead RD , Tanumihardjo SA , Ngalombi S , Halati S , Mapango C , Sheftel J , Jefferds MED . J Nutr 2021 151 (4) 1025-1028 BACKGROUND: High-dose vitamin A (VA) supplements (VAS) can temporarily affect VA status. Hence, micronutrient surveys might need to be timed around VAS campaigns to accurately estimate VA deficiency (VAD) prevalence. Little is known about optimal timing of micronutrient surveys when the modified-relative-dose-response (MRDR) is used as a VA indicator. OBJECTIVES: We evaluated the association between days since the end of a VAS campaign and MRDR values in children aged 12-23 mo in Uganda. METHODS: We pooled data from 2 cross-sectional, population-based surveys in eastern Uganda conducted in 2015-2016 (n = 118 children). We estimated the prevalence of VAD (MRDR ≥0.060). Days since the end of a VAS campaign ("days since VAS") was calculated as the interview date minus the end date of the VAS campaign. The MRDR value was assessed using HPLC. We excluded children whose MRDR values were below the limit of detection (<0.007). We used linear regression to evaluate the association between days since VAS and log-transformed MRDR. In adjusted analyses, we controlled for potential confounders. Statistical analyses accounted for the surveys' complex design. RESULTS: The prevalence of VAD was 5.2% (95% CI: 1.1%, 9.3%). Mean days since VAS was 54.1 d (range 39-68 d). Days since VAS was not associated with log-transformed MRDR in unadjusted analyses ($\hat{\beta } = \ $0.0055; 95% CI: -0.009, 0.020; P = 0.45) or adjusted analyses ($\hat{\beta } = $ -0.0073; 95% CI: -0.024, 0.010; P = 0.39). CONCLUSIONS: MRDR measurement through a nutrition survey began as early as 1.3 mo after the end of a VAS campaign in eastern Uganda. Days since the end of a VAS campaign was not associated with MRDR in Ugandan children aged 12-23 mo. Future studies should consider longitudinal designs and evaluate time since VAS and MRDR in children of different ages and in regions with higher VAD prevalence. |
Intraindividual double burden of overweight or obesity and micronutrient deficiencies or anemia among women of reproductive age in 17 population-based surveys
Williams AM , Guo J , Addo OY , Ismaily S , Namaste SML , Oaks BM , Rohner F , Suchdev PS , Young MF , Flores-Ayala R , Engle-Stone R . Am J Clin Nutr 2019 112 468s-477s 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) > 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. |
Intraindividual double burden of overweight and micronutrient deficiencies or anemia among preschool children
Engle-Stone R , Guo J , Ismaily S , Addo OY , Ahmed T , Oaks B , Suchdev PS , Flores-Ayala R , Williams AM . Am J Clin Nutr 2019 112 478s-487s 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. |
Prevalence and predictors of high blood pressure among women of reproductive age and children aged 10 to 14 years in Guatemala
Pickens CM , Flores-Ayala R , Addo OY , Whitehead RD Jr , Palmieri M , Ramirez-Zea M , Hong Y , Jefferds ME . Prev Chronic Dis 2020 17 E66 INTRODUCTION: Data on the prevalence and predictors of high blood pressure among children and non-pregnant women of reproductive age are sparse in Guatemala. Our objective was to identify the prevalence and predictors of high blood pressure among women of reproductive age and children in Guatemala. METHODS: We analyzed data on blood pressure among 560 children aged 10 to 14 years and 1,182 non-pregnant women aged 15 to 49 from a cross-sectional, nationally representative household survey, SIVESNU (Sistema de Vigilancia Epidemiológica de Salud y Nutrición). We defined high blood pressure among children by using 2004 and 2017 US pediatric guidelines. We defined high blood pressure among women by using 1999 World Health Organization (WHO) and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used multivariable logistic regression to identify significant predictors of high blood pressure. A base model included key covariates (age, ethnicity, socioeconomic index, anthropometric indicators) and accounted for complex sampling. We used backward elimination to identify additional candidate predictor variables. RESULTS: High blood pressure was prevalent among 8.0% (95% confidence interval [CI], 5.4%-10.7%) and 14.0% (95% CI, 10.6%-17.5%) of children using 2004 and 2017 guidelines, respectively; and among 12.7% (95% CI, 10.7%-14.8%) and 41.1% (95% CI, 37.7%-44.4%) of women using 1999 WHO and 2017 ACC/AHA guidelines, respectively. Levels of awareness, treatment, and control of high blood pressure were low in women. Among children, significant predictors of high blood pressure were obesity, overweight, and indigenous ethnicity. Among women, significant predictors of high blood pressure included obesity, overweight, and diabetes. CONCLUSION: The prevalence of high blood pressure was high among Guatemalan women and children. Overweight and obesity were strong risk factors for high blood pressure. Increasing obesity prevention and control programs may help prevent high blood pressure, and expanding high blood pressure screening and treatment could increase awareness and control of high blood pressure in Guatemala. |
Factors associated with anaemia in a nationally representative sample of nonpregnant women of reproductive age in Nepal
Ford ND , Bichha RP , Parajuli KR , Paudyal N , Joshi N , Whitehead RDJr , Chitekwe S , Mei Z , Flores-Ayala R , Adhikari DP , Rijal S , Jefferds ME . Matern Child Nutr 2020 18 Suppl 1 e12953 We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia among a nationally representative sample of nonpregnant women 15- 49 years (n = 1, 918). Haemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood. Soil-transmitted helminth and Helicobacter pylori infections were assessed from stool. Sociodemographic, household, and health characteristics and diet were ascertained by interview. We conducted bivariate analyses between candidate predictors and anaemia (haemoglobin <12.0 g/ dL, altitude- and smoking-adjusted). Candidate predictors that were significant in bivariate models (P < 0.05) were included in the multivariable logistic regression model, accounting for complex sampling design. Anaemia prevalence was 20.2% (95% confidence interval [CI] [17.6, 22.8]). Associated with reduced anaemia odds were living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.35, 95% CI [0.21, 0.60] and AOR 0.41, 95% CI [0.29, 0.59], respectively), recent cough (AOR 0.56, 95% CI [0.38, 0.82]), hormonal contraceptive use (AOR 0.58; 95% CI [0.38, 0.88]), ln ferritin (micrograms per litre; AOR 0.43, 95% CI [0.35, 0.54]), and ln retinol binding protein (micrograms per litre; AOR 0.20, 95% CI [0.11, 0.37]). Residing in a house with an earth floor (AOR 1.74, 95% CI [1.18, 2.56]), glucose-6- phosphate dehydrogenase deficiency (AOR 2.44, 95% CI [1.66, 3.60]), and haemoglobinopathies (AOR 6.15, 95% CI [3.09, 12.26]) were associated with increased anaemia odds. Interventions that improve micronutrient status, ensure access to hormonal birth control, and replace dirt floors to reduce infection risk might help reduce anaemia in this population. |
Age, ethnicity, glucose-6-phosphate dehydrogenase deficiency, micronutrient powder intake, and biomarkers of micronutrient status, infection, and inflammation are associated with anemia among children 6-59 months in Nepal
Ford ND , Bichha RP , Parajuli KR , Paudyal N , Joshi N , Whitehead RD , Chitekwe S , Mei Z , Flores-Ayala R , Adhikari DP , Rijal S , Jefferds ME . J Nutr 2019 150 (4) 929-937 BACKGROUND: Anemia is a major concern for children in Nepal; however, little is known about context-specific causes of anemia. OBJECTIVE: We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anemia in a nationally representative, population-based sample of children 6-59 mo (n = 1367). METHODS: Hemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood samples. Soil-transmitted helminth (STH) and Helicobacter pylori infections were assessed from stool. Anthropometry was measured with standard procedures. Sociodemographic and household characteristics, diet, micronutrient powder (MNP) intake, pica, and morbidity recall were ascertained by caregiver interview. Multivariable logistic regression that accounted for complex sampling design, determined predictors of anemia (hemoglobin <11.0 g/dL, altitude adjusted); candidate predictors were variables with P < 0.05 in bivariate models. RESULTS: Anemia prevalence was 18.6% (95% CI: 15.8, 21.4). MNP intake [adjusted OR (AOR): 0.25, 95% CI: 0.07, 0.86], log (ln) ferritin (mug/L) (AOR: 0.49, 95% CI: 0.38, 0.64), and ln RBP (mumol/L) (AOR: 0.42, 95% CI: 0.18, 0.95) were associated with reduced odds of anemia. Younger age (6-23 mo compared with 24-59 mo; AOR: 2.29, 95% CI: 1.52, 3.46), other Terai ethnicities (AOR: 2.59, 95% CI: 1.25, 5.35) and Muslim ethnicities (AOR: 3.15, 95% CI: 1.30, 7.65) relative to Brahmin/Chhetri ethnicities, recent fever (AOR: 1.68, 95% CI: 1.08, 2.59), ln C-reactive protein (mg/L) (AOR: 1.23, 95% CI: 1.03, 1.45), and glucose-6-phosphate dehydrogenase deficiency (AOR: 2.84, 95% CI: 1.88, 4.30) were associated with increased odds of anemia. CONCLUSION: Both nonmodifiable and potentially modifiable factors were associated with anemia. Thus some but not all anemia might be addressed through effective public health policy, programs, and delivery of nutrition and infection prevention and control. |
Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge
Williams AM , Ladva CN , Leon JS , Lopman BA , Tangpricha V , Whitehead RD , Armitage AE , Wray K , Morovat A , Pasricha SR , Thurnham D , Tanumihardjo SA , Shahab-Ferdows S , Allen L , Flores-Ayala RC , Suchdev PS . Am J Clin Nutr 2019 110 (6) 1456-1464 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 alpha-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. |
Reply to ST McSorley et al
Suchdev PS , Young MF , Williams AM , Addo Y , Namaste SML , Aaron GJ , Neufeld L , Raiten DJ , Flores-Ayala R . Am J Clin Nutr 2018 108 (1) 202-203 We thank McSorley, Talwar, and McMillan for their comments on the series of publications on assessing iron status in settings of inflammation, from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Specifically, the authors highlight the lack of availability of α1-acid glycoprotein (AGP) in clinical settings as a measure of inflammation and suggest instead, to use C-reactive protein (CRP) and serum albumin, which are more routinely available. We acknowledge that assessment of the acute phase response is complicated and that many potential biomarkers of inflammation could be used depending on factors such as the stage of inflammation (e.g., acute compared with chronic), clinical compared with population use, and applicability in resource-limiting settings. The advantages and disadvantages of available biomarkers of inflammation have been recently reviewed, and there has been a call for field-friendly and cost-effective biomarkers that are standardized across laboratories (1, 2). In the datasets that were compiled for the BRINDA project, no surveys measured albumin, so we were unable to assess its relationship with the various biomarkers of nutrition. Serum albumin, which has a long half-life (∼20 d), is most commonly used to identify malnutrition in clinical settings; however, because albumin also acts as a negative acute phase protein, concentrations are lowered by infection, injury, or inflammation irrespective of nutritional status (3, 4). We concur with the authors that the utility of serum albumin or other inflammatory biomarkers, as a potential replacement of AGP as a measure of long-term inflammation, could be explored further. |
Accuracy and reliability of a low-cost, handheld 3D imaging system for child anthropometry
Conkle J , Suchdev PS , Alexander E , Flores-Ayala R , Ramakrishnan U , Martorell R . PLoS One 2018 13 (10) e0205320 The usefulness of anthropometry to define childhood malnutrition is undermined by poor measurement quality, which led to calls for new measurement approaches. We evaluated the ability of a 3D imaging system to correctly measure child stature (length or height), head circumference and arm circumference. In 2016-7 we recruited and measured children at 20 facilities in and around metro Atlanta, Georgia, USA; including at daycare, higher education, religious, and medical facilities. We selected recruitment sites to reflect a generally representative population of Atlanta and to oversample newborns and children under two years of age. Using convenience sampling, a total of 474 children 0-5 years of age who were apparently healthy and who were present at the time of data collection were included in the analysis. Two anthropometrists each took repeated manual measures and repeated 3D scans of each child. We evaluated the reliability and accuracy of 3D scan-derived measurements against manual measurements. The mean child age was 26 months, and 48% of children were female. Based on reported race and ethnicity, the sample was 42% Black, 28% White, 8% Asian, 21% multiple races, other or race not reported; and 16% Hispanic. Measurement reliability of repeated 3D scans was within 1 mm of manual measurement reliability for stature, head circumference and arm circumference. We found systematic bias when analyzing accuracy-on average 3D imaging overestimated stature and head circumference by 6 mm and 3 mm respectively, and underestimated arm circumference by 2 mm. The 3D imaging system used in this study is reliable, low-cost, portable, and can handle movement; making it ideal for use in routine nutritional assessment. However, additional research, particularly on accuracy, and further development of the scanning and processing software is needed before making policy and clinical practice recommendations on the routine use of 3D imaging for child anthropometry. |
Prevalence thresholds for wasting, overweight and stunting in children under 5 years
de Onis M , Borghi E , Arimond M , Webb P , Croft T , Saha K , De-Regil LM , Thuita F , Heidkamp R , Krasevec J , Hayashi C , Flores-Ayala R . Public Health Nutr 2018 22 (1) 1-5 OBJECTIVE: Prevalence ranges to classify levels of wasting and stunting have been used since the 1990s for global monitoring of malnutrition. Recent developments prompted a re-examination of existing ranges and development of new ones for childhood overweight. The present paper reports from the WHO-UNICEF Technical Expert Advisory Group on Nutrition Monitoring. DESIGN: Thresholds were developed in relation to sd of the normative WHO Child Growth Standards. The international definition of 'normal' (2 sd below/above the WHO standards median) defines the first threshold, which includes 2.3 % of the area under the normalized distribution. Multipliers of this 'very low' level (rounded to 2.5 %) set the basis to establish subsequent thresholds. Country groupings using the thresholds were produced using the most recent set of national surveys. SETTING: One hundred and thirty-four countries. SUBJECTS: Children under 5 years. RESULTS: For wasting and overweight, thresholds are: 'very low' ( approximately 6 times 2.5 %). For stunting, thresholds are: 'very low' ( approximately 12 times 2.5 %). CONCLUSIONS: The proposed thresholds minimize changes and keep coherence across anthropometric indicators. They can be used for descriptive purposes to map countries according to severity levels; by donors and global actors to identify priority countries for action; and by governments to trigger action and target programmes aimed at achieving 'low' or 'very low' levels. Harmonized terminology will help avoid confusion and promote appropriate interventions. |
Assessment of iron status in settings of inflammation: challenges and potential approaches
Suchdev PS , Williams AM , Mei Z , Flores-Ayala R , Pasricha SR , Rogers LM , Namaste SM . Am J Clin Nutr 2017 106 1626s-1633s The determination of iron status is challenging when concomitant infection and inflammation are present because of confounding effects of the acute-phase response on the interpretation of most iron indicators. This review summarizes the effects of inflammation on indicators of iron status and assesses the impact of a regression analysis to adjust for inflammation on estimates of iron deficiency (ID) in low- and high-infection-burden settings. We overviewed cross-sectional data from 16 surveys for preschool children (PSC) (n = 29,765) and from 10 surveys for nonpregnant women of reproductive age (WRA) (n = 25,731) from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Effects of C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) concentrations on estimates of ID according to serum ferritin (SF) (used generically to include plasma ferritin), soluble transferrin receptor (sTfR), and total body iron (TBI) were summarized in relation to infection burden (in the United States compared with other countries) and population group (PSC compared with WRA). Effects of the concentrations of CRP and AGP on SF, sTfR, and TBI were generally linear, especially in PSC. Overall, regression correction changed the estimated prevalence of ID in PSC by a median of +25 percentage points (pps) when SF concentrations were used, by -15 pps when sTfR concentrations were used, and by +14 pps when TBI was used; the estimated prevalence of ID in WRA changed by a median of +8 pps when SF concentrations were used, by -10 pps when sTfR concentrations were used, and by +3 pps when TBI was used. In the United States, inflammation correction was done only for CRP concentrations because AGP concentrations were not measured; regression correction for CRP concentrations increased the estimated prevalence of ID when SF concentrations were used by 3 pps in PSC and by 7 pps in WRA. The correction of iron-status indicators for inflammation with the use of regression correction appears to substantially change estimates of ID prevalence in low- and high-infection-burden countries. More research is needed to determine the validity of inflammation-corrected estimates, their dependence on the etiology of inflammation, and their applicability to individual iron-status assessment in clinical settings. |
Improving the quality of child anthropometry: Manual anthropometry in the Body Imaging for Nutritional Assessment Study (BINA)
Conkle J , Ramakrishnan U , Flores-Ayala R , Suchdev PS , Martorell R . PLoS One 2017 12 (12) e0189332 Anthropometric data collected in clinics and surveys are often inaccurate and unreliable due to measurement error. The Body Imaging for Nutritional Assessment Study (BINA) evaluated the ability of 3D imaging to correctly measure stature, head circumference (HC) and arm circumference (MUAC) for children under five years of age. This paper describes the protocol for and the quality of manual anthropometric measurements in BINA, a study conducted in 2016-17 in Atlanta, USA. Quality was evaluated by examining digit preference, biological plausibility of z-scores, z-score standard deviations, and reliability. We calculated z-scores and analyzed plausibility based on the 2006 WHO Child Growth Standards (CGS). For reliability, we calculated intra- and inter-observer Technical Error of Measurement (TEM) and Intraclass Correlation Coefficient (ICC). We found low digit preference; 99.6% of z-scores were biologically plausible, with z-score standard deviations ranging from 0.92 to 1.07. Total TEM was 0.40 for stature, 0.28 for HC, and 0.25 for MUAC in centimeters. ICC ranged from 0.99 to 1.00. The quality of manual measurements in BINA was high and similar to that of the anthropometric data used to develop the WHO CGS. We attributed high quality to vigorous training, motivated and competent field staff, reduction of non-measurement error through the use of technology, and reduction of measurement error through adequate monitoring and supervision. Our anthropometry measurement protocol, which builds on and improves upon the protocol used for the WHO CGS, can be used to improve anthropometric data quality. The discussion illustrates the need to standardize anthropometric data quality assessment, and we conclude that BINA can provide a valuable evaluation of 3D imaging for child anthropometry because there is comparison to gold-standard, manual measurements. |
Iron status of toddlers, nonpregnant females, and pregnant females in the United States
Gupta PM , Hamner HC , Suchdev PS , Flores-Ayala R , Mei Z . Am J Clin Nutr 2017 106 1640s-1646s Background: Total-body iron stores (TBI), which are calculated from serum ferritin and soluble transferrin receptor concentrations, can be used to assess the iron status of populations in the United States.Objective: This analysis, developed to support workshop discussions, describes the distribution of TBI and the prevalence of iron deficiency (ID) and ID anemia (IDA) among toddlers, nonpregnant females, and pregnant females.Design: We analyzed data from NHANES; toddlers aged 12-23 mo (NHANES 2003-2010), nonpregnant females aged 15-49 y (NHANES 2007-2010), and pregnant females aged 12-49 y (NHANES 1999-2010). We used SAS survey procedures to plot distributions of TBI and produce prevalence estimates of ID and IDA for each target population. All analyses were weighted to account for the complex survey design.Results: According to these data, ID prevalences (+/- SEs) were 15.1% +/- 1.7%, 10.4% +/- 0.5%, and 16.3% +/- 1.3% in toddlers, nonpregnant females, and pregnant females, respectively. ID prevalence in pregnant females increased significantly with each trimester (5.3% +/- 1.5%, 12.7% +/- 2.3%, and 27.5% +/- 3.5% in the first, second, and third trimesters, respectively). Racial disparities in the prevalence of ID among both nonpregnant and pregnant females exist, with Mexican American and non-Hispanic black females at greater risk of ID than non-Hispanic white females. IDA prevalence was 5.0% +/- 0.4% and 2.6% +/- 0.7% in nonpregnant and pregnant females, respectively.Conclusions: Available nationally representative data suggest that ID and IDA remain a concern in the United States. Estimates of iron-replete status cannot be made at this time in the absence of established cutoffs for iron repletion based on TBI. The study was registered at clinicaltrials.gov as NCT03274726. |
Monitoring and surveillance for multiple micronutrient supplements in pregnancy
Mei Z , Jefferds ME , Namaste S , Suchdev PS , Flores-Ayala RC . Matern Child Nutr 2017 14 Suppl 5 e12501 The World Health Organization (WHO) recommends iron-folic acid (IFA) supplementation during pregnancy to improve maternal and infant health outcomes. Multiple micronutrient (MMN) supplementation in pregnancy has been implemented in select countries and emerging evidence suggests that MMN supplementation in pregnancy may provide additional benefits compared to IFA alone. In 2015, WHO, the United Nations Children's Fund (UNICEF), and the Micronutrient Initiative held a "Technical Consultation on MMN supplements in pregnancy: implementation considerations for successful incorporation into existing programmemes," which included a call for indicators needed for monitoring, evaluation, and surveillance of MMN supplementation programmes. Currently, global surveillance and monitoring data show that overall IFA supplementation programmes suffer from low coverage and intake adherence, despite inclusion in national policies. Common barriers that limit the effectiveness of IFA-which also apply to MMN programmes-include weak supply chains, low access to antenatal care services, low-quality behaviour change interventions to support and motivate women, and weak or non-existent monitoring systems used for programme improvement. The causes of these barriers in a given country need careful review to resolve them. As countries heighten their focus on supplementation during pregnancy, or if they decide to initiate or transition into MMN supplementation, a priority is to identify key monitoring indicators to address these issues and support effective programmes. National and global monitoring and surveillance data on IFA supplementation during pregnancy are primarily derived from cross-sectional surveys and, on a more routine basis, through health and logistics management information systems. Indicators for IFA supplementation exist; however, the new indicators for MMN supplementation need to be incorporated. We reviewed practice-based evidence, guided by the WHO/Centers for Disease Control and Prevention logic model for vitamin and mineral interventions in public health programmes, and used existing manuals, published literature, country reports, and the opinion of experts, to identify monitoring, evaluation, and surveillance indicators for MMN supplementation programmes. We also considered cross-cutting indicators that could be used across programme settings, as well as those specific to common delivery models, such as antenatal care services. We then described mechanisms for collecting these data, including integration within existing government monitoring systems, as well as other existing or proposed systems. Monitoring data needs at all stages of the programme lifecycle were considered, as well as the feasibility and cost of data collection. We also propose revisions to global-, national-, and subnational-surveillance indicators based on these reviews. |
Factors associated with inflammation in preschool children and women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project
Merrill RD , Burke RM , Northrop-Clewes CA , Rayco-Solon P , Flores-Ayala R , Namaste SM , Serdula MK , Suchdev PS . Am J Clin Nutr 2017 106 348S-358S Background: In many settings, populations experience recurrent exposure to inflammatory agents that catalyze fluctuations in the concentrations of acute-phase proteins and certain micronutrient biomarkers such as C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), ferritin, and retinol. Few data are available on the prevalence and predictors of inflammation in diverse settings.Objective: We aimed to assess the relation between inflammation (CRP concentration >5 mg/L or AGP concentration >1 g/L) and covariates, such as demographics, reported illness, and anthropometric status, in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y).Design: Cross-sectional data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 29,765 PSC in 16 surveys and 25,731 WRA in 10 surveys were used to model bivariable and multivariable relations.Results: The inflammation prevalence was 6.0-40.2% in PSC and 7.9-29.5% in WRA (elevated CRP) and 21.2-64.3% in PSC and 7.1-26.7% in WRA (elevated AGP). In PSC, inflammation was consistently positively associated with recent fever and malaria but not with other recent illnesses. In multivariable models that were adjusted for age, sex, urban or rural residence, and socioeconomic status, elevated AGP was positively associated with stunting (height-for-age z score <-2) in 7 of 10 surveys. In WRA, elevated CRP was positively associated with obesity [body mass index (in kg/m2) ≥30] in 7 of 9 surveys. Other covariates showed inconsistent patterns of association with inflammation. In a pooled analysis of surveys that measured malaria, stunting was associated with elevated AGP but not CRP in PSC, and obesity was associated with both elevated CRP and AGP in WRA.Conclusions: Recent morbidity and abnormal anthropometric status are consistently associated with inflammation across a range of environments, whereas more commonly collected demographic covariates were not. Because of the challenge of defining a general demographic population or environmental profile that is more likely to experience inflammation, inflammatory markers should be measured in surveys to account for their effects. |
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