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Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

ABSTRACT: 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 ?-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.

SUBMITTER: McDonald CM

PROVIDER: S-EPMC7138668 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

McDonald Christine M CM Suchdev Parminder S PS Krebs Nancy F NF Hess Sonja Y SY Wessells K Ryan KR Ismaily Sanober S Rahman Sabuktagin S Wieringa Frank T FT Williams Anne M AM Brown Kenneth H KH King Janet C JC

The American journal of clinical nutrition 20200401 4

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age ...[more]

PMID: 32266402

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Project description:BackgroundThe associations between anemia and household water source and sanitation remain unclear.ObjectivesWe 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.MethodsWe 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.ResultsAccess 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%).ConclusionsAlthough 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.

Project description:BackgroundAccurate 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.ObjectivesWe 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).MethodsWe 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).ResultsThe 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.ConclusionsOur 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.

Project description:BackgroundAnemia is a worldwide concern. Nutritional deficiencies and inflammation are considered main contributors, but zinc deficiency has only recently been associated with anemia.ObjectivesIn 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.MethodsCross-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.ResultsData 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.ConclusionsZinc 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.

Project description:Serum ferritin concentration is the preferred biomarker to assess population iron status in the absence of inflammation. Interpretation of this biomarker is complicated in populations with a high burden of infection, however, because inflammation increases serum ferritin concentration independently of iron status. We aimed to compare estimates of iron status of Kenyan pregnant women, with circulating ferritin concentrations adjusted for inflammation using newly proposed methods by the BRINDA project, or using previously proposed adjustment methods. We re-analyzed data from pregnant Kenyan women living in a rural area where malaria is highly endemic (n = 470) or in an urban area (n = 402). As proposed by the BRINDA group, we adjusted individual ferritin concentration by internal regression for circulating concentrations of C-reactive protein (CRP) and α₁-acid glycoprotein (AGP). Other adjustment methods comprised: (a) arithmetic correction factors based on CRP or AGP; (b) exclusion of subjects with inflammation (CRP >5 mg/L or AGP >1 g/L); and (c) higher ferritin cut-off value (<30 μg/L). We additionally adjusted for Plasmodium infection as appropriate. Lastly, we assessed iron status without adjustment for inflammation. All correction methods increased prevalence of iron deficiency compared to the unadjusted estimates. This increase was more pronounced with the internal regression correction method. The iron deficiency prevalence estimate increased from 53% to 87% in rural Kisumu study and from 30% to 41% in the urban Nairobi study after adjusting for inflammation (CRP and AGP) using the BRINDA internal regression method. When we corrected for both inflammation and Plasmodium infection using the regression correction, it resulted in lower prevalence estimates compared to uninfected women. Application of linear regression methods to adjust circulating ferritin concentration for inflammation leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.

Project description:IntroductionDuring pregnancy and lactation minerals such as zinc are required to support maternal and infant health. Zinc is involved in various cellular processes, with requirements increasing in pregnancy and lactation. In the setting of a randomized trial, we investigated the effects on human milk (HM) zinc concentrations of a micronutrient-containing supplement including zinc in the intervention (but not control) group, started preconception and taken throughout pregnancy until birth. Additionally, we characterized longitudinal changes in HM concentrations of zinc and other minerals (calcium, copper, iodine, iron, magnesium, manganese, phosphorus, potassium, selenium, and sodium).MethodsHM samples were collected across 7 time points from 1 week to 12 months from lactating mothers from Singapore (n = 158) and New Zealand (n = 180). HM minerals were quantified using sector field inductively coupled plasma mass spectrometry. Potential intervention effects on HM mineral concentrations were assessed using linear mixed models with a repeated measures design and time-weighted area-under-the-curve analyses.ResultsOver the first 3 months of lactation, HM zinc concentrations were 11% higher in the intervention group compared to the control group (p = 0.021). Higher HM zinc concentrations were most evident at 6 weeks of lactation. The intervention had no effect on HM concentrations of other minerals, which were not differently supplemented to the control and intervention groups. Temporal changes in HM minerals over 12 months of lactation were studied in the New Zealand mothers; HM zinc and copper concentrations progressively decreased throughout 12 months, while iron, potassium, sodium, and phosphorus decreased until 6 months then plateaued. HM calcium and magnesium initially increased in early lactation and iodine remained relatively constant throughout 12 months. HM manganese and selenium fell over the initial months of lactation, with a nadir at 6 months, and increased thereafter. The contrasting patterns of changes in HM mineral concentrations during lactation may reflect different absorption needs and roles at different stages of infancy.DiscussionOverall, this study indicates that HM zinc concentrations are influenced by maternal supplementation during preconception and pregnancy. Further studies are required to understand the associations between HM zinc and other minerals and both short- and long-term offspring outcomes.Trial registrationClinicalTrials.gov, identifier: NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

Dataset Information

Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Publications

Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

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