Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia.Objectives: The aims of the project were to 1) identify factors associated with inflammation, 2) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA).Design: The BRINDA database inclusion criteria included surveys that 1) were conducted after 2004, 2) had target groups of PSC, WRA, or both, and 3) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis.Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses.Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to which real-world data can be applied. Findings can inform guidelines and strategies to prevent and control micronutrient deficiencies and anemia globally.
Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol-binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP<0.7μmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5mg/L or alpha1-acid glycoprotein (AGP) >1g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP=exp(InRBP - β1(lnCRPobs-lnCRPref) - β2(lnAGPobs-lnAGPref)). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79μmol/L (95% CI: 0.76, 0.82) vs. 0.95μmol/L (95% CI: 0.92, 0.97), P<0.001). Using approaches 2-5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10-17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations.
by
Rebecca D. Merrill;
Rachel M. Burke;
Christine A. Northrop-Clewes;
Pura Rayco-Solon;
Rafael Flores-Ayala;
Sorrel M.L. Namaste;
Mary K. Serdula;
Parminder S Suchdev
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), α-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.
by
Ashley L. Ware;
Jessica W. O'Brien;
Nicole Crocker;
Benjamin N. Deweese;
Scott C. Roesch;
Claire Coles;
Julie A Kable;
Phillip A. May;
Wendy O. Kalberg;
Elizabeth R. Sowell;
Kenneth Lyons Jones;
Edward P. Riley;
Sarah N. Mattson
Background: This study examined prevalence of psychiatric disorders and behavioral problems in children with and without prenatal alcohol exposure (AE) and attention-deficit/hyperactivity disorder (ADHD). Methods: Primary caregivers of 344 children (8 to 16 years, M = 12.28) completed the Computerized Diagnostic Interview Schedule for Children-IV (C-DISC-4.0) and the Child Behavior Checklist (CBCL). Subjects comprised 4 groups: AE with ADHD (AE+, n = 85) and without ADHD (AE-, n = 52), and nonexposed with ADHD (ADHD, n = 74) and without ADHD (CON, n = 133). The frequency of specific psychiatric disorders, number of psychiatric disorders (comorbidity), and CBCL behavioral scores were examined using chi-square and analysis of covariance techniques. Results: Clinical groups had greater frequency of all psychiatric disorders, except for anxiety, where the AE- and CON groups did not differ. There was a combined effect of AE and ADHD on conduct disorder. For comorbidity, children with ADHD had increased psychiatric disorders regardless of AE, which did not have an independent effect on comorbidity. For CBCL scores, there were significant main effects of AE and ADHD on all scores and significant AE × ADHD interactions for Withdrawn/Depressed, Somatic Complaints, Attention, and all Summary scores. There was a combined effect of AE and ADHD on Externalizing, Total Problems, and Attention Problems. Conclusions: Findings indicate that ADHD diagnosis elevates children's risk of psychiatric diagnoses, regardless of AE, but suggest an exacerbated relation between AE and ADHD on conduct disorder and externalizing behavioral problems in children. Findings affirm a poorer behavioral prognosis for alcohol-exposed children with ADHD and suggest that more than 1 neurobehavioral profile may exist for individuals with AE.
Thiazide-induced potassium loss may contribute to new onset diabetes (NOD). KCNJ1 encodes a potassium channel and one study observed that a KCNJ1 single-nucleotide polymorphism (SNP) was associated with changes in fasting glucose (FG) during hydrochlorothiazide (HCTZ) treatment. We used linear regression to test association of KCNJ1 SNPs and haplotypes with FG changes during HCTZ treatment in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. We used logistic regression to test association of KCNJ1 variation with NOD in HCTZ-treated patients from the International Verapamil SR Trandolapril Study (INVEST). Multivariate regression analyses were performed by race/ethnicity with false discovery rate (FDR) correction. In PEAR blacks, a KCNJ1 SNP was associated with increased FG during HCTZ treatment (beta=8.47, P FDR =0.009). KCNJ1 SNPs and haplotypes were associated with NOD risk in all INVEST race/ethnic groups (strongest association: odds ratio 2.14 (1.31-3.53), P FDR =0.03). Our findings support that KCNJ1 variation is associated with HCTZ-induced dysglycemia and NOD.
Postpartum depression (PPD) is a relatively common and often severe mood disorder that develops in women after childbirth. The aetiology of PPD is unclear, although there is emerging evidence to suggest a psychoneuroimmune connection. Additionally, deficiencies in n-3 PUFA, B vitamins, vitamin D and trace minerals have been implicated. This paper reviews evidence for a link between micronutrient status and PPD, analysing the potential contribution of each micronutrient to psychoneuroimmunological mechanisms of PPD. Articles related to PPD and women’s levels of n-3 PUFA, B vitamins, vitamin D and the trace minerals Zn and Se were reviewed. Findings suggest that while n-3 PUFA levels have been shown to vary inversely with PPD and link with psychoneuroimmunology, there is mixed evidence regarding the ability of n-3 PUFA to prevent or treat PPD. B vitamin status is not clearly linked to PPD, even though it seems to vary inversely with depression in non-perinatal populations and may have an impact on immunity. Vitamin D and the trace minerals Zn and Se are linked to PPD and psychoneuroimmunology by intriguing, but small, studies. Overall, evidence suggests that certain micronutrient deficiencies contribute to the development of PPD, possibly through psychoneuroimmunological mechanisms. Developing a better understanding of these mechanisms is important for guiding future research, clinical practice and health education regarding PPD.
We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
Background: Vitamin D deficiency is highly prevalent among hemodialysis patients, but little data exist in support of an optimal repletion regimen.
Objective: The objective was to ascertain the efficacy of weekly very-high-dose cholecalciferol (vitamin D3) in correcting vitamin D insufficiency and deficiency in patients with stage 5D chronic kidney disease.
Design: We conducted a prospective, double-blind, randomized controlled pilot study that compared placebo with very high doses of oral cholecalciferol for 3 wk (200,000 IU/wk) in hemodialysis patients. We examined the rate of correction of vitamin D insufficiency or deficiency and the effect of treatment on markers of mineral metabolism and routine laboratory variables.
Results: Twenty-seven subjects received placebo, and 25 received cholecalciferol. The majority (94%) of subjects had serum 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study groups were similar with respect to baseline clinical characteristics, with the exception of hemoglobin concentrations, which were lower in the cholecalciferol-treated group (P < 0.04). At follow-up, 90.5% of subjects treated with cholecalciferol achieved serum 25(OH)D concentrations ≥30 ng/mL in contrast to 13.6% of the placebo group. There were no significant changes in serum calcium, phosphate, or intact parathyroid hormone during the study.
Conclusion: Short-term, high-dose oral cholecalciferol treatment of vitamin D deficiency in hemodialysis patients appears to be effective and with no evidence of toxic effects. This trial was registered at clinicaltrials.gov as NCT00912782.
The content of sulfur amino acid (SAA) in a meal affects postprandial plasma cysteine concentrations and the redox potential of cysteine/cystine. Because such changes can affect enzyme, transporter, and receptor activities, meal content of SAA could have unrecognized effects on metabolism during the postprandial period. This pilot study used proton NMR (1H-NMR) spectroscopy of human plasma to test the hypothesis that dietary SAA content changes macronutrient metabolism. Healthy participants (18–36 y, 5 males and 3 females) were equilibrated for 3 d to adequate SAA, fed chemically defined meals without SAA for 5 d (depletion), and then fed isoenergetic, isonitrogenous meals containing 56 mg·kg−1·d−1 SAA for 4.5 d (repletion). On the first and last day of consuming the chemically defined meals, a morning meal containing 60% of the daily food intake was given and plasma samples were collected over an 8-h postprandial time course for characterization of metabolic changes by 1H-NMR spectroscopy. SAA-free food increased peak intensity in the plasma 1H-NMR spectra in the postprandial period. Orthogonal signal correction/partial least squares-discriminant analysis showed changes in signals associated with lipids, some amino acids, and lactate, with notable increases in plasma lipid signals (TG, unsaturated lipid, cholesterol). Conventional lipid analyses confirmed higher plasma TG and showed an increase in plasma concentration of the lipoprotein lipase inhibitor, apoC-III. The results show that plasma 1H-NMR spectra can provide useful macronutrient profiling following a meal challenge protocol and that a single meal with imbalanced SAA content alters postprandial lipid metabolism.
Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer.