Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case-control study.

PURPOSE: Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status. METHODS: This is a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13-17 years. We assessed depression severity using the Children's Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire. RESULTS: SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) µg/L) and controls (32.5 (22.6, 48.3) µg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls. CONCLUSION: Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. RESULTS: Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. CONCLUSIONS: Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.

Consumption Pattern of Tea Is Associated with Serum Ferritin Levels of Women of Childbearing Age in Nandi County, Kenya: A Cross-Sectional Study.

INTRODUCTION: Tea consumption with meals affects iron absorption, increasing the risk of iron deficiency. Our study investigated the association between tea consumption patterns and serum ferritin levels among women of childbearing age (WCA) in Nandi County, Kenya. METHODS: We conducted a cross-sectional analytical study among 160 WCA selected using a systematic random sampling technique from Kapsabet Ward. Information on tea consumption practices was gathered using a researcher-administered questionnaire, and serum ferritin and C-reactive protein were measured. We assessed associations between tea consumption and iron status of respondents by multivariable regression analysis, adjusting for potential confounders, including parasitic infections and recent severe blood losses. RESULTS: The prevalence of anaemia and iron deficiency among the study participants were 86.2% and 45%, respectively. Majority (90.6%) of the respondents consumed tea or coffee, with an infusion time of more than 5 min (60.0%) and a moderate tea strength (64.1%), within 1 h before or after meals. Iron deficiency was associated the number of teacups consumed (adjusted odds ratio = 7.282, 95% CI = 3.580-14.812). CONCLUSION: High tea consumption is positively associated with iron deficiency among WCA. Lower tea infusion strength, shorter tea infusion duration, and a lower number of teacups overall consumed, as well as consuming tea 1 h before or after meals instead of with meals, may be recommended for better outcomes in iron status among WCA.

Abnormal Iron Status and Adverse Outcome After Elective Cardiac Surgery: A Prospective, Observational Multicenter Study.

OBJECTIVES: To investigate the incidence of preoperative abnormal iron status and its association with packed red blood cell (PRBC) transfusion, postoperative major complications, and new onset of clinically significant disability in patients undergoing elective cardiac surgery. DESIGN: A prospective, observational multicenter cohort study. SETTING: Three cardiac surgical centers in the Netherlands between 2019 and 2021. Recruitment was on hold between March and May 2020 due to COVID-19. PATIENTS: A total of 427 patients aged 60 years and older who underwent elective on-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a 30-day PRBC transfusion. Secondary endpoints were postoperative major complications within 30 days (eg, acute kidney injury, sepsis), and new onset of clinically significant disability within 120 days of surgery. Iron status was evaluated before surgery. Abnormal iron status was present in 45.2% of patients (n = 193), and most frequently the result of iron deficiency (27.4%, n = 117). An abnormal iron status was not associated with PRBC transfusion (adjusted relative risk [ARR] 1.2; 95% CI 0.9-1.8: p = 0.227) or new onset of clinically significant disability (ARR 2.0; 95% CI 0.9-4.6: p = 0.098). However, the risk of postoperative major complications was increased in patients with an abnormal iron status (ARR 1.7; 95% CI 1.1-2.5: p = 0.012). CONCLUSIONS: An abnormal iron status before elective cardiac surgery was associated with an increased risk of postoperative major complications but not with PRBC transfusion or a new onset of clinically significant disability.

Relationship between hemoglobin and grip strength in older adults: the ActiFE study.

INTRODUCTION: Although anemia is associated with low muscle strength, hemoglobin has been rarely studied considering ferritin. AIM: To analyze the association between hemoglobin and grip strength in community-dwelling older adults. METHODS: We used data from a German cohort of adults ≥ 65 years, excluding those with CRP > 10 mg/L or taking iron supplements. Grip strength (kg) was measured using a Jamar dynamometer. Analysis was performed using multiple linear regression, adjusted for established confounders. Due to interaction, age-stratified (< 80, 80 +), further sex-stratified analysis in those < 80 years old and ferritin-stratified in men < 80 years were performed. RESULTS: In total, 1294 participants were included in this analysis (mean age 75.5 years, 549 (42.3%) women, 910 (70.3%) < 80 years). On average, hemoglobin and grip strength were 14.9 g/dL and 41.3 kg for men, 13.9 g/dL and 25.1 kg for women. Hemoglobin was significantly positively associated with grip strength only among women < 80 years (ß 0.923 [95% CI 0.196, 1.650]). For men < 80 years, the association was significant when ferritin was ≥ 300 µg/L (ß 2.028 [95% CI 0.910, 3.146]). No association was detected among those participants 80 + . DISCUSSION AND CONCLUSIONS: Our data show an association between hemoglobin and grip strength only in women < 80 years old. For men < 80 years, the association was only significant with ferritin levels ≥ 300 µg/L. Considering the decreasing levels of hemoglobin and grip strength and the high prevalence of iron deficiency in older adults further analyses investigating this relationship with more iron specific parameters such as transferrin saturation are warranted.

Causal relationship between iron status and preeclampsia-eclampsia: a Mendelian randomization analysis.

BACKGROUND: Preeclampsia/eclampsia is a severe pregnancy-related disorder associated with hypertension and organ damage. While observational studies have suggested a link between maternal iron status and preeclampsia/eclampsia, the causal relationship remains unclear. The aim of this study was to investigate the genetic causality between iron status and preeclampsia/eclampsia using large-scale genome-wide association study (GWAS) summary data and Mendelian randomization (MR) analysis. METHODS: Summary data for the GWAS on preeclampsia/eclampsia and genetic markers related to iron status were obtained from the FinnGen Consortium and the IEU genetic databases. The "TwoSampleMR" software package in R was employed to test the genetic causality between these markers and preeclampsia/eclampsia. The inverse variance weighted (IVW) method was primarily used for MR analysis. Heterogeneity, horizontal pleiotropy, and potential outliers were evaluated for the MR analysis results. RESULTS: The random-effects IVW results showed that ferritin (OR = 1.11, 95% CI: .89-1.38, p = .341), serum iron (OR = .90, 95% CI: .75-1.09, p = .275), TIBC (OR = .98, 95% CI: .89-1.07, p = .613), and TSAT (OR = .94, 95% CI: .83-1.07, p = .354) have no genetic causal relationship with preeclampsia/eclampsia. There was no evidence of heterogeneity, horizontal pleiotropy, or possible outliers in our MR analysis (p > .05). CONCLUSIONS: Our study did not detect a genetic causal relationship between iron status and preeclampsia/eclampsia. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.

Population Iron Status in Canada: Results from the Canadian Health Measures Survey 2012-2019.

BACKGROUND: In Canada, population iron status estimates are dated (2009-2011) and did not consider the presence of inflammation. OBJECTIVES: This study aimed to update iron status estimates in Canada using serum ferrin (SF) and evaluate different correction methods for inflammation based on c-reactive protein (CRP). METHODS: Data from the Canadian Health Measures Survey cycles 3-6 (2012-2019) formed a multiyear, cross-sectional, nationally representative sample (3-79 y) (n = 21,453). WHO cutoffs for SF and hemoglobin were used to estimate iron deficiency (ID), iron deficiency anemia (IDA), anemia, and elevated iron stores. ID was first estimated without considering inflammation. Correction approaches evaluated were excluding individuals with CRP >5 mg/L, using modified SF cutoffs, and regression correction. RESULTS: Total population uncorrected prevalence estimates were 7% (95% CI: 6.2, 7.9) ID, 6.1% (95% CI: 5.2, 7.0) anemia, and 2.0% (95% CI: 1.6, 2.4) IDA. The uncorrected prevalence of ID was the highest among females of reproductive age with 21.3% (95% CI: 17.6, 25.0) and 18.2% (95% CI: 15.4, 21.1) in 14-18 y and 19-50 y, respectively. Corrected ID estimates were higher than the uncorrected values, independent of the correction approach. Regression correction led to a moderate increase in the prevalence to 10.5% for the total population, whereas applying the higher modified SF cutoffs (70 µg/L for those older than 5 y) led to the largest increases in the prevalence, to 12.6%. Applying modified cutoffs led to implausibly high ID estimates among those with inflammation. Elevated iron stores were identified in 17.2% (95% CI: 16.2, 18.2) of the population, mostly in adult males. CONCLUSIONS: Correction methods for estimating population iron status need further research. Considering the fundamental drawbacks of each method, uncorrected and regression-corrected estimates provide a reasonable range for ID in the Canadian population. Important sex-based differences in iron status and a public health ID problem of moderate magnitude among females of reproductive age are evident in Canada.

CDC's Vitamin A Laboratory-External Quality Assessment Program Shows Little Change in Laboratory Performance for Multiple Nutritional Biomarkers over a 10-Year Period (2008-2017).

BACKGROUND: The Vitamin A Laboratory-External Quality Assessment (VITAL-EQA) program operated by the CDC provides analytical performance assessment to low-resource laboratories conducting serum vitamins A (VIA), D (VID), B-12 (B12), and folate (FOL), as well as ferritin (FER) and CRP measurements for public health studies. OBJECTIVES: We aimed to describe the long-term performance of VITAL-EQA participants from 2008 to 2017. METHODS: Participating laboratories received 3 blinded serum samples biannually for duplicate analysis over 3 d. We assessed results (n = 6) for relative difference (%) from the CDC target value and imprecision (% CV) and conducted descriptive statistics on the aggregate 10-year and round-by-round data. Performance criteria were based on biologic variation and deemed acceptable (optimal, desirable, or minimal performance) or unacceptable (less than minimal performance). RESULTS: Thirty-five countries reported VIA, VID, B12, FOL, FER, and CRP results from 2008-2017. The proportion of laboratories with acceptable performance ranged widely by round: VIA 48%-79% (for difference) and 65%-93% (for imprecision), VID 19%-63% and 33%-100%, B12 0%-92% and 73%-100%, FOL 33%-89% and 78%-100%, FER 69%-100% and 73%-100%, and CRP 57%-92% and 87%-100%. On aggregate, ≥60% of laboratories achieved acceptable differences for VIA, B12, FOL, FER, and CRP (only 44% for VID), and over 75% of laboratories achieved acceptable imprecision for all 6 analytes. Laboratories participating continuously in 4 rounds (2016-2017) showed generally similar performance compared to laboratories participating occasionally. CONCLUSIONS: Although we observed little change in laboratory performance over time, on aggregate, >50% of the participating laboratories achieved acceptable performance, with acceptable imprecision being achieved more often than acceptable difference. The VITAL-EQA program is a valuable tool for low-resource laboratories to observe the state of the field and track their own performance over time. However, the small number of samples per round and the constant changes in laboratory participants make it difficult to identify long-term improvements.

Iron Status and Associated Factors among Canadian Women: Results from the Canadian Health Measures Survey.

BACKGROUND: Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women. OBJECTIVES: This study investigated associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada. METHODS: Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 µg/L) or elevated iron stores (SF >150 µg/L). RESULTS: Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 µg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women. CONCLUSIONS: Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.

Maternal factors associated with iron deficiency without anaemia in early pregnancy: ECLIPSES study.

Several population-specific genetic, sociodemographic, and maternal lifestyle factors are related to iron status in early pregnancy, and their identification would allow preventive actions to be taken. The study aimed to identify maternal factors associated with iron deficiency (ID) in early pregnancy in non-anaemic pregnant women from a European Mediterranean country. Cross-sectional study using the initial population of the ECLIPSES study performed in non-anaemic pregnant women before gestational week 12. Serum ferritin (SF) and haemoglobin concentrations were measured to evaluate iron status, and ID was defined as SF < 15 µg/L. Several sociodemographic and lifestyle data were recorded and used as covariates in the multivariate-adjusted regression models. Out of the 791 participants, 13.9% had ID in early pregnancy. Underweight (OR 3.70, 95%CI 1.22, 15.53) and parity (1 child: OR 2.03, 95%CI 1.06, 3.88; ≥ 2 children: OR 6.96, 95%CI 3.09, 15.69) increased the odds of ID, while a high intake of total meat (≥ 108.57 g/day: OR 0.37, 95%CI 0.15, 0.87), red/processed meat (≥ 74.29 g/day: OR 0.70, 95%CI 0.35, 0.98), protein (≥ 65.05 g/day: OR 0.85, 95%CI 0.30, 0.99), and dietary iron (≥ 8.58 mg/day: OR 0.58, 95%CI 0.35, 0.94) protected against it. Smoking was also associated with a reduction in ID odds (OR 0.34, 95%CI 0.12, 0.99). Baseline BMI, parity, smoking, and diet are associated with ID in early pregnancy in non-anaemic women. Pregnancy planning policies should focus on women at higher risk of ID, such as those who are underweight, multiparous, or following vegetarian diets. This clinical trial was registered at www.clinicaltrialsregister.eu as EudraCT number 2012-005,480-28 and at www.clinicaltrials.gov with identification number NCT03196882.

Role of oral iron supplementation for anemia secondary to acute nonvariceal upper gastrointestinal bleeding: a randomized controlled trial.

BACKGROUND AND AIM: Although acute upper gastrointestinal bleeding (UGIB) can lead to anemia, evidence regarding the effects of oral iron supplementation on UGIB-induced anemia following discharge remains lacking. The present study aimed to investigate the effects of oral iron supplementation on hemoglobin response and iron storage in patients with anemia secondary to nonvariceal UGIB. METHODS: This randomized controlled trial included 151 patients with nonvariceal UGIB who had anemia at discharge. Patients were assigned to a 1:1 block in which they were either administered 6 weeks of 600 mg/d oral ferrous fumarate (treatment group, n = 77) or treated without iron supplementation (control group, n = 74). The primary outcome was composite hemoglobin response (hemoglobin elevation greater than 2 g/dL or no anemia at the end of treatment [EOT]). RESULTS: The proportion of patients achieving composite hemoglobin response was greater in the treatment group than in the control group (72.7% vs 45.9%; adjusted risk ratio [RR], 2.980; P = 0.004). At EOT, the percentage change in the hemoglobin level (34.2 ± 24.8% vs 19.4 ± 19.9%; adjusted coefficient, 11.543; P < 0.001) was significantly higher in the treatment group than in the control group; however, the proportions of patients with a serum ferritin level <30 µg/L and a transferrin saturation <16% were lower in the treatment group (all P < 0.05). No significant differences in treatment-associated adverse effects and adherence rates were observed between the groups. CONCLUSION: Oral iron supplementation exerts beneficial effects on anemia and iron storage following nonvariceal UGIB without significantly impacting rates of adverse effects or adherence.

Associations of an industry-relevant metal mixture with verbal learning and memory in Italian adolescents: The modifying role of iron status.

BACKGROUND: Biomarker concentrations of metals are associated with neurodevelopment, and these associations may be modified by nutritional status (e.g., iron deficiency). No prior study on associations of metal mixtures with neurodevelopment has assessed effect modification by iron status. OBJECTIVES: We aimed to quantify associations of an industry-relevant metal mixture with verbal learning and memory among adolescents, and to investigate the modifying role of iron status on those associations. METHODS: We used cross-sectional data from 383 Italian adolescents (10-14 years) living in proximity to ferroalloy industry. Verbal learning and memory was assessed using the California Verbal Learning Test for Children (CVLT-C), and metals were quantified in hair (manganese, copper, chromium) or blood (lead) using inductively coupled plasma mass spectrometry. Serum ferritin, a proxy for iron status, was measured using immunoassays. Covariate-adjusted associations of the metal mixture with CVLT subtests were estimated using Bayesian Kernel Machine Regression, and modification of the mixture associations by ferritin was examined. RESULTS: Compared to the 50th percentile of the metal mixture, the 90th percentile was associated with a 0.12 standard deviation [SD] (95% CI = -0.27, 0.50), 0.16 SD (95% CI = -0.11, 0.44), and 0.11 SD (95% CI = -0.20, 0.43) increase in the number of words recalled for trial 5, long delay free, and long delay cued recall, respectively. For an increase from its 25th to 75th percentiles, copper was beneficially associated the recall trials when other metals were fixed at their 50th percentiles (for example, trial 5 recall: ß = 0.31, 95% CI = 0.14, 0.48). The association between copper and trial 5 recall was stronger at the 75th percentile of ferritin, compared to the 25th or 50th percentiles. CONCLUSIONS: In this metal mixture, copper was beneficially associated with neurodevelopment, which was more apparent at higher ferritin concentrations. These findings suggest that metal associations with neurodevelopment may depend on iron status, which has important public health implications.

Effects of egg as an early complementary food on growth of 6- to 9-month-old infants: a randomised controlled trial.

OBJECTIVE: To assess the effect of daily egg consumption for six months on linear growth (primary outcome), weight-for-age, weight-for-length, mid-upper arm circumference-for-age, head circumference-for-age Z-scores, gross motor milestones development, anaemia and iron status (secondary outcomes) in a low socioeconomic community. PARTICIPANTS: Infants aged 6 to 9 months living in the peri-urban Jouberton area, in the Matlosana Municipality, South Africa. DESIGN: A randomised controlled trial with a parallel design was implemented. Eligible infants were randomly allocated to the intervention (n 250) receiving one egg/day and the control group (n 250) receiving no intervention. The participants were visited weekly to monitor morbidity and gross motor development, with information on adherence collected for the intervention group. Trained assessors took anthropometric measurements, and a blood sample was collected to assess anaemia and iron status. There was blinding of the anthropometric assessors to the groups during measurements and the statistician during the analysis. RESULTS: Baseline prevalence of stunting, underweight, wasting, overweight and anaemia was 23·8 %, 9·8 %, 1·2 %, 13·8 % and 29·2 %, respectively, and did not differ between groups. Overall, 230 and 216 participants in the intervention and control groups completed the study, respectively. There was no intervention effect on length-for-age, weight-for-age, weight-for-length Z-scores, gross motor milestone development, anaemia and iron status. CONCLUSIONS: Daily egg intake did not affect linear growth, underweight, wasting, motor milestones development, anaemia and iron status. Other interventions are necessary to understand the effect of animal-source food intake on children's growth and development. This trial was registered at https://clinicaltrials.gov/ (NCT05168085).

Inflammatory diets are associated with lower total iron binding capacity in sera of young adults.

Chronic, systemic inflammation, which is associated with obesity and numerous other diseases, impairs iron status by increasing hepcidin concentration. Inflammation also decreases the concentration of transferrin, the main iron transport protein and a negative acute phase protein, which is indirectly assessed by measuring total iron binding capacity (TIBC). However, the contribution of diet-induced inflammation has not been studied. Data from two studies, namely Diet and Inflammation and Selenium and Inflammation Studies (total n=98) were used to assess the associations among Dietary Inflammatory Index (DII®) scores derived from three-day dietary records, body mass index (BMI=weight[kg]/height[m]2), inflammatory and hematological markers among young adults with normal-weight, overweight or obesity. Subjects' diets were also categorized as less inflammatory diets (LID) and inflammatory diets (ID) using cluster analysis. Independent t-test and regression analyses were used to assess associations in the data. Intakes of iron, proteins, fat, fiber, and calories were higher in the LID group compared to the ID group (p<0.05). Demographic characteristics and concentrations of C-reactive protein (CRP) and iron status biomarkers did not differ significantly between the two groups (p>0.05). Higher DII score was associated with increasing CRP (ß+SE=0.23+0.07, p=0.002) and lower TIBC (ß+SE=-8.46+3.44, p=0.02), independent of BMI category. The LID diet was associated with higher TIBC (ß+SE=29.87+10.75, p=0.007) compared to the ID diet. In conclusion, inflammatory diets may impair iron status by reducing the iron binding capacity of transferrin.

Micronutrient status of New Zealand adolescent women consuming vegetarian and non-vegetarian diets.

BACKGROUND AND OBJECTIVES: Globally, there appears to be an ever-increasing interest in adopting a vegetarian diet. However, there are concerns that avoiding meat may increase the risk of anaemia and micronutrient deficiencies, especially for vulnerable populations, such as adolescent women. The objective of this study was to compare the micronutrient status of vegetarian and non-vegetarian adolescent women in New Zealand. METHODS AND STUDY DESIGN: Adolescent women aged 15-18 y were recruited from eight locations across New Zealand. Blood samples were analysed for: haemoglobin, serum ferritin, soluble transferrin receptor, zinc, selenium, retinol binding protein, folate, vitamin B-12, vitamin D and parathyroid hormone. RESULTS: Of the 182 participants who provided a blood sample, 15% self-identified as vegetarian (n=27). On average, vegetarians had 3.1% (95% CI -5.8 to -0.4, p=0.025) lower haemoglobin, and 8.3% (95%CI -14.1 to -2.1, p=0.004) lower selenium. In contrast, serum folate was 80.5% (95% CI 45.7 to 123.7, p<0.001) higher. The prevalence of zinc and selenium deficiency was higher among vegetarians (50% and 12%, respectively) than non-vegetarians (21%, and 2%, respectively). CONCLUSIONS: Adolescent vegetarian women may be at increased risk of deficiency of micronutrients commonly found in animal products, including zinc and selenium, and may benefit from following dietary practices that enhance micronutrient intake and absorption.

The Iron Status of Children with and without Sickle Cell Disease at the University of Ilorin Teaching Hospital, Nigeria.

BACKGROUND: Children with sickle cell disease (SCD) are at potential risk of iron overload from chronic transfusion and probable iron deficiency due to accelerated growth. However, only few studies on the iron status of children with SCD in Nigeria are available. METHODOLOGY: A cross-sectional study compared the iron status of 109 children with sickle cell disease with 109 age and sex-matched haemoglobin AA controls at the University of Ilorin Teaching Hospital. Parameters assayed were serum iron, ferritin, transferrin, and haemoglobin (Hb) concentrations. Considering the appropriate reference values for age and sex, these parameters were used to classify the children into high, normal, or low iron status. RESULTS: The median (interquartile range) serum ferritin level of 180.00 (237.50)ng/ml for the SCD subjects was significantly higher than 70.00 (120.00)ng/ml observed among controls, but the mean Hb and median serum transferrin levels were significantly lower in the subjects compared with the corresponding values in the controls, each showing statistical significance (p<0.05). The median serum iron levels did not differ significantly between the SCD (112µg/dl) and non-SCD (128µg/dl), p=0.309. A high proportion of subjects had low HB status (96.3%) compared with controls (56.9%), p=0.001. A significantly higher proportion of subjects (78%) had high ferritin status compared with the controls (48.3%; p <0.001). Ten (9.1%) SCD children had low serum iron status compared to 28 (25.7%) HbAA controls, p=0.002. Thirty-four (31.2) subjects had low transferrin status which was significantly higher than the corresponding number of controls (8;7.3%; p<0.001). CONCLUSION: The children with SCD in the index study were iron-sufficient.

CONTEXTE: Les enfants atteints de la drépanocytose (SCD) sont potentiellement exposés à un excès de fer dû aux transfusions chroniques et à une éventuelle carence en fer due à la croissance accélérée. Cependant, seulement quelques études sur l'état du fer chez les enfants atteints de la SCD au Nigéria sont disponibles. MÉTHODE: Une étude transversale a comparé l'état du fer de 109 enfants atteints de la drépanocytose à celui de 109 témoins de même âge et de même sexe porteurs d'hémoglobine AA à l'hôpital universitaire d'Ilorin. Les paramètres analysés étaient les concentrations de fer sérique, de ferritine, de transferrine et d'hémoglobine (Hb). En utilisant les valeurs de référence appropriées pour l'âge et le sexe, ces paramètres ont été utilisés pour classer les enfants en fonction de leur statut en fer, à savoir élevé, normal ou faible. RÉSULTATS: Le niveau médian (plage interquartile) de ferritine sérique de 180,00 (237,50) ng/ml chez les sujets atteints de SCD était significativement plus élevé que les 70,00 (120,00) ng/ml observés chez les témoins, mais la concentration moyenne en Hb et le niveau médian de transferrine sérique étaient significativement plus bas chez les sujets par rapport aux valeurs correspondantes chez les témoins, chaque différence étant statistiquement significative (p<0,05). Les niveaux médians de fer sérique ne différaient pas de manière significative entre les sujets atteints de SCD (112 µg/dl) et les témoins non atteints de SCD (128 µg/dl), p=0,309. Une proportion élevée de sujets présentait un faible statut en Hb (96,3 %) par rapport aux témoins (56,9 %), p=0,001. Une proportion significativement plus élevée de sujets (78 %) avait un statut élevé en ferritine par rapport aux témoins (48,3 % ; p <0,001). Dix (9,1 %) enfants atteints de SCD avaient un faible statut en fer sérique par rapport à 28 (25,7%) témoins HbAA, p=0,002. Trente-quatre (31,2 %) des sujets avaient un faible statut en transferrine, ce qui était significativement plus élevé que le nombre correspondant de témoins (8 ; 7,3 % ; p<0,001). CONCLUSION: Les enfants atteints de la SCD dans cette étude étaient suffisamment approvisionnés en fer.

Mild to Moderate Food Deprivation Increases Hepcidin and Results in Hypoferremia and Tissue Iron Sequestration in Mice.

BACKGROUND: Short-term starvation and severe food deprivation (FD) reduce dietary iron absorption and restricts iron to tissues, thereby limiting the amount of iron available for erythropoiesis. These effects may be mediated by increases in the iron regulatory hormone hepcidin; however, whether mild to moderate FD has similar effects on hepcidin and iron homeostasis is not known. OBJECTIVES: To determine the effects of varying magnitudes and durations of FD on hepcidin and indicators of iron status in male and female mice. METHODS: Male and female C57BL/6J mice (14 wk old; n = 170) were randomly assigned to consume AIN-93M diets ad libitum (AL) or varying magnitudes of FD (10%, 20%, 40%, 60%, 80%, or 100%). FD was based on the average amount of food consumed by the AL males or females, and food was split into morning and evening meals. Mice were euthanized at 48 h and 1, 2, and 3 wk, and hepcidin and indicators of iron status were measured. Data were analyzed by Pearson correlation and one-way ANOVA. RESULTS: Liver hepcidin mRNA was positively correlated with the magnitude of FD at all time points (P < 0.05). At 3 wk, liver hepcidin mRNA increased 3-fold with 10% and 20% FD compared with AL and was positively associated with serum hepcidin (R = 0.627, P < 0.0001). Serum iron was reduced by ∼65% (P ≤ 0.01), and liver nonheme iron concentrations were ∼75% greater (P ≤ 0.01) with 10% and 20% FD for 3 wk compared with AL. Liver hepcidin mRNA at 3 wk was positively correlated with liver Bmp6 (R = 0.765, P < 0.0001) and liver gluconeogenic enzymes (R = >0.667, P < 0.05) but not markers of inflammation (P > 0.05). CONCLUSIONS: FD increases hepcidin in male and female mice and results in hypoferremia and tissue iron sequestration. These findings suggest that increased hepcidin with FD may contribute to the disturbances in iron homeostasis with undernutrition.

Implication of asymptomatic and clinical Plasmodium falciparum infections on biomarkers of iron status among school-aged children in Malawi.

BACKGROUND: Iron status is considered as a continuum from an iron deficiency with anaemia, without anaemia, varying amounts of stored iron to iron overload. The burden of Plasmodium falciparum infections is typically high among school-aged children (SAC). Nonetheless, SAC are often less likely to be covered by malaria interventions, making them a group with an untreated reservoir of parasite transmission. This study aimed to assess the effects of asymptomatic and clinical malaria infections on biochemical markers of iron status among SAC in Malawi. METHODS: Data from the 2015-2016 Malawi Micronutrient Survey (MNS) was used and multivariable logistic regression models using a generalized estimating equation to account for the complex cluster survey design were constructed. Blood samples of 684 children aged 5 to 14 years old were evaluated for clinical and asymptomatic malaria infections. Furthermore, blood samples were used to estimate haemoglobin (Hb), serum ferritin (SF) and, soluble transferrin receptors (sTfR) concentrations. RESULTS: Of the 684 SAC analysed, approximately 42% had asymptomatic malaria, while 41.0% had clinical malaria. Anaemia (low Hb levels), iron deficiency (low SF concentration), and functional iron deficiency (high sTfR levels) were found in 20%, 5%, and 30% of the children, respectively. School-aged children with asymptomatic malaria had increased odds of being anaemic (adjusted odds ratio [aOR]: 3.71, 95% confidence interval [CI]: 2.29-5.99) and increased levels of sTfR (aOR: 3.00, 95% CI 2.01-4.47). Similarly, SAC with clinical malaria had increased odds of being anaemic (aOR: 3.54, 95% CI 2.19-5.72) and increased levels of sTfR (aOR: 3.02, 95% CI 2.02-4.52). CONCLUSIONS: Both asymptomatic and clinical malaria were independent risk factors for anaemia and functional iron deficiency (FID). The notion that asymptomatic and clinical malaria were associated with both anaemia and FID underscores the need for public health programmers to consider adding mass screening and treatment for malaria to existing school-based health programmes.