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Whole-blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We aimed to determine the effects of ferritin-guided donation intervals for blood donor health and blood supply in the Netherlands. In this stepped-wedge cluster-randomised trial (FIND'EM), the 138 fixed and mobile donation centres in the Netherlands are organised into 29 geographical clusters and the clusters were randomly assigned to four treatment groups, with two groups being further split into two per a protocol amendment. Eligible donors were whole-blood donors who consented for use of their leftover material in the study. Each group was sequentially crossed over from the existing policy (haemoglobin-based screening; control) to a ferritin-guided donation interval policy over a 3-year period. In the intervention groups, in addition to the existing haemoglobin screening, ferritin was measured in all new donors and at every fifth donation in repeat donors. Subsequent donation intervals were extended to 6 months if ferritin concentrations were 15–30 ng/mL and to 12 months if they were less than 15 ng/mL. Outcomes were measured cross-sectionally across all donation centres at four timepoints. Primary outcomes were ferritin and haemoglobin concentrations, iron deficiency, and haemoglobin-based deferrals. We assessed all outcomes by sex and menopausal status and significance for primary outcomes was indicated by a p value of less than 0·0125. This trial is registered in the Dutch trial registry, NTR6738, and is complete. Between Sept 11, 2017, and Nov 27, 2020, 412 888 whole-blood donors visited a donation centre, and we did measurements on samples from 37 621 donations from 36 099 donors. Over 38 months, ferritin-guided donation intervals increased mean ferritin concentrations (by 0·18 log10 ng/mL [95% CI 0·15–0·22; p<0·0001] in male donors, 0·10 log10 ng/mL [0·06–0·15; p<0·0001] in premenopausal female donors, and 0·17 log10 ng/mL [0·12–0·21; p<0·0001] in postmenopausal female donors) and mean haemoglobin concentrations (by 0·30 g/dL [95% CI 0·22–0·38; p<0·0001] in male donors, 0·12 g/dL [0·03–0·20; p<0·0074] in premenopausal female donors, and 0·16 g/dL [0·05–0·27; p<0·0044] in postmenopausal female donors). Iron deficiency decreased by 36–38 months (odds ratio [OR] 0·24 [95% CI 0·18–0·31; p<0·0001] for male donors, 0·49 [0·37–0·64; p<0·0001] for premenopausal female donors, and 0·24 [0·15–0·37; p<0·0001] for postmenopausal female donors). At 36–38 months, haemoglobin-based deferral decreased significantly in male donors (OR at 36–38 months 0·21 [95% CI 0·10–0·40, p<0·0001]) but not significantly in premenopausal or postmenopausal female donors (0·81 [0·54–1·20; p=0·29] and 0·50 [95% CI 0·25–0·98; p=0·051], respectively). Ferritin-guided donation intervals significantly improved haemoglobin and ferritin concentrations and significantly decreased iron deficiency over the study period. Haemoglobin-based deferrals decreased significantly for male donors, but not female donors. Although this intervention is overall beneficial for maintenance of iron and haemoglobin concentrations in donors, increased efforts are needed to recruit and retain donors. The Sanquin Research Programming Committee.

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50 mg Fe as FeSO4 (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time × treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammation.

Background and aimIron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years.MethodsSecondary analysis of the DO-HEALTH trial, a 3-year clinical trial including 2157 community-dwelling adults aged ≥ 70 years from Austria, France, Germany, Portugal and Switzerland. Iron deficiency was defined as soluble transferrin receptor (sTfR) > 28.1 nmol/L. Prevalence and incidence rate (IR) of iron deficiency per 100 person-years were examined overall and stratified by sex, age group, and country. Sensitivity analysis for three commonly used definitions of iron deficiency (ferritin < 45 μg/L, ferritin < 30 μg/L, and sTfR–ferritin index > 1.5) were also performed.ResultsOut of 2157 participants, 2141 had sTfR measured at baseline (mean age 74.9 years; 61.5% women). The prevalence of iron deficiency at baseline was 26.8%, and did not differ by sex, but by age (35.6% in age group ≥ 80, 29.3% in age group 75–79, 23.2% in age group 70–74); P < 0.0001) and country (P = 0.02), with the highest prevalence in Portugal (34.5%) and the lowest in France (24.4%). As for the other definitions of iron deficiency, the prevalence ranged from 4.2% for ferritin < 30 µg/L to 35.3% for sTfR–ferritin index > 1.5. Occurrences of iron deficiency were observed with IR per 100 person-years of 9.2 (95% CI 8.3–10.1) and did not significantly differ by sex or age group. The highest IR per 100 person-years was observed in Austria (20.8, 95% CI 16.1–26.9), the lowest in Germany (6.1, 95% CI 4.7–8.0). Regarding the other definitions of iron deficiency, the IR per 100 person-years was 4.5 (95% CI 4.0–4.9) for ferritin < 45 µg/L, 2.4 (95% CI 2.2–2.7) for ferritin < 30 µg/L, and 12.2 (95% CI 11.0–13.5) for sTfR–ferritin index > 1.5.ConclusionsIron deficiency is frequent among relatively healthy European older adults, with people aged ≥ 80 years and residence in Austria and Portugal associated with the highest risk.

Background/ObjectivesWe examined the prevalence of anaemia, iron deficiency, and inflammation during pregnancy and their associations with adverse pregnancy and infant outcomes in India.Subjects/MethodsThree hundred and sixty-six women participating in a randomised trial of vitamin B12 supplementation were monitored to assess haemoglobin (Hb), serum ferritin (SF), hepcidin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) during pregnancy. Women received vitamin B12 supplementation (50 µg per day) or placebo daily; all women received daily prenatal iron–folic acid supplementation. Binomial and linear regression models were used to examine the associations of maternal iron biomarkers with pregnancy and infant outcomes.ResultsThirty percent of women were anaemic (Hb < 11.0 g/dl), 48% were iron deficient (SF < 15.0 µg/l), and 23% had iron deficiency anaemia at their first prenatal visit. The prevalence of inflammation (CRP > 5.0 mg/l: 17%; AGP > 1.0 g/l: 11%) and anaemia of inflammation (Hb < 11.0 g/dl, SF > 15.0 µg/l, plus CRP > 5.0 mg/l or AGP > 1.0 g/l: 2%) were low. Infants born to anaemic women had a twofold higher risk of low birth weight (<2500 g; risk ratio [RR]: 2.15, 95%CI: 1.20–3.84, p = 0.01), preterm delivery (RR: 2.67 (1.43–5.00); p = 0.002), underweight (WAZ < −2; RR: 2.20, 95%CI: 1.16–4.15, p = 0.02), and lower MUAC (β(SE): −0.94 (0.45)cm, p = 0.03). Similarly, maternal Hb concentrations predicted higher infant birth weight (p = 0.02) and greater gestational age at delivery (β(SE): 0.28 (0.08) weeks, p = 0.001), lower risk of preterm delivery (<37 weeks; RR: 0.76, 95%CI: 0.66–86, p < 0.0001); and higher infant MUAC (β(SE): 0.36 (0.13) cm, p = 0.006). Maternal SF concentrations were associated with greater birth length (β(SE): 0.44 (0.20) cm, p < 0.03). Findings were similar after adjusting SF concentrations for inflammation. IDA was associated with higher risk of low birth weight (RR: 1.99 (1.08–3.68); p = 0.03) and preterm birth (RR: 3.46 (1.81–6.61); p = 0.0002); and lower birth weight (p = 0.02), gestational age at birth (p = 0.0002), and infant WAZ scores (p = 0.02).ConclusionsThe prevalence of anaemia and iron deficiency was high early in pregnancy and associated with increased risk of adverse pregnancy and infant outcomes. A comprehensive approach to prevent anaemia is needed in women of reproductive age, to enhance haematological status and improve maternal and child health outcomes.

Background The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). Methods This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6–59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sT f R) and body iron stores (BIS). We used Pearson’s chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). Results The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4–56.5)% while that of ID and IDA were 55.7(48.6–62.5)% and 34.3(28.2–41.0)% when using sT f R criterion and 29.1(24.4–34.4)% and 28.9(23.7–34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9–20.3)% for FSMS-RUTF, 18.2(11.9–26.8)% for MSMS-RUTF and 24.5(15.8–35.9)% for PM-RUTF; p  = 0.023] and IDA [7.9(3.4–17.3)% for FSMS-RUTF, 10.9(4.8–22.6)% for MSMS-RUTF and 20.5(10.7–35.5)% for PM-RUTF; p  = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p  = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2–0.5) with p  < 0.001 for FSMS-RUTF and 0.6 (0.3–1.0) with p  = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. Conclusions Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. Trial registration This study was registered on 15 April 2015 ( PACTR201505001101224 ).

Adolescent girls are an important target group for micronutrient interventions particularly in Sub-Saharan Africa where adolescent pregnancy and micronutrient deficiencies are common. When consumed in sufficient amounts and at levels appropriate for the population, fortified foods may be a useful strategy for this group, but little is known about their effectiveness and timing (regarding menarche), particularly in resource-poor environments. We evaluated the effect of consuming multiple micronutrient-fortified biscuits (MMB), sold in the Ghanaian market, 5 d/week for 26 weeks compared with unfortified biscuits (UB) on the micronutrient status of female adolescents. We also explored to what extent the intervention effect varied before or after menarche. Ten2Twenty-Ghana was a 26-week double-blind, randomised controlled trial among adolescent girls aged 10–17 years (n 621) in the Mion District, Ghana. Biomarkers of micronutrient status included concentrations of Hb, plasma ferritin (PF), soluble transferrin receptor (TfR) and retinol-binding protein (RBP), including body-iron stores. Intention-to-treat analysis was supplemented by protocol-specific analysis. We found no effect of the intervention on PF, TfR and RBP. MMB consumption did not affect anaemia and micronutrient deficiencies at the population level. MMB consumption increased the prevalence of vitamin A deficiency by 6·2 % (95 % CI (0·7, 11·6)) among pre-menarche girls when adjusted for baseline micronutrient status, age and height-for-age Z-score, but it decreased the prevalence of deficient/low vitamin A status by −9·6 % (95 % CI (−18·9, −0·3)) among post-menarche girls. Consuming MMB available in the market did not increase iron status in our study, but reduced the prevalence of deficient/low vitamin A status in post-menarcheal girls.

The present study aimed to determine the prevalence of anaemia, iron deficiency (ID) and iron-deficiency anaemia (IDA) among female adolescents in the Gaza Strip, Palestine, as well as the risk factors involved in these conditions. The study was conducted using the quantitative descriptive method with a cross-sectional design. Data were collected using an FFQ and sociodemographic, sedentary behaviour and physical activity questionnaires. Anthropometric measurements and blood analyses were also conducted. The study population included all Palestinian female adolescents enrolled in secondary schools in the academic years 2015-2016. Five female secondary schools were selected randomly from five governorates of the Gaza Strip. Female adolescents (n 330) aged 15-19 years in the selected secondary schools were enrolled randomly. Prevalence of anaemia, ID and IDA among female adolescents in the Gaza Strip, Palestine, was 35·8, 40·3 and 26·0 %, respectively. A significant association (P<0·05) existed between ID, anaemia and IDA and dietary habits, including skipping breakfast and amount of junk food intake. Also, low consumption of fruits and vegetables was associated with IDA in the female adolescents. A statistically significant association was found between mother's education and ID but not with the other sociodemographic factors. The study shows that there is an alarming problem of anaemia and IDA in the Gaza Strip, Palestine. This may indicate that there are insufficient nutrition education programmes, particularly inside schools or by the mass media.

To determine the prevalence, risk factors and prognosis of anemia in representative community-based patients with type 2 diabetes. Data from the Fremantle Diabetes Study Phase II (FDS2; n=1551, mean age 65.7years, 51.9% males) and Busselton Diabetes Study (BDS; n=186, mean age 70.2years, 50.0% males) cohorts, and from 186 matched BDS participants without diabetes, were analyzed. The prevalence of anemia (hemoglobin ≤130g/L males, ≤120g/L females) was determined in each sample. In FDS2, associates of anemia were assessed using multiple logistic regression and Cox proportional hazards modeling identified predictors of death during 4.3±1.2years post-recruitment. The prevalence of anemia at baseline was 11.5% in FDS2 participants, 17.8% in BDS type 2 patients and 5.4% in BDS participants without diabetes. In FDS2, 163 of 178 patients with anemia (91.6%) had at least one other risk factor (serum vitamin B12<140pmol/L, serum ferritin <30μg/L and/or transferrin saturation<20%, serum testosterone <10nmol/L (males), glitazone therapy, estimated glomerular filtration rate (eGFR) <60mL/min 1.73m2, malignancy, hemoglobinopathy). More anemic than non-anemic FDS2 patients died (28.7% versus 8.0%; P<0.001). After adjustment for other independent predictors (age as time-scale, male sex, Aboriginality, marital status, smoking, eGFR), anemia was associated with a 57% increase in mortality (P=0.015). Type 2 diabetes at least doubles the risk of anemia but other mostly modifiable risk factors are usually present. Anemia is associated with an increased risk of death after adjustment for other predictors.

Nutrition is one of many factors affecting the cognitive development of children. In Cambodia, 55% of children <5 y were anemic and 40% stunted in 2010. Currently, no data exists on the nutritional status of Cambodian school-aged children, or on how malnutrition potentially affects their cognitive development. To assess the anthropometric and micronutrient status (iron, vitamin A, zinc, iodine) of Cambodian schoolchildren and their associations with cognitive performance. School children aged 6-16 y (n = 2443) from 20 primary schools in Cambodia were recruited. Anthropometry, hemoglobin, serum ferritin, transferrin receptors, retinol-binding protein and zinc concentrations, inflammation status, urinary iodine concentration and parasite infection were measured. Socio-economic data were collected in a sub-group of children (n = 616). Cognitive performance was assessed using Raven's Colored Progressive Matrices (RCPM) and block design and picture completion, two standardized tests from the Wechsler Intelligence Scale for Children (WISC-III). The prevalence of anemia, iron, zinc, iodine and vitamin A deficiency were 15.7%; 51.2%, 92.8%, 17.3% and 0.7% respectively. The prevalence of stunting was 40.0%, including 10.9% of severe stunting. Stunted children scored significantly lower than non-stunted children on all tests. In RCPM test, boys with iron-deficiency anemia had lower scores than boys with normal iron status (-1.46, p<0.05). In picture completion test, children with normal iron status tended to score higher than iron-deficient children with anemia (-0.81; p = 0.067) or without anemia (-0.49; p = 0.064). Parasite infection was associated with an increase in risk of scoring below the median value in block design test (OR = 1.62; p<0.05), and with lower scores in other tests, for girls only (both p<0.05). Poor cognitive performance of Cambodian school-children was multifactorial and significantly associated with long-term (stunting) and current nutritional status indicators (iron status), as well as parasite infection. A life-cycle approach with programs to improve nutrition in early life and at school-age could contribute to optimal cognitive performance.

Iron supplementation may have adverse health effects in infants, probably through manipulation of the gut microbiome. Previous research in low-resource settings have focused primarily on anemic infants. This was a double blind, randomized, controlled trial of home fortification comparing multiple micronutrient powder (MNP) with and without iron. Six-month-old, non- or mildly anemic, predominantly-breastfed Kenyan infants in a rural malaria-endemic area were randomized to consume: (1) MNP containing 12.5 mg iron (MNP+Fe, n = 13); (2) MNP containing no iron (MNP−Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6–9 months of age. Fecal microbiota were profiled by high-throughput bacterial 16S rRNA gene sequencing. Markers of inflammation in serum and stool samples were also measured. At baseline, the most abundant phylum was Proteobacteria (37.6% of rRNA sequences). The proteobacterial genus Escherichia was the most abundant genus across all phyla (30.1% of sequences). At the end of the intervention, the relative abundance of Escherichia significantly decreased in MNP−Fe (−16.05 ± 6.9%, p = 0.05) and CONTROL (−19.75 ± 4.5%, p = 0.01), but not in the MNP+Fe group (−6.23 ± 9%, p = 0.41). The second most abundant genus at baseline was Bifidobacterium (17.3%), the relative abundance of which significantly decreased in MNP+Fe (−6.38 ± 2.5%, p = 0.02) and CONTROL (−8.05 ± 1.46%, p = 0.01), but not in MNP-Fe (−4.27 ± 5%, p = 0.4445). Clostridium increased in MNP-Fe only (1.9 ± 0.5%, p = 0.02). No significant differences were observed in inflammation markers, except for IL-8, which decreased in CONTROL. MNP fortification over three months in non- or mildly anemic Kenyan infants can potentially alter the gut microbiome. Consistent with previous research, addition of iron to the MNP may adversely affect the colonization of potential beneficial microbes and attenuate the decrease of potential pathogens.