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Dry skin or xerosis is a common ailment occurring both as a separate disease entity and as a symptom of other diseases, e.g. it is a cardinal symptom of atopic dermatitis1 . Infections have been described in xerosis associated with dermatitis2 . Whether xerosis without dermatitis is a risk factor for skin infections remains unknown. We therefore tested if individuals with xerosis had a risk of skin infections.

Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation., Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women.

Background The pathophysiology of xerosis depends on extrinsic and intrinsic exposures. Residential hard water may constitute such an exposure. Objectives To estimate the prevalence of xerosis and to compare water hardness exposure in blood donors with and without xerosis. Methods In this retrospective cohort study in 2018–2019, blood donors with self-reported moderately or severely dry skin were compared to blood donors without dry skin. Blood donors with ichthyosis, lichen planus and psoriasis were excluded. Water hardness data was collected from the Geology Survey of Denmark and Greenland. Results Overall, 4,748 of 30,721 (15.5%; 95% confidence interval 15.1–15.9%) blood donors had xerosis. After excluding blood donors with ichthyosis, lichen planus and psoriasis, 4,416 blood donors (2,559 females; median age 38.4 years [interquartile range 28.0–49.8]; 700 smokers) remained in this study. Water softer than 12–24 degrees Deutsche härte was associated with decreased probability of xerosis (odds ratio 0.83; 95% confidence interval 0.74–0.94) and water harder than 12–24 degrees Deutsche härte was associated with increased probability of xerosis (odds ratio 1.22; 95% confidence interval 1.03–1.45). The association between water hardness and xerosis remained significant after excluding blood donors with dermatitis. Conclusions Water hardness is associated with xerosis independent of other dermatoses.

Background Blood donors are at increased risk of developing iron deficiency, and several studies have recommended iron supplementation for this group. The aim of this study was to investigate the effect of oral iron supplementation on risk of infections among healthy blood donors. Study design and methods We included 82,062 participants from the Danish Blood Donor Study who completed a questionnaire on health-related items including use of oral iron supplementation. Infection outcomes were ascertained by using ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis was used as the statistical model. Risk estimates are presented as crude hazard ratios (HRs) with 95% confidence intervals (CIs). Results During 19,978 person-years of observation, 6983 donors redeemed at least one prescription of antimicrobials. Similarly, during 19,829 person-years of observation, 242 donors were treated for infection at a hospital. Use of oral iron supplementation was not associated with redeemed prescriptions of antimicrobials in any strata: premenopausal women-HR 1.00, 95% CI 0.91-1.10; postmenopausal women-HR 1.07, 95% CI 0.87-1.32; and men-HR 1.01, 95% CI 0.84-1.21. In addition, use of oral iron supplementation was not associated with risk of hospital-based treatment for infection. Conclusion In a large cohort of blood donors, use of oral iron supplementation was not associated with subsequent short-term risk of infection. These findings are important to help understanding the safety of using oral iron supplementation among blood donors and the general population.

Background The prevalence of iron depletion is high among premenopausal women who donate blood frequently. Studies in nondonor populations indicate that iron deficiency anemia is associated with an increased risk of low birth weight. This prompts concerns that iron deficiency induced by frequent blood donation might impair subsequent fetal development. Study design and methods The aim of this study was to assess whether prepregnancy donation intensity affects the birth weight of singletons born at term (gestational week 38 or later) to nulliparous female donors in Denmark. We identified 293,897 first live singleton births to Danish women between 1997 and 2012 with complete information on gestational age, birth weight, child sex, parental age, maternal smoking status during pregnancy, and parental education length and annual income. Linear regression analysis was applied, with birth weight as outcome, number of donations within the 3 years before pregnancy as the explanatory variable, and confounding variables as described. Results Birth weight among children of low-intensity donors (n = 22,120) was 12.6 g (95% confidence interval, 6.7-18.6) higher than nondonors (n = 268,253) after controlling for the above-mentioned factors. The higher birth weight among low-intensity donors can be explained by the healthy donor effect. In fully adjusted analyses, birth weight among children of high-intensity donors (n = 3,524) was 20.2 g (95% confidence interval, 5.1-35.3 g) lower compared with low-intensity donors. This reduced birth weight among high-intensity donors compared to low-intensity donors may reflect blood donation-induced iron deficiency. Conclusions Our results show that high prepregnancy donation intensity is inversely associated with birth weight of singletons born at term to nulliparous women.

To study whether low serum ferritin (s-ferritin) levels are associated with recurrent pregnancy loss (RPL), and whether low s-ferritin predicts the risk of another pregnancy loss or the ability to conceive.Cohort study.Fertility clinic at a university hospital.Eighty-four women referred to the RPL Unit and 153 women of reproductive age with no known fertility problem. s-Ferritin levels were measured in serum samples taken before pregnancy attempt.None.s-Ferritin levels were correlated to pregnancy history, ability to conceive, and time to conception during the first 2 years after sampling. Furthermore, s-ferritin levels were correlated to outcome of the first pregnancy after referral for RPL.Women with RPL had lower s-ferritin than the comparison group, 39.9 μg/L versus 62.2 μg/L, and had a higher prevalence of low iron stores (s-ferritin30 μg/L), 35.7% versus 13.7%. We found an inverse relationship between s-ferritin level and number of pregnancy losses before referral. We did not find s-ferritin level to be associated with ability to conceive or time to pregnancy in either group. Nor did s-ferritin level predict the risk of losing the first pregnancy after referral for RPL.The inverse relationship between s-ferritin levels and previous pregnancy losses suggests that low s-ferritin is associated with a more severe reproductive disturbance in women with RPL. Whether low s-ferritin is causally related to RPL and if such women could benefit from iron supplementation to achieve a live birth warrants further investigation.

BACKGROUND: Occasionally blood donation has a negative influence on some donors, while others express feelings of increased energy or wellbeing after donation. Some donors even report symptoms such as headache or feelings of unease indicating “it is time to donate blood again.” This study aims to determine symptoms and frequencies of blood donors experiencing positive and negative effects of blood donation, and study possible associations with sex, age, body mass index, smoking status, and hemoglobin level. STUDY DESIGN AND METHODS: We developed and validated a questionnaire with eight predefined physical and psychological symptoms related to blood donation using a 5-point Likert Scale. Participants in The Danish Blood Donor Study were asked to indicate if they experienced the present symptom prior to and/or after the donation. RESULTS: A total of 6,073 donors were included. Of the donors, 61% experienced one or more effects of blood donation. Positive effects were experienced by 18% of the donors, 29% experienced negative effects, and 14% experienced both. Most notable positive effects were alleviated headache (14%), feeling lighter (14%), and less tiredness (7%). Most notable negative effects were less energy (25%), more dizziness (22%), and more tiredness (21%). Logistic regression analysis revealed that positive effects were more likely among donors with higher BMI, older donors, and smokers. Negative effects were more likely among younger donors, donors with lower BMI, and among female donors. CONCLUSION: Analyses indicate that susceptibility to blood donation effects varies by BMI, sex, smoking status, and age, and therefore should be taken into consideration when informing donors about potential effects of blood donation.

BACKGROUND: Studies confirm that calcium inhibits iron absorption. Danish tap water comes from groundwater, which contains varying amounts of calcium depending on the subsoil. We investigated the association of calcium in drinking water with iron levels in Danish blood donors.STUDY DESIGN AND METHODS: We used data on Danish blood donors including dietary and lifestyle habits, blood donation history, and physiologic characteristics including measures of ferritin levels along with information on area of residence from The Danish Blood Donor Study. Data on calcium levels in groundwater ("water hardness") were obtained through the Geological Survey of Denmark and Greenland. We performed multiple linear and logistic regression analyses to evaluate the effect of water hardness on ferritin levels and risk of having iron deficiency (defined as ferritin levels RESULTS: There was a significant negative association between water hardness and ferritin levels in both men and women. Risk of iron deficiency was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing water hardness. In analyses restricted to individuals who received supplemental iron tablets no significant association between groundwater hardness and ferritin levels was observed.CONCLUSIONS: As measured by ferritin levels, residential drinking water calcium content is associated with blood donors- iron levels and risk of iron deficiency. However, effect sizes are small.

AIMS: This study aimed at quantifying the healthy donor effect by comparing self-perceived mental and physical health between blood donors and non-donors.BACKGROUND: In theory, the selection process known as the healthy donor effect should result in better self-perceived, health-related quality of life in donors than in non-donors.METHODS: The Short Form-12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS).RESULTS: A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non-donors, whereas MCS was only marginally high in older donors compared with non-donors. In contrast, PCS was almost similar for both young donors and non-donors. With the increase in age, non-donors had lower PCS than donors.CONCLUSIONS: Two selection patterns were revealed. Among young individuals, better self-perceived mental health was associated with a blood donor. With the increase in age, better self-perceived physical health was associated with blood donation.

BACKGROUND Genomewide association studies have reported alleles in the ABO locus to be associated with ferritin levels. These studies warrant the investigation of a possible association between the ABO blood group and ferritin levels. We aimed to explore if ABO blood group is associated with iron stores expressed as ferritin levels. STUDY DESIGN AND METHODS Ferritin levels were measured at least once for 30,595 Danish Blood Donor Study participants. Linear regression analyses were performed with the ABO blood group as explanatory variable and adjusted for age, number of donations 3 years before the ferritin measurement, and time since latest donation. In addition, a subanalysis was performed on 15,280 individuals in which further adjustments for body mass index, smoking status, and C-reactive protein levels were possible. Furthermore, logistic regression analyses were performed to determine if ABO blood group was associated with a ferritin level of less than 15 ng/mL. RESULTS Non-O blood group donors had lower ferritin levels than blood group O donors, regardless of sex. Accordingly, risk of ferritin level of less than 15 ng/mL was increased for individuals with non-O blood group compared with O blood group. In subanalyses similar associations were observed, albeit in women the association between blood group and risk of a ferritin level below 15 ng/mL was no longer significant. ABO blood group was not associated with red blood cell indices such as mean cell volume and mean cell hemoglobin content. CONCLUSION Donors with non-O blood group have lower ferritin levels than donors with other blood groups.

OBJECTIVE: Restless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by uncomfortable sensations in the legs. RLS often occurs as a comorbid condition. Besides an increased risk of iron deficiency, blood donors are considered to be generally healthy. Blood donors are therefore an ideal population for studying factors associated with RLS occurrence, herein the role of iron. It is suggested that RLS is linked to sex, age, low socioeconomic status, unhealthy lifestyle, and iron deficiency. The objective of this study is therefore to estimate the RLS prevalence and identify associated biological, sociodemographic, economic, and lifestyle factors in a population of blood donors.METHODS: A total of 13,448 blood donors enrolled in the Danish Blood Donor Study from May 2015 to May 2016. RLS cases were identified using the validated Cambridge-Hopkins RLS-questionnaire. Logistic regression models were applied to assess the relationship between RLS and data on socially related factors collected using questionnaires and population registers.RESULTS: In this study, 7.2% women and 4.5% men were classified with RLS. RLS was associated with: female sex, high age, smoking, frequent alcohol consumption, and low education. RLS-related symptoms were associated with obesity, parity and donation intensity three years prior to inclusion among women. RLS was not related to: reduced plasma ferritin, employment status, and income.CONCLUSIONS: RLS is a frequent disorder in otherwise healthy individuals. The associations discovered in this study can be utilized in preventing or reducing RLS symptoms.

BACKGROUND Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated. STUDY DESIGN AND METHODS Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation. RESULTS Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94). CONCLUSIONS Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.

Iron deficiency is prevalent in blood donor populations where up to 39%, 22% and 9% of frequently donating premenopausal women, postmenopausal women and men may be iron-deficient, respectively. Moreover, iron deficiency is a global health issue estimated to concern as many as 2·7 billion people and explain half of the cases of anaemia worldwide. Iron deficiency manifesting as anaemia could affect the developing foetus and especially cognitive development. Furthermore, iron deficiency (anaemia) may impair scholastic achievements and work productivity and increase fatigue. Moreover, iron deficiency has been associated with impaired innate and specific immunity in in vitro studies. Lastly, iron supplementation may improve endurance, athletic performance and symptoms of restless leg syndrome. However, most of the effects of iron deficiency (anaemia) have not been assessed among blood donors and no association between restless leg syndrome and ferritin levels in blood donors has been established. Blood donors are in general characterized by a good health, and studies indicate that blood donors live a healthier life and have a lower mortality compared to the general population. The underlying excellent health of blood donors needs to be carefully considered when possible health effects of blood donations are investigated. Iron deficiency is a global challenge with a high prevalence in blood donors. Any possible negative health outcome associated with iron deficiency needs to be examined in a blood donor population.

Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.

BACKGROUND: Due to physiological demands, children and premenopausal women are at risk of developing iron deficiency. In premenopausal women, the risk may be further increased by repeated whole blood donations. Short-term consequences of iron deficiency in infancy include impaired cognitive development and lower IQ scores. This prompts concern that maternal iron deficiency before or during pregnancy may have long-term consequences for the offspring, for example, by affecting scholastic attainment. The aim of this study was to evaluate if prepregnancy donation intensity is associated with offspring scholastic attainment measured as grade averages in standardized national written examinations in Denmark. STUDY DESIGN AND METHODS: By using the Danish personal identification number as key, we obtained information on donation intensity before pregnancy, school grade, year of graduation, age of the students, students' sex, and parental length of education and income from various nationwide registers. Linear regression analyses were performed, with grade average as outcome and maternal donation status as explanatory variable (nondonor, n = 177,078; low-frequency donor, n = 4995 [one to five donations in the 3 years before pregnancy]; high-frequency donor, n = 414 [six or more donations in the 3 years before pregnancy), and further adjusted for the covariates listed above. RESULTS: Adjusted normalized (mean, 0; standard deviation [SD], 1) test scores were statistically significantly higher for children of active female donors compared with children of nondonors (SD, 0.104; 95% confidence interval, 0.079–0.129). We observed no differences in scholastic attainment between children of low-frequency donors and high-frequency donors. CONCLUSION: Prepregnancy donation intensity, as a proxy of iron stores, is not associated with subsequent offspring scholastic attainment.

Blood banks are in a unique position to create biobanks and general health studies since existing infrastructure can readily be reemployed. The available tools for creating biobanks include access to potential study participants (blood donors), handling and storage of biological repositories, and collection facilities with experienced staff. The needed tools not readily available are automated high throughput research analysers with data capture possibilities and freezing facilities. Lastly, designated information platforms e.g. a study webpage should be constructed to facilitate information to participants. The challenges encountered when creating a biobank in a blood bank are many. First, motivation for staff members are potentially needed because extra work may be put upon them in order to include blood donors in research biobanks. Second, in order to accommodate future possible health research projects it is recommended to acquire a broad informed consent for these type of studies. A broad informed consent warrants a clear policy on return of research findings to the study participants. Lastly, the collection of outcome variables must be planned. In Denmark national health registries on admission and diseases are of great value for follow-up data. Otherwise, each subsequent donation after enrollment may serve as a potential way to collect follow-up data or follow-up data may be collected through mailed out questionnaires. Experience from the Danish Blood Donor Study (DBDS) has shown the feasibility of establishing a research biobank within a blood bank by using the existing infrastructure.

BACKGROUND: Restless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and is thus linked with psychosocial distress. Due to the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications.METHODS: Complete data, including the Cambridge-Hopkins RLS questionnaire, the 12-item short-form standardized health survey (SF-12), the Major Depression Inventory (MDI), body mass index, smoking status, alcohol consumption, and education were available for 24,707 participants enrolled in the Danish Blood Donor Study from May 1, 2015 to February 1, 2017. Information on quality of sleep was available for all RLS cases. T-tests and multivariable logistic regression models were applied to examine the associations of RLS and MDI scores, and the physical and mental component scores (PCS and MCS) of SF-12, respectively. Analyses were conducted separately for men and women.RESULTS: RLS associated with poorer MCS and poorer PCS. Moreover, Participants with RLS were more likely to classify with depressive disorder. Poor quality of sleep was associated with depressive disorder and poorer MCS among RLS cases, and with poorer PCS in female RLS cases.CONCLUSION: Thus, we demonstrated that RLS is associated with a significantly lower HRQL and a higher prevalence of depressive disorder among otherwise healthy individuals.

BACKGROUND Health-related quality of life (HRQL) represents people's subjective assessment of their mental and physical well-being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self-reported mental component score (MCS; SF-12) and physical component score (PCS; SF-12) in Danish blood donors. STUDY DESIGN AND METHODS Complete relevant data, including the 12-item short-form health survey (SF-12), plasma ferritin levels, age, body mass index, smoking status, C-reactive protein levels, number of donations in the previous 3 years, and PCS and MCS, were available for 8692 men and 7683 women enrolled from March 1, 2010, to December 31, 2010. Multivariable linear and logistic (cutoff at the 10th percentile) regression analyses were used to assess the relationship between iron deficiency (ferritin

The T-allele in the single nucleotide polymorphism rs6897932 in the gene encoding the IL-7 receptor α (IL7RA) is associated with reduced risk of autoimmune diseases including multiple sclerosis and also affects the course of HIV infection. Low-grade inflammation (LGI) and self-reported, health-related quality of life (HRQL) are often associated with chronic diseases and widely used in assessing and monitoring health status. The aim of the present study was to evaluate whether the T-allele in rs6897932 is associated with reduced risk of LGI (hsCRP 3-10 mg/L), history of infectious mononucleosis (IM), and HRQL in healthy individuals. A total of 17, 293 healthy Danish individuals from the Danish Blood Donor Study were included in the analyses. We tested rs6897932 as a predictor of LGI, self-reported IM, and HRQL in univariable and multivariable models stratified by sex. No associations between rs6897932 and LGI, self-reported IM or HRQL were found in men or women. This suggests that rs6897932 is not associated with general inflammation, and the reported associations between the T-allele in rs6897932 with several autoimmune diseases may be mediated through effects on a restricted part of the immune system.

Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c-aAb in question. A negative correlation between high levels of IL-6-specific c-aAb and plasma levels of C-reactive protein was observed, indicating cytokine-neutralizing levels of c-aAb in healthy blood donors. There was no substantial correlation between high levels of the five individual c-aAb investigated in this study. These data suggest that autoimmunity against endogenous cytokines is a relatively common phenomenon in healthy individuals, and that predictive factors for high, potentially neutralizing c-aAb levels vary depending on the cytokine in question, and may differ from predictors of general c-aAb presence.

Background Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood. Study Design and Methods In the Danish Blood Donor Study, we assessed the effect of blood donation frequency, physiologic factors, lifestyle and supplemental factors, and dietary factors on ferritin levels. We used multiple linear and logistic regression analyses stratified by sex and menopausal status. Results Among high-frequency donors (more than nine donations in the past 3 years), we found iron deficiency (ferritin below 15 ng/mL) in 9, 39, and 22% of men, premenopausal women, and postmenopausal women, respectively. The strongest predictors of iron deficiency were sex, menopausal status, the number of blood donations in a 3-year period, and the time since last donation. Other significant factors included weight, age, intensity of menstruation, iron tablets, vitamin pills, and consumption of meat and wine. Conclusion The study confirms iron deficiency as an important problem, especially among menstruating women donating frequently. The risk of iron depletion was largely explained by sex, menopausal status, and donation frequency. Other factors, including dietary and supplemental iron intake, had a much weaker effect on the risk of iron depletion.

Background and Objectives Chronic inflammation can lead to anaemia of chronic disease due to the sequestration of iron caused by inflammatory cytokines and the protein hepcidin. However, the effect of low-grade inflammation (LGI) on haemoglobin among healthy individuals is not known. This study examines the effect of LGI on haemoglobin among Danish blood donors. Materials and Methods We performed multivariable linear regression to assess the effect of LGI (i.e. high-sensitivity C-reactive protein above 3 mg/l but below 10 mg/l) on haemoglobin in 17 322 Danish blood donors. We also performed multivariable logistic regression to evaluate the effect of LGI on the risk of having low haemoglobin (below the 10th percentile among men and women, respectively). We adjusted for donation activity, age, sex, low ferritin, oral contraceptives and menopause. All analyses were stratified by current smoking status. Results LGI was associated with lower haemoglobin (0·08 mm lower [0·12 g/dl], 95% confidence interval (CI): −0·11–0·05) and increased risk of low haemoglobin (OR = 1·22, 95% CI: 1·05–1·43) in non-smokers. Conversely, LGI was associated with higher haemoglobin in smokers (0·12 mm [0·19 g/dl], 95% CI: 0·06–0·18). Conclusion In this first study of LGI and haemoglobin in healthy individuals, there was a negative association between LGI and haemoglobin in non-smokers. The association was positive in smokers, probably because smoking leads to both increased inflammation and increased haemoglobin through CO exposure.

Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated.Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation.Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94).Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.

Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear.The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9-associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin15 ng/mL).In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant.Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron stores in men.

It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels.Initiated in 2010, the Danish Blood Donor Study is a population-based study and biobank. We performed multivariable linear regression analysis to assess the effects of donation activity, physiologic and lifestyle factors, and diet on Hb levels among 15,197 donors. We also performed multivariable logistic regression to evaluate the effects of these factors on the risk of having low Hb (defined as Hb below the 10th percentile among men and women, respectively) and of a decrease in Hb greater than 0.5 mmol/L (0.8 g/dL) between successive donations. All analyses were performed stratified for sex and smoking status. We also tested a previously used model for the prediction of Hb.The strongest predictors of Hb and risk of low Hb were low ferritin (15 ng/mL) and current use of iron supplementation (yes/no). No dietary factors were found to be consistently significant in multivariable models predicting Hb levels, risk of having low Hb, or risk of a decrease in Hb greater than 0.5 mmol/L. We found similar effects to previous studies of factors in the predictive model, with little additional effect of including smoking status and ferritin.As ferritin was the strongest predictor of Hb, this study supports the implementation of regular ferritin measurement as a method of risk assessment among blood donors.

Health-related quality of life (HRQL) represents people's subjective assessment of their mental and physical well-being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self-reported mental component score (MCS; SF-12) and physical component score (PCS; SF-12) in Danish blood donors.Complete relevant data, including the 12-item short-form health survey (SF-12), plasma ferritin levels, age, body mass index, smoking status, C-reactive protein levels, number of donations in the previous 3 years, and PCS and MCS, were available for 8692 men and 7683 women enrolled from March 1, 2010, to December 31, 2010. Multivariable linear and logistic (cutoff at the 10th percentile) regression analyses were used to assess the relationship between iron deficiency (ferritin 15 ng/mL) and MCS and PCS, respectively. Analyses were performed separately for men and women.There was no significant relationship between iron deficiency and self-reported mental or physical health.This study found no association between iron stores and self-reported HRQL among Danish blood donors.

BackgroundC-reactive protein (CRP) is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI), is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors.MethodsWe measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L) and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI).ResultsWe found LGI in a total of 1,561 (10.0%) participants. LGI was more frequent in women using combined oral contraception (OC) (29.9%) than in men (6.1%) and women not using OC (7.9%). Among premenopausal women, OC was the strongest predictor of LGI (odds ratio = 8.98, pConclusionHigh BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment.