The Danish Blood Donor Study (DBDS) was established to study the impact of blood donation on the health of blood donors and to answer broader health-related research questions. The cohort is now a nationwide research resource. The cohort was initiated in 2010 and by 2015 it covered all blood donation facilities in Denmark. As of February 2022, DBDS includes 138 491 participants (51% women, age span at inclusion 18–70 years) who have completed a total of 371 589 questionnaires and with 1 091 499 person-years of follow-up. Information on participants from national health registries provides prospective data on hospital contacts, diagnoses, prescriptions, vital status and more. Upon inclusion, a whole-blood sample is stored for DNA extraction. At every donation, a plasma sample is stored by the blood bank. Participants permit the use of their historical and future plasma samples for research. In total, samples from 2 293 916 donations have been collected thus far and inclusion is ongoing. Detailed information on the Danish Blood Donor Study is available at [http://www.dbds.dk], or contact the steering committee [info@dbds.dk]. The Danish Blood Donor Study (DBDS) was established as a platform for the study of health effects of blood donation and as a public health study. Previous results from the Scandinavian Donations and Transfusions Database (SCANDAT, a database including all electronically recorded Danish and Swedish blood donations since the 1980s and 1970s, respectively),1 linked to the national health registers, demonstrated a lower mortality among blood donors when compared with the background population.2 In addition, blood donors donating frequently had a lower mortality than infrequent donors.3 The original research question was thus: is blood donation per se beneficial to the health of the blood donors, or are active blood donors healthier than the rest of the population because of donor selection bias? As a group, blood donors are healthier than the general population. This phenomenon is known as the Healthy Donor Effect (HDE) and results from a selection bias similar to the Healthy Worker Effect.4,5 Just as the Healthy Worker Effect can mask possible occupational hazards, the HDE may mask deleterious effects of blood donation, inasmuch as only healthy individuals may donate. As blood banks, we are obligated to ensure that donors are in good health both before and after donating blood. We therefore need studies that reveal possible detrimental effects of blood donation, and to further elucidate the HDE. The cohort was also established to assess general health-related research questions. Despite the HDE, some blood donors ultimately fall ill, and with increasing ‘time since last donation’, the mortality among lapsed or deferred donors approaches the mortality of the background population.2,3 Several features add value to the study of blood donors: blood donors typically return to donate blood several times over the span of years. A cohort of blood donors therefore provides a unique opportunity to track changes in health, lifestyle, disease emergence and other exposures/parameters between donations. Hence, large blood donor studies and biobanks with consecutive samples are useful to investigate plasma biomarkers predicting disease. Candidate biomarkers can be measured over time in the same donor and changes recorded. The DBDS has already proved to be a useful platform for the study of general health-related research questions.6–15 Large-scale blood donor studies can thus be leveraged for public health research within biological, psychological and social aspects of general health, as long as the HDE is taken into account. Given our cohort infrastructure, we are also able to conduct recall by genotype or phenotype studies. The statistical noise from pre-existing disease on dynamic biomarkers is minimized by the fact that blood donors are only allowed to donate if they consider themselves to be in good health and are free of overt disease. For that reason, the cohort is also suitable for the identification of healthy controls for other studies. Furthermore, the high number of blood donations continuously taking place in all parts of the country, even during a pandemic, renders real-time surveillance studies of infectious diseases possible. The DBDS was initiated in the Capital and Central Denmark Regions in March 2010. From January 2012, the study was expanded to include the Zealand and North Denmark Regions. The Region of Southern Denmark joined the study in June 2015, at which point the cohort became nationwide. The DBDS is an ongoing, national prospective cohort of blood donors. Before or during donation, blood donors aged 18 years or above who have previously donated blood at least once receive oral and written information about the study and are invited to join the cohort by signing a consent form. The participants can withdraw consent at any time; see Table 1 for characteristics of participants (at baseline) and non-participants in the study. In the current dataset (28 February 2022), 138 491 participants have completed a total of 371 589 questionnaires (Table 2). To define the population of blood donors not included in DBDS, we identified all donations from non-participants (not yet invited blood donors) from 1 March 2010 to 28 February 2022 from SCANDAT. A single donation from each non-participating donor was sampled randomly as the index donation for that donor, and the age and measurements at that donation were used to characterize the donor. By this method, participants were slightly older, had more donations in the previous 5 years and had similar haemoglobin values compared with non-participants. The number of blood donors who have declined to participate upon invitation is 4.0%. Characterization of the cohort Results are reported as medians (interquartile ranges), numbers, or percentages. BMI, body mass index; Short form 12, The 12-Item Short Form Health Survey. Blood donors not participating are defined as donors who had not yet received invitation and participant information. The number of blood donors who have declined to participate upon invitation is 4.0%. Full blood donors/plasma donors are defined as donors with at least one full blood/plasma donation during the past year before inclusion (including the inclusion donation). Short form 12: higher scores reflect higher self-reported health-related quality of life. Characterization of the cohort Results are reported as medians (interquartile ranges), numbers, or percentages. BMI, body mass index; Short form 12, The 12-Item Short Form Health Survey. Blood donors not participating are defined as donors who had not yet received invitation and participant information. The number of blood donors who have declined to participate upon invitation is 4.0%. Full blood donors/plasma donors are defined as donors with at least one full blood/plasma donation during the past year before inclusion (including the inclusion donation). Short form 12: higher scores reflect higher self-reported health-related quality of life. Samples and data collected Short form 12 self-reported health-related quality of life (HRQL) Vitamin and iron supplements, diet and alcohol consumption Smoking habits Mononucleosis Menopause status and use of contraceptives Exercise, height and weight Asthma and allergy ADHD Restless legs syndrome Hidradenitis suppurativa and acnes Depression Migraine Height and weight Smoking and alcohol habits Short form 12 HRQL Endometriosis Sleep pattern Stress Migraine Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis) General infections Pain Family disease history Height and weight Smoking and alcohol habits Short form 12 HRQL Sleep pattern Stress Pain Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis, superficial fungus infection) Gastrointestinal symptoms and defaecation pattern Dental status and history of caries Family disease history Height and weight Smoking habits Short form 12 HRQL Short form 12 self-reported health-related quality of life (HRQL) Vitamin and iron supplements, diet and alcohol consumption Smoking habits Mononucleosis Menopause status and use of contraceptives Exercise, height and weight Asthma and allergy ADHD Restless legs syndrome Hidradenitis suppurativa and acnes Depression Migraine Height and weight Smoking and alcohol habits Short form 12 HRQL Endometriosis Sleep pattern Stress Migraine Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis) General infections Pain Family disease history Height and weight Smoking and alcohol habits Short form 12 HRQL Sleep pattern Stress Pain Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis, superficial fungus infection) Gastrointestinal symptoms and defaecation pattern Dental status and history of caries Family disease history Height and weight Smoking habits Short form 12 HRQL Questionnaire data, samples and measurements collected during the years. EDTA, ethylenediamine tetraacetic acid; suPAR:,soluble urokinase-type plasminogen activator receptor; IgE, immunoglobulin E; ADHD, attention-deficit/hyperactivity disorder. e-Boks is a public digital mailbox, which all citizens aged 15 years or above use for communication with the Danish public authorities. Infinium Global Screening Array, Illumina. Specific IgE for the nine most common respiratory sensitizers, Phadiatop. Samples and data collected Short form 12 self-reported health-related quality of life (HRQL) Vitamin and iron supplements, diet and alcohol consumption Smoking habits Mononucleosis Menopause status and use of contraceptives Exercise, height and weight Asthma and allergy ADHD Restless legs syndrome Hidradenitis suppurativa and acnes Depression Migraine Height and weight Smoking and alcohol habits Short form 12 HRQL Endometriosis Sleep pattern Stress Migraine Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis) General infections Pain Family disease history Height and weight Smoking and alcohol habits Short form 12 HRQL Sleep pattern Stress Pain Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis, superficial fungus infection) Gastrointestinal symptoms and defaecation pattern Dental status and history of caries Family disease history Height and weight Smoking habits Short form 12 HRQL Short form 12 self-reported health-related quality of life (HRQL) Vitamin and iron supplements, diet and alcohol consumption Smoking habits Mononucleosis Menopause status and use of contraceptives Exercise, height and weight Asthma and allergy ADHD Restless legs syndrome Hidradenitis suppurativa and acnes Depression Migraine Height and weight Smoking and alcohol habits Short form 12 HRQL Endometriosis Sleep pattern Stress Migraine Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis) General infections Pain Family disease history Height and weight Smoking and alcohol habits Short form 12 HRQL Sleep pattern Stress Pain Skin diseases (hidradenitis suppurativa, hyperhidrosis, xerosis, psoriasis, atopic dermatitis, superficial fungus infection) Gastrointestinal symptoms and defaecation pattern Dental status and history of caries Family disease history Height and weight Smoking habits Short form 12 HRQL Questionnaire data, samples and measurements collected during the years. EDTA, ethylenediamine tetraacetic acid; suPAR:,soluble urokinase-type plasminogen activator receptor; IgE, immunoglobulin E; ADHD, attention-deficit/hyperactivity disorder. e-Boks is a public digital mailbox, which all citizens aged 15 years or above use for communication with the Danish public authorities. Infinium Global Screening Array, Illumina. Specific IgE for the nine most common respiratory sensitizers, Phadiatop. To ensure a cost-effective design that allows donors to be enrolled even after their donation has begun, only routine blood samples are used in the study. In Denmark, archive samples (5 mL EDTA gel-separated tubes, various vendors) are routinely collected at every donation. For study participants, 1.2 mL of plasma from all archive samples are reserved for research purposes whether drawn at inclusion, at subsequent donations or from historical samples. Samples used for blood group typing or viral screening are recapped and whole blood is made available for DNA extraction. Whenever a participant donates blood, the data from the donation becomes available for the study. The possibility for measuring biomarkers in consecutive samples from the same donor allows for detailed studies of biomarker dynamics. This is, to our knowledge, the most comprehensive platform for collecting sequential samples in any cohort study. By February 2022, a total of 2 293 916 unique plasma samples were available (Table 2). After enrolment, the participants are followed at subsequent blood donations and through national health registers. The blood bank follow-up allows for additional data collection: the donor may be asked to fill out new questionnaires and biological sampling may take place. The participants are followed through the national registers also after ceasing their blood donor career. Outcomes, exposures and confounding factors can be assessed by register linkage via the unique personal identification number to a collection of nationwide registers regarding sociodemographics (education, employment, income, civil status, vital status, history of emigration) and health (filled prescriptions, general practitioner contacts, inpatient and outpatient hospital contacts, causes of death) as outlined elsewhere.16 Loss to follow-up in the traditional sense does not occur. The first questionnaire used in DBDS was a paper-based four-page questionnaire with health-related questions (see overview of questionnaire versions and included items in Table 2 and Venn diagram in Figure 1). In the design of this questionnaire, it was paramount to limit the number of questions to avoid physical bottlenecks in the flow of blood donors passing through the blood bank facility. The questionnaire took an average of 8 min to complete. The questionnaires were scanned, and a software package was used for capturing and storing data. For all questionnaires, data were manually validated by visually comparing the captured data with those of the original questionnaire. Captured data were corrected when in disagreement with the paper form. Subsequent random quality checks comprised 1% of all questionnaires, and the error rate per field was below 0.1%. Venn diagram illustrating participants in the Danish Blood Donor Study (DBDS) and their questionnaire responses to the four versions of questionnaires covering a period from 2010 to 2022 In June 2015, the paper questionnaire was replaced by an electronic version that was fully implemented in early 2016. The electronic questionnaire given to participants in three iterations comprises items concerning specific disease entities or traits different from those included in the paper-based version, and is therefore given to both new and previously included participants when attending the blood bank (Table 2). Donors fill out the questionnaire using their own electronic device or by using tablets supplied by the blood bank. The donors sign onto the web-based questionnaire using their unique civil registration number. The questionnaire platform is flexible: it incorporates conditional questions and allows targeted questions for specific subgroups, i.e. specific questions for participants according to age, sex etc. In addition to baseline questionnaires, follow-up questionnaires on migraine and allergy and several COVID-19 specific questionnaires have been sent to participants using the public electronic mailing system, e-Boks. The questionnaire uses the open-source survey software tool LimeSurvey [https://www.limesurvey.org/ver. 2.06+]. Data are automatically encrypted and stored on a secure server.17 Several biomarkers have been measured in baseline and sequential plasma samples (Table 2).7,10,11,13–15,18,19 Additionally, the measurement of 54 immunological biomarkers using a V-PLEX Human Biomarker 54-Plex Kit (MesoScale) in 10 006 donors was recently finalized. Furthermore, genetic markers were assessed in a large fraction of the donors, counting 100 177 participants by February 2022 and growing. The Infinium Global Screening Array (Illumina Inc., USA) was used to genotype more than 650 000 single nucleotide polymorphisms allowing for genome-wide association studies (GWAS).19–22 The genotyping was performed at deCODE genetics (Reykjavik, Iceland). Sequential questionnaire and biomarker data are continually linked to registry data as described (Table 2). The cohort has already proved useful for both of its primary objectives: the study of donor health and generic health-related research questions. More than 60 peer-reviewed papers have already been published. Briefly, we have confirmed iron deficiency as a major health issue among blood donors and that sex, age and donation frequency are by far the most important predictors of iron deficiency. Specifically, we found that high-frequency blood donors, i.e. donors who have donated nine times or more within the previous 3 years, are very likely to be iron deficient (ferritin below 15 ng/mL; 39% of premenopausal women, 22% of postmenopausal women, 9% of men). Conversely, dietary habits are less strongly associated with the risk of iron deficiency.14 Using genetic data, we showed that single nucleotide polymorphisms associated with haemochromatosis may protect against iron depletion.23 Moreover, 46 novel loci affecting iron homeostasis were identified through a GWAS meta-analysis and are potentially involved in iron homeostasis through mechanisms such as absorption, iron recycling, erythropoiesis and hepcidin regulation.21 We also showed that iron deficiency is not associated with self-reported health.13 However, iron deficiency was the strongest predictor of low haemoglobin among blood donors, and the study supported ferritin monitoring in blood donors as a means to identify donors at risk of developing low haemoglobin.10 In this context, we find that the use of oral iron supplementation is not associated with short-term risk of infections.24 Further, we found that donors who deem themselves to be in good mental health donate more frequently and are less likely to drop out of the donor corps compared with those in worse mental health.25 The study serves as a platform for generic health research. Several projects are in the pipeline and the following list of published results is by no means exhaustive. We have shown that obesity is associated with an increased risk of infections by using the Danish health registers.9 We found that carriers of the C-C are at increased risk of to disease when compared with Additionally, we have reported that as a between 3 and 10 is very among taking oral with a of in this In the is only in not taking oral and in DBDS has to other research may a specific IgE phenotype those with single diseases more the of individuals with and is increasing over time in Restless legs syndrome is associated with major among blood donors using we identified three novel and loci affecting the of urokinase-type plasminogen activator and is associated with of and we found low to the for the of The data can also be used in other We have shown an association between and for infectious and used donors from the DBDS to that the same are found when general infectious as the Furthermore, the platform has to the in the the in the blood has to the COVID-19 surveillance in Denmark by measurements of and rate among active and blood The for this large public health study was available in the Danish blood blood routinely new donors, contact information and Donors are to questionnaires at every donation, blood is already drawn from the donors, are in place for the unique of samples and for the and of samples are Further, donors the blood as to blood, in other participants typically be be for the inclusion of participants and a be established for collection and of samples and data. In our blood donors are to participate in research which is in a very high the DBDS is cost-effective compared with other large population studies. of the infrastructure, we are also able to include samples taken during to the blood before the donor joined the study. Data and blood samples from are thus available to research at to no A population study of this that includes consecutive plasma samples with such sampling time is unique to the This design to study disease and biomarkers that over time before disease becomes the study a prospective For consider the of a new screening for a specific disease. Participants with the disease can be identified in the The biomarker can be measured in several samples before and as to the of the as possible. the biomarker be samples can be and the of the biomarker over time can be assessed In to blood donor and population studies in other parts of the the DBDS from the unique Danish national registers. The registers a of including the study of generic health questions. The in the Danish Blood Donor Participants are included at an donation and may donate several times over the of years. At each a plasma sample is participants may a which is in the samples are available for measurements if a biomarker is to be assessed have been made to the The questionnaire is not as comprehensive as in other studies. This is a to the risk of in the which likely the rate and the of mL plasma is collected during each This sample is to the inclusion of donors already and to since no blood samples need be Blood donors are healthier than the general population because they are and because donors are by questionnaires for risk factors associated with a blood donor population be used to assess the of health and disease in the general population. in the study of be in other However, the HDE may also be an in the study of biomarkers and other risk factors for we can that the donor was when it can be that if a biomarker is it was before phenotype The DBDS is a platform for studies out by the Danish blood and The study is by a steering committee who to regarding The blood donors participate in the DBDS to the of their donation, i.e. to research for the of future information can be found at our We to by the steering committee [info@dbds.dk]. Data that projects and from the on Health and the Danish Data The DBDS was by the Central Denmark and Zealand on Health and the Data The DBDS study was by the Danish on Health was by the Data The DBDS was in with the outlined in the of above of the The DBDS cohort is and the data are collected by the steering committee with and and this and the study. and and data. the were involved in the and the The of the Danish Blood Donor Study was supported by the Danish Regions and the Danish for The study is by the Danish Regions and and Denmark. for specific projects has been received from the Danish Blood Donor the for the of and from the and We the Danish blood donors for their in the Danish Blood Donor and the at the blood for this study possible.
No takes yet. Share an insight, caveat, or question.
Erikstrup et al. (2022) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: