Early-life exposure to perfluoroalkyl substances and serum antibody concentrations towards common childhood vaccines in 18-month-old children in the Odense Child Cohort.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with reduced antibody response to childhood vaccinations. Previous studies have mostly focused on antibodies against diphtheria or tetanus, while fewer studies have assessed antibodies toward attenuated viruses, such as measles, mumps or rubella (MMR). Therefore, we set out to determine associations between prenatal and early postnatal PFAS exposure and vaccine-specific Immunoglobulin G (IgG) in the background-exposed Odense Child Cohort. Blood samples were drawn in pregnancy at gestation weeks 8-16 and from the offspring at age 18 months. In the maternal serum samples we quantified perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). In the offspring serum samples we quantified the same five PFAS compounds and IgG towards diphtheria, tetanus and MMR. A total of 880 and 841 children were included in the analyses of diphtheria and tetanus or MMR, respectively. Multiple linear regression models were used for estimation of difference in virus-specific IgG per doubling of PFAS concentrations. Maternal PFAS concentrations were non-significantly inversely associated with most vaccine-specific antibody concentrations. Likewise, child PFAS concentrations were associated with non-significant reductions of antibodies towards tetanus and MMR. A significant reduction in the percent difference in mumps antibody concentration per doubling of child PFNA (-9.2% (95% confidence interval: -17.4;-0.2)), PFHxS (-8.3% (-15.0;-1.0) and PFOS (-7.9% (-14.8;-0.4) was found. These findings are of public health concern, as inadequate response towards childhood vaccines may represent a more general immune dysfunction.

A Danish national, multicentre evaluation of the new donor vigilance system among different staff groups.

BACKGROUND AND OBJECTIVES: Two years after implementing a new national donor vigilance system, the Danish Haemovigilance Committee conducted a nationwide survey to evaluate the implementation among different staff groups. We present the results here. MATERIALS AND METHODS: The study was designed as an anonymous online survey to evaluate the satisfaction with the new registration, understanding of the parameters used and the user-friendliness. The REDCap platform was used. The questionnaire consisted of 22 questions. Ordinal variables were answered using five-point Likert scale (1 = strongly disagree to 5 = strongly agree). The data were analysed using descriptive statistics. Successful implementation was defined as mean overall satisfaction ≥4 and mean understanding of the individual components (adverse reaction category, severity and imputability) in the registration ≥4. RESULTS: In all, 104 staff members (77.9% donation staff) participated. The mean (SD) overall satisfaction among all participants was 3.96 (0.94), highest among medical doctors (4.43 (0.78)) and lowest for administrative or other personnel (2.78 (1.09)). The mean scores for understanding the adverse reaction categories, severity and imputability were 3.92 (0.94), 3.92 (0.94) and 3.88 (1.00), respectively. Experience with a previous donor vigilance system was associated with lower scores. The most successful implementation programme included a medical doctor for introduction and a contact person. CONCLUSION: The goal for successful implementation was not met. However, the overall attitude towards the new registration was positive and indicates that the system is suitable for different staff groups. Our results suggest that implementation could benefit from special attention to administrative staff and those accustomed to another donor vigilance system.

The new donor vigilance system in Denmark reveals regional differences in adverse reactions supposedly caused by variation in the registration.

BACKGROUND AND OBJECTIVES: In recent years, there has been an increased focus among blood bank professionals on the health and safety of blood donors. In 2019, the Danish Haemovigilance Committee designed a national donor vigilance system to improve the registration of adverse reactions (AR) in blood donors. The new donor vigilance system was implemented on 1 January 2020 and we here present the results from the first year of registration. MATERIALS AND METHODS: AR categories, severity level and imputability score were defined based on the definitions from the International Society of Blood Transfusion, AABB and the European Commission directive 2005/61/EC, respectively. RESULTS: Across all severity levels, AR in Danish blood donors were found to be rare (1498 per 100,000 donations). Only 0.2% of the registered reactions were classified as serious (2.7 per 100,000 donations). Large regional differences were seen in the registration of citrate reactions and haematomas. CONCLUSION: Significant differences across regions in what to categorize as an AR were persistent even when including a severity score in the reporting. The Danish Haemovigilance Committee will commence a national work to align the definitions but suggests that this matter is raised to an international level as part of the current work to agree upon definitions for assessment of donor AR.

Combinations of self-reported rhinitis, conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes.

BACKGROUND: Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed. OBJECTIVES: The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen-specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors. METHODS: From the nationwide population-based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop). RESULTS: The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants. CONCLUSION: Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self-reported ARC represent a primarily sIgE-positive phenotype, while those with either AR or AC represent more diverse phenotypes.

The donors perceived positive and negative effects of blood donation.

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.

Herpes Simplex Virus Type 1 infection is associated with suicidal behavior and first registered psychiatric diagnosis in a healthy population.

Increasing evidence shows that latent infections and inflammation is associated with cognitive and behavioral changes in humans. This case-control study investigates the association between Herpes Simplex Virus Type 1 (HSV-1) infection and C-reactive Protein (CRP) levels, and psychiatric disorders and suicidal behavior. Public health register data from 81,912 participants in the Danish Blood Donor Study, were reviewed to identify individuals registered with an ICD-10 code of any psychiatric diagnosis, or who had attempted or committed suicide. We found 1,504 psychiatric cases and 353 suicidal cases; for all cases, controls were frequency-matched by age and sex, resulting in 5,336 participants. Plasma samples were analyzed for IgG-class antibodies against HSV-1 and CRP. HSV-1 infection was associated with suicidal behavior (odds-ratio, 1.40; 95% confidence interval [CI] 1.11-1.77). Accounting for temporality, HSV-1 infection was associated with having first psychiatric disorder after the date of blood collection (incidence rate ration, 1.44; 95% CI, 1.05-1.95). No association between CRP and psychiatric disorders or suicidal behavior was found. The finding that HSV-1 was associated with suicidal behavior and first psychiatric disorder indicates that infection may play a role in the etiology and pathogenesis of suicidal behavior and development of psychiatric disorders.

Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders.

BACKGROUND: Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior. METHODS: This case-control study reviews register data on 81,912 individuals from the Danish Blood Donor Study to identify individuals who have a psychiatric diagnosis (N = 2591), have attempted or committed suicide (N = 655), or have had traffic accidents (N = 2724). For all cases, controls were frequency matched by age and sex, resulting in 11,546 participants. Plasma samples were analyzed for immunoglobulin G (IgG) antibodies against Toxoplasma gondii and cytomegalovirus (CMV). RESULTS: T. gondii was detected in 25·9% of the population and was associated with schizophrenia (odds ratio [OR], 1·47; 95% confidence interval [CI], 1·03-2·09). Accounting for temporality, with pathogen exposure preceding outcome, the association was even stronger (IRR, 2·78; 95% CI, 1·27-6·09). A very weak association between traffic accident and toxoplasmosis (OR, 1·11; 95% CI, 1·00-1·23, p = 0.054) was found. CMV was detected in 60·8% of the studied population and was associated with any psychiatric disorder (OR, 1·17; 95% CI, 1·06-1·29), but also with a smaller group of neurotic, stress-related, and somatoform disorders (OR, 1·27; 95% CI, 1·12-1·44), and with attempting or committing suicide (OR, 1·31; 95% CI, 1·10-1·56). Accounting for temporality, any psychiatric disorder (IRR, 1·37; 95% CI, 1·08-1·74) and mood disorders (IRR, 1·43; 95% CI, 1·01-2·04) were associated with exposure to CMV. No association between traffic accident and CMV (OR, 1·06; 95% CI, 0·97-1·17) was found. CONCLUSIONS: This large-scale serological study is the first study to examine temporality of pathogen exposure and to provide evidence of a causal relationship between T. gondii and schizophrenia, and between CMV and any psychiatric disorder.