Antibody response to SARS-CoV-2 mRNA vaccination in Danish adults exposed to perfluoroalkyl substances (PFASs): The ENFORCE study.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFASs) have immunotoxic effects in children while studies in adults, including recent studies on the SARS-CoV-2 vaccine response have been less consistent. In a cohort of 50-69-year-olds repeatedly vaccinated against COVID-19 in Denmark from early 2021, we aimed to assess the association between serum-PFAS concentrations and SARS-CoV-2 antibody responses. METHODS: We assessed serum-PFAS concentrations among 371 middle-aged adults from the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE) who had received their first vaccination against COVID-19. Following the second dose and the booster (third) Pfizer-BioNTech mRNA vaccination, we measured the specific spike IgG antibody response. Associations between serum-PFAS concentrations at inclusion and spike IgG antibody concentrations after vaccination were assessed using median regression, and analyses were adjusted for age, sex, presence of diabetes, number of vaccines received, and time since vaccination. We further examined the associations between serum-PFAS concentrations at inclusion and changes in spike IgG antibody concentration between the second dose and booster (third) vaccination. RESULTS: Serum-PFAS concentrations were not associated with spike IgG antibody concentrations after the SARS-CoV-2 vaccinations, but the increase in response after the booster (third) vaccination compared to after the second vaccination was consistently lower at higher serum-PFAS concentrations. Each doubling in the concentration of seven serum-PFASs was associated with a 802 BAU/mL lower median increase in spike IgG antibody response after the booster (third) vaccination (95% CI: -1812; 208) adjusted for confounders. DISCUSSION: As many adults were probably not immunological naïve prior to vaccination, our results were likely affected by individual variability in immune response to the vaccination. Despite this uncertainty, the diminished increase in SARS-CoV-2 spike antibody response after the booster (third) vaccination at higher PFAS exposure may potentially reflect an immunotoxic impact of the PFASs.

Social disparity is associated with an increased risk of acute and chronic pancreatitis.

AIM: To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. METHODS: Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. RESULTS: The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14-80%), 99 (95% CI: 26-214%), and 56% (95% CI: 26-94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet.Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06-1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. CONCLUSION: This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet.

Characteristics associated with non-initiation and non-completion of human papillomavirus vaccination among Danish girls: a nationwide register-based cohort study.

AIM: The aim was to identify maternal and paternal socioeconomic and demographic characteristics for non-initiation and non-completion of the human papillomavirus (HPV) vaccination among Danish girls including time-trends. METHODS: This nationwide register-based cohort study included all girls residing in Denmark who were offered free-of-charge HPV vaccination as a part of the childhood vaccination program between 2009 and 2018 (birth cohorts 1996-2005). The study samples included 296,461 daughter-mother dyads and 291,025 daughter-father dyads. Data from the Danish Vaccination Register were linked with socioeconomic and demographic data from Statistics Denmark. HPV vaccination status was classified as 'non-initiation' for girls who received no HPV vaccine and as 'non-completion' for girls who initiated the HPV vaccination program but did not receive all the scheduled HPV vaccines. Data were analyzed using logistic regression models. RESULTS: Non-initiation of HPV vaccination was 13.7%, and non-completion was 24.2% among girls who initiated the HPV vaccination program. Girls of parents who were descendants of immigrants (adjusted odds ratio: 1.50; 95% confidence interval: 1.35-1.68), were at least 35-years old at time of birth, had basic or no education, had a low income, were not in the labor market, and were unmarried had the highest non-initiation and non-completion odds. The associations between socioeconomic and demographic characteristics and HPV vaccination uptake were similar for mothers and fathers. CONCLUSIONS: Despite free-of-charge availability to HPV vaccination in Denmark, we found disparities in non-initiation and non-completion of HPV vaccination among Danish girls by both mothers' and fathers' socioeconomic and demographic characteristics.

Predictors of serum- per- and polyfluoroalkyl substance (PFAS) concentrations among infants in Guinea-Bissau, West Africa.

BACKGROUND: Knowledge about PFAS exposure in Africa is limited. We have previously detected six types of PFAS in the serum of infants from Guinea-Bissau, West Africa. The aim of this study was to identify predictors of the infant serum-PFAS concentrations. METHODS: This cross-sectional study was based on a subset of data from a randomized controlled trial of early measles vaccination performed in 2012-2015 in three rural regions of Guinea-Bissau. Blood samples were obtained from 237 children aged 4-to-7 months, and six types of PFAS were quantified in serum. Location of residence was recorded, and information about predictors related to socioeconomic status as well as maternal and child characteristics were obtained through structured interviews with the mothers through routine surveillance. Associations between potential predictors and infant serum-PFAS concentrations were examined in linear regression models while adjusting for potential confounding and mediating factors as identified in a directed acyclic graph. RESULTS: Infants from the Cacheu region had the lowest concentrations of perfluorooctanoic acid (PFOA), while infants from the Oio region had the lowest concentrations of all other PFAS. Compared to infants from Oio, infant serum-perfluorooctane sulfonic acid (PFOS) concentrations were 94.1% (95% CI: 52.4, 147.1%) and 81.9% (95% CI: 45.7, 127.1%) higher in Cacheu and Biombo, respectively. Higher maternal age and lower parity were associated with slightly higher child-serum perfluorohexane sulfonic acid (PFHxS) concentrations, while infants with higher socioeconomic status and infants breastfed without supplementary solid foods at inclusion had higher average concentrations of most PFAS, although the confidence intervals were wide and overlapped zero. DISCUSSION: Location of residence was the most important determinant of serum-PFAS concentrations among Guinea-Bissau infants, indicating a potential role of diet as affected by the global spread of PFAS, but future studies should explore reasons for the regional differences in PFAS exposure.

Alcohol Drinking Patterns and Risk of Developing Acute and Chronic Pancreatitis.

AIM: The aim was to analyze the effects of drinking pattern and type of alcohol on risk of acute and chronic pancreatitis. METHODS: Prospective cohort study based on data from 316,751 men and women participating in the Danish National Health Surveys 2010 and 2013. Self-reported questionnaire-based alcohol parameters and information on pancreatitis was obtained from national health registers. Cox regression models were used adjusting for baseline year, gender, age, smoking, Body Mass Index, diet and education. RESULTS: Development of acute and chronic pancreatitis increased with alcohol intake with a significant increase among abstainers and those drinking >14 drinks per week compared with individuals drinking 1-7 drinks per week. Frequent binge drinking and frequent drinking (every day) was associated with increased development of acute and chronic pancreatitis compared with those drinking 2-4 days per week. Problematic alcohol use according to the CAGE-C questionnaire was associated with increased development of acute and chronic pancreatitis.Intake of more than 14 drinks of spirits per week was associated with increased development of acute and chronic pancreatitis, and more than 14 drinks of beer per week were associated with increased development of chronic pancreatitis, whereas drinking wine was not associated with development of pancreatitis. CONCLUSION: This large prospective population study showed a J-shaped association between alcohol intake and development of pancreatitis. Drinking every day, frequent binge drinking and problematic alcohol use were associated with increased development of pancreatitis and drinking large amounts of beer and spirits might be more harmful than drinking wine.

HPV vaccination and side effects.

In Denmark, the proportion of children completing the HPV vaccination program is lower than for other vaccines, and the relatively low uptake is believed to be influenced by a media debate on suspected side effects of HPV vaccination. Based on a systematic PubMed search, this review identified 14 Danish studies that compared symptoms or disease incidence among HPV-vaccinated individuals with the incidence in a control group. Most studies showed no association between HPV vaccination and subsequent illness.

Per- and Polyfluoroalkyl Substances and Breastfeeding as a Vulnerable Function: A Systematic Review of Epidemiological Studies.

Milk formation in the breast during breastfeeding is a complex hormonally regulated process, potentially sensitive to the effects of endocrine-disrupting chemical exposures. The environmental chemicals, per- and polyfluoroalkyl substances (PFAS) are known endocrine disruptors. PFAS exposure have been associated with insufficient mammary gland development in mice and reduced breastfeeding duration in humans. The aim of this review was to gather the epidemiological evidence on the association between PFAS exposure and breastfeeding duration. Using PubMed and Embase, we performed a systematic literature search (on 23 January 2023) to identify epidemiological studies examining the association between maternal PFAS exposure and breastfeeding duration. Animal studies, reviews, and non-English studies were excluded. The risk of bias was assessed using the risk of bias in non-randomized studies of exposures tool. Estimates describing the association between PFAS exposure and the duration of breastfeeding were identified, and the data were synthesized separately for each type of PFAS and for the duration of exclusive and total breastfeeding. Six studies with between 336 and 2374 participants each were identified. PFAS exposure was assessed in serum samples (five studies) or based on residential address (one study). Five out of six studies found shorter total duration of breastfeeding with higher PFAS exposure. The most consistent associations were seen for perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). The finding of a potential causal association between PFAS exposure and breastfeeding duration is in agreement with findings from experimental studies.

Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years.

Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.

Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later: The European Youth Heart Study.

OBJECTIVE: To investigate the long-term association of exposure to perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15 years) on indicators of adiposity and glucose metabolism in adolescence (15 years) and young adulthood (21 years). Secondarily, we aim to clarify the degree of tracking of exposure from childhood into young adulthood. RESEARCH DESIGN AND METHODS: Data derived from a large multicenter prospective cohort study, in which the same participants have been observed from childhood (N = 590), during adolescence (N = 444), and into young adulthood (N = 369). Stored plasma samples were analyzed for PFOS and PFOA. Indicators of adiposity comprising body height, body weight, sum of four skinfolds, and waist circumference, as well as indicators of glucose metabolism, comprising fasting blood glucose, triglyceride, and insulin levels, ß-cell function, and insulin resistance, have been collected at all study waves. Multiple linear regression was applied in order to model earlier exposure on later outcome while controlling for baseline outcome levels, sex, age, and socioeconomic factors. RESULTS: Childhood exposure to PFOS was associated with indicators of adiposity at 15 years of age that are displayed in elevated BMI, skinfold thickness, and waist circumference, as well as increased skinfold thickness and waist circumference at 21 years of age. PFOA exposure in childhood was associated with decreased ß-cell function at 15 years of age. We did not observe associations between exposure during adolescence and indicators of adiposity and glucose metabolism in young adulthood. CONCLUSIONS: This study found evidence for childhood exposure to PFOS and PFOA predicting adiposity at 15 and 21 years of age and impaired ß-cell function at 15 years of age, respectively.

Polychlorinated biphenyl exposure and glucose metabolism in 9-year-old Danish children.

CONTEXT: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. OBJECTIVE: We aimed to determine whether concurrent plasma PCB concentration was associated with markers of glucose metabolism in healthy children. SETTING AND DESIGN: Cross-sectional study of 771 healthy Danish third grade school children ages 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 schools stratified according to location and socioeconomic character; 509 (9.7 ± 0.8 y, 53% girls) had adequate amounts available for PCB analyses. OUTCOME MEASURES: Fasting serum glucose and insulin were measured and a homeostasis assessment model of insulin resistance (HOMA-IR) and ß-cell function (HOMA-B) calculated. Plasma PCB congeners and other persistent compounds were measured and ΣPCB calculated. RESULTS: PCBs were present in plasma at low concentrations, median, 0.19 µg/g lipid (interquartile range, 0.12-0.31). After adjustment for putative confounding factors, the second, third, fourth, and fifth quintiles of total PCB were significantly inversely associated with serum insulin (-14.6%, -21.7%, -18.9%, -23.1%, P trend < .01), compared with the first quintile, but not with serum glucose (P = .45). HOMA-IR and HOMA-B were affected in the same direction due to the declining insulin levels with increasing PCB exposure. Similar results were found for individual PCB congeners, for ßHCB (hexachlorobenzen) and pp-DDE (dichlorodiphenyldichloroethylene). CONCLUSIONS: A strong inverse association between serum insulin and PCB exposure was found while fasting glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low-fit children, but rather through a toxicity to ß-cells. It remains to be demonstrated whether lower HOMA-B is caused by destruction of ß-cell-reducing peripheral insulin resistance and thereby increase fasting glucose as previously found.