Time trends in per- and polyfluoroalkyl substances (PFAS) concentrations in the Danish population: A review based on published and newly analyzed data.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals used in many industries and everyday consumer products and exposure has been linked to several adverse health outcomes. Currently, no systematic monitoring of PFAS levels in the general Danish population has been conducted. OBJECTIVE: To study temporal trends of PFAS concentrations in the Danish population. MATERIALS AND METHODS: In August 2023, we performed a search for original peer-reviewed reports in PubMed using combinations of search terms for PFAS and Denmark. Reports were included if they comprised a Danish study population and direct measurements of PFAS in serum or plasma samples. Scatter plots of medians presented in the reports were used to visualize time-trends of PFAS concentrations among Danish individuals. RESULTS: We included 29 reports based on a total of 18,231 individuals from 19 Danish study populations. A total of 24 PFAS measured in serum or plasma were presented in the reports, the most frequent being PFOS, PFOA, PFDA, PFNA, PFHpA, PFHpS, and PFHxS. Median concentrations of PFOS ranged from 4.0 ng/mL to 44.5 ng/mL, PFOA ranged from 0.8 ng/mL to 9.7 ng/mL, while lower concentrations were presented for the other PFAS. Median concentrations of PFOS and PFOA increased from 1988 until the late 1990s followed by a decrease until 2021. A less clear time-trend were observed for the other PFAS. CONCLUSION: Blood concentrations of PFOS and PFOA in the Danish population have declined substantially from the late 1990s until 2021 reflecting a phase-out of the production and regulation of the use of these PFAS. Time-trends for PFDA, PFNA, PFHpA, PFHpS, and PFHxS were less evident, yet a tendency toward a decline was observed. As only some of the compounds are measured, it is not possible to determine if the decrease in some PFAS is outweighed by an increase in others.

Exposure to airborne polychlorinated biphenyls and type 2 diabetes in a Danish cohort.

BACKGROUND: Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. METHODS: The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977-2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. RESULTS: We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02-1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300-899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87-1.11; 900-3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83-1.10). DISCUSSION: We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.

Risk of cardiovascular diseases following residential exposure to airborne polychlorinated biphenyls: A register-based cohort study.

BACKGROUND: Indoor air in buildings constructed with materials containing polychlorinated biphenyls (PCBs) may be contaminated with especially lower-chlorinated PCBs. So far, the cardiovascular consequences of living with such contamination are unknown. OBJECTIVES: To determine the risk of cardiovascular disease (CVD) following residential exposure to predominantly lower-chlorinated PCBs in indoor air. METHODS: The Health Effects of PCBs in Indoor Air (HESPAIR) cohort is register-based with 51 921 residents of two residential areas near Copenhagen: Farum Midtpunkt and Brøndby Strand Parkerne. Here, indoor air was contaminated with PCB in one third of the apartments due to construction with materials containing PCB. Individual PCB exposure was estimated based on register-based information on relocation dates and indoor air PCB measurements in subsets of the apartments. Information on CVD was retrieved from the Danish National Patient Register for the follow-up period of 1977-2018. We estimated adjusted hazard ratios using Cox regression with time-varying exposure. RESULTS: Cumulative residential exposure to airborne PCB was not associated with a higher overall risk for CVD (HR for highly exposed (≥3300 ng/m3 PCB × year): 1.02, 95% CI 0.94-1.10). This was also the case for most of the specific cardiovascular diseases, apart from acute myocardial infarction where a higher risk was observed for residents exposed to ≥3300 ng/m3 PCB × year compared to the reference group (HR 1.17, 95% CI 1.00-1.35). However, no exposure-response relationship was apparent and additional adjustment for education attenuated the risk estimate. DISCUSSION: In this, to our knowledge, first study ever to examine the risk of CVD following residential exposure to PCBs in indoor air, we observed limited support for cardiovascular effects of living in PCB-contaminated indoor air. Considering the prevalence of exposure to airborne PCBs and lack of literature on their potential health effects, these findings need to be corroborated in other studies.

Maternal fever during pregnancy and male offspring reproductive health: A longitudinal cohort study in young Danish males.

BACKGROUND: Maternal fever during pregnancy has been associated with an increased risk of genital malformations, but the implication for long-term reproductive health in the offspring is unknown. OBJECTIVES: To investigate associations between timing, duration, and temperature of fetal exposure to maternal fever and sons' semen quality, testicular volume, and levels of reproductive hormones in early adulthood. Further, to examine whether concurrent use of antipyretics and/or antibiotics modified the effect. MATERIALS AND METHODS: We used the Fetal Programming of Semen Quality cohort consisting of men born to women enrolled in the Danish National Birth Cohort. Self-reported information on maternal fever was collected twice during pregnancy (median 16 and 31 pregnancy weeks) and categorized as any fever during pregnancy, fever during early pregnancy (weeks 1-15), and fever exclusively during late pregnancy (weeks 16-42). Semen quality and concentrations of reproductive hormones were measured at a clinical examination at the age of 18.9 years. We used negative binomial regression to examine the associations, adjusting for maternal age at birth, maternal smoking, family occupational status, and precision variables related to semen quality and hormonal levels, for example, abstinence time. RESULTS: 986 men were included in the study, of which 23% had mothers reporting at least one episode of fever. We found no strong indications of associations between maternal fever during pregnancy and male reproductive health in young men. Concurrent use of antipyretics and antibiotics did not modify the association. DISCUSSION: Strengths include the large sample size, prospectively collected data, and the adjustment for maternal factors during pregnancy and important precision variables. A limitation is the crude self-reported information on maternal fever. CONCLUSION: We found no evidence to support that timing, duration, or temperature of maternal fever during pregnancy has a long-term impact on semen characteristics, testicular volume, or level of reproductive hormones in male offspring.

Cancer Risk following Residential Exposure to Airborne Polychlorinated Biphenyls: A Danish Register-Based Cohort Study.

BACKGROUND: Polychlorinated biphenyls (PCBs) are biopersistent chemicals classified as human carcinogens. This classification is primarily based on evidence on higher-chlorinated PCBs found in food. The carcinogenic potential of airborne lower-chlorinated PCBs remains largely unexplored. OBJECTIVES: We aimed to investigate cancer risk following residential exposure to airborne PCBs. METHODS: Cancer risk was examined in the Health Effects of PCBs in Indoor Air (HESPAIR) cohort of 38,613 residents of two partly PCB-contaminated residential areas in Greater Copenhagen, identified by nationwide registries. PCB exposure was based on relocation dates and indoor air PCB measurements in subsets of apartments. Cancer diagnoses were extracted from the Danish Cancer Registry for the follow-up period of 1970-2018. We estimated adjusted hazard ratios with time-varying cumulative exposure and a 10-y lag using Cox regression. RESULTS: Overall risk of cancer was not associated with PCByear, [hazard ratio (HR) for high-exposed vs. low-exposed =0.98; 95% confidence interval (CI): 0.88, 1.09], but residents exposed to ≥3,000 ng/m3 PCB×year had higher risk of liver cancer (HR =2.81; 95% CI: 1.28, 6.15) and meningiomas (HR =3.49; 95% CI: 1.84, 6.64), with indications of exposure-response relationships. Results were suggestive of a higher risk of pancreatic cancer (HR =1.59; 95% CI: 0.95, 2.64) at the highest aggregated PCB level. For testis cancer, a higher risk was observed among residents exposed to 300-949 ng/m3 PCB×year relative to residents exposed to <300 ng/m3 PCB×year (HR =2.97; 95% CI: 1.41, 6.28), but the risk was not higher for residents exposed to ≥950 ng/m3 PCB×year. Apart from this, the risk of specific cancers was similar across exposure groups. DISCUSSION: In this, to our knowledge, first population-based cohort study of residential exposure to airborne PCBs, we found no association between exposure to PCBs in indoor air in private homes and the risk for most of the specific cancers. Higher risk of liver cancer and meningiomas were observed. https://doi.org/10.1289/EHP10605.

Fetal exposure to maternal stress and male reproductive function in a cohort of young adults.

OBJECTIVE: To study associations between maternal stress during pregnancy and reproductive function in young men. DESIGN: A cohort study nested in a population-based birth cohort. SETTING: Not applicable. PATIENTS: Young men (n = 1,052; response rate, 19%) participated in the Fetal Programming of Semen Quality cohort from 2017 to 2019. They were recruited from pregnancies in the Danish National Birth Cohort (1996-2001). The men completed an online questionnaire, clinical examination, and collection of blood and semen samples. EXPOSURES: Information on maternal life and emotional stresses was available from a telephone interview covering the interval from the beginning of pregnancy to approximately gestational week 30. MAIN OUTCOME MEASURE(S): We applied negative binomial, linear, and logistic regression to examine associations between life and emotional stress scores (range, 0-18) and reproductive function. The primary outcomes were measures of semen quality, and the secondary outcomes included reproductive hormone levels and testicular volume. RESULT(S): Overall, we observed no negative associations between maternal life or emotional stress and male reproductive function. Maternal emotional stress was associated with higher total sperm count (16% difference; 95% confidence interval [CI], 1-33), serum estradiol (11% difference; 95% CI, 2-21), and calculated free testosterone (ß = 17.8; 95% CI, 1.26-34.3). The results were robust to inverse probability weighting introduced to account for selection. CONCLUSION(S): Although our findings may appear reassuring, further efforts to validate the measures of stress during pregnancy and improve our understanding of the full spectrum of fetal stress exposures and consequences for health later in life are needed.

Associations between health-risk behaviours and non-condom use among 28,620 Danish students: a cross-sectional study.

PURPOSE: Investigations into the associations between health-risk behaviours and non-condom use are important for planning effective preventive interventions targeted sexually transmitted infections. To date, there are no such studies on the Danish general population. The aim of this study was to examine associations between health-risk behaviours (including daily smoking, frequent binge-drinking, cannabis use within the last month and illicit drug use) and non-condom use among Danish students. MATERIAL AND METHOD: Cross-sectional data from 28,620 sexually active students aged 15-25 years from the Danish National Youth Study 2014 were analysed using multilevel logistic regression. RESULTS: Health-risk behaviours (daily smoking, frequent binge-drinking, cannabis use within the last month and illicit drug use) were significantly associated with higher odds for non-condom use among Danish students, even after adjustment for age, gender, education, religion, and geographical region. The associations remained significant after adjusting for the remaining health-risk behaviours. CONCLUSION: Overall, the study showed a clear association between health-risk behaviours and non-condom use among Danish students. The findings of this study have important implications for future planning of more targeted health promotion intervention programmes aimed to increase condom use among young people as a means to reduce sexually transmitted infections.

Maternal exposure to airborne polychlorinated biphenyls (PCBs) and risk of adverse birth outcomes.

Human health effects of airborne lower-chlorinated polychlorinated biphenyls (LC-PCBs) are largely unexplored. Since PCBs may cross the placenta, maternal exposure could potentially have negative consequences for fetal development. We aimed to determine if exposure to airborne PCB during pregnancy was associated with adverse birth outcomes. In this cohort study, exposed women had lived in PCB contaminated apartments at least one year during the 3.6 years before conception or the entire first trimester of pregnancy. The women and their children were followed for birth outcomes in Danish health registers. Logistic regression was performed to estimate odds ratios (OR) for changes in secondary sex ratio, preterm birth, major congenital malformations, cryptorchidism, and being born small for gestational age. We performed linear regression to estimate difference in birth weight among children of exposed and unexposed mothers. All models were adjusted for maternal age, educational level, ethnicity, and calendar time. We identified 885 exposed pregnancies and 3327 unexposed pregnancies. Relative to unexposed women, exposed women had OR 0.97 (95% CI 0.82, 1.15) for secondary sex ratio, OR 1.13 (95% CI 0.76, 1.67) for preterm birth, OR 1.28 (95% CI 0.81, 2.01) for having a child with major malformations, OR 1.73 (95% CI 1.01, 2.95) for cryptorchidism and OR 1.23 (95% CI 0.88, 1.72) for giving birth to a child born small for gestational age. The difference in birth weight for children of exposed compared to unexposed women was - 32 g (95% CI-79, 14). We observed an increased risk of cryptorchidism among boys after maternal airborne LC-PCB exposure, but due to the proxy measure of exposure, inability to perform dose-response analyses, and the lack of comparable literature, larger cohort studies with direct measures of exposure are needed to investigate the safety of airborne LC-PCB exposure during pregnancy.

Per- and polyfluoroalkyl substances and male reproductive health: a systematic review of the epidemiological evidence.

Exposure to environmental pollutants may produce impairment of male reproductive health. The epidemiological literature evaluating potential consequences of human exposure to per- and polyfluoroalkyl substances (PFAS) has grown in recent years with concerns for both pre- and postnatal influences. The aim of this systematic review was to assess available evidence on associations between PFAS exposures in different stages of life and semen quality, reproductive hormones, cryptorchidism, hypospadias, and testicular cancer. A systematic search of literature published prior to March 9th, 2020, was performed in the databases PubMed and Embase®. Predefined criteria for eligibility were applied by two authors screening study records independently. Among the 242 study records retrieved in the literature search, 26 studies were eligible for qualitative assessment. While several investigations suggested weak associations for single compounds and specific outcomes, a lack of consistency across studies limited conclusions of overall evidence. The current gap in knowledge is particularly obvious regarding exposures prior to adulthood, exposure to combinations of both PFAS and other types of environmental chemicals, and outcomes such as cryptorchidism, hypospadias, and testicular cancer. Continued efforts to clarify associations between PFAS exposure and male reproductive health through high-quality epidemiological studies are needed.

Semen quality among young healthy men taking protein supplements.

OBJECTIVE: To study the association between use of protein supplements (PS) and semen quality among young men. DESIGN: Cross-sectional study. SETTING: Not applicable PATIENT(S): We used data from the Fetal Programming of Semen Quality (FEPOS) cohort, which is a subsample of 778 men whose mothers enrolled in the Danish National Birth Cohort 1996-2002. INTERVENTION(S): Semen samples were collected from April 2017 to March 2019. Relative difference in semen characteristics according to self-reported PS use was estimated with negative binomial regression adjusting for lifestyle factors including exercise, body mass index, and use of anabolic steroids, and maternal and paternal factors potentially confounding the association between PS and semen quality. MAIN OUTCOME MEASURE(S): Negative binomial regression yielded the best fit and was used to estimate the percent difference with 95% confidence intervals in semen volume, sperm concentration, total sperm count, proportions of progressive, nonprogressive, and immotile sperm, and percentage of morphologically normal sperm in former and current users of PS relative to never users. RESULT(S): PS was used currently by 28% and formerly by 24% of participants. PS use was not associated with reduced semen quality in terms of semen volume, sperm concentration, total sperm count, morphology, or motility in either crude or adjusted analyses. CONCLUSION: This study showed no association between use of PS and semen quality characteristics. Still, we encourage others to repeat the study, as even a small harmful effect would have a large impact on the population level because of the widespread use of PS among young men.

Changes in Emotional Vitality as a Predictor of Levels and Change in Allostatic Load: Longitudinal Results From the Whitehall II Cohort Study.

OBJECTIVE: Increasing evidence has shown an association between reduced psychological well-being and long-term morbidity. However, longitudinal studies addressing potential biobehavioral mechanisms, such as physiological function, are lacking. The aim of this study is to examine the association between changes in emotional vitality on levels and changes in allostatic load (AL), a measure of multisystem physiological dysregulation, as well as its composite risk markers. METHODS: Participants comprised 5919 British civil servants from phases 3, 5, and 7 of the Whitehall II study. Psychological well-being was operationalized as emotional vitality. AL was measured using nine biomarkers of the cardiovascular, metabolic, and immune system. Linear mixed-effect models were used to determine the association between changes in emotional vitality between phases 3 and 5 and subsequent levels and change in AL from phases 5 to 7. Generalized linear models were used to address the association between changes in emotional vitality and individual risk markers. RESULTS: Increase in emotional vitality was associated with a lower mean level of AL, whereas the AL slope was not markedly affected. Among the included risk markers, only interleukin-6 was weakly associated with changes in emotional vitality, with a 7% reduced risk of high levels of interleukin-6 per one-unit increase in emotional vitality. CONCLUSION: This study found that an increase in emotional vitality was associated with subsequent lower levels, but not rate of change, of AL over time. Further research is needed to address the relationship between trajectories of psychological well-being and physiological dysregulation.

Ethnic differences in cardiovascular morbidity and mortality among patients with breast cancer in the Netherlands: a register-based cohort study.

OBJECTIVES: Cardiovascular disease (CVD) is of increasing concern among breast cancer survivors. However, evidence on ethnic differences in CVD among women with breast cancer is sparse. We assessed ethnic differences in cardiovascular morbidity and mortality among patients with breast cancer in the Netherlands. METHODS: A nationwide register-based cohort study comprising all women with a first admission for breast cancer (n=127 714) between 1996 and 2010 in the Netherlands was conducted. Differences in CVD admission, CVD mortality and overall CVD event, which comprised a CVD admission and/or CVD mortality, between the largest ethnic minority groups (Surinamese, Moroccan, Turkish, Antillean and Indonesian) and the Dutch general population (henceforth, Dutch) were investigated using Cox proportional hazard models. RESULTS: The incidence of cardiovascular outcomes varied by the ethnic group. The incidence of an overall cardiovascular event was significantly higher for women with breast cancer from Suriname (HR 1.46; 95% CI 1.29 to 1.64) and Turkey (HR 1.25; 95% CI 1.03 to 1.51), compared with Dutch women with breast cancer. In contrast, Indonesian women with breast cancer had a significantly lower risk (HR 0.88; 95% CI 0.81 to 0.96) of a cardiovascular event compared with Dutch women with breast cancer. The risk of a cardiovascular event did not differ between Moroccan and Dutch women with breast cancer, whereas for Antillean women the risk was not significantly higher. CONCLUSIONS: Our findings suggest that Surinamese and Turkish women with breast cancer are disadvantaged in terms of cardiovascular outcomes compared with Dutch women with breast cancer. More work is needed to unravel the potential factors contributing to these differences.

Refugees and family-reunified immigrants have a high incidence of HIV diagnosis and late presentation compared with Danish born: a nationwide register-based cohort study.

PURPOSE: Migrants represent a considerable proportion of HIV diagnoses in Europe and are considered a group at risk of late presentation. This study examined the incidence of HIV diagnoses and the risk of late presentation according to migrant status, ethnic origin and duration of residence. METHODS: We conducted a historically prospective cohort study comprising all adult migrants to Denmark between 1.1.1993 and 31.12.2010 (n = 114.282), matched 1:6 to Danish born by age and sex. HIV diagnoses were retrieved from the National Surveillance Register and differences in incidence were assessed by Cox regression model. Differences in late presentation were assessed by logistic regression. RESULTS: Both refugees (HR = 5.61; 95% CI 4.45-7.07) and family-reunified immigrants (HR = 10.48; 95% CI 8.88-12.36) had higher incidence of HIV diagnoses compared with Danish born and the incidence remained high over time of residence for both groups. Migrants from all regions, except Western Asia and North Africa, had higher incidence than Danish born. Late presentation was more common among refugees (OR = 1.87; 95% CI 1.07-3.26) and family-reunified immigrants (OR = 2.30; 95% CI 1.49-3.55) compared with Danish born. Southeast Asia and Sub-Saharan Africa were the only regions with a higher risk of late presentation. Late presentation was only higher for refugees within 1 year of residence, whereas it remained higher within 10 years of residence for family-reunified immigrants. CONCLUSIONS: This register-based study revealed a higher incidence of HIV diagnoses and late presentation among migrants compared with Danish born and the incidence remained surprisingly high over time.