Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure.

BACKGROUND: Organic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study. METHODS: The study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994-2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model. RESULTS: For organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure. CONCLUSION: Exposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD. TRIAL REGISTRATION NUMBER: j.no.: 1-16-02-196-17.

Occupational exposure to respirable crystalline silica and incident idiopathic interstitial pneumonias and pulmonary sarcoidosis: a national prospective follow-up study.

BACKGROUND: Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. METHODS: The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. RESULTS: Mean cumulative exposure was 125 µg/m3-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m3-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m3-years of 1.20 (95% CI 1.17 to 1.23). CONCLUSION: This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.

Birth by caesarean section and semen quality in adulthood: a Danish population-based cohort study.

BACKGROUND: The caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons' semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality. METHODS: This study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs). RESULTS: Among included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): - 7.5% (- 14.1% to - 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally. CONCLUSIONS: This large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

Caesarean section is one of the most frequently used interventions during childbirth and global cesarean delivery rates continue to increase. The rising cesarean delivery rate has been reported to be related with series of adverse health outcomes in children, such as asthma, allergies, obesity, diabetes and even poor emotional, behavioral and educational outcomes. Still, it remains unknown whether children's reproductive health is affected by this delivery mode.Based on data from the Fetal Programming of Semen Quality cohort (FEPOS,) nested within the Danish National Birth Cohort, we have therefore analyzed the potential effect of caesarean section on son's semen quality in 1044 young men. We found a slightly higher progressive sperm motility among sons born by caesarean section compared to sons born by vaginal delivery. No differences, however, were observed for semen volume, sperm concentration and morphology between the two delivery modes.The FEPOS cohort is the largest population-based male offspring cohort worldwide. This is the first study aiming to examine the association between caesarean section and semen quality in adulthood. Although the findings need to be confirmed in other studies, it is reassuring that this large population-based cohort study finds no significant evidence for an adverse effect on semen quality in adult sons born by caesarean section.

Selection bias in a male-offspring cohort investigating fecundity: is there reason for concern?

STUDY QUESTION: Is there risk of selection bias in etiological studies investigating prenatal risk factors of poor male fecundity in a cohort of young men? SUMMARY ANSWER: The risk of selection bias is considered limited despite a low participation rate. WHAT IS KNOWN ALREADY: Participation rates in studies relying on volunteers to provide a semen sample are often very low. Many risk factors for poor male fecundity are associated with participation status, and as men with low fecundity may be more inclined to participate in studies of semen quality, a risk of selection bias exists. STUDY DESIGN, SIZE, DURATION: A population-based follow-up study of 5697 young men invited to the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Young men (age range: 18 years, 9 months to 21 years, 4 months) born 1998-2000 by mothers included in the DNBC were invited to participate in FEPOS. In total, 1173 men answered a survey in FEPOS (n = 115 participated partly); of those, 1058 men participated fully by also providing a semen and a blood sample at a clinical visit. Differential selection according to parental baseline characteristics in the first trimester, the sons' own characteristics from the FEPOS survey, and urogenital malformations and diseases in reproductive organs from the Danish registers were investigated using logistic regression. The influence of inverse probability of selection weights (IPSWs) to investigate potential selection bias was examined using a predefined exposure-outcome association of maternal smoking in the first trimester (yes, no) and total sperm count analysed using adjusted negative binomial regression. A multidimensional bias analysis on the same association was performed using a variety of bias parameters to assess different scenarios of differential selection. MAIN RESULTS AND THE ROLE OF CHANCE: Participation differed according to most parental characteristics in first trimester but did not differ according to the prevalence of a urogenital malformation or disease in the reproductive organs. Associations between maternal smoking in the first trimester and male fecundity were similar when the regression models were fitted without and with IPSWs. Adjusting for other potential risk factors for poor male fecundity, maternal smoking was associated with 21% (95% CI: -32% to -9%) lower total sperm count. In the bias analysis, this estimate changed only slightly under realistic scenarios. This may be extrapolated to other exposure-outcome associations. LIMITATIONS, REASONS FOR CAUTION: We were unable to directly assess markers of male fecundity for non-participants from, for example an external source and therefore relied on potential proxies of fecundity. We did not have sufficient power to analyse associations between prenatal exposures and urogenital malformations. WIDER IMPLICATIONS OF THE FINDINGS: The results are reassuring when using this cohort to identify causes of poor male fecundity. The results may be generalized to other similar cohorts. As the young men grow older, they can be followed in the Danish registers, as an external source, to examine, whether participation is associated with the risk of having an infertility diagnosis. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University and Independent Research Fund Denmark (9039-00128B). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal vitamin D levels and male reproductive health: a population-based follow-up study.

Maternal vitamin D levels during pregnancy may be important for reproductive health in male offspring by regulating cell proliferation and differentiation during development. We conducted a follow-up study of 827 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, nested in the Danish National Birth Cohort to investigate if maternal vitamin D levels were associated with measures of reproductive health in adult sons. These included semen characteristics, testes volume, and reproductive hormone levels and were analysed according to maternal vitamin D (25(OH)D3) levels during pregnancy. In addition, an instrumental variable analysis using seasonality in sun exposure as an instrument for maternal vitamin D levels was conducted. We found that sons of mothers with vitamin D levels < 25 nmol/L had 11% (95% CI - 19 to - 2) lower testes volume and a 1.4 (95% CI 1.0 to 1.9) times higher risk of having low testes volume (< 15 mL), in addition to 20% (95% CI - 40 to 9) lower total sperm count and a 1.6 (95% CI 0.9 to 2.9) times higher risk of having a low total sperm count (< 39 million) compared with sons of mothers with vitamin D levels > 75 nmol/L. Continuous models, spline plots and an instrumental variable analysis supported these findings. Low maternal vitamin D levels were associated with lower testes volume and lower total sperm count with indications of dose-dependency. Maternal vitamin D level above 75 nmol/L during pregnancy may be beneficial for testes function in adult sons.

Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the COVID-19 pandemic, 2020-2021.

OBJECTIVE: Most earlier studies on occupational risk of COVID-19 covering the entire workforce are based on relatively rare outcomes such as hospital admission and mortality. This study examines the incidence of SARS-CoV-2 infection by occupational group based on real-time PCR (RT-PCR) tests. METHODS: The cohort includes 2.4 million Danish employees, 20-69 years of age. All data were retrieved from public registries. The incidence rate ratios (IRRs) of first-occurring positive RT-PCR test from week 8 of 2020 to week 50 of 2021 were computed by Poisson regression for each four-digit Danish Version of the International Standard Classification of Occupations job code with more than 100 male and 100 female employees (n=205). Occupational groups with low risk of workplace infection according to a job exposure matrix constituted the reference group. Risk estimates were adjusted by demographic, social and health characteristics including household size, completed COVID-19 vaccination, pandemic wave and occupation-specific frequency of testing. RESULTS: IRRs of SARS-CoV-2 infection were elevated in seven healthcare occupations and 42 occupations in other sectors, mainly social work activities, residential care, education, defence and security, accommodation and transportation. No IRRs exceeded 2.0. The relative risk in healthcare, residential care and defence/security declined across pandemic waves. Decreased IRRs were observed in 12 occupations. DISCUSSION: We observed a modestly increased risk of SARS-CoV-2 infection among employees in numerous occupations, indicating a large potential for preventive actions. Cautious interpretation of observed risk in specific occupations is needed because of methodological issues inherent in analyses of RT-PCR test results and because of multiple statistical tests.

Night work during pregnancy and small for gestational age: a Danish nationwide register-based cohort study.

OBJECTIVE: The aim was to investigate the association between night work during pregnancy and risk of having a small for gestational age (SGA) child. METHODS: This cohort study had payroll data with detailed information on working hours for employees in all Danish administrative regions (primarily hospital employees) between 2007 and 2015, retrieved from the Danish Working Hour Database. Pregnancies, covariates and outcome were identified from the national birth registry. We used logistic regression to investigate the association between intensity and duration of night work during the first 32 pregnancy weeks and SGA. The adjusted model included age, body mass index, socioeconomic status and smoking. Using quantitative bias analysis and G-estimation, we explored potential healthy worker survivor bias (HWSB). RESULTS: The final cohort comprised 24 548 singleton pregnancies in 19 107 women, primarily nurses and medical doctors. None of the dimensions of night work were associated with an increased risk of SGA. We found a tendency towards higher risk of SGA in pregnancies where the women stopped having night shifts during pregnancy. Using G-estimation we found an OR<1 for the association between night work and SGA if all workers continued having night work during pregnancy compared with daywork only. CONCLUSION: We found no increased risk of SGA in association with night work during pregnancy among healthcare workers. G-estimation was not precise enough to estimate the observed indication of HWSB. We need better data on pregnancy discomforts and complications to be able to safely rule out HWSB.

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.

Impact of a manager-oriented intervention on occupational exposures and well-being among pregnant hospital and day-care employees: A cluster randomised trial.

BACKGROUND: Pregnancy can make it difficult to cope with demands at work and may affect women's well-being. We investigated if a manager-targeted educational intervention reduced demanding occupational exposures and improved the psychosocial work environment and well-being among pregnant employees. METHODS: Data came from a cluster randomised trial in Danish hospitals and day-care institutions. Work units were assigned randomly and were non-blinded to the intervention, where managers were either invited to participate in a three-hour seminar addressing job adjustment in pregnancy or assigned to a control group undertaking their usual practice. Self-reported outcomes by pregnant employees at the work units were the proportion of pregnant employees with demanding occupational exposures, good psychosocial work environment and good well-being. Mixed logistic regression was applied in the population of responders and in intention-to-treat analyses using multiple imputations. RESULTS: We included 915 pregnant employees: 451 in the intervention group and 464 in the control group. Of 216 invited managers, 103 (48%) participated in the seminar. A total of 339 (37%) pregnant employees answered the questionnaire. The proportion of pregnant employees who had demanding occupational exposures, good psychosocial work environment and good well-being in the intervention versus the control group were 36% versus 39% (odds ratio (OR)=0.90, 95% confidence interval (CI) 0.57-1.44), 56% versus 59% (OR=1.01, 95% CI 0.60-1.71) and 77% versus 73% (OR=1.13, 95% CI 0.68-1.87), respectively. CONCLUSIONS: This manager-targeted educational intervention did not reduce demanding occupational exposures and did not improve the psychosocial work environment or the well-being among pregnant employees in hospital and day-care settings. Comprehensive and participatory interventions may be considered in future studies.

Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study.

INTRODUCTION: The risk of asbestosis, malignant mesothelioma and lung cancer among motor vehicle mechanics is of concern because of potential exposure to chrysotile asbestos during brake, clutch and gasket repair and maintenance. Asbestos has also been used in insulation and exhaust systems. METHODS: We examined the long-term risk of incident mesothelioma, lung cancer, asbestosis and other lung diseases and mortality due to mesothelioma, lung cancer, asbestosis and other lung diseases in a nationwide cohort of all men registered as motor vehicle mechanics since 1970 in Denmark. This was compared with the corresponding risk in a cohort of male workers matched 10:1 by age and calendar year, with similar socioeconomic status (instrument makers, dairymen, upholsterers, glaziers, butchers, bakers, drivers, farmers and workers in the food industry, trade or public services). RESULTS: Our study included 138 559 motor vehicle mechanics (median age 24 years; median follow-up 20 years (maximum 45 years)) and 1 385 590 comparison workers (median age 25 years; median follow-up 19 years (maximum 45 years)). Compared with other workers, vehicle mechanics had a lower risk of morbidity due to mesothelioma/pleural cancer (n=47 cases) (age-adjusted and calendar-year-adjusted HR=0.74 (95% CI 0.55 to 0.99)), a slightly increased risk of lung cancer (HR=1.09 (95% CI 1.03 to 1.14)), increased risk of asbestosis (HR=1.50 (95% CI 1.10 to 2.03)) and a chronic obstructive pulmonary disease risk close to unity (HR=1.02 (95% CI 0.99 to 1.05)). Corresponding HRs for mortality were 0.86 (95% CI 0.64 to 1.15) for mesothelioma/pleural cancer, 1.06 (95% CI 1.01 to 1.12) for lung cancer, 1.79 (95% CI 1.10 to 2.92) for asbestosis, 1.06 (95% CI 0.86 to 1.30) for other lung diseases caused by external agents and 1.00 (95% CI 0.98 to 1.01) for death due to all causes. CONCLUSIONS: We found that the risk of asbestosis was increased among vehicle mechanics. The risk of malignant mesothelioma/pleural cancers was not increased among vehicle mechanics.

Time course of symptoms in posttraumatic stress disorder with delayed expression: A systematic review.

OBJECTIVE: To examine the hypothesis that PTSD with delayed expression in some cases occurs without subthreshold PTSD symptoms above background levels bridging the gap between the traumatic exposure(s) and the clinical diagnosis. METHODS: We performed systematic searches of peer-reviewed papers in English referenced in Pubmed, Embase, or PsycINFO and ascertained 34 prospective studies of PTSD symptom trajectories identified by latent class growth statistical modeling. Studies with delayed and low-stable trajectories provided appropriate data for this study. We computed the difference between the delayed trajectory PTSD symptom sumscore and the low-stable PTSD sumscore at the observed points in time after the traumatic event(s). RESULTS: In 29 study populations, the latent class growth analyses displayed delayed trajectories, and in these, we identified 110 data points (% PTSD sumscore difference/months since traumatic exposure). The median PTSD symptom sumscore was 25% higher during the initial 6 months among individuals in the delayed trajectory compared to those in low-stable trajectory. From this level, the difference widened and reached a plateau of 40-50% higher. The variation was large, and the baseline participation rate and loss to follow-up were exceeding 25% in the majority of the studies. Heterogeneity of populations, measures, and analyses precluded formal meta-analysis. CONCLUSION: Delayed PTSD is preceded by PTSD symptoms during the first year in most cases. Still, few individuals may experience an asymptomatic delay. The results underpin the rationale for monitoring PTSD symptoms and may inform forensic assessments in that delayed PTSD without symptoms bridging the traumatic event is rare.

Occupational inhalant exposures and longitudinal lung function decline.

BACKGROUND: Airborne exposures at the workplace are believed to be associated with lung function decline. However, longitudinal studies are few, and results are conflicting. METHODS: Participants from two general population-based cohorts, the Copenhagen City Heart Study and the Copenhagen General Population Study, with at least two lung function measurements were followed for a mean of 9 years (range 3-27 years). Occupational exposure was assigned to each year of follow-up between the two lung function measurements by a job exposure matrix. Associations between mean occupational exposure per year and mean annual decline in forced expiratory volume in 1 s (FEV1) were investigated using linear mixed-effects models according to cohort and time period (1976-1983 and 2003-2015). We adjusted for sex, height, weight, education, baseline FEV1 and pack-years of smoking per year during follow-up. RESULTS: A total of 16 144 individuals were included (mean age 48 years and 43% male). Occupational exposure to mineral dusts, biological dusts, gases and fumes and a composite category was not associated with FEV1 decline in analyses with dichotomised exposure. In analyses with an indexed measure of exposure, gases and fumes were associated with an FEV1 change of -5.8 mL per unit per year (95% CI -10.8- -0.7 mL per unit per year) during 1976-1983, but not during 2001-2015. CONCLUSION: In two cohorts from the Danish general population, occupational exposure to dusts, gases and fumes was not associated with excess lung function decline in recent years but might have been of importance decades ago.

Chronic productive cough and inhalant occupational exposure-a study of the general population.

PURPOSE: Occupational inhalant exposures have been linked with a higher occurrence of chronic productive cough, but recent studies question the association. METHODS: We included participants from two general population studies, the Copenhagen City General Population Study and the Copenhagen City Heart Study, to assess contemporary (year 2003-2017) and historical (1976-1983) occupational inhalant hazards. Job titles one year prior to study inclusion and an airborne chemical job-exposure matrix (ACE JEM) were used to estimate occupational exposure. The association between occupational exposures and self-reported chronic productive cough was studied using generalized estimating equations stratified by smoking status and cohort. RESULTS: The population consisted of 5210 working individuals aged 20-65 from 1976 to 1983 and 64,279 from 2003 to 2017. In smokers, exposure to high levels of mineral dust, biological dust, gases & fumes and the composite variable vapours, gases, dusts or fumes (VGDF) were associated with chronic productive cough in both cohorts with odds ratios in the range of 1.2 (95% confidence interval, 1.0;1.4) to 1.6 (1.2;2.1). High levels of biological dust were only associated with an increased risk of a chronic productive cough in the 2003-2017 cohort (OR 1.5 (1.1;2.0)). In non-smokers, high levels of VGDF (OR 1.5 (1.0;2.3)) and low levels of mineral dust (OR 1.7 (1.1;2.4)) were associated with chronic productive cough in the 1976-1983 cohort, while no associations were seen in non-smokers in the 2003-2017 cohort. CONCLUSION: Occupational inhalant exposure remains associated with a modestly increased risk of a chronic productive cough in smokers, despite declining exposure levels during the past four decades.

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.

Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal.

Early retirement among Danish female cleaners and shop assistants according to work environment characteristics and upper extremity complaints: an 11-year follow-up study.

BACKGROUND: Studies have shown a negative social gradient in the incidence of early retirement. To prevent undesired early retirement, there is a need for knowledge of specific predictors in addition to social factors with a limited potential for change. The main purpose of this study was to examine musculoskeletal complaints and working conditions as predictors of early retirement among Danish female cleaners. METHODS: Using Cox regression with an adjustment for extraneous factors, we compared the risk of disability pension and retirement before the nominal retirement age (65 years) in an 11-year cohort study with registry-based follow-up of 1430 female cleaners and 579 shop assistants. In subsequent analyses of female cleaners, disability pension and voluntary early retirement were modeled according to work characteristics and upper extremity complaints. RESULTS: The adjusted hazard rate (HR) for disability pension among cleaners compared to the control group was 2.27 (95% CI 1.58 to 3.28) and, for voluntary early retirement, 1.01 (95% CI 0.85 to 1.20). In the subset of cleaners, the predictors of disability pension were persistent shoulder pain HR: 1.98 (95% CI 1.47 to 2.67), elbow pain HR: 1.41 (95% CI 1.02 to 1.94) and symptoms of nerve entrapment of the hand HR: 1.58 (95% CI 1.14 to 2.20). Predictors of voluntary early retirement were persistent shoulder pain HR: 1.40 (95% CI 1.16 to 1.67) and floor mopping for more than 10 h per week HR: 1.20 (95% CI 1.03 to 1.40). CONCLUSION: Cleaners have a twofold higher risk of disability pension compared to the control group. Risk factors for disability pension among cleaners were persistent shoulder and elbow pain together with symptoms of nerve entrapment of the hand. The findings of specific health related predictors of early retirement could be used in secondary prevention with targeted temporary reduced workload.

Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a systematic review.

BACKGROUND: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with reduced fetal growth. However, the results of human studies are inconsistent. OBJECTIVES: To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. METHODS: Systematic literature searches were performed in MEDLINE and EMBASE. We included original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant articles. Study characteristics and results were extracted to structured tables. The completeness of reporting as well as the risk of bias and confounding were assessed. RESULTS: Fourteen studies were eligible. In utero PFOA exposure was associated with decreased measures of continuous birth weight in all studies, even though the magnitude of the association differed and many results were statistically insignificant. PFOS exposure and birth weight were associated in some studies, while others found no association. CONCLUSIONS: Higher PFOS and PFOA concentrations were associated with decreased average birth weight in most studies, but only some results were statistically significant. The impact on public health is unclear, but the global exposure to PFASs warrants further investigation.

Isothiazolinones in commercial products at Danish workplaces.

BACKGROUND: In recent years, a steep increase in the frequency of occupational contact allergy to isothiazolinones has been reported from several European countries. OBJECTIVE: To examine the extent and occurrence of isothiazolinones in different types of product at Danish workplaces. METHODS: Seven different isothiazolinones were identified in the Dictionary of Contact Allergens: Chemical Structures, Sources, and References from Kanerva's Occupational Dermatitis. By use of the chemical names and Chemical Abstracts Service numbers for these chemicals, information on products registered in the Danish Product Register Database (PROBAS) was obtained. RESULTS: All seven isothiazolinones were registered in PROBAS. The top three isothiazolinones registered were: benzisothiazolinone (BIT), registered in 985 products, methylisothiazolinone (MI), registered in 884 products, and methylchloroisothiazolinone (MCI)/MI, registered in 611 products. The concentration ranges were 0.01 ppm to 45% for BIT, 0.01 ppm to 10% for MI, and 0.01 ppm to 14.1% for MCI/MI. The most common product type was 'paint and varnish'; five of the seven isothiazolinones were registered in this type of product. CONCLUSION: Isothiazolinones are present in multiple products registered for use at workplaces, and may occur in high concentrations.

Maternal coffee consumption and biomarkers of reproductive health in young, adult sons: a cohort study.

It has been proposed that poor semen quality may have its origins from fetal programming due to environmental factors. We investigated whether maternal coffee consumption during early pregnancy was associated with biomarkers of reproductive health in adult sons in the Fetal Programming of Semen Quality (FEPOS) cohort. In 2017-2019, 1058 young men provided a semen and blood sample and self-measured their testis volume. Daily maternal coffee consumption was reported by the mothers around gestational week 17. We estimated relative percentage differences with 95 % confidence intervals (CI) for semen quality measures, testis volume, and reproductive hormone levels according to maternal coffee consumption during pregnancy. Maternal coffee consumption (yes/no (reference)) was associated with lower semen volume (-7.0 % (95 % CI:-12.9;-0.7)), lower proportion of morphologically normal spermatozoa (-8.3 % (95 % CI:-16.5;0.8)), higher proportion of non-progressive and immotile spermatozoa (4.3 % (95 % CI:-1.5;10.3)), and lower testis volume (-4.8 % (95 % CI:-9.0;-0.4)). No indication of a dose-response association or threshold effects was observed in the categorized and continuous analyses. No associations with reproductive hormone levels were observed in any of the analyses. Overall, the study does not provide obvious indications that maternal coffee consumption in early pregnancy deteriorates male offspring fecundity. While some minor changes were observed, most estimates were small with confidence intervals overlapping the null. Future studies, preferably with greater exposure contrast, are warranted before a conclusion can be drawn as to whether maternal coffee consumption during pregnancy constitutes a risk for reproductive health in adult sons.

Maternal intake of paracetamol during pregnancy and biomarkers of male fecundity in young adult sons.

Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality and changes in reproductive hormones. In this longitudinal study, we included 1058 young adult men born 1998-2000 into the Danish National Birth Cohort with follow-up at 18-21 years of age. The exposure, maternal intake of paracetamol, was modelled in three ways: dichotomized, trimester-specific, and as duration of exposure categorized into: short (1-2 weeks), medium (3-9 weeks) or long duration (>9 weeks) vs. no intake. Outcomes included semen characteristics, self-measured testis volume, and reproductive hormone levels. We used negative binominal regression to estimate the percentage difference and 95% confidence interval (CI) for each outcome. In total, 547 (48%) sons were prenatally exposed to paracetamol due to maternal intake at least once. Maternal intake of paracetamol during pregnancy was not associated with any of the biomarkers in the dichotomized or trimester-specific exposure models. For duration of exposure, sons of mothers with long duration of maternal intake of paracetamol showed tendencies towards lower semen concentration (-14% [95% CI: -31%; 8%]), a higher proportion of nonprogressive and immotile spermatozoa (8% [95% CI: -4%; 21%]) and higher DNA Fragmentation Index (16% [95% CI: -1%; 36%]) compared to son of mothers with no intake. Maternal intake of paracetamol during pregnancy was not clearly associated with biomarkers of male fecundity in adult sons. However, it cannot be ruled out that long duration of maternal intake of paracetamol might be associated with impaired semen characteristics.