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.

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.

Maternal use of nitrosatable drugs during pregnancy and adult male reproductive health: A population-based cohort study.

BACKGROUND: Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite. OBJECTIVES: We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated. METHOD: We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias. RESULTS: In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulations were detected. CONCLUSIONS: The results suggest that maternal use of nitrosatable drugs does not have a harmful influence on the male fecundity of the offspring.

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.

Validity of self-reported night shift work among women with and without breast cancer.

OBJECTIVES: This study aimed to estimate the validity of self-reported information on ever-night shift work among women with and without breast cancer and illustrate the consequences for breast cancer risk estimates. METHODS: During 2015-2016, 225 women diagnosed with breast cancer and 1800 matched controls without breast cancer employed within the Danish hospital regions during 2007-2016 participated in a questionnaire-based survey. Their reported night shift work status was linked with objective payroll register day-by-day working hour data from the Danish Working Hour Database and the Danish Cancer Registry. For the breast cancer patients and their matched controls, we estimated sensitivity and specificity for ever-working night shifts using the payroll data as the gold standard. We also used quantitative bias analysis to estimate the impact on relative risk estimates for a hypothetical population. RESULTS: For breast cancer patients, we observed a sensitivity of ever-night shifts of 86.2% and a specificity of never-night shifts of 82.6%. For controls, the sensitivity was 80.6% and the specificity 83.7%. Odds ratio for breast cancer in a hypothetical population decreased from 1.12 [95% confidence interval (CI) 1.03-1.21] to 1.05 (95% CI 0.95-1.16) when corrected by the sensitivity and specificity estimates. CONCLUSION: This study shows that female breast cancer patients had slightly better recall of previous night shift work than controls. Additionally, both breast cancer patients and controls recalled previous never-night shift work with low specificity. The net effect of this misclassification is a small over-estimation of the relative breast cancer risk due to night shift work.

Sleep duration and biomarkers of fecundity in young men: a cross-sectional study from a population-based cohort.

BACKGROUND: Poor male fecundity is of concern and warrants the identification of potential modifiable risk factors. Short and long sleep duration might be risk factors for poor male fecundity although evidence in this research field is inconsistent. OBJECTIVES: To investigate the association between sleep duration and biomarkers of male fecundity in young men. MATERIALS AND METHODS: We conducted a cross-sectional study of 1,055 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, Denmark, 2017-2019. Sleep duration was obtained from an online survey answered by the participants prior to the clinical visit, where semen and blood samples were obtained, and testis volume was self-assessed using an Orchidometer. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analysed according to sleep duration using multivariable negative binomial regression models. Sleep duration was dichotomised (recommended (6-9 h/night) versus deviant sleep) and visualised continuously as restricted cubic spline plots. RESULTS: Deviation from recommended sleep duration was associated with higher high DNA stainability (HDS) of 5% (95% CI: -1%; 13%), higher testosterone of 3% (95% CI: 0%; 7%) and higher free androgen index (FAI) of 6% (95% CI: 0%; 13%). The spline plots overall supported these results, suggesting u-shaped associations between sleep duration and HDS, testosterone and FAI, a linear association between sleep duration and semen volume and sex hormone binding globulin (SHBG) and an inverse u-shaped association with normal morphology. DISCUSSION: Information on sleep duration was obtained by self-report in broad categories with at least 3 h intervals. We were not able to investigate short or long sleep duration separately, since only few participants reported this. CONCLUSION: Sleep duration was associated with some biomarkers of fecundity in young men. Maintaining a recommended sleep duration may thus be beneficial for young men with regard to reproductive health.

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.

Night shift work characteristics and risk of incident coronary heart disease among health care workers: national cohort study.

BACKGROUND: Night work has been associated with coronary heart disease. The present study examined exposure-response relations between quantitative night work characteristics and coronary heart disease (angina pectoris or myocardial infarction) with the aim to contribute to evidence-based recommendations for low-risk night work schedules. METHODS: We followed 100 149 night workers (80% women) and 153 882 day workers (78% women), all health care workers in Denmark with day by day payroll information on night shifts from 2007 to 2015. We analysed data with Poisson regression stratified by sex and adjusted for age, calendar year, diabetes, family history of cardiovascular disease, educational level, occupation, indicators for obesity, hypercholesterolaemia, and hypertension. RESULTS: Female and male night workers worked on average 1.7 and 1.8 night shifts per month for an average duration of less than 4 years. During follow-up, 1198 night and 2128 day workers were hospitalized with first-time coronary heart disease. When compared with day workers, the overall incidence rate ratios for female and male night workers were 1.06 [95% confidence interval (CI): 0.97, 1.17] and 1.22 (95% CI 1.07, 1.39). Highest risks were observed in top exposure categories for several night work characteristics. However, no consistent exposure-response relations by number of monthly night shifts, cumulative night shifts, years with rotating night shifts, years with any night shift and consecutive night shifts were observed among the night workers of either sex. CONCLUSIONS: This study of a population with low exposure to night work does not indicate that reducing extent of monthly night shifts, cumulative night shifts, years with rotating night shifts, years with any night shift and consecutive night shifts would reduce the risk of coronary heart disease.

Parental age at birth and biomarkers of fecundity in young Danish men.

BACKGROUND: High parental age is associated with adverse birth and genetic outcomes, but little is known about fecundity in male offspring. OBJECTIVES: We investigated if high parental age at birth was associated with biomarkers of male fecundity in a large population-based sample of young men. MATERIALS AND METHODS: We conducted a study of 1057 men from the Fetal Programming of Semen Quality (FEPOS) cohort, a sub-cohort of sons born 1998-2000 into the Danish National Birth Cohort. Semen characteristics and reproductive hormone concentrations were measured in samples provided by the men 2017-2019. Testis volume was determined by self-measurement. Data on the parental age was drawn from registers. Adjusted relative difference in percentage with 95% confidence intervals were estimated for each outcome according to pre-specified maternal and paternal age groups (< 30 (reference), 30-34 and ≥ 35) as well as for combinations of parental age groups, using multivariable negative binomial regression models. RESULTS: We did not observe consistent associations between parental age and biomarkers of fecundity, although sons of mothers ≥ 35 years had lower sperm concentration (-15% (95% CI: -30, 3)) and total sperm count (-10% (95% CI: -25, 9)). The analysis with parental age combinations showed lower sperm concentration with high age of the parents (both ≥ 35 years: -27%, 95% CI: -40, -19) when compared to the reference where both parents were below 30 years. DISCUSSION AND CONCLUSION: We found no strong association between higher parental age and biomarkers of fecundity in young men. However, we cannot exclude poorer semen characteristics in sons born by older mothers or with high age of both parents.

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.

COVID-19-related hospital admission in spouses of partners in at-risk occupations.

OBJECTIVE: This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020-21. METHODS: Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates. RESULTS: The risk of COVID-19-related hospital admission was increased among spouses with partners in high-risk occupations [adjusted IRR (IRRadj)1.59, 95% confidence interval (CI) 1.1-2.2], but not intermediate-risk occupations (IRRadj 0.97 95% 0.8-1.3). IRR for having a partner in a high-risk job was elevated during the first three pandemic waves but not in the fourth (IRRadj 0.48 95% CI 0.2-1.5). Sex did not modify the risk of hospital admission. CONCLUSIONS: SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential.

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.

Maternal intake of folate and folic acid during pregnancy and markers of male fecundity: A population-based cohort study.

BACKGROUND: Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of the developing reproductive organs. OBJECTIVES: To examine the association between maternal intake of folate from diet and folic acid from supplements during pregnancy and markers of fecundity in young men. MATERIALS AND METHODS: We conducted a follow-up study using a Danish mother-son cohort of 787 young men born 1998-2000. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analyzed according to total folate calculated as dietary folate equivalents from diet and supplements in midpregnancy, using multivariable negative binomial regression models. Total folate was analyzed in quintiles, continuous per standard deviation decrease (SD: 318 µg/day) and as restricted cubic splines. RESULTS: Low maternal intake of total folate was associated with lower total sperm count (-5% (95% confidence intervals [CI]: -11%; 2%)), a lower proportion of non-progressive and immotile spermatozoa (-5% [95% CI: -8%; -3%]), and lower testes volume (-4% [95% CI: -6%; -2%]) per SD decrease in total folate intake. Spline plots supported these findings. DISCUSSION: The finding of a lower proportion of non-progressive and immotile spermatozoa, and hence a higher proportion of motile spermatozoa, in men of mothers with a lower intake of total folate in midpregnancy was surprising and may be a chance finding. CONCLUSION: Lower maternal intake of total folate in midpregnancy was associated with lower sperm count and lower testes volume, however, also with a lower proportion of non-progressive and immotile spermatozoa in adult men. Whether this actually affects the ability to obtain a pregnancy warrants further investigation.

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.

Occupational risk of COVID-19 related hospital admission in Denmark 2020-2021: a follow-up study.

OBJECTIVE: Mounting evidence indicates increased risk of COVID-19 among healthcare personnel, but the evidence on risks in other occupations is limited. In this study, we quantify the occupational risk of COVID-19-related hospital admission in Denmark during 2020-2021. METHODS: The source population included 2.4 million employees age 20-69 years. All information was retrieved from public registers. The risk of COVID-19 related hospital admission was examined in 155 occupations with at least 2000 employees (at-risk, N=1 620 231) referenced to a group of mainly office workers defined by a COVID-19 job exposure matrix (N=369 341). Incidence rate ratios (IRR) were computed by Poisson regression. RESULTS: During 186 million person-weeks of follow-up, we observed 2944 COVID-19 related hospital admissions in at-risk occupations and 559 in referents. Adjusted risk of such admission was elevated in several occupations within healthcare (including health care assistants, nurses, medical practitioners and laboratory technicians but not physiotherapists or midwives), social care (daycare assistants for children aged 4-7, and nursing aides in institutions and private homes, but not family daycare workers) and transportation (bus drivers, but not lorry drivers). Most IRR in these at-risk occupations were in the range of 1.5-3. Employees in education, retail sales and various service occupations seemed not to be at risk. CONCLUSION: Employees in several occupations within and outside healthcare are at substantially increased risk of COVID-19. There is a need to revisit safety measures and precautions to mitigate viral transmission in the workplace during the current and forthcoming pandemics.

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.

Nitrate in Maternal Drinking Water during Pregnancy and Measures of Male Fecundity in Adult Sons.

Animal studies indicate deleterious effects of nitrate exposure on fecundity, but effects in humans are unknown, both for the prenatal and postnatal periods. We aimed to investigate if exposure to nitrate in maternal drinking water during the sensitive period of fetal life is associated with measures of fecundity in the adult sons. In a sub-analysis, the potential effects of nitrate exposure in adulthood were investigated. This cohort included 985 young adult men enrolled in The Fetal Programming of Semen Quality Cohort (FEPOS). Semen characteristics, testes volume and reproductive hormones were analyzed in relation to nitrate concentration in maternal drinking water, using a negative binomial regression model. The nitrate concentration in drinking water was obtained from monitoring data from Danish waterworks that were linked with the mothers' residential address during pregnancy. The median nitrate concentration in maternal drinking water was 2 mg/L. At these low exposure levels, which are far below the World Health Organization's (WHO) guideline value of 50 mg/L, we did not find indications of harmful effects of nitrate on the investigated measures of male fecundity.

Occupational risk of COVID-19 across pandemic waves: a two-year national follow-up study of hospital admissions.

OBJECTIVE: Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. METHODS: The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20-69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. RESULTS: We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. CONCLUSION: Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.