Sesilje Bondo Petersen

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

BACKGROUND More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commissions list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Night work and hypertensive disorders of pregnancy: a national register-based cohort study

Objective The aim of this study was to investigate whether night work expressed by number and duration of night shifts, number of consecutive night shifts, and number of quick returns during the first 20 weeks of pregnancy is a risk factor for hypertensive disorders of pregnancy (HDP). Methods The study population comprised Danish workers in public administration and hospitals who gave birth between 2007 and 2013. Exposure was assessed objectively through payroll data. Information on the outcome was retrieved from the National Patient Register. We performed logistic regression on the risk for HDP according to night work adjusted for age, body mass index (BMI), parity, socioeconomic status, and sickness absence prior to pregnancy. Results Among 18 724 workers, 60% had at least one night shift during the first 20 weeks of pregnancy. The prevalence of HDP was 3.7%. Among night workers, the risk of HDP grew with increasing number of consecutive night shifts [odds ratio (OR) 1.41, 95% confidence interval (CI) 1.01-1.98) and of quick returns after night shifts (OR 1.28, 95% CI 0.87-1.95). Among obese women (body mass index ≥30 kg/m 2), those who worked long night shifts and longer spells of consecutive night shifts, and had the highest number of quick returns after night shifts, had a 4-5 fold increased risk of HDP compared to day workers. Conclusion Working consecutive night shifts and quick returns after night shifts during the first 20 pregnancy weeks was associated with an increased risk of HDP, particularly among obese women.

Job-exposure matrices addressing lifestyle to be applied in register-based occupational health studies

Objectives Information about lifestyle factors in register-based occupational health studies is often not available. The objective of this study was therefore to develop gender, age and calendar-time specific job-exposure matrices (JEMs) addressing five selected lifestyle characteristics across job groups as a tool for lifestyle adjustment in register-based studies. Methods We combined and harmonised questionnaire and interview data on lifestyle from several Danish surveys in the time period 1981–2013 for 264 054 employees registered with a DISCO-88 code (the Danish version of International Standard Classification of Occupations (ISCO)-88) in a nationwide register-based Danish Occupational Cohort. We modelled the probability of specified lifestyles in mixed models for each level of the four-digit DISCO code with age and sex as fixed effects and assessed variation in terms of intraclass correlation coefficients (ICCs) and exposure-level percentile ratios across jobs for six different time periods from 1981 through 2013. Results The ICCs were overall low (0.26%–7.05%) as the within-job group variation was large relative to the between job group variation, but across jobs the calendar period-specific ratios between highest and lowest predicted levels were ranging from 1.2 to 6.9, and for the 95%/1% and the 75%/5% percentile ratios ranges were 1.1–2.8 and 1.1–1.6, respectively, thus indicating substantial contrast for some lifestyle exposures and some occupations. Conclusions The lifestyle JEMs may prove a useful tool for control of lifestyle-related confounding in register-based occupational health studies where lacking information on individual lifestyle factors may compromise internal validity.

Physical work demands and psychosocial working conditions as predictors of musculoskeletal pain: a cohort study comparing self-reported and job exposure matrix measurements

Objectives Determining exposure to occupational factors by workers’ job titles is extensively used in epidemiological research. However, the correspondence of findings regarding associations to health between job exposure matrices (JEMs) and individual-level exposure data is largely unknown. We set out to examine the prospective associations of physical work demands and psychosocial working conditions with musculoskeletal pain, comparing JEMs with individual-level self-reported exposures. Methods We analysed data of 8132 participants from the Work Environment and Health in Denmark cohort study. Using random intercept multilevel modelling, we constructed age-specific and sex-specific JEMs estimating predicted exposures in job groups. We analysed associations between working conditions (individual and JEM level) at baseline and musculoskeletal pain at follow-up using multilevel modelling stratified by sex, adjusting for age, education and baseline pain. Results Any consistent associations present in the individual-level analysis were also found in the JEM-level analysis. Higher pain levels at follow-up was seen for employees with higher baseline physical work demands, women exposed to violence and men with lower decision authority, whether measured at the individual or JEM level. Higher JEM-level quantitative demands were associated with less pain, but no association was seen at the individual level. Conclusions We found predominately comparable prospective associations between working conditions and pain, whether using JEMs or individual level exposures, with the exception of quantitative demands. The results suggest that, with few notable exceptions, findings obtained using JEMs may be comparable with those obtained when using self-reported exposures.

0294 Job-exposure matrix addressing smoking in the nationwide danish occupational cohort, doc*x

Objectives To develop a job-exposure matrix (JEM) addressing smoking to allow for confounder adjustment in register-based occupational health studies. Methods We combined and harmonised questionnaire and interview data on smoking from several Danish cohort studies and surveys in the time-period 1981–2013 for 2 64 054 employees registered with a DISCO-88 code (the Danish version of ISCO-88) in the Danish nationwide JEM database, DOC*X. We modelled the probability of being a smoker, and the amount of smoking (g/d) among smokers. In mixed models, age and sex were included as fixed effects and DISCO as random effect for six different time-periods. Results The proportion of smokers decreased linearly from 56% in 1981–90% to 19% after 2010, whereas the amount increased from 15.9 g/d in 1981 to 16.5 g/d in 1991–95, and then declined to 13.2 g/d after 2010. In general, the quality of the JEM increased by calendar year, as 23% and 71% of the DISCO-codes were represented in the first and latest time-period, respectively, on the most detailed 4 digit DISCO-level. This was also reflected in the calculated interclass correlation coefficient (ICC), which increased by calendar year. The within job-group variation was large relative to the between jobs variation, but the range between jobs was in general high, as the probability ranged from 6% to 40% and the amount from 8.0 to 19.5 g/d after 2010. Conclusions We succeeded addressing a smoking JEM with substantial variability between jobs, which may prove a useful tool for confounder adjustment in register-based occupational studies.

0336 Impact of job group on risk of retirement in denmark 1980–2012

Objectives Age at permanent retirement is of interest both from an occupational health perspective as an indicator of health risks and from a societal perspective, where keeping an ageing population at work is a priority. The Danish nationwide individual level database DOC*X includes labour market affiliation and job type for employed residents in Denmark in the years 1970–2012. The aim of this study is to investigate differences in retirement between job titles. Methods Data on permanent retirement was obtained from administrative registries for the years 1980–1990 and 1994–2012. Each job title was coded by the Danish version of the International Standard Classification of Occupations (DISCO-88). We calculated mean age at retirement in years (MAR) and age-and-sex standardised retirement risk ratios (SRR) according to five year periods and DISCO-88 groups (first digit). Results The number of employed persons varied between 2.0 and 2.7 million yearly, whereof job title was identified for around 75%. MAR was substantially higher among persons with non-manual compared to manual jobs (men: 64.6 versus 61.6 years) and (women: 63.3 versus 60.8 years). In 2011–2012 SRR was between 0.44 and 1.55 for women and 0.40 and 1.12 for men. Manual jobs had consistently increased SSR throughout the study period, but the relative difference between manual and non-manual jobs increased from 2.0 in the early 1980’ties to 5.4 in the mid-1990’ties and decreased to 1.9 in the latest years. Conclusion Manual jobs have an increased standardised retirement risk and a lower mean age of retirement compared to non-manual jobs.

0207 Hypertensive disorders of pregnancy among night workers in danish hospitals: a national register-based cohort study

Objective Few studies investigated hypertensive disorders of pregnancy (HDP) in relation to work at night with inconclusive results and crude exposure assessment. Our aim is to investigate the risk of HDP after work at night during pregnancy based on objective exposure assessment from The Danish Working Hour Database (DWHD), which contains information on working hours from all public hospital employees in Denmark. Methods The study population (n=20,385) comprised women from DWHD who have given birth at least once between 2007 and 2013. Night and day shifts were defined as at least three hours between 00:00 and 05:00 and between 06:00 and 20:00 respectively. Cases of HDP defined as gestational hypertension or preeclampsia/eclampsia were retrieved from The Danish National Patient Registry. We analysed the risk of HDP by number of night shifts during the first 20 weeks of gestation by logistic regression adjusted for relevant covariates. Results The risk of HDP among women working 1–3 and>=4 night shifts during the first 20 pregnancy weeks was OR=0.94 (95%CI 0.77, 1.16) and OR=1.03 (0.75, 1.41), respectively, compared to day workers. Stratified analyses revealed an increased risk of HDP among women older than 35 years who worked at night compared to day workers (OR=1.76; 1.05, 3.04 p value for interaction <0.001). Conclusion Our results of no overall increased risk of HDP among night workers are reassuring. The post hoc result finding of increased risk among women older than 35 years needs cautious interpretation.