Leadership at work and risk of treatment for depressive and anxiety disorders in Denmark. A nationwide prospective study with register-based follow up.

Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders.

Exposure to chlorpyrifos and pyrethroid insecticides and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in preschool children from the Odense Child Cohort.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings. OBJECTIVES: To investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort. METHODS: Spot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported "ADHD scale" from the "Child Behavior Checklist 1½-5" (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex. RESULTS: Most pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 µg/L and 1.62 µg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 µg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5. CONCLUSION: In this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing.

Workplace bullying, symptoms of anxiety and the interaction with leadership quality - a longitudinal study using dynamic panel models with fixed effects.

OBJECTIVES: Workplace bullying has been suggested to increase symptoms of anxiety. A reverse relationship has also been proposed. However, so far only few earlier studies have investigated this topic and the reported associations might partly be explained by unmeasured individual characteristics. In this study, we aim to examine the temporality and directionality between workplace bullying and anxiety symptoms, taking time-invariant characteristics into account. Furthermore, we aim to examine whether leadership quality modifies these associations. METHODS: We included 13 491 individuals from two nationwide cohort studies in Sweden and Denmark. Using cross-lagged structural equation models (SEM) and dynamic panel models with fixed effects, we examined contemporaneous and lagged associations between self-reported workplace bullying and anxiety. Cohort-specific results were estimated and combined using fixed-effect meta-analysis. RESULTS: The cross-lagged SEM models supported contemporaneous and lagged relationships in both directions (from workplace bullying to symptoms of anxiety and vice versa). In contrast, only contemporaneous relationships remained statistically significant and of considerable magnitude in the dynamic panel models with fixed effects. Specifically, exposure to workplace bullying was related to a concurrent increase in anxiety symptoms (b=0.61, 95% confidence interval 0.32-0.90). No support of interaction with leadership quality was found. CONCLUSIONS: The results indicate that onset of workplace bullying is associated with an immediate or short-term increase in anxiety symptoms. This study provides novel insights regarding temporal aspects and causal inference of the bullying-anxiety relationship useful for managing psychological hazards and preventing mental illness at work.

Do different job demands interact as predictors of long-term sickness absence? A register-based follow-up on 55 467 Danish workers.

OBJECTIVES: To assess interactions between combinations of quantitative demands, emotional demands, unclear and contradictory demands, and violence/threats of violence in the prospective association with risk of long-term sickness absence (LTSA). METHODS: We included 55 467 employees from the 2012, 2014 and 2016 waves of the Work Environment and Health in Denmark (WEHD) survey. We measured the four independent variables in the WEHD survey and assessed risk of LTSA in a national register during 12 months of follow-up. Using Cox proportional hazards models, adjusted for age, sex, educational attainment and job group, we estimated risk of LTSA and assessed deviation from additivity using relative excess risk due to interaction (RERI). RESULTS: For combinations of high emotional demands and high quantitative demands (HR 1.50; 95% CI 1.33 to 1.70; RERI 0.06; 95% CI -0.15 o 0.26) and high emotional demands and violence/threats of violence (HR 1.76; 95% CI 1.53 to 2.02; RERI 0.12; 95% CI -0.43 to 0.66) we found no indications of deviations from additive effects in predicting LTSA. For combinations of violence/threats of violence and high quantitative demands (HR 1.90; 95% CI 1.64 to 2.20; RERI 0.36; 95% CI 0.01 to 0.71) and unclear and contradictory demands and high quantitative demands (HR 1.46; 95% CI 1.31 to 1.62; RERI 0.23; 95% CI 0.04 to 0.42) the results indicated an excess risk of LTSA above additivity (ie, superadditivity). CONCLUSIONS: Participants reporting high quantitative demands combined with either violence/threats of violence or unclear and contradictory demands showed a higher risk of LTSA than expected, indicating superadditivity. Results have implications for preventing negative health effects related to adverse psychosocial working conditions.

No association between maternal and child PFAS concentrations and repeated measures of ADHD symptoms at age 2½ and 5 years in children from the Odense Child Cohort.

INTRODUCTION: The potential impact of exposure to perfluoroalkyl substances (PFAS) on childhood Attention-Deficit Hyperactivity-Disorder (ADHD) is unclear and deserves scrutiny. The majority of previously conducted longitudinal studies found no association between maternal serum-PFAS concentrations and ADHD symptoms in the offspring, but some studies observed possible associations with postnatal PFAS exposures, mainly in girls. OBJECTIVE: To investigate the association between maternal and child serum concentrations of five PFAS and symptoms of ADHD at ages 2½ and 5 years. METHODS: In the Odense Child Cohort (OCC) women were recruited in early pregnancy in 2010-12 and their children are being prospectively followed. Mothers donated serum samples in the first trimester and children at age 18 months to be analyzed for perfluorohexane sulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). Parents completed the Child Behavior Check List for ages 1.5-5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at age 2½ years and again at 5 years. Negative binomial and logistic regression models taking account of repeated measures were used to investigate the association between maternal and child serum-PFAS concentrations and the ADHD symptom score. Effect modification by child sex was investigated as well. RESULTS: A total of 1138 mother-child pairs were included. At age 2½ years, 17.4% of the children had an ADHD scale score ≥ 5 (equivalent to the 90th percentile), whereas the proportion was 15.8% at age 5. We found no association between either maternal or child PFAS concentrations in serum and symptoms of ADHD at age 2½ or 5 years, and no evidence of effect modification by sex. CONCLUSION: We found no evidence of an association between early-life PFAS exposure and the risk of developing symptoms of ADHD.

Prenatal exposure to pyrethroid and organophosphate insecticides and language development at age 20-36 months among children in the Odense Child Cohort.

BACKGROUND: Prenatal exposure to organophosphate and pyrethroid insecticides has been associated with impaired neurodevelopment. Few longitudinal studies have investigated associations with early language development in populations with mainly low dietary exposure. OBJECTIVE: To investigate associations between biomarkers of maternal gestational exposure to organophosphate and pyrethroid insecticides and the child's language development at age 20-36 months in the prospective Odense Child Cohort. METHODS: Metabolites of organophosphate and pyrethroid insecticides were measured in maternal urine samples collected at gestational week 28. Language development was assessed among 755 singletons at age 20-36 months using the Vocabulary and Complexity scores of the MacArthur-Bates Communicative Development Inventories, standardized into age and sex specific percentile scores according to a Danish reference study. Multiple logistic regression models were used to estimate the odds of scoring below the 15th percentile scores in relation to maternal urinary insecticide metabolite concentrations after adjustment for confounders. RESULTS: The generic pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA) and the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPY) were detectable in more than 90% of the urine samples analyzed. Likewise, 82.2% had detectable concentrations of diethyl phosphates (DE) and 58.4% of dimethyl phosphates (DM), both of which are common metabolites of organophosphate insecticides. None of the metabolites was associated with higher odds of delayed results below the 15th percentile language scores. In contrast, reduced probability for scoring below the 15th percentile Vocabulary score was seen for the highest tertile of 3-PBA in boys and for the upper tertile of TCPY and DE in girls. CONCLUSION: In this prospective cohort, with predominantly dietary insecticide exposure, we found no evidence that gestational exposure to organophosphate or pyrethroid insecticides adversely affected early language development in the children. The observed indication of a positive effect of insecticides on language development may be explained by residual and unmeasured confounding from socioeconomic factors and dietary habits. Follow-up of these children should include assessment of more complex cognitive functions in later childhood, as well as associations with their own postnatal insecticide exposure.

Exposure to perfluoroalkyl substances during fetal life and hospitalization for infectious disease in childhood: A study among 1,503 children from the Odense Child Cohort.

INTRODUCTION: The immunosuppressive properties of PFASs are widely recognized. Early-life exposure to PFAS has been linked to reduced immune response to childhood vaccinations and increased rates of common infectious diseases, but implications for hospitalizations are unclear. OBJECTIVES: To investigate the association between maternal serum concentrations of five PFASs during pregnancy and the child's rate of hospitalization due to common infectious diseases between birth and 4 years of age. METHODS: Serum samples from first trimester pregnant women from the Odense Child Cohort (OCC) collected in 2010-2012 were analyzed for concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and three other PFASs. Data on child hospitalizations with an ICD-10 code for infectious disease was obtained from the Danish National Patient Register. The following were identified: upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), gastrointestinal infections (GI), and other infections. The Andersen-Gill Cox proportional hazard model for recurrent events was used to investigate the association between PFAS exposure and hospitalizations. The resulting estimates were hazard ratios (HRs), which express the relative change in the instantaneous risk of hospitalization with a doubling in maternal PFAS concentration. RESULTS: A total of 1,503 mother-child pairs were included, and 26% of the children were hospitalized at least once for infectious disease. A doubling in maternal PFOS concentration was associated with a 23% increase in the risk of hospitalization due to any infection (HR: 1.23 (95% CI: 1.05, 1.44). There was indication of an interaction between child sex and PFOS (p = 0.07) and PFDA (p = 0.06), although in opposite directions. Further, every doubling of PFOA or PFOS increased the risk of LRTI by 27% (HR: 1.27 (1.01, 1.59)) and 54% (HR: 1.54 (1.11, 2.15)), respectively. Similar tendencies were seen for URTI and the group of other infections. For GIs, the opposite pattern of association was seen as HR's were consistently below 1 (PFOA, HR: 0.55 (0.32, 0.95)). DISCUSSION: We found an association between PFOS and the overall risk of infectious disease, and between PFOS and PFOA exposures and the risk of LRTI's. These results are in agreement with previous findings from the OCC, in which maternal PFOS and PFOA concentrations were positively associated with the number of days that the children experienced fever, thereby suggesting that PFOS and PFOA may affect the prevalence of both mild and more severe infectious diseases even in a rather low-exposed population.

Maternal urinary concentrations of pyrethroid and chlorpyrifos metabolites and attention deficit hyperactivity disorder (ADHD) symptoms in 2-4-year-old children from the Odense Child Cohort.

BACKGROUND: Pyrethroids and chlorpyrifos are widely used insecticides, but the potential impact of prenatal exposure on child neurodevelopment has only been addressed in few longitudinal studies. OBJECTIVES: To investigate associations between prenatal exposure to pyrethroids and chlorpyrifos and traits of ADHD in 2-4-year-old children. METHODS: Metabolites of chlorpyrifos and pyrethroids were measured in maternal urine collected at gestational week 28 among 1207 women from the Odense Child Cohort. Of these, 948 completed the Child Behavior Check List for ages 1.5-5 years (CBCL: 1½-5). Negative binomial and logistic regression models were used to estimate relative differences in ADHD problem scores (CBCL: 1½-5 subscale) expressed as the ratio of expected scores between exposure groups and the odds (OR) of scoring equal to or above the 90th percentile in relation to maternal urinary metabolite concentrations (continuous ln2-transformed or categorized into tertiles). The analyses were adjusted for maternal education level, parental psychiatric diagnosis, child age and sex. RESULTS: The chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPY), the generic pyrethroid metabolite, 3-phenoxybenzoic acid (3-PBA), and the metabolite of trans-isomers of permethrin, cypermethrin, and cyfluthrin, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-DCCA), were detected in 90%, 94%, and 11%, respectively, of the urine samples. Each doubling in maternel 3-PBA concentration was associated with a 3% increase in the ADHD score (Ratio: 1.03 (95% CI: 1.00,1.07)) and a 13% higher odds of having a ADHD score ≥ the 90th percentile (OR: 1.13 (1.04,1.38)). Similar associations were seen for 3-PBA as categorical variable (p-trend=0.052 in negative binimoal regression, p-trend=0.007 in logistic regression). Furthermore, concurrent concentrations of 3-PBA and TCPY above their medians were associated with higher ADHD score (Ratio: 1.20 (1.04, 1.38)) and higher odds of scoring ≥ the 90th percentile (OR: 1.98 (1.26, 3.11)). Maternal trans-DCCA above the detection level increased the odds of ADHD symptoms (OR: 1.76 (1.08, 2.86)). The associations were not modified by sex. CONCLUSIONS: Prenatal exposure to pyrethroids was associated with ADHD related traits at 2-4 years of age. Considering the widespread use of pyrethroids these results are of concern.

Associations of maternal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-D with birth outcomes and anogenital distance at 3 months in the Odense Child Cohort.

In Odense Child Cohort (OCC), concentrations of the pesticide metabolites 3-phenoxybenzoic acid (3-PBA), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-Dichlorophenoxyacetic acid (2,4-D) and dialkyl phosphates (DAPs) were measured in urine samples collected in gestational week 28 in up to 858 women. Gestational length, birth weight, head and abdominal circumference were obtained from birth records and anogenital distance (AGD) was measured at age three month. We did not find consistent dose-related associations between pesticide metabolite concentrations and birth outcomes or AGD. However, females tended to have shorter abdominal circumference with higher maternal 3-PBA concentrations (ß: -0.3 (95% CI: -0.5, -0.003) cm). Further, a non-significant dose-related elongation of AGD in females was seen for 3-PBA (p-trend: 0.14) and diethyl phosphates (p-trend: 0.08). In males, exposure to 2,4-D in the second compared to the first tertile showed a statistically significant shorter AGD (ß: -1.55 (-2.81, -0.28) mm). These findings may suggest a weak disturbance of sex-hormone action.

Prenatal phthalate exposure and language development in toddlers from the Odense Child Cohort.

BACKGROUND: Phthalates are a group of chemicals found in a variety of consumer products. They have anti-androgenic properties and human studies have reported associations between prenatal phthalate exposure and neuropsychological development in the offspring despite different cognitive tests, different ages and varying timing of exposure. OBJECTIVES: To investigate the association between prenatal phthalate exposure and language development in children aged 20-36months. METHODS: In the Odense Child Cohort, we analyzed 3rd trimester urine samples of 518 pregnant women for content of metabolites of diethyl, di-n-butyl, diisobutyl, butylbenzyl, di(2-ethylhexyl), and diisononyl phthalate, adjusted for osmolality. Language development was addressed using the Danish version of the MacArthur-Bates Communicative Development Inventories "Words and Sentences". Associations were assessed using logistic regression models comparing children below and above the 15th percentile while stratifying by sex and adjusting for maternal age and educational level. RESULTS: Phthalate metabolites were detectable in all samples although in lower levels than previous studies. Among boys, increased prenatal phthalate exposure was associated with lower scores in language development; odds ratios for vocabulary score below the 15th percentile with doubling in monoethyl phthalate, and summed di-(2-ethylhexyl) phthalate metabolites were respectively 1.24 (95% confidence interval: 1.05,1.46), and 1.33 (1.01,1.75). Similar associations were found for language complexity. No associations were found for girls. CONCLUSIONS: Our findings are notable, as adverse associations were suggested even in this low-level exposed population, with only one spot urine sample for exposure assessment and control for confounders. Lower scores in early language development are of relevance to health as this test predicts later educational success.

Association between prenatal exposure to perfluorinated compounds and symptoms of infections at age 1-4years among 359 children in the Odense Child Cohort.

INTRODUCTION: Perfluorinated alkylated substances (PFAS) are persistent industrial chemicals that have resulted in global environmental exposures. Previous epidemiological studies have reported possible effects on the immune system after developmental PFAS exposure, but the possible impact on childhood infectious disease is unclear. OBJECTIVES: To investigate the association between prenatal exposure to PFAS and symptoms of infections at age 1-4years. METHODS: The Odense Child Cohort is an on-going prospective study on children's health, where serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA) were measured in 649 pregnant women before gestational week 16. Of these women, 359 reported on symptoms of infection in their child every two weeks for a one-year period. The association between prenatal exposure to PFAS and the symptoms was estimated using a logistic regression model and a negative binomial regression model. For the latter, the outcome was reported as an incidence rate-ratio (IRR), and all models were adjusted for maternal age, educational level, parity and child age. RESULTS: On average, the children experienced symptoms of infection 23% of the time during one year. PFOS exposure in the high tertile compared to the low tertile was associated with a statistically significant increased proportion of days with fever (IRR: 1.65 (95% CI: 1.24, 2.18), P-trend<0.001) and an increased odds of experiencing days with fever above the median (OR: 2.35 (95% CI: 1.31, 4.11). The latter tendency was also apparent for PFOA (OR: 1.97 (95% CI: 1.07, 3.62). Further, higher concentrations of PFOS and PFOA tended to increase the number of episodes of co-occurrence of fever and coughing and fever and nasal discharge during the one-year study period. CONCLUSION: We found a positive association between prenatal exposure to PFOS and PFOA and the prevalence of fever, which may be a sensitive marker of infection. This finding is in agreement with an immunotoxic effect of prenatal exposure to PFAS. The wider implications for childhood infectious disease deserve attention.