Psychosocial work factors and sick leave risk after a terrorist bomb attack: a survey and registry-based longitudinal study of governmental employees in Norway.

OBJECTIVES: Studies show that social support may reduce the negative psychological effects of terror. The aim was to explore the effects of the psychosocial work environment on sick leave risk among governmental employees after a workplace bomb attack. DESIGN: We linked longitudinal survey data collected at 10 and 22 months after the bombing with registry data on doctor-certified sick leave collected from 42 months before the attack to 33 months after the attack. ORs and rate ratios were estimated with mixed effects hurdle models. SETTING: The bombing of the government ministries in Oslo, Norway, 22 July 2011. PARTICIPANTS: We identified 1625 participants from a cohort of 3520 employees working in the ministries during the bombing in 2011. RESULTS: After adjustment for confounders, social support from coworkers reduced the odds of sick leave (OR 0.80, 95% CI 0.68 to 0.93), and there was marginal evidence for reduced odds with support from superior (OR 0.87, 95% CI 0.87 to 1.03). A social work climate, an innovative climate and a human resource primacy climate (HRP) reduced the sick leave risk (eg, HRP OR 0.77, 95% CI 0.66 to 0.90). The hurdle model found no associations between psychosocial support at work and the duration of sick leave. CONCLUSIONS: Psychosocial support at work can enhance employees' work ability after terror and reduce the sick leave risk by more than 20%. However, a supportive psychosocial work environment did not reduce the duration of sickness absence. The protective role of psychosocial work factors on sick leave may be most significant when employees are at work and interact with their work environment.

Seasonal and pandemic influenza during pregnancy and risk of fetal death: A Norwegian registry-based cohort study.

Previous studies of fetal death with maternal influenza have been inconsistent. We explored the effect of maternal influenza-like illness (ILI) in pregnancy on the risk of fetal death, distinguishing between diagnoses during regular influenza seasons and the 2009/2010 pandemic and between trimesters of ILI. We used birth records from the Medical Birth Registry of Norway to identify fetal deaths after the first trimester in singleton pregnancies (2006-2013). The Norwegian Directorate of Health provided dates of clinical influenza diagnoses by primary-health-care providers, whereas dates of laboratory-confirmed influenza A (H1N1) diagnoses were provided by the Norwegian Surveillance System for Communicable Diseases. We obtained dates and types of influenza vaccinations from the Norwegian Immunisation Registry. Cox proportional-hazards regression models were fitted to estimate hazard ratios (HRs) of fetal death, with associated 95% confidence intervals (CIs), comparing women with and without an ILI diagnosis in pregnancy. There were 2510 fetal deaths among 417,406 eligible pregnancies. ILI during regular seasons was not associated with increased risk of fetal death: adjusted HR = 0.90 (95% CI 0.64-1.27). In contrast, ILI during the pandemic was associated with substantially increased risk of fetal death, with an adjusted HR of 1.75 (95% CI 1.21-2.54). The risk was highest following first-trimester ILI (adjusted HR = 2.28 [95% CI 1.45-3.59]). ILI during the pandemic-but not during regular seasons-was associated with increased risk of fetal death in the second and third trimester. The estimated effect was strongest with ILI in first trimester.

A genome-wide scan of cleft lip triads identifies parent-of-origin interaction effects between ANK3 and maternal smoking, and between ARHGEF10 and alcohol consumption.

Background: Although both genetic and environmental factors have been reported to influence the risk of isolated cleft lip with or without cleft palate (CL/P), the exact mechanisms behind CL/P are still largely unaccounted for. We recently developed new methods to identify parent-of-origin (PoO) interactions with environmental exposures (PoOxE) and applied them to families with children born with isolated cleft palate only. Here, we used the same genome-wide association study (GWAS) dataset and methodology to screen for PoOxE effects in the larger sample of CL/P triads. Methods: Genotypes from 1594 complete triads and 314 dyads (1908 nuclear families in total) with CL/P were available for the current analyses. Of these families, 1024 were Asian, 825 were European and 59 had other ancestries. After quality control, 341,191 SNPs remained from the original 569,244. The exposures were maternal cigarette smoking, use of alcohol, and use of vitamin supplements in the periconceptional period. The methodology applied in the analyses is implemented in the R-package Haplin. Results: Among Europeans, there was evidence of a PoOxSmoke effect for ANK3 with three SNPs (rs3793861, q=0.20, p=2.6e-6; rs7087489, q=0.20, p=3.1e-6; rs4310561, q=0.67, p=4.0e-5) and a PoOxAlcohol effect for ARHGEF10 with two SNPs (rs2294035, q=0.32, p=2.9e-6; rs4876274, q=0.76, p=1.3e-5). Conclusion: Our results indicate that the detected PoOxE effects have a plausible biological basis, and thus warrant replication in other independent cleft samples. Our demonstration of the feasibility of identifying complex interactions between relevant environmental exposures and PoO effects offers new avenues for future research aimed at unravelling  the complex etiology of cleft lip defects.

Association of Household Income With Life Expectancy and Cause-Specific Mortality in Norway, 2005-2015.

Importance: Examining causes of death and making comparisons across countries may increase understanding of the income-related differences in life expectancy. Objectives: To describe income-related differences in life expectancy and causes of death in Norway and to compare those differences with US estimates. Design and Setting: A registry-based study including all Norwegian residents aged at least 40 years from 2005 to 2015. Exposures: Household income adjusted for household size. Main Outcomes and Measures: Life expectancy at 40 years of age and cause-specific mortality. Results: In total, 3 041 828 persons contributed 25 805 277 person-years and 441 768 deaths during the study period (mean [SD] age, 59.3 years [13.6]; mean [SD] number of household members per person, 2.5 [1.3]). Life expectancy was highest for women with income in the top 1% (86.4 years [95% CI, 85.7-87.1]) which was 8.4 years (95% CI, 7.2-9.6) longer than women with income in the lowest 1%. Men with the lowest 1% income had the lowest life expectancy (70.6 years [95% CI, 69.6-71.6]), which was 13.8 years (95% CI, 12.3-15.2) less than men with the top 1% income. From 2005 to 2015, the differences in life expectancy by income increased, largely attributable to deaths from cardiovascular disease, cancers, chronic obstructive pulmonary disease, and dementia in older age groups and substance use deaths and suicides in younger age groups. Over the same period, life expectancy for women in the highest income quartile increased 3.2 years (95% CI, 2.7-3.7), while life expectancy for women in the lowest income quartile decreased 0.4 years (95% CI, -1.0 to 0.2). For men, life expectancy increased 3.1 years (95% CI, 2.5-3.7) in the highest income quartile and 0.9 years (95% CI, 0.2-1.6) in the lowest income quartile. Differences in life expectancy by income levels in Norway were similar to differences observed in the United States, except that life expectancy was higher in Norway in the lower to middle part of the income distribution in both men and women. Conclusions and Relevance: In Norway, there were substantial and increasing gaps in life expectancy by income level from 2005 to 2015. The largest differences in life expectancy between Norway and United States were for individuals in the lower to middle part of the income distribution.

Body mass index, smoking, and risk of death between 40 and 70 years of age in a Norwegian cohort of 32,727 women and 33,475 men.

Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40-69 years) death risk-overall and by causes-in a Norwegian cohort of 32,727 women and 33,475 men who were 35-49 years old when baseline measurements and lifestyle information were collected in 1974-1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11% in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5-24.9 BMI group to 31% (adjusted 28%) in obese (BMI > 30 kg/m(2)) heavy smokers (≥20 cigarettes/day). The corresponding figures in men were 10% and 53% (adjusted 45%). Obese never smokers and light (1-9 cigarettes/day) smokers in the 22.5-24.9 BMI groups both experienced a twofold increase in middle age risks of death. For women, cancer (56%) was the most common cause of death followed by cardiovascular disease (22%). In men, cardiovascular disease was most common (41%) followed by cancer (34%). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths.

Relative importance of risk factors for coronary heart disease--the Hordaland Homocysteine study.

OBJECTIVES: The aim was to rank coronary heart disease (CHD) risk factors according to their importance in predicting CHD morbidity and mortality using a scale-independent statistical approach. DESIGN: We studied 15 515 community-dwelling adults in a population-based cohort established during 1992-93 in Western Norway. Participants were 40-42 and 65-67 years old at baseline and were followed through 2006. Endpoints were non-fatal/fatal acute myocardial infarction (AMI) and CHD death. Each factor was rank transformed and scaled to the range 0-5 before estimation of Cox models. Hazard ratios (HR) may thus be interpreted as HR per quintile increment for each factor, and the magnitude of the HR was used to rank the risk factors according to strength. RESULTS: Total cholesterol and triglycerides were important risk factors for both CHD death and non-fatal/fatal AMI only in the middle-aged group. Risk factors were generally stronger in the middle-aged, except total homocysteine which was significantly associated with CHD death in the oldest group only. The only significant difference between men and women was found for single living which was an important risk factor for non-fatal/fatal AMI in middle-aged women but not in middle-aged men. CONCLUSIONS: We have demonstrated a simple method for direct and scale-independent comparison of the strength of both categorical and continuous risk factors. The importance of individual risk factors differed substantially between the two age groups.

Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts.

Orofacial clefts are common birth defects with strong evidence for both genetic and environmental causal factors. Candidate gene studies combined with exposures known to influence the outcome provide a highly targeted approach to detecting GxE interactions. We developed a new statistical approach that combines the case-control and offspring-parent triad designs into a "hybrid design" to search for GxE interactions among 334 autosomal cleft candidate genes and maternal first-trimester exposure to smoking, alcohol, coffee, folic acid supplements, dietary folate and vitamin A. The study population comprised 425 case-parent triads of isolated clefts and 562 control-parent triads derived from a nationwide study of orofacial clefts in Norway (1996-2001). A full maximum-likelihood model was used in combination with a Wald test statistic to screen for statistically significant GxE interaction between strata of exposed and unexposed mothers. In addition, we performed pathway-based analyses on 28 detoxification genes and 21 genes involved in folic acid metabolism. With the possible exception of the T-box 4 gene (TBX4) and dietary folate interaction in isolated CPO, there was little evidence overall of GxE interaction in our data. This study is the largest to date aimed at detecting interactions between orofacial clefts candidate genes and well-established risk exposures.

Intake of probiotic food and risk of spontaneous preterm delivery.

BACKGROUND: Preterm delivery represents a substantial problem in perinatal medicine worldwide. Current knowledge on potential influences of probiotics in food on pregnancy complications caused by microbes is limited. OBJECTIVE: We hypothesized that intake of food with probiotics might reduce pregnancy complications caused by pathogenic microorganisms and, through this, reduce the risk of spontaneous preterm delivery. DESIGN: This study was performed in the Norwegian Mother and Child Cohort on the basis of answers to a food-frequency questionnaire. We studied intake of milk-based products containing probiotic lactobacilli and spontaneous preterm delivery by using a prospective cohort study design (n = 950 cases and 17,938 controls) for the pregnancy outcome of spontaneous preterm delivery (< 37 gestational weeks). Analyses were adjusted for the covariates of parity, maternal educational level, and physical activity. RESULTS: Pregnancies that resulted in spontaneous preterm delivery were associated with any intake of milk-based probiotic products in an adjusted model [odds ratio (OR): 0.857; 95% CI: 0.741, 0.992]. By categorizing intake into none, low, and high intakes of the milk-based probiotic products, a significant association was observed for high intake (OR: 0.820; 95% CI: 0.681, 0.986). CONCLUSION: Women who reported habitual intake of probiotic dairy products had a reduced risk of spontaneous preterm delivery.

Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.

BACKGROUND: Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects. Two complementary statistical methods, TRIMM and HAPLIN, were used to detect multi-marker effects in population-based samples from Norway (562 case-parent and 592 control-parent triads) and Denmark (235 case-parent triads). We analyzed isolated cleft lip with or without cleft palate (iCL/P) and isolated cleft palate only (iCP) separately and assessed replication by looking for genes detected in both populations by both methods. In iCL/P, neither TRIMM nor HAPLIN detected more genes than expected by chance alone; furthermore, the selected genes were not replicated across the two methods. In iCP, however, FLNB was identified by both methods in both populations. Although HIC1 and ZNF189 did not fully satisfy our stringency criterion for replication, they were strongly associated with iCP in TRIMM analyses of the Norwegian triads. CONCLUSION/SIGNIFICANCE: Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.

Genetic determinants of facial clefting: analysis of 357 candidate genes using two national cleft studies from Scandinavia.

BACKGROUND: Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 case-parent triads). METHODOLOGY/PRINCIPAL FINDINGS: We used two complementary statistical methods, TRIMM and HAPLIN, to look for associations across these two national samples. TRIMM tests for association in each gene by using multi-SNP genotypes from case-parent triads directly without the need to infer haplotypes. HAPLIN on the other hand estimates the full haplotype distribution over a set of SNPs and estimates relative risks associated with each haplotype. For isolated cleft lip with or without cleft palate (I-CL/P), TRIMM and HAPLIN both identified significant associations with IRF6 and ADH1C in both populations, but only HAPLIN found an association with FGF12. For isolated cleft palate (I-CP), TRIMM found associations with ALX3, MKX, and PDGFC in both populations, but only the association with PDGFC was identified by HAPLIN. In addition, HAPLIN identified an association with ETV5 that was not detected by TRIMM. CONCLUSION/SIGNIFICANCE: Strong associations with seven genes were replicated in the Scandinavian samples and our approach effectively replicated the strongest previously known association in clefting--with IRF6. Based on two national cleft cohorts of similar ancestry, two robust statistical methods and a large panel of SNPs in the most promising cleft candidate genes to date, this study identified a previously unknown association with clefting for ADH1C and provides additional candidates and analytic approaches to advance the field.