A population-based study of testicular cancer risk among children and young adults from Norway and Utah, USA.

Similar family-based cancer and genealogy data from Norway and Utah allowed comparisons of the incidence of testicular cancer (TC), and exploration of the role of Scandinavian ancestry and family history of TC in TC risk. Our study utilizes data from the Utah Population Database and Norwegian Population Registers. All males born during 1951-2015 were followed for TC until the age of 29 years. A total of 1,974,287 and 832,836 males were born in Norway and Utah, respectively, of whom 2,686 individuals were diagnosed with TC in Norway and 531 in Utah. The incidence per year of TC in Norway (10.6) was twice that observed in Utah (5.1) for males born in the last period (1980-1984). The incidence rates of TC in Utah did not differ according to the presence or absence of Scandinavian ancestry (p = 0.669). Having a brother diagnosed with TC was a strong risk factor for TC among children born in Norway and Utah, with HR = 9.87 (95% CI 5.68-17.16) and 6.02 (95% CI 4.80-7.55), respectively; with even higher HR observed among the subset of children in Utah with Scandinavian ancestry (HR = 12.30, 95% CI 6.78-22.31). A clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah was observed. These differences in TC rates point to the possibility of environmental influence. Family history of TC is a strong risk factor for developing TC in both populations.

Is the Association of Early Day Care Attendance with Childhood Asthma Explained by Underlying Susceptibility?

BACKGROUND: Previous studies of early day care attendance and asthma development are inconsistent, which may be explained by inadequate control of confounding and effect modification. We examined the effect of early day care on the risk of asthma taking into account the underlying susceptibility to asthma. METHODS: The study included 55,404 children participating in the Norwegian Mother, Father and Child Cohort Study. Asthma at age 7 was defined by dispensed asthma medications in the Norwegian Prescription Database. We defined a disease risk score (DRS) to account for an underlying susceptibility to asthma including a range of hereditary and nonhereditary predictors of asthma. We assessed confounding and modifying effects of DRS on the association between day care and asthma. RESULTS: Day care before 18 months was associated with a lower risk of asthma by age 7 (adjusted risk ratio [RR] = 0.85; 95% confidence interval [CI] = 0.78, 0.92) when compared with home care. DRS modified the estimated effect of day care on asthma risk. Among the 80% of children with DRS between 0.03 and 0.16, day care was associated with a reduced asthma risk (RRs between 0.79 and 0.87), whereas among 0.5% of children with a high DRS (above 0.28), estimated effect of day care on asthma increased gradually (RR for the highest DRS 2.2; 1.0-4.9). CONCLUSIONS: In our study, among most children, early day care was associated with reduced asthma risk at 7 years, and increased risk in a small group of children with very high underlying susceptibility to asthma.

Childhood central nervous system tumors and leukemia: Incidence and familial risk. A comparative population-based study in Utah and Norway.

BACKGROUND: In this study, we aimed to evaluate incidence rates and family risk of the most common childhood cancers, tumors in the central nervous system (CNS), and leukemia among individuals from Norway and individuals with Scandinavian ancestry living in Utah. METHODS: We used the Utah Population Database and the Norwegian National Population Register linked to Cancer registries to identify cancers in children born between 1966 and 2015 and their first-degree relatives. We calculated incidence rates and hazards ratios. RESULTS: The overall incidence of CNS tumors increased with consecutive birth cohorts similarly in Utah and Norway (both P < 0.001). Incidence rates of leukemia were more stable and similar in both Utah and in Norway with 4.6/100 000 person-years among children (<15 years) born in the last cohort. A family history of CNS tumors was significantly associated with risk of childhood CNS tumors in Utah HR = 3.05 (95% CI 1.80-5.16) and Norway HR = 2.87 (95% CI 2.20-3.74). In Norway, children with a first-degree relative diagnosed with leukemia had high risk of leukemia (HR = 2.39, 95% CI 1.61-3.55). CONCLUSION: Despite geographical distance and assumed large lifestyle differences, two genetically linked pediatric populations show similar incidences of CNS tumors and leukemia in the period 1966-2015. CNS tumors and leukemia aggregated in families in both countries.

Oral health and cardiovascular disease risk factors and mortality of cerebral haemorrhage, cerebral infarction and unspecified stroke in elderly men: A prospective cohort study.

Background: Stroke mortality comprises different specific diagnoses as cerebral infarction, different haemorrhagic conditions and unspecified stroke. This study seeks to explore the prediction of oral health indicators versus known cardiovascular disease risk factors for stroke mortality. Methods: Altogether, 12,764 men aged 58 to 77 years were invited to the health screening Oslo II in the year 2000. It included general medical measurements and questionnaire information. Mortality data were supplied by Statistics Norway for the 6530 attending men. Cox proportional hazards regression analyses were used to establish prediction models for mortality. Results: Oral health by number of tooth extractions >10 was found to be an independent predictor for cerebral infarction hazard ratio = 2.92, 95% confidence interval (1.24-6.89). This was independent of HDL-Cholesterol (inversely) hazard ratio = 0.21, 95% confidence interval (0.06-0.76), frequent alcohol consumption (drinking 4-7 times per week) hazard ratio = 3.58, 95% confidence interval (1.40-9.13) and diabetes hazard ratio = 4.28, 95% confidence interval (1.68-10.89). Predictors for cerebral haemorrhage were age, hs-C-reactive protein and body mass index (inversely). Age and total cholesterol (inversely) were predictors for unspecified stroke. Conclusions: Oral health measured by number of tooth extractions >10 was an independent predictor for cerebral infarction in addition to age, HDL-C, hs-C-reactive protein and diabetes. The pattern of risk factors varied between the specific stroke diagnoses.

Family history of cancer and risk of paediatric and young adult's testicular cancer: A Norwegian cohort study.

BACKGROUND: The aim of this study was to examine the association of a family history of cancer with the risk of testicular cancer in young adults. METHODS: This is a prospective cohort study including 1,974,287 males born 1951-2015, of whom 2686 were diagnosed with TC before the age of 30. RESULTS: A history of TC in male relatives was significantly associated with a diagnosis of TC among children and young adults, including brothers (6.3-fold), sons (4.7-fold), fathers (4.4-fold), paternal uncles (2.0-fold) and maternal uncles (1.9-fold). Individuals with a father diagnosed with a carcinoma or sarcoma showed an elevated risk (1.1-fold and 1.8-fold, respectively). A family history of mesothelioma was positively associated with a risk of TC [(father (2.8-fold), mother (4.6-fold) and maternal uncles and aunt (4.4-fold)]. Elevated risks were also observed when siblings were diagnosed with malignant melanoma (1.4-fold). The risk of TC was also increased when fathers (11.1-fold), paternal (4.9-fold) and maternal uncles and aunts (4.6-fold) were diagnosed with malignant neuroepithelial-tumours. CONCLUSION: We found an increased risk of TC among children and young adults with a family history of TC, carcinoma, mesothelioma, sarcoma, malignant melanoma and malignant neuroepithelial tumours. Hereditary cancer syndromes might underlie some of the associations reported in this study.

Maternal history of miscarriages and measures of fertility in relation to childhood asthma.

BACKGROUND: It remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (ART). OBJECTIVE: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. METHODS: We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. RESULTS: ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more. CONCLUSION: Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.

Agreement between self-reported and registry-based use of sleep medications and tranquilizers.

PURPOSE: The purpose of the present study was to assess the agreement between self-reported use of sleep medications and tranquilizers and dispensed hypnotics and anxiolytics. METHODS: Self-reported medication use was obtained from the population-based survey Health and Environment in Oslo (HELMILO) (2009-2010) (n = 13 019). Data on dispensed hypnotics and anxiolytics were obtained from the Norwegian Prescription Database (NorPD). As measures of validity, we calculated sensitivity and specificity using both self-reports and prescription records as the reference standard. Furthermore, we calculated Cohen's kappa. Current self-reported medication use was compared with prescription data in time windows of both 100 and 200 days preceding questionnaire completion. RESULTS: The highest sensitivity was observed for current sleep medication use in the 100-day time window (sensitivity = 0.76, 95% confidence interval [CI]: 0.74, 0.79) when using prescription records as the reference standard. Sensitivity was generally lower for tranquilizers compared with sleep medications. Cohen's kappa showed the highest agreement for the 200-day time window with substantial agreement for sleep medications (kappa = 0.64; 95% CI: 0.62, 0.67) and moderate agreement for tranquilizers (kappa = 0.45; 95% CI: 0.41, 0.48). CONCLUSIONS: The present study suggests moderate to substantial agreement between self-reported use of sleep medications and tranquilizers and dispensed drugs in a general adult population. The magnitude of agreement varied according to drug category and time window. Since self-reported and registry-based use of these drug classes does not match each other accurately, limitations of each data source should be considered when such medications are applied as the exposure or outcome in epidemiologic studies.

Association of Maternal Psychosocial Stress With Increased Risk of Asthma Development in Offspring.

Prenatal maternal psychosocial stress might influence the development of childhood asthma. Evaluating paternal psychosocial stress and conducting a sibling comparison could provide further insight into the role of unmeasured confounding. We examined the associations of parental psychosocial stress during and after pregnancy with asthma at age 7 years in the Norwegian Mother and Child Cohort Study (n = 63,626; children born in 2000-2007). Measures of psychosocial stress included lifetime major depressive symptoms, current anxiety/depression symptoms, use of antidepressants, anxiolytics, and/or hypnotics, life satisfaction, relationship satisfaction, work stress, and social support. Childhood asthma was associated with maternal lifetime major depressive symptoms (adjusted relative risk (aRR) = 1.19, 95% confidence interval (CI): 1.09, 1.30), in addition to symptoms of anxiety/depression during pregnancy (aRR = 1.17, 95% CI: 1.06, 1.29) and 6 months after delivery (aRR = 1.17, 95% CI: 1.07, 1.28). Maternal negative life events during pregnancy (aRR = 1.10, 95% CI: 1.06, 1.13) and 6 months after delivery (aRR = 1.14, 95% CI: 1.11, 1.18) were also associated with asthma. These associations were not replicated when evaluated within sibling groups. There were no associations with paternal psychosocial stress. In conclusion, maternal anxiety/depression and negative life events were associated with offspring asthma, but this might be explained by unmeasured maternal background characteristics that remain stable across deliveries.

Family history of cancer and the risk of childhood solid tumours: a Norwegian nationwide register-based cohort study.

This corrects the article DOI: 10.1038/bjc.2017.85.

Maternal Folate Intake during Pregnancy and Childhood Asthma in a Population-based Cohort.

RATIONALE: A potential adverse effect of high folate intake during pregnancy on children's asthma development remains controversial. OBJECTIVES: To prospectively investigate folate intake from both food and supplements during pregnancy and asthma at age 7 years when the diagnosis is more reliable than at preschool age. METHODS: This study included eligible children born 2002-2006 from the Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort, linked to the Norwegian Prescription Database. Current asthma at age 7 was defined by asthma medications dispensed at least twice in the year (1,901 cases; n = 39,846) or by maternal questionnaire report (1,624 cases; n = 28,872). Maternal folate intake was assessed with a food frequency questionnaire validated against plasma folate. We used log-binomial and multinomial regression to calculate adjusted relative risks with 95% confidence intervals. MEASUREMENTS AND MAIN RESULTS: Risk of asthma was increased in the highest versus lowest quintile of total folate intake with an adjusted relative risk of 1.23 (95% confidence interval, 1.06-1.44) that was similar for maternally reported asthma. Mothers in the highest quintile had a relatively high intake of food folate (median, 308; interquartile range, 241-366 µg/d) and nearly all took at least 400 µg/d of supplemental folic acid (median, 500; interquartile range, 400-600 µg/d). CONCLUSIONS: In this large prospective population-based cohort with essentially complete follow-up, pregnant women taking supplemental folic acid at or above the recommended dose, combined with a diet rich in folate, reach a total folate intake level associated with a slightly increased risk of asthma in children.

Preeclampsia and Hypertension During Pregnancy in Areas with Relatively Low Levels of Traffic Air Pollution.

Objectives Air pollution exposure may contribute to the development of preeclampsia and hypertension during pregnancy. However, the evidence for such a relation is still limited. We investigated the associations between exposure for moderate to low levels of air pollution during pregnancy and preeclampsia and gestational hypertension in selected urban and county areas of Norway. Methods This study used a sub-group of 17,533 women in the Norwegian Mother and Child Cohort Study. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy. Information on preeclampsia and gestational hypertension were obtained from the Medical Birth Registry of Norway and information on lifestyle factors was collected from questionnaires completed by the women during pregnancy. Results Moderate mean levels of NO2 (13.6 ± 6.9 µg/m3) at residential address during pregnancy were not associated with preeclampsia and pregnancy hypertension. We found no statistically significant associations per 10 µg/m3 change in NO2 exposure and preeclampsia (adjusted OR 0.89, 95% CI 0.74, 1.08) or hypertension during pregnancy (adjusted OR 0.91, 95% CI 0.78, 1.06). Conclusions for Practice In this large Norwegian pregnancy cohort, we found no statistically significant associations for moderate to low levels of pregnancy NO2 exposure and preeclampsia or hypertension during pregnancy.

The Influence of Meteorological Factors and Atmospheric Pollutants on the Risk of Preterm Birth.

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure.

Road traffic noise and registry based use of sleep medication.

BACKGROUND: Road traffic noise has been associated with adverse health effects including sleep disturbances. Use of sleep medication as an indicator of sleeping problems has rarely been explored in studies of the effects of traffic noise. Furthermore, using registry data on sleep medications provides an opportunity to study the effects of noise on sleep where attribution of sleep problems to noise is not possible. METHODS: We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-10) (n = 13,019). Individual data on sleep medications was obtained from the Norwegian Prescription Database (NorPD). Noise levels (L night) were modeled for the most exposed façade of the building at each participant's home address. Logistic regression models adjusted for potential confounders were used to analyze the association between traffic noise and sleep medication use both for one whole year and for the summer season. The results were reported as changes in the effect estimate per 5 decibel (dB) increase in noise level. RESULTS: We observed no association between traffic noise and sleep medication use during one year [odds ratio (OR) = 1.00; 95% confidence interval (CI): 0.96, 1.04]. For sleep medication use in the summer season, there was a positive, however non-significant association (OR = 1.04; 95% CI: 0.99, 1.10). Among individuals sleeping with the bedroom window open, the association increased slightly and was borderline statistically significant (OR = 1.06; 95% CI: 1.00, 1.12). CONCLUSIONS: We found no evidence of an association between traffic noise and sleep medication use during one year. However, for the summer season, there was some suggestive evidence of an association. These findings indicate that season may play a role in the association between traffic noise and sleep, possibly because indoor traffic noise levels are likely to be higher during summer due to more frequent window opening. More studies are, however, necessary in order to confirm this.

Maternal plasma total neopterin and kynurenine/tryptophan levels during pregnancy in relation to asthma development in the offspring.

BACKGROUND: Neopterin levels and kynurenine/tryptophan ratios (KTRs) increase with IFN-γ stimulation, indicating TH1 immunity, and thus might be inversely associated with asthma. OBJECTIVE: We sought to examine the association of maternal neopterin levels and KTRs during pregnancy with asthma in the offspring. METHODS: We analyzed the associations of maternal plasma total neopterin levels and KTRs in midpregnancy with asthma at age 7 years among 2883 children in the Norwegian Mother and Child Cohort Study. Asthma was classified either based on registered dispensed asthma medications in the Norwegian Prescription Database or maternal report. We calculated adjusted relative risks using log-binomial regression. RESULTS: The median gestational week of blood sampling was 18 weeks (interquartile range, 17-19 weeks). The risk of dispensed asthma medications at age 7 years was highest among children of mothers in the highest quartile of neopterin levels, whereas the risk was similar in the 3 lowest quartiles. The adjusted relative risk of dispensed asthma medications was 1.66 (95% CI, 1.16-2.38) when comparing children of mothers in the highest quartile with those in the 3 lowest quartiles. A similar association was observed for maternal report of asthma at age 7 years. When we evaluated allergic versus nonallergic asthma, neopterin levels tended to be associated with nonallergic asthma. Maternal KTR was not associated with asthma development. CONCLUSIONS: Our findings indicate that high maternal levels of neopterin, a marker of cellular immune activation, during pregnancy were positively associated with asthma in offspring. Experimental studies would be needed to further elucidate underlying mechanisms.

Risk of fetal death after pandemic influenza virus infection or vaccination.

BACKGROUND: During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination. METHODS: We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. RESULTS: There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). CONCLUSIONS: Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

Pre-eclampsia and childhood asthma.

Studies of pre-eclampsia and childhood asthma are conflicting, and none have performed a formal mediation analysis of preterm birth.We examined the association between pre-eclampsia and asthma at 7 years using national registries, including all births in Norway from 1999 to 2006 (n=406 907), and a subsample of children in the Norwegian Mother and Child Cohort Study (MoBa) (n=45 028) using log-linear regression. We performed a mediation analysis of preterm birth, and a sibling comparison to evaluate unobserved confounding.There was a positive association between pre-eclampsia and asthma in the registry study, with an adjusted relative risk of 1.31 (95% CI 1.22-1.41), but not in MoBa, which had an adjusted relative risk of 1.19 (95% CI 0.99-1.44). The odds ratios for the direct effect not mediated through preterm birth and the indirect effect in the registry linkage were 1.19 (95% CI 1.10-1.29) and 1.12 (95% CI 1.11-1.14), respectively. The sibling comparison indicated no association between pre-eclampsia and asthma (adjusted OR 1.07, 95% CI 0.87-1.33).In this large study, which used different datasets and analytic approaches, there was little evidence for an association between pre-eclampsia and childhood asthma. The association was weak and largely explained by pre-term birth and confounders shared by siblings.

Association of psychological distress late in life and dementia-related mortality.

OBJECTIVE: It is not fully understood how subjective feelings of psychological distress prognosticate dementia. Our aim was to investigate the association between self-reported psychological distress and risk of dementia-related mortality. METHOD: We included 31,043 eligible individuals between the ages of 60 and 80 years, at time of examination, from the CONOR (Cohort of Norway) database. They were followed for a period of 17.4 years (mean 11.5 years). The CONOR Mental Health Index, a seven-item self-report scale was used. A cut-off score equal to or above 2.15 on the scale denoted psychological distress. Cox regression was used to assess the association between psychological distress and risk of dementia-related mortality. RESULTS: Total number of registered deaths was 11,762 and 1118 (9.5%) were classified as cases of dementia-related mortality. We found that 2501 individuals (8.1%) had psychological distress, of these, 119 (10.6%) had concomitant dementia-related mortality. Individuals with psychological distress had an increased risk of dementia-related mortality HR = 1.52 (95% confidence interval (CI) 1.25-1.85) after adjusting for age, gender and education. The association remained significant although attenuated when implemented in a full adjusted model, including general health status, smoking, obesity, hypertension, diabetes and history of cardiovascular disease; hazard ratio, HR = 1.30 (95% CI 1.06-1.59). CONCLUSION: Our results indicate that psychological distress in elderly individuals is associated with increased risk of dementia-related mortality. Individuals at increased risk of dementia may benefit from treatments or interventions that lessen psychological distress, but this needs to be confirmed in future clinical studies.

Childhood sensorineural hearing loss: effects of combined exposure with aging or noise exposure later in life.

The aim of the study was to examine childhood high-frequency sensorineural hearing loss (HF-SNHL) and the effects of combined exposure with aging or noise exposure on HF hearing thresholds in adulthood. Population-based cohort study of 30,003 adults (mean age 40 years) underwent an audiometry and completed a hearing questionnaire. At age 7-13 years, the same people had participated in a longitudinal school hearing investigation, in which 283 participants were diagnosed with HF-SNHL [PTA 3-8 kHz ≥ 25 dB HL (mean 45 dB HL), worse hearing ear], and 29,720 participants had normal hearing thresholds. The effect of childhood HF-SNHL on adult hearing threshold was significantly moderated by age. Age stratified analyses showed that the difference in HF hearing thresholds between adults with and without childhood HF-SNHL was 33 dB (95 % CI 31-34) in young adults (n = 173, aged 20-39 years) and 37 dB (95 % CI 34-39) in middle-aged adults (n = 110, aged 40-56 years). The combined exposure of childhood HF-SNHL and noise exposure showed a simple additive effect. It appears to be a super-additive effect of childhood-onset HF-SNHL and aging on adult hearing thresholds. An explanation might be that already damaged hair cells are more susceptible to age-related degeneration. To exclude possible birth cohort effects, the finding should be confirmed by a study with several audiometries in adulthood.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project.

BACKGROUND: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 µm (PM2.5), less than 10 µm (PM10), and between 10 µm and 2.5 µm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 µg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 µg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 µg/m(3) (1.07, 1.01-1.13). INTERPRETATION: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING: European Community's Seventh Framework Program (FP7/2007-2011).