Wenche Nystad

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 Communitys Seventh Framework Program (FP7/2007-2011).

450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.

Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

BACKGROUND Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. METHODS We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. FINDINGS A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. INTERPRETATION Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. FUNDING The European Union.

Folic acid supplements in pregnancy and early childhood respiratory health

Background: Folate supplementation is recommended for pregnant women to reduce the risk of congenital malformations. Maternal intake of folate supplements during pregnancy might also influence childhood immune phenotypes via epigenetic mechanisms. Objective: To investigate the relationship between folate supplements in pregnancy and risk of lower respiratory tract infections and wheeze in children up to 18 months of age. Methods: In the Norwegian Mother and Child Cohort Study, questionnaire data collected at several time points during pregnancy and after birth on 32 077 children born between 2000 and 2005 were used to assess the effects of folate supplements during pregnancy on respiratory outcomes up to 18 months of age, while accounting for other supplements in pregnancy and supplementation in infancy. Results: Folate supplements in the first trimester were associated with increased risk of wheeze and respiratory tract infections up to 18 months of age. Adjusting for exposure later in pregnancy and in infancy, the relative risk for wheeze for children exposed to folic acid supplements in the first trimester was 1.06 (95% CI 1.03 to 1.10), the relative risk for lower respiratory tract infections was 1.09 (95% CI 1.02 to 1.15) and the relative risk for hospitalisations for lower respiratory tract infections was 1.24 (95% CI 1.09 to 1.41). Conclusions: Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. The results suggest that methyl donors in the maternal diet during pregnancy may influence respiratory health in children consistent with epigenetic mechanisms.

Spirometry centile charts for young Caucasian children: The asthma UK collaborative initiative

RATIONALE Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. CONCLUSIONS We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

Feasibility of measuring lung function in preschool children

Background: There have been difficulties in applying spirometric tests to children of preschool age. Methods: The feasibility of measuring lung function was examined in 652 children aged 3–6 years using dynamic spirometry with an animation programme and the guidelines approved by the European Respiratory Society. Results: Data from 603 (92%) children with at least two acceptable forced expiratory manoeuvres were analysed; 408 (68%) achieved at least three acceptable manoeuvres. Children with only two acceptable manoeuvres were younger, shorter, and weighed less (p<0.001). The lower levels of lung function in this group were partly explained by body size. 63% of those with three acceptable manoeuvres had a difference of ≤5% between the highest and second highest forced expiratory volume in 1 second (FEV1); when a difference of ≤10% was applied, 91% of the children were included. A similar trend was seen for forced vital capacity (FVC). The acceptability and reproducibility increased with increasing age, and levels of lung function increased linearly with age. The linear regression model showed that standing height was a satisfactory predictor of lung function; the explained fraction of variance (R2) was 59% for FEV1. Most FVC manoeuvres in children older than 3 years were acceptable and reproducible. Conclusions: Spirometric testing is feasible in preschool children and may be useful for both clinical practice and research. This study may fill the deficiency in reference values for European preschool children.

Asthma and Allergic Rhinitis at 4 Years of Age in Relation to Fish Consumption in Infancy

It has been suggested that consumption of fish and polyunsaturated fatty acids could have a protective effect against inflammation in the airways and the development of asthma and other allergic diseases. Our objective was to test the hypothesis that fish consumption during the first year of life decreases the risk of childhood asthma and allergic rhinitis. We assessed the relation between introduction of fish in the diet during the first year of life and risk of asthma and allergic rhinitis in a prospective 4-year cohort study of 2531 Norwegian children. We estimated odds ratios (OR) in logistic regression analysis adjusting for potential confounders. A total of 47.6% children had fish during the first year of life. The adjusted OR for allergic rhinitis was 0.45 (95% confidence interval [CI] = 0.28, 0.74) and for asthma 0.84 (95% CI = 0.57, 1.22). Fish consumption in the first year of life may reduce the risk of developing asthma and allergic rhinitis in childhood.

Early Respiratory Infections, Asthma, and Allergy: 10-Year Follow-up of the Oslo Birth Cohort

Objective. It has been hypothesized that early infections protect against the development of atopic disease, but there have been few long-term follow-up studies. We estimated the associations between early respiratory infections and doctor-diagnosed asthma, allergic rhinitis, and skin-prick sensitization in children at 10 years of age in the Oslo Birth Cohort, established in 1992–1993. We also considered birth order and attendance at a child care center as proxy measures of increased exposure to infections early in life. Methods. A total of 2540 children were followed from birth to the age of 10 years. Experiences of respiratory infections were recorded in follow-up surveys at 6 and 12 months. At age 10, questions were asked about current symptoms of asthma and allergic rhinitis and about having ever received a doctor diagnosis for these diseases. A subsample (n = 1740) of the cohort was tested for skin-prick test reactivity. Results. Current asthma was related to lower respiratory tract infection (adjusted odds ratio [OR]: 2.1; 95% confidence interval: 1.3–3.0) and croup (adjusted OR: 2.3; 95% confidence interval: 1.3–4.2) in the first year. ORs for allergic rhinitis and skin-prick sensitization were smaller but mainly positive. Birth order and child care attendance at age 1 year were not significantly associated with any of the studied outcomes. Conclusions. Early respiratory infections did not protect against the development of asthma, allergic rhinitis, or sensitization to common allergens during the first 10 years of life but increased the risk for asthma symptoms at age 10 in this population.

Changing prevalence of asthma in school children: evidence for diagnostic changes in asthma in two surveys 13 yrs apart

It is still unclear whether the reported increase in the prevalence of asthma is real or due to changes in diagnostic criteria. The objectives of this study were to compare the prevalence of diagnosed asthma with the prevalence of respiratory symptoms, and to compare the association between asthma and other atopic diseases in 1981 and 1994. The study populations comprised randomly selected school classes in Oslo in 1981 (n=1,772) and 1994 (n=2,577). The main outcomes in these comparable cross-sectional studies of children, 6-16 yrs of age, were parent-reported prevalence of diagnosed asthma, respiratory symptoms, eczema and hay fever. The questionnaire was identical in 1981 and 1994. The response rates were 94% (1,674 out of 1,772) in 1981 and 85% (2,188 out of 2,577) in 1994. The lifetime prevalence of asthma increased from 3.4% in 1981 to 9.3% in 1994; odds ratio (OR) 2.9 (95% confidence interval (95% CI) 2.1-4.0) comparing 1994 to 1981. The prevalence of occasional wheezing increased from 9.0 to 10.8%; OR 1.2 (95% CI 1.0-1.5), and attacks of wheezing from 3.7 to 6.8%; OR 1.8 (95% CI 1.3-2.5). Survival analyses for 3 year birth cohorts showed that asthma was more readily diagnosed in the latest birth cohort (1985-1988). The association between asthma and other atopic diseases decreased during the period under study. The increase in diagnosed asthma and respiratory symptoms supports a true increase in asthma. However, the larger increase in diagnosed asthma than wheezing and a reduced association between asthma and other atopic diseases suggest that the increase in asthma may be explained, in part, by changes in diagnostic criteria.

Correlates of regular exercise during pregnancy: the Norwegian Mother and Child Cohort Study

The aims of this study were to describe the level of exercise during pregnancy and to assess factors associated with regular exercise. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, 34 508 pregnancies were included in the present study. Data were collected by self‐completed questionnaires in gestational weeks 17 and 30, and analyzed by logistic regression analysis. The results are presented as adjusted odds ratios (aOR) with a 95% confidence interval. The proportion of women exercising regularly was 46.4% before pregnancy and decreased to 28.0 and 20.4% in weeks 17 and 30, respectively. Walking and bicycling were the most frequently reported activities before and during pregnancy. The prevalence of swimming tended to increase from prepregnancy to week 30. Exercising regularly prepregnancy was highly related to regular exercise in week 17, aOR=18.4 (17.1–19.7) and 30, aOR 4.3 (4.1–4.6). Low gestational weight gain was positively associated with regular exercise in week 30, aOR=1.2 (1.1–1.4), whereas being overweight before pregnancy was inversely associated with regular exercise in week 17, aOR=0.8 (0.7–0.8) and 30, aOR=0.7 (0.6–0.7). Also, women experiencing a multiple pregnancy, pelvic girdle pain, or nausea were less likely to exercise regularly.