Long-Term Traffic-Related Exposures and Asthma Onset in Schoolchildren in Oslo, Norway

BACKGROUND: Whether there is a causal relation between long-term exposure to traffic and asthma development is so far not clear. This may be explained by inaccurate exposure assessment. OBJECTIVE: We investigated the associations of long-term traffic-related exposures with asthma onset assessed retrospectively and respiratory symptoms in 9- to 10-year-old children. METHODS: We collected information on respiratory outcomes and potential confounding variables by parental questionnaire in 2,871 children in Oslo. Nitrogen dioxide exposure was assessed by the EPISODE dispersion model and assigned at updated individual addresses during lifetime. Distance to major road was assigned at birth address and address by date of questionnaire. Cox proportional hazard regression and logistic regression were used. RESULTS: We did not find positive associations between any long-term traffic-related exposure and onset of doctor-diagnosed asthma. An interquartile range (IQR) increase of NO(2) exposure before asthma onset was associated with an adjusted risk ratio of 0.82 [95% confidence interval (CI), 0.67-1.02]. Handling early asthma cases (children /= 4 years of age) were positive but not statistically significant. For current symptoms, an IQR increase of previous year's NO(2) exposure was associated with adjusted odds ratios of 1.01 (95% CI, 0.83-1.23) for wheeze, 1.10 (95% CI, 0.79-1.51) for severe wheeze, and 1.01 (95% CI, 0.84-1.21) for dry cough. CONCLUSIONS: We were not able to find positive associations of long-term traffic-related exposures with asthma onset or with current respiratory symptoms in 9- to 10-year-old children in Oslo

The association between alcohol consumption and risk of hip fracture differs by age and gender in Cohort of Norway: a NOREPOS study

Under embargo until: 13.07.2019Summary: The association between alcohol consumption and hip fracture differed by gender: Men aged 30–59 years drinking frequently or 14+ gl/week had higher risk than moderate drinkers. No significant association was seen in older men. Women not drinking alcohol had higher risk than those drinking moderately both regarding frequency and amount. Introduction: We aimed to examine alcohol consumption and risk of hip fracture according to age and gender in the population-based Cohort of Norway (1994–2003). Methods: Socio-demographics, lifestyle, and health were self-reported and weight and height were measured in 70,568 men and 71,357 women ≥ 30 years. Information on subsequent hip fractures was retrieved from hospitals’ electronic patient registries during 1994–2013. Frequency of alcohol consumption was categorized: never/seldom, moderate (≤ 2–3 times/week), or frequent (≥ 4 times/week), and amount as number of glasses per week: 0, 1–6, 7–13, 14–27, and 28+. Type of alcohol (wine vs. beer/hard liquor) was also examined. Cox’s proportional hazards regression was used to estimate hazard ratios (HRs) stratified on gender and baseline age < 60 and ≥ 60 years. Results: During median 15-year follow-up, 1558 men and 2511 women suffered a hip fracture. Using moderate drinkers as reference, men < 60 years drinking frequently had multivariable adjusted HR = 1.73 (CI 1.02–2.96) for hip fracture and more than 2.5 times higher risk if they consumed 14+ glasses compared to 1–6 glasses per week. In other groups of age and gender, no statistically significant increased risk was found in those consuming the highest levels of alcohol. Compared to women with moderate or frequent alcohol use, never/seldom-drinking women had the highest fracture risk. In women, use of wine was associated with lower fracture risk than other types of alcohol. Conclusions: Risk of hip fracture was highest in men < 60 years with the highest frequency and amount of alcohol consumption and in non-drinking women.acceptedVersio

Prediction of gestational age based on genome-wide differentially methylated regions

BACKGROUND: We explored the association between gestational age and cord blood DNA methylation at birth and whether DNA methylation could be effective in predicting gestational age due to limitations with the presently used methods. We used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa 1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both ultrasound and the last menstrual period. We evaluated associations between DNA methylation and gestational age and developed a statistical model for predicting gestational age using MoBa 1 for training and MoBa 2 for predictions. The prediction model was additionally used to compare ultrasound and last menstrual period-based gestational age predictions. Furthermore, both CpGs and associated genes detected in the training models were compared to those detected in a published prediction model for chronological age. RESULTS: There were 5474 CpGs associated with ultrasound gestational age after adjustment for a set of covariates, including estimated cell type proportions, and Bonferroni-correction for multiple testing. Our model predicted ultrasound gestational age more accurately than it predicted last menstrual period gestational age. CONCLUSIONS: DNA methylation at birth appears to be a good predictor of gestational age. Ultrasound gestational age is more strongly associated with methylation than last menstrual period gestational age. The CpGs linked with our gestational age prediction model, and their associated genes, differed substantially from the corresponding CpGs and genes associated with a chronological age prediction model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1063-4) contains supplementary material, which is available to authorized users

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.</jats:p

Early life growth and associations with lung function and bronchial hyperresponsiveness at 11-years of age

Low birthweight and being born small-for-gestational age (SGA) are linked to asthma and impaired lung function. Particularly, poor intrauterine growth followed by rapid catch-up growth during childhood may predispose for respiratory disease. Bronchial hyperresponsiveness (BHR) is an essential feature of asthma, but how foetal and early childhood growth are associated with BHR is less studied. Our hypothesis was that children born SGA or with accelerated early life growth have increased BHR and altered lung function at 11-years of age. We studied the associations between SGA and early childhood growth with lung function and BHR at 11-years of age in a subgroup of 468 children from the Norwegian Mother, Father and Child Cohort Study (MoBa), and included data from the Medical Birth Registry of Norway (MBRN). Weight at 6 months of age was positively associated with forced vital capacity (adjusted Beta: 0.121; 95% Confidence interval: 0.023, 0.219) and negatively associated with the ratio of forced expiratory flow in first second/forced vital capacity (−0.204; −0.317, −0.091) at 11-years of age. Similar patterns were found for weight at 36 months and for change in weight from birth to 6 months of age. SGA or other various variables of early childhood growth were not associated with BHR at 11-years of age. Early life growth was associated with an obstructive lung function pattern, but not with BHR in 11-year old children. Foetal growth restriction or weight gain during early childhood do not seem to be important risk factors for subsequent BHR in children.acceptedVersio

Airway symptoms and atopy in young children prescribed asthma medications:A large-scale cohort study

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age‐intervals (0‐6, 6‐18, 18‐36 months, and 3‐7 years). Primary outcomes were dispensed asthma medications (no medication, short‐acting β‐2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0‐6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups.publishedVersio

25-hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)

The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR > 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR < 0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points