The influence of early-life animal exposure on the risk of childhood atopic dermatitis, asthma and allergic rhinoconjunctivitis: findings from the Danish National Birth Cohort

BACKGROUND: Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. METHODS: We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child's 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure. RESULTS: Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70-0.94 and 0.88, 95% CI: 0.82-0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05-1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81-0.95 to 1.00, 95% CI: 0.91-1.10). CONCLUSIONS: The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure

Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes:An individual-participant data meta-analysis of >35.000 European children

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (β = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p &lt; 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p &lt; 0.001) with a stronger association observed in females (p &lt; 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = −0.04; 95 %CI: −0.07, −0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p &lt; 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.</p

Associations of Maternal Educational Level, Proximity to Green Space During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood:A Proof-of-Concept Federated Analysis in 18 Birth Cohorts

International sharing of cohort data for research is important and challenging. We explored the feasibility of multicohort federated analyses by examining associations between 3 pregnancy exposures (maternal education, exposure to green vegetation, and gestational diabetes) and offspring body mass index (BMI) from infancy to age 17 years. We used data from 18 cohorts (n = 206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13, and 14-17 years. Associations were estimated using linear regression via 1-stage individual participant data meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z score comparing low with high education, at age 2-3 years = 0.03 (95% confidence interval (CI): 0.00, 0.05), at 4-7 years = 0.16 (95% CI: 0.14, 0.17), and at 8-13 years = 0.24 (95% CI: 0.22, 0.26)). Gestational diabetes was positively associated with BMI from age 8 years (BMI z score difference = 0.18, 95% CI: 0.12, 0.25) but not at younger ages; however, associations attenuated towards the null when restricted to cohorts that measured gestational diabetes via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age 1 year but not at older ages. Opportunities of cross-cohort federated analyses are discussed.</p

Associations of Maternal Educational Level, Proximity to Green Space During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood:A Proof-of-Concept Federated Analysis in 18 Birth Cohorts

International sharing of cohort data for research is important and challenging. We explored the feasibility of multicohort federated analyses by examining associations between 3 pregnancy exposures (maternal education, exposure to green vegetation, and gestational diabetes) and offspring body mass index (BMI) from infancy to age 17 years. We used data from 18 cohorts (n = 206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13, and 14-17 years. Associations were estimated using linear regression via 1-stage individual participant data meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z score comparing low with high education, at age 2-3 years = 0.03 (95% confidence interval (CI): 0.00, 0.05), at 4-7 years = 0.16 (95% CI: 0.14, 0.17), and at 8-13 years = 0.24 (95% CI: 0.22, 0.26)). Gestational diabetes was positively associated with BMI from age 8 years (BMI z score difference = 0.18, 95% CI: 0.12, 0.25) but not at younger ages; however, associations attenuated towards the null when restricted to cohorts that measured gestational diabetes via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age 1 year but not at older ages. Opportunities of cross-cohort federated analyses are discussed.</p

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: A meta-analysis of 150 000 European children

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections

Effective discrimination in mark schemes

Effective assessment is often measured in terms of mark re-mark reliability: the extent to which the same mark would be awarded to a candidate by two different examiners or, alternatively, by the same examiner on two different occasions. Reliability, however, can come at the expense of validity: the extent to which an assessment tests the skills it purports to test. The validity of an assessment can be compromised by any element of the specification, the examination paper or the mark scheme. With the use of a hypothetical illustration and a case study, this paper explores the effect that a mark scheme can have on the validity of an assessment; focussing particularly on a mark&apos;s worth across the mark range for an item. It proposes a number of techniques which might be used to identify areas of weakness in a mark scheme and areas where the mark scheme does not provide for effective discrimination between candidates