Background Children growing up in socioeconomically disadvantaged circumstances are more likely to develop asthma. Examining how the social patterning of asthma and its risk factors varies across country contexts may increase our understanding of the pathways to inequalities and potential targets for intervention. This study aimed to examine the social patterning of asthma and the early-life factors that could act as mediators of inequalities, and quantify the extent of mediation by early-life factors across country contexts.

Methods We used harmonised individual participant data for up to 107,884 mother-child dyads from seven birth cohorts across six European countries (Denmark, France, the Netherlands, Norway, Spain, UK). Maternal education during pregnancy was used as the primary exposure measure of early-life socioeconomic circumstances (SECs); household income was used as an alternative measure of SECs in sensitivity analysis. The outcome was current asthma at school-age (4 to 9 years), defined as any two of: i) parental-reported doctor diagnosis, ii) symptoms of wheeze in the past year, iii) asthma medication use in the past year. All analyses were conducted using the federated analysis platform DataSHIELD. Inequalities were examined using adjusted Poisson regression models fitted separately for each cohort and combined using random-effects meta-analysis. The mediating effects of modifiable early-life risk factors (maternal smoking during pregnancy, preterm birth, caesarean section delivery, low birthweight and breastfeeding duration) were examined using counterfactual mediation analysis.

Results The percentage of mothers with a low-medium education level ranged from 35.9% (MoBa – Norway) to 87.1% (ALSPAC – UK), and the prevalence of school-age asthma ranged between 5.6% (MoBa – Norway) and 17.1% (ALSPAC – UK). Disparities in asthma by SECs were evident in most cohorts: children of mothers with low-medium education had a 17% increased risk of developing asthma in meta-analysis (95% CI: 8%-27%, I ²=21.5%), with cohort-specific adjusted risk ratios ranging between 1.07 (0.97–1.18, DNBC - Denmark) and 1.61 (1.08–2.40, EDEN - France). The early-life risk factors investigated as potential mediators were similarly socially patterned, but with greater heterogeneity between cohorts (I ² range = 66.2-95.3%). The mediation analysis suggested that these factors play a relevant role in mediating observed inequalities, which was consistent across cohorts (proportion mediated: 0.08-0.72). Similar results were observed for household income.

Conclusion There was a consistent tendency for children from less advantaged SECs to be at greater risk of asthma in the European cohorts examined. Our results suggest that greater perinatal support may help to reduce these inequalities.