How do growth and nutrition explain social inequalities in lung function in children with cystic fibrosis? A longitudinal mediation analysis using interventional disparity effects with time-varying mediators and intermediate confounders.

Background Deprivation is associated with poorer growth, worse lung function and shorter life expectancy in children with cystic fibrosis (CF). While early growth is associated with lung function when first measured at around age 6, it is unclear whether improving early growth in the most disadvantaged children would reduce inequalities in lung function. Methods We used data from children born 2000-2010 and followed up to 2016 in the UK CF Registry. To estimate the association between deprivation and lung function at around age six, and the causal contribution of early weight trajectories, we extended the mediation analysis approach based on interventional disparity effects to the setting of a longitudinally measured mediator. We adjusted for baseline confounding by sex, birthyear and genotype and accounted for time-varying intermediate confounding by lung infection. Results 853 children were included in the study, including 165 and 172 children from the least and most deprived population quintiles, respectively. The average difference in lung function between the least and most deprived quintile of children, was 4.51 percent of predicted forced expiratory volume in one second (95% CI: 1.08-7.93). We estimated this would be reduced to 3.97 percentage points (95% CI: 0.57-7.38) if early weight trajectories in the most deprived children were shifted to the distribution observed in the least disadvantaged children. Conclusion Socio-economic conditions are strongly associated with lung function for children with CF which we estimated would only be marginally reduced if early weight trajectories could be improved for the most disadvantaged children.