Abstract
Abstract Background Psychological and emotional stress can cause inflammation, leading to immune-mediated inflammatory diseases (IMID) and impact the disease course in adults with IBD but the relationship in children remains understudied. [1,2] In a population-based cohort study, we aimed to estimate the effect of childhood adversities on developing a severe disease course in paediatric-onset IBD (pIBD) and IMID (pIMID) Methods Using the Danish registries, we identified all individuals born between 1981 and 2001 who were diagnosed with pIMID before age 18 (defined as IBD [most common pIMID], autoimmune liver disease, juvenile idiopathic arthritis, systemic lupus erythematosus, or vasculitis). We used nationwide health and socioeconomic registries to model childhood adversity from ages 0 to 15. We divided it into 5 trajectories: low adversity, early-life material deprivation, persistent material deprivation, loss or threat of loss, and high adversity.[3] The trajectories were modelled based on poverty, unemployment, death or severe illness, parental drug or alcohol abuse, maternal separation, or foster care. The outcome was developing a severe disease course as defined by requiring biologics, steroid dependency, surgery (disease-specific), hospitalisation (>5 days), and complications indicative of disease progression. We used Cox regression to estimate sex-adjusted hazard ratios (aHR) with age as the underlying timescale. Person time started at pIMID diagnosis and ended at the earliest of the outcome, emigration, death, or 31 DEC 2021. The low adversity trajectory was used as comparator for all analyses. Results Of 5,847 incident pIMID patients (3,014 [52%] pIBD), 3,829 (65%) developed a severe pIMID disease course. Table 1 presents patient characteristics. Patients with persistent material deprivation were more likely to develop steroid dependency (aHR 1.15 [95%CI:1.01-1.30]), require surgery (1.30 [95%CI: 1.07-1.58)] and prolonged hospitalisation (aHR 1.67 [95%CI: 1.42-1.96]), and develop complications (aHR 1.32 [95%CI: 1.03-1.70]). Patients with persistent material deprivation and high adversity were less likely to receive biologics (aHR 0.86 [95%CI: 0.75-0.99] and aHR 0.65 [95%CI: 0.48-0.87], respectively). Figure 1 presents the cumulative risks of developing a severe disease course. Conclusion Childhood adversity, especially persistent material deprivation, is associated with developing a severe disease course in pIBD and pIMID, indicating substantial social inequality despite the universal free healthcare setting. It should be investigated whether this effect represents physiological changes or is mediated through socioeconomic factors such as poor family support. References 1:Schneider KM, Blank N, Alvarez Y, et al. The enteric nervous system relays psychological stress to intestinal inflammation. Cell. 2023;186(13):2823-2838.e20. doi:10.1016/j.cell.2023.05.001 2:Zhao J, Xue E, Zhou S, et al. Allostatic load increases the incidence and risk of adverse prognosis in inflammatory bowel disease. Aliment Pharmacol Ther. 2024;60(8):1062-1074. doi:10.1111/apt.18217 3:Rod NH, Bengtsson J, Budtz-Jørgensen E, et al. Trajectories of childhood adversity and mortality in early adulthood: a population-based cohort study. The Lancet. 2020;396(10249):489-497. doi:10.1016/S0140-6736(20)30621-8
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