Impact of Maternal Smoking, Offspring Smoking, and Genetic Susceptibility on Crohn’s Disease and Ulcerative Colitis

The long-term impact of maternal smoking during pregnancy [MSDP] on the risk of Crohn's disease [CD] and ulcerative colitis [UC] in adult offspring remains uncertain. The present study aimed to investigate the individual and combined effects of early life exposure [MSDP], offspring personal behaviour [smoking], and genetic risk on the development of CD and UC in adult offspring. We conducted a prospective cohort study using UK Biobank data, including 334 083 participants recruited between 2006 and 2010, with follow-up until December 31, 2021. Multivariable Cox regression models were used to evaluate the associations of genetic factors, maternal and personal smoking, and their combination with CD and UC. Participants exposed to MSDP had an 18% increased risk of CD compared to those without MSDP (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.01-1.39). However, no significant association was found between MSDP and UC risk [HR = 1.03, 95% CI = 0.92-1.16]. Personal smoking increased the risk of CD and UC, and had a numerically amplified effect with MSDP. Participants with high genetic risk and MSDP had a 2.01-fold [95% CI = 1.53-2.65] and a 2.45-fold [95% CI = 2.00-2.99] increased risk of CD and UC, respectively, compared to participants without MSDP and with low genetic risk. Our prospective cohort study provides evidence that MSDP increases the risk of CD in adult offspring, whereas no evidence supports their causal association. Additionally, smoking and genetic susceptibility had a numerically amplified effect with MSDP on CD and UC, but the interaction lacked statistical significance.