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

Background and Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.