How long is long enough? Timing of pre-conceptional remission predicts relapse risk during pregnancy in IBD

Background and Aims: Inflammatory bowel disease (IBD) often coincides with pregnancy, and disease activity during pregnancy increases the risk of adverse outcomes. We aimed to determine how disease course before conception influences relapse risk during pregnancy, adjusting for established risk factors. Methods: In this multicenter, retrospective cohort study, we included adult women with IBD who were pregnant during treatment at one of three university hospitals between 2017 and 2022. Using generalized estimating equations, we evaluated associations between relapse during pregnancy and pre-conceptional flares, categorized into three time intervals. Analyses were adjusted for phenotype, disease duration, surgical history, biologic use, smoking, and assisted reproduction. Interaction analyses were conducted with matched non-pregnant women. Results: We included 386 women (63.4% Crohn's disease, 36.6% ulcerative colitis) with 476 pregnancies. Pre-conceptional flares were significantly associated with relapse if they occurred <3 months [adjusted odds ratio (aOR) 5.289, 95% CI 2.6-10.8, P <. 001] or 3-6 months prior to conception (aOR 2.910, 95% CI 1.0-8.2, P =. 043), but not 6-12 months prior (aOR 1.636, 95% CI 0.8-3.2, P =. 146). Other predictors were not significantly associated with relapse. There was no significant interaction between pregnancy and pre-conceptional disease activity. Conclusions: This large multicenter study demonstrates that disease activity within 6 months before conception significantly increases the risk of relapse during pregnancy in women with IBD. Our study is the first to assess both the pre-conceptional disease course and a broad set of known risk factors in a real-world cohort.