Inflammatory bowel disease, periconceptional disease activity, and risk of major congenital anomalies: A nationwide cohort study

Background: It is uncertain whether the risk of major congenital anomalies (mCAs) is increased in children of women with inflammatory bowel disease (IBD). Methods: We aimed to determine the risk of mCAs in a Swedish nationwide cohort of 13,131 singleton live births from 1997-2020 to women with IBD and 61,909 matched children to women without IBD from the general population. We additionally examined mCAs according to periconceptional histological inflammation (vs. Remission: 1,124 and 646 births, respectively) or clinically active IBD (vs. Quiescent: 3,380 and 6,603 births, respectively). Adjusted risk ratios (aRRs) for overall and organ-specific mCAs were estimated using generalized linear models. These models adjusted for maternal socio-demographics, comorbidities, body mass index, and smoking. Results: There were 38.0 (n=499) mCAs per 1000 births to women with IBD vs. 33.9 (n=2,101) in matched comparators and a risk difference of 1 extra mCA per 246 births to women with IBD (aRR=1.11; 95%CI=1.01-1.23). Risks of heart defects and mCAs of the urinary system partly drove estimates. The risk of mCAs was similar in children of women with ulcerative colitis and Crohn’s disease. Periconceptional histological inflammation (vs. remission) or clinically active (vs. quiescent) IBD did not further influence the risk of mCA in the child (aRR=0.87 [95%CI=0.55-1.40] and aRR=1.04 [95%CI=0.85-1.27], respectively). Conclusions: Children of women with IBD had a heightened susceptibility to mCAs, although absolute and relative risks were lower than previously reported. IBD activity was not linked to mCA risks, but those analyses included relatively few events.