Histological remission in inflammatory bowel disease and risk of adverse pregnancy outcomes: A nationwide study

Background: Inflammatory bowel disease (IBD) has been linked to adverse pregnancy outcomes, but it is unclear how risks vary by histological activity. Methods: We performed a nationwide study of Swedish women diagnosed with IBD 1990–2016 and a pre-pregnancy (<12 months) colorectal biopsy with vs. without histological inflammation (1223 and 630 births, respectively). We also examined pregnancy outcomes in 2007–2016 of women with vs. without clinically active IBD (i.e., IBD-related hospitalization, surgery, or medication escalation) <12 months before pregnancy (2110 and 4993 births, respectively). Accounting for smoking, socio-demographics, and comorbidities, generalized linear models estimated adjusted risk ratios (aRRs) for preterm birth (<37 gestational weeks) and small-for-gestational age (SGA, <10th percentile weight for age). Findings: Of infants to women with vs. without histological inflammation, 9.6% (n = 117) and 6.5% (n = 41) were preterm, respectively (aRR = 1.46; 95%CI = 1.03–2.06). Histological inflammation was associated with preterm birth in ulcerative colitis (UC) (aRR = 1.64; 95%CI = 1.07–2.52), especially extensive colitis (aRR = 2.37; 95%CI = 1.12–5.02), but not in Crohn's disease (aRR = 0.99; 95%CI = 0.55–1.78). Of infants to women with vs. without histological inflammation, 116 (9.6%) and 56 (8.9%), respectively, were SGA (aRR = 1.09; 95%CI = 0.81–1.47). Clinically active disease before pregnancy was linked to preterm birth (aRR = 1.42; 95%CI = 1.20–1.69), but not to SGA birth (aRR = 1.13; 95%CI = 0.96–1.32). Finally, of infants to women without clinical activity, histological inflammation was not significantly associated with preterm birth (aRR = 1.20; 95%CI = 0.68–2.13). Interpretation: Histological and clinical activity in IBD, especially in UC, were risk factors for preterm birth. Further research is needed to determine the importance of pre-pregnancy histological activity in women without clinically-defined disease activity. Funding: The Swedish Society of Medicine.