Exposure to biologic therapy and associated maternal and neonatal outcomes in pregnancies complicated by inflammatory bowel disease

Abstract

Background: There is growing evidence that biologic therapy is safe in pregnancies complicated by inflammatory bowel disease and that its use outweighs the risk of worsening disease activity, which is associated with adverse pregnancy outcomes. To our knowledge, there are limited data regarding the use of biologic therapy and the associated maternal adverse effects such as the risk of hypertensive outcomes, postoperative complications, and infectious risk.

Objective: Our objective was to evaluate a variety of obstetrical complications including maternal infectious outcomes, hypertensive outcomes, other adverse maternal outcomes including postoperative complications, venous thromboembolism, and postpartum hemorrhage; we also evaluated the neonatal outcomes associated with biologic use in pregnancies affected by inflammatory bowel disease.

Study design: This was a retrospective cohort study including patients with inflammatory bowel disease who were pregnant and delivered at our institution. The maternal demographics and the incidence of maternal and neonatal outcomes were compared among groups on the basis of biologic exposure using the chi-square or Fisher exact test for categorical variables and the t test or Mann-Whitney test for continuous variables. Multivariable logistic regression analysis was performed on composite outcomes adjusting for age, disease activity, maternal obesity, history of cesarean delivery, and history of corticosteroid use in pregnancy. The statistical significance was defined as P<.05.

Results: A total of 322 patients who were pregnant, had inflammatory bowel disease, and delivered at our institution from 2012 to 2019, were included for analysis. Of these, 112 (34%) were on biologics during pregnancy. The patients in the biologic group had significantly lower body mass indices than the patients in the nonbiologic group (median body mass index, 22.4 vs 24.0, respectively; P=.04), and they were less likely to be multiparous (41% vs 59%, respectively; P=.003). In addition, more patients in the biologic group were likely to have Crohn disease with previous inflammatory bowel disease surgery (33% vs 20%, respectively; P=.01); otherwise, the 2 groups had similar baseline characteristics. Maternal infectious and hypertensive outcomes occurred significantly more frequently in the biologic group than the nonexposed group (22% vs 7%; P=.0003 and 19% vs 8%; P=.003, respectively). This remained statistically significant in multivariable logistic regression models. Specifically, maternal infectious and hypertensive outcomes occurred significantly more frequently in the patients on a single-agent antitumor necrosis factor treatment than the patients on no inflammatory bowel disease medication (24% vs 6%; P=.002; 22% vs 6%; P=.004), which remained statistically significant in multivariable logistic regression models. There was no difference in the neonatal adverse outcomes between the 2 groups.

Conclusion: Our data suggest an association between antepartum biologic use- specifically antitumor necrosis factor alpha therapy-and an increased risk of maternal infectious and hypertensive outcomes. This increased risk may be related to underlying disease activity and the same should be incorporated into a discussion with the patient. However, the discussion must be balanced with the important benefit of optimal disease control associated with biologic use in patients being treated for IBD.

Keywords: antitumor necrosis factor alpha; biologics; hypertensive outcome; infectious outcome; inflammatory bowel disease; maternal morbidity; neonatal outcomes; pregnancy.