DOP016 Long-term safety of in utero exposure to anti-tumor necrosis factor for the treatment of inflammatory bowel diseases: results from the multicenter European TEDDY study

Abstract

Background: Long-term safety of anti-tumor necrosis factor therapy (anti-TNF) during pregnancy has hardly been studied. Aim(s): To estimate the relative risk of severe infections in offspring of mothers with inflammatory bowel disease (IBD) exposed in utero to anti-TNF Methods: For this retrospective multicenter cohort study we identi-fied: offspring of mothers with IBD under anti-TNF (with or without thiopurines) at any time during pregnancy or 3 months before conception (Exposed group, EG). The non-exposed group (NEG) consisted of offspring of mothers with IBD treated neither with anti-TNFalpha nor with thiopurines during this time period. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared by the log-rank test. Cox-regression analysis was performed to identify independent predictive factors for severe infections. AEG-REDCap provided the study e-CRF Results: In total, 841 children were included, 388 (46%) of them ex-posed in utero to anti-TNF drugs; 38% of the mothers maintained anti-TNF throughout the whole pregnancy. From children exposed to anti-TNF, 99 (25%) were also exposed to thiopurines. Median (IQR) follow-up after delivery was 54 (9-202) months in the EG and 72 (13-216) months in the NEG (p<0.01). The proportions of CD diagnosis and previous surgery were higher in the EG than in the NEG (75 vs. 42%, p<0.001, and 35 vs. 18%, p<0.01, respectively). Other relevant characteristics were similar between both groups. The proportion of pregnancy complications was similar among both groups. Delivery complications were more frequent in the EG (57 vs. 43%, p<0.01), with a higher rate of caesarean sections in the EG (44 vs. 32%, p<0.01). The proportion of newborn complications was higher in the EG (25 vs. 16%, p<0.01), with a higher rate of low-birth weight in this group (11 vs. 7%, p=0.05) and more frequent need of intensive care unit admission in the EG (7 vs. 3%, p<0.01). The proportion of breastfed babies was higher in the NEG in comparison with the EG (79 vs. 57%, p<0.001). A total of 90 children (11%) developed severe infections during follow-up. The incidence rate of severe infections was similar between NEG and EG (1.6 vs. 2.8% person-years, p=0.2). In multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (HR=2.5; 95% CI: 1.5-4.3). anti-TNF exposure during pregnancy was not associated with a higher risk of severe infections (HR: 1.2; 95% CI: 0.8-1.8) Conclusion(s): The exposition to anti-TNFalpha in utero seems not to be associated with a higher risk of infections in children, neither in the short, nor in the long-term.