Background & Aims

Limited data are available on the risk of major congenital malformations (MCM) of thiopurines and anti-TNF during pregnancy. In this study, we assess the risk of MCM associated with maternal exposure to thiopurines and anti-TNF for the treatment of inflammatory bowel disease (IBD) during pregnancy.

Methods

Using the nationwide comprehensive EPI-MERES registry, we identified all births >22 weeks of pregnancy in mothers with IBD in France between April 2010 and December 2021. We compared the risks of 75 individual MCMs according to thiopurines and anti-TNF exposure during the first trimester of pregnancy, accounting for maternal and pregnancy characteristics using propensity score weighting. Sensitivity analyses were conducted to assess estimates robustness.

Results

Among a total of 39,515 births (5223 exposed to thiopurines, 6528 to anti-TNF and 28,827 unexposed), 717 (181.5/10,000) had ≥1 MCM. The overall prevalence of MCM ranged from 175.2/10,000 among unexposed births to 197.2/10,000 among those exposed to thiopurine, and 203.7/10,000 among those exposed to anti-TNF. None of the 75 MCMs was consistently associated with in utero exposure to thiopurines in the main and sensitivity analyses. However, anti-TNF exposure was associated with an increased risk of talipes equinovarus in the main analysis (aRR 2.17, 95%CI: 1.04-4.53) and in sensitivity analyses (aRR ranging between 2.15 and 2.40).

Conclusions

This study provides no evidence of substantial risk of MCM associated with in utero exposure to thiopurines or anti-TNF, except for talipes equinovarus, which appears increased with exposure to anti-TNF. This finding needs to be confirmed in further studies.