Impact of in utero exposure to IBD treatment

August 9, 2022

Issue 15

Clinical Question

Does in utero exposure to anti-TNFs and thiopurines increase childhood risk of infection?

Editor’s Bottom Line

Use of combination anti-TNF and thiopurine therapy during pregnancy is associated with an increase in infection during the first year of life. Although residual confounding cannot be excluded, pregnancy planning is a good opportunity to revisit maintenance strategies for IBD.

Reference

Meyer A, Taine M, Drouin J, et al. Serious Infections in Children Born to Mothers With Inflammatory Bowel Disease With In Utero Exposure to Thiopurines and Anti-Tumor Necrosis Factor. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1269–81.e9.; https://www.cghjournal.org/article/S1542-3565(21)00760-6/fulltext

Synopsis

There have been conflicting data on the impact of in utero exposure to anti-TNF agents and thiopurines on infection risk during early childhood. In this study, French researchers analyzed information from a national health database between 2010 and 2018 and compared serious infections during the first five years of life among 3,392 children exposed to thiopurine monotherapy in utero, 3,399 whose mothers received anti-TNF monotherapy, 816 who were exposed to combination therapy, and 18,954 who were not exposed to either drug class. All of the mothers had medical record data for at least two years preceding pregnancy and none had received methotrexate, vedolizumab, or ustekinumab during pregnancy.  

Findings showed that serious infections in the first year of life occurred at a rate of 116.9 serious infections per patient year (PPY) among unexposed children, 116.4 PPY among those exposed to thiopurine monotherapy, 140.3 PPY among those exposed to anti-TNF monotherapy, and 159.3 PPY among those exposed to combination therapy.

In a propensity-weighted analysis, the risk of serious infections during the first year of life for children exposed to either thiopurine monotherapy or anti-TNF monotherapy was similar to the risk of serious infections in children whose mothers did not receive either of these treatments during pregnancy (adjusted Hazard Ratio [aHR], 0.94; 95% Confidence Interval [CI], 0.83–1.07 for thiopurines and aHR, 1.10; 95% CI, 0.95–1.27 for anti-TNF). However, there was a 36% increased risk of serious infections during the first year of life among children whose mothers received combination therapy during pregnancy (aHR, 1.36; 95% CI, 1.04–1.79).

Serious infections that were significantly more frequent among children exposed to combination treatment were those of the nervous system (aHR, 3.23; 95% CI, 1.12–9.32) and those of viral etiology (aHR, 1.52; 95% CI, 1.06–2.2). The analysis found no increase in serious infections between the second and fifth years of life among children whose mothers received thiopurines or anti-TNF treatments during pregnancy.

Details

Study Design: Population-based analysis

Funding: The French National Health Service

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2a