Commentary on “ Pregnancy outcomes in women with inflammatory bowel disease following exposure to thiopurines and antitumor necrosis factor drugs: A systematic review with meta-analysis”

With great interest, we read the systematic review and meta-analysis by Mozaffari et al. ¹ who underline that active inflammatory bowel disease (IBD) during pregnancy is related to adverse pregnancy outcomes. ^{2 –5} We agree with the authors that studies assessing the safety of IBD drugs during pregnancy to maintain disease remission such as thiopurines and antitumor necrosis factor are conflicting.

The authors concluded that the presence of congenital abnormalities was higher in thiopurine-exposed children than in children who were not exposed to an IBD drug In utero. This conclusion is based on the results of two studies: a population-based study by Norgard et al. ⁶ and a partial prospective and partial retrospective study by Coelho et al. ⁷ Only the study by Norgard et al. demonstrated a high rate of congenital abnormalities (n = 4; 15.4%) in 26 thiopurine-exposed children. In this study, women suffering from Crohn’s disease with an active prescription for azathioprine or mercaptopurine during the time of conception until the end of the third trimester were retrospectively evaluated. However, due to the nature of this study, medication adherence could not be assessed. In addition, no data on folic acid intake were obtained, which is of importance when describing congenital abnormalities. Also, specific details regarding the described congenital abnormalities (i.e. minor or major congenital abnormalities) are lacking.

Other studies exist showing an association between thiopurine use and its adverse pregnancy outcomes, including congenital abnormalities. ^{8 –10} However, due to the retrospective nature of these studies, it was not possible to determine the influence of confounding factors such as disease activity, smoking, folic acid intake, and obstetrical complications. Therefore, the authors stated that they could not rule out the possibility that the association was caused by confounding factors. Overall, most clinical studies, including one small prospective study, ¹¹ show that there is no association between maternal thiopurine use and adverse pregnancy outcomes, including congenital abnormalities. ^{7,11 –13} Therefore, we feel that the study by Mozaffari et al. should be interpreted with caution as the evidence that thiopurine use during pregnancy leads to a higher risk of congenital abnormalities is frail.

More prospective studies assessing the effect of thiopurine use on pregnancy outcomes, including adjustments for important confounding factors, are needed. However, based on the current available data, we advise to continue thiopurine treatment throughout pregnancy, as disease activity during pregnancy likely outweighs possible risks related to thiopurine use, including congenital abnormalities.