Reproduction in Patients with Inflammatory Bowel Disease: finding the balance

This thesis aimed to provide more insight into important clinical topics regarding IBD and reproduction. As described in this thesis, an uncomplicated pregnancy course is feasible for patients suffering from IBD. However, complications may occur due to disease activity during conception and pregnancy underlining the importance of disease remission. Finding the balance between IBD treatment in patients to maintain disease remission and at the same time consider fetal safety remains challenging. We show in this thesis that the use of adalimumab, an anti-TNF-α type that is increasingly used as maintenance treatment for IBD, by fathers at the time of conception is probably safe. We also show that anti-TNF-α and thiopurine, both often used as maintenance treatment for IBD, are of low risk during pregnancy for mother and their offspring. However, we found an altered thiopurine metabolism during pregnancy and a difference in transmission of anti-TNF-α drugs over the placenta between anti-TNF-α types, without affecting health outcomes of mothers and their offspring. In this thesis we investigated the long-term health of 1000 children born to mothers with IBD and assessed the effect of different types of drugs on health outcomes of children. We found no association between the use of thiopurine and/or anti-TNF-α during pregnancy and the following child’s health outcomes: infections, adverse reactions to vaccinations, growth, auto-immune diseases and malignancies. This result is reassuring regarding the use of IBD medication during pregnancy indicating that thiopurine and/or anti-TNF-α and have no or little influence on long-term health development of in utero exposed children. In addition, we found that children born with detectable anti-TNF-α levels respond adequately to the vaccination against hepatitis B.

Overall, this thesis adds to the current data regarding reproduction in patients with IBD and shows favourable outcomes for mothers and children in case disease remission is maintained. This underlines the importance of finding the balance between maintaining disease remission in mothers with IBD drugs and at the same time minimising fetal drug exposure.