Pregnancy Exposure to TNF alpha inhibitors and Immunological effecT in infants

Relapse of inflammatory bowel disease (IBD) activity during conception and pregnancy is associated with a negative pregnancy outcome; prematurity and low birth weight. Therefore, disease remission during this period is of utmost importance and it is advised to maintain drugs such as Anti- Tumor Necrosis Factor alpha (anti TNFα), thiopurines and 5-aminosalicylic acid. Most IBD drugs are considered of low risk during pregnancy, since no increase of congenital malformations has been reported so far. However the effects on the developing immune system, after intra-uterine exposure, remain unknown. Anti TNFα drugs are effectively transferred through the placenta resulting in high levels in the new-borns. It is known that live vaccines must be avoided until the levels of anti TNFα are undetectable, as there has been one report of an infant, who died after a BCG vaccination associated with exposure to anti-TNFα in utero. Since studies are scarce and most of the data were collected retrospectively, there is an urgent need for prospective studies focussing on the impact of exposure to biologicals, especially anti-TNFα, in utero on the development of the immune system and the potential risk of clinical complications.

Main aim of this prospective longitudinal observational study is to answer the following questions: Does intra uterine exposure to anti TNFα 1) change the developing adaptive and innate immune system 2) have persistent/long term effects on the immune system 3) lead to more frequent and/or more severe infections?
Infants with intrauterine exposure to anti-TNFα used for maternal IBD will be compared to children exposed to other immunosuppressive drugs and to healthy children. Infants will be clinically monitored and repeated immunological studies will be performed in order to assess their immune status and susceptibility to infections.

Results will be used to guide immunosuppressive strategies during pregnancy in women with IBD. If intra uterine exposure to anti TNFα does indeed lead to abnormalities in the development of the immune system, new follow-up strategies will be developed for the detection and treatment of potential long-term complications

Intra uterine exposure to anti-TNFα inhibitors influences the normal development of the immune system, leading to immunodeficiency and immune dysregulation, with the potential to cause short term and long-term morbidity. TNFα plays an important role in both innate as adaptive immune system. We hypothesize that intra uterine exposure to anti-TNFα inhibitors will affect the immune system in multiple ways having both an effect when (high) concentrations are present during pregnancy as well as beyond the neonatal period- because of the long half-life of this biological-, which may further affect the developing immune system. A prolonged effect may even be present after anti-TNFα inhibitors are no longer detectable, due to epigenetic changes in immune cells.

birth, age 3 months, age 5 months, age 12 months

non applicable