High Intra-Uterine Exposure to Infliximab Following Maternal Anti-Tnf Treatment During Pregnancy

Zuzana Zelinkova (1) , Colin de Haar , Lissy de Ridder , Marie Pierik (2) , Ernst J Kuipers (3) , Maikel Peppelenbosch , C. Janneke van Der Woude (4)

1 Gastroenterology and Hepatology
2 gastroenterology
3 Gastroenterology &Hepatology
4 Gastroenterology and Hepatology

Background: Typically, inflammatory bowel disease (IBD) patients are in their reproductive years, raising questions about safely using anti-tumor necrosis factor antibodies like infliximab (IFX) during pregnancy. IgG antibodies naturally cross the placenta, especially during the last trimester. To prevent fetal intra-uterine exposure, stopping IFX treatment at gestational week 30 is recommended. However, whether this limits intra-uterine and early post-natal IFX exposure is unestablished. Aim: To determine the intra-uterine exposure to IFX following maternal treatment with IFX. Methods: Four pregnant IBD patients intentionally continued IFX during pregnancy. IFX levels were assessed in newborns' cord blood and the mothers' peripheral blood at delivery. The children's development during the first 3-6 months, infections, vaccine reactions and antibody responses to vaccinations against Haemophilus influenzae type b and Pneumococcus were assessed. Results: The patients stopped IFX therapy at gestational week 21, 26, 26, and 30, respectively. In three infants, therapeutic IFX levels were present in cord blood at levels of 5.5-13.7 g/mL and were two- to three-fold higher than in the peripheral blood of their mothers. During the 3-6-month follow-up, the children developed normally without signs of infections or allergic reactions, and had normal antibody titers after routine childhood vaccinations. Conclusion: The use of IFX until gestational week 30 leads to fetal intra-uterine exposure to IFX at levels that exceed those in the mothers' peripheral blood. Although no short-term complications were detected, the high IFX levels observed in newborns raise concerns about unknown effects of IFX on the developing immune system.

Mots clés: Medicine

Zuzana Zelinkova, Colin de Haar, Lissy de Ridder, Marie Pierik, Ernst J Kuipers, et al.. High Intra-Uterine Exposure to Infliximab Following Maternal Anti-Tnf Treatment During Pregnancy. Alimentary Pharmacology and Therapeutics, 2011, 33 (9), pp.1053. ⟨10.1111/j.1365-2036.2011.04617.x⟩. ⟨hal-00618185⟩