Azathioprine use during pregnancy: Unexpected intrauterine exposure to metabolites

INTRODUCTION: The use of azathioprine (AZA) in the treatment of autoimmune diseases during pregnancy are believed to be relatively safe, particularly taking into account the potential risks for mother and fetus should the underlying disease become active due to withdrawal of this thiopurine. However, essential evidence on the safety of AZA use during pregnancy is lacking. The determination of the intrauterine exposure to maternal AZA use may provide additional and crucial insights into the safety and teratogenicity of this drug. METHODS: We describe three patients with Crohn's disease and autoimmune hepatitis who were treated with AZA throughout all trimesters of their pregnancies. Thiopurine metabolites (6-thioguaninenucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP)) were measured in the red blood cells (RBC) of mother and infant directly after delivery. RESULTS: The 6-TGN concentration was slightly lower in the RBC of the infant than the mother. No 6-MMP could be detected in the infant. CONCLUSION: The placenta forms a (relative) barrier to AZA and its metabolites. Intrauterine exposure to 6-TGN may be minimized by careful therapeutic drug monitoring of the mother during pregnancy.