Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites.
BACKGROUND
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.


CONCLUSIONS
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.
de Boer
Nanne K H
NK
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Jarbandhan
Soeresh V A
SV
de Graaf
Peer
P
Mulder
Chris J J
CJ
van Elburg
Ruurd M
RM
van Bodegraven
Adriaan A
AA
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D013873:Thionucleotides / Q000097:blood*
D007166:Immunosuppressive Agents; D013873:Thionucleotides; D001379:Azathioprine