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Intrauterine exposure of thiopurine therapy in pregnant patients with IBD

The latest issue of Gut investigates intrauterine exposure and the pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease.

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Several studies have demonstrated a favourable safety profile for thiopurine use for inflammatory bowel disease (IBD) during pregnancy.

Dr Bindia Jharap and colleagues from the Netherlands performed a study in pregnant patients with IBD who were using thiopurines, in order to determine the influence of pregnancy on thiopurine metabolism and to assess intrauterine exposure of the fetus to thiopurines.

Female patients with IBD receiving steady-state thiopurines and planning a pregnancy were prospectively enrolled.

6-Thioguanine nucleotide (6-TGN) and methylmercaptopurine concentrations were determined, combined with routine laboratory tests, before, during and after pregnancy.

Thiopurine metabolites were measured in umbilical cord blood immediately after delivery.

About 60% of the infants were born with anemia
Gut

The researchers evaluated 30 patients who were using azathioprine or mercaptopurine.

During pregnancy, the team observed that the median 6-TGN decreased over time.

While methylmercaptopurine increased, without causing myelotoxicity or hepatotoxicity.

After delivery, both 6-TGN and methylmercaptopurine levels returned to preconception baseline levels.

The team found that fetal 6-TGN concentrations correlated positively with maternal 6-TGN levels.

No methylmercaptopurine was detected in the newborns, except one born with pancytopenia and high alkaline phosphatase activity, and the mother of this infant had severe pre-eclampsia.

The team noted that all infants had normal Apgar scores, but 60% had anemia at birth.

The research team observed no major congenital abnormalities.

Dr Jharap's team comments, "Pregnancy has a major effect on maternal thiopurine metabolism."

"In utero the unborn child is exposed to 6-TGN, but not to methylmercaptopurine."

"About 60% of the infants were born with anemia, which raises the question whether infants should be tested for possible anemia immediately after birth."

Gut 2014; 63: 451-457 
19 February 2014

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