What are the risks of 6-mercaptopurin treatment during pregnancy?/nA woman with Crohn´s disease is

Fråga: What are the risks of 6-mercaptopurin treatment during pregnancy? A woman with Crohn´s disease is treated with 6-mercaptopurin (6-MP) 50 mg daily. She is now in week 12 of pregnancy. The 6-MP treatment began before conception.

Sammanfattning: There is no substantial increase in the risk of fetal malformation associated with the use of 6-MP in pregnancy at doses used in inflammatory bowel disease treatment.

There is no reason to terminate a pregnancy due to early exposure to 6-MP. It appears safe to continue the treatment throughout the pregnancy. The underlying disease may warrant extra monitoring of fetal growth.

Svar: A question about azathioprine (AZA) treatment for Crohn´s disese and pregnancy has been answered previously (1). AZA is rapidly converted in vivo to 6-MP.

An updated search of the literature revealed a retrospective cohort study of 155 patients (71% female) with ulcerative colitis or Crohn´s disease who had conceived at least one pregnancy. There were 160 (from 79 women and 81 men) pregnancies in patients who were treated with 6-MP before or at the time of conception, some of the patients continued the treatment throughout the pregnancy. The controls were 165 (from 92 women and 73 men) pregnancies conceived and completed before the 6-MP treatment began. There were no statistically significant differences in pregnancy outcome (spontaneous abortions, abortion due to birth defect, major congenital malformation, neoplasia, increased infections). The mean dose of 6-MP was 70 mg, range from 25 mg every other day to 175 mg daily. According to the authors of this study, there appears to be no difference between AZA and 6-MP when looking at efficacy and toxicity (2).

In the Swedish Birth Medical Registry there are 140 reports of AZA use during pregnancy. 7.9% of the children had some malformation. The frequency of prematurity and low birth weight was higher than normal, which probably can be attributed to the mother´s underlying disease (3). There are no cases of exposure to 6-MP during pregnancy reported (4) There is no reason to terminate a pregnancy due to early exposure to 6-MP.

There may be a higher risk of adverse pregnancy outcomes associated with 6-MP treatment in chemoterapeutic doses (5).

Apart from the dose, genetic variations may influence the teratogenicity of AZA and 6-MP. People with reduced activity of thiopurine methyl transferase (TPMT) may experince potentially toxic drug levels when treated with conventional doses of AZA or 6-MP. This seems likely to increase their risk of an adverse pregnancy outcome, but this has not been studied. 1/300 people lacks the enzyme activity altogether and 5-10% have intermediate enzyme activity. However, this should not be a problem for a patient who is already on 6-MP treatment and tolerates it well when she becomes pregnant (5).