Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease

J Clin Gastroenterol. 2003 Apr;36(4):303-9. doi: 10.1097/00004836-200304000-00005.


Purpose: 6-Mercaptopurine (6-MP) has proven efficacy in the therapy of inflammatory bowel disease. Its teratogenicity is demonstrated in animal studies when used at very high doses, whereas human data suggest that 6-MP at maintenance doses is safe. We report the outcome of 72 pregnancies in patients with inflammatory bowel disease who were previously treated with 6-MP with three different doses of 50, 75, and 100 mg/d, for a median duration of 18 months, along with long-term follow-up of the children.

Methods: We have compared the outcome of pregnancies and development of the offspring in the following two groups: group 1, patients with inflammatory bowel disease who conceived 6 months to 22 years after stopping 6-MP (median 72 months); and group 2, patients with inflammatory bowel disease who never received 6-MP prior to conception. All pregnancies were evaluated in terms of outcome: live full-term birth, premature delivery, stillbirth, spontaneous abortion, ectopic pregnancy, and therapeutic dilatation and curettage. Data on children were obtained regarding birth weight, congenital anomalies, and development.

Results: Group 1 included 72 pregnancies carried by 29 women. There were 51 live births (4 premature), 16 spontaneous abortions, 1 stillbirth, 2 therapeutic abortions due to abnormal amniocentesis, and 2 ectopic pregnancies. The total incidence of fetal loss was 29.2%. In group 2, 75 women had 140 pregnancies resulting in 120 live births (8 premature), 18 spontaneous abortions, and 2 stillbirths. There were no cases of ectopic pregnancies or abnormal amniocentesis. The total incidence of fetal loss was 14.3%. There was no increase in the incidence of developmental defects when the mothers had been treated with 6-MP prior to pregnancy.

Conclusions: The incidence of fetal loss is higher in women with inflammatory bowel disease who had been previously treated with 6-MP compared with those who had not. Whether this was related to the older age at conception in 6-MP group, longer duration of disease, initially more severe disease, or use of 6-MP we cannot tell.

Publication types

  • Comparative Study

MeSH terms

  • Abortion, Spontaneous
  • Adult
  • Case-Control Studies
  • Child Development
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Embryonic and Fetal Development / physiology
  • Female
  • Fetal Death*
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / drug therapy*
  • Mercaptopurine / adverse effects*
  • Mercaptopurine / therapeutic use
  • Obstetric Labor, Premature
  • Pregnancy
  • Pregnancy Complications / epidemiology
  • Pregnancy Complications / etiology*
  • Pregnancy Outcome*
  • Prevalence
  • Probability
  • Reference Values
  • Risk Assessment


  • Mercaptopurine