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

Abstract

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.

• Authors: Jusuf Zlatanic, Burton I Korelitz, Ramona Rajapakse, Peter S Kim, Steven D Rubin, Peter J Baiocco, Georgia Panagopoulos
• Journal: Journal of clinical gastroenterology (J Clin Gastroenterol) Vol. 36 Issue 4 Pg. 303-9 (Apr 2003) ISSN: 0192-0790 [Print] United States
• PMID: 12642735 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Mercaptopurine

Topics

• 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, drug therapy)
• Mercaptopurine (adverse effects, therapeutic use)
• Obstetric Labor, Premature
• Pregnancy
• Pregnancy Complications (epidemiology, etiology)
• Pregnancy Outcome
• Prevalence
• Probability
• Reference Values
• Risk Assessment