Complications of pregnancy and child development after cessation of treatment with 6-mercaptopurine for inflammatory bowel disease.
OBJECTIVE
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.
Zlatanic
Jusuf
J
Department of Medicine, Lenox Hill Hospital, NYU School of Medicine, New York, NY, USA.
Korelitz
Burton I
BI
Rajapakse
Ramona
R
Kim
Peter S
PS
Rubin
Steven D
SD
Baiocco
Peter J
PJ
Panagopoulos
Georgia
G
D000022:Abortion, Spontaneous; D000328:Adult; D016022:Case-Control Studies; D002657:Child Development; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005313:Fetal Death; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy*; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000209:etiology*; D011256:Pregnancy Outcome; D015995:Prevalence; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment
D015122:Mercaptopurine