Healthy offspring in parents both receiving thiopurines

Abstract

Dear Sir: In a recent study Francella et al. investigated the effects of 6-mercaptopurine (6-MP) on the outcome of pregnancy in patients with inflammatory bowel disease (IBD) and on safety of in utero exposed offsprings.1Francella A. Dyan A. Bodian C. Rubin P. Chapman M. Present D.H. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease a retrospective cohort study.Gastroenterology. 2003; 124: 9-17Abstract Full Text Full Text PDF PubMed Scopus (282) Google Scholar Among 155 IBD affected females and males 325 pregnancies were examined. All pregnancies occurred after the diagnosis of IBD and were analyzed as to whether the patient had taken 6-MP before or at the time of conception. Outcomes were compared to 84 pregnancies induced before treatment with 6-MP. There was no statistical difference between both groups regarding to conception failures, defined as a spontaneous abortion, abortion secondary to a birth defect, ectopic pregnancy, embryonic pregnancy, embryonic demise, major congenital malformations, neoplasias, or increased infections. The authors concluded that the use of 6-MP before, at the time of conception or during pregnancy appears to be safe and that by discontinuing 6-MP the risk of exacerbation of IBD for fetus and mother would outweigh the potential hazards of maintaining the treatment during pregnancy. We would like to add to the literature the case of a couple of patients with Crohn’s disease (CD) who delivered a healthy baby while both mother and father were exposed to thiopurines at the time of conception. The 35-year-old woman has been treated with azathioprine (AZA) due to chronic active disease since January 2000. After 20 months of AZA treatment at a dosage of 125 mg per day (2 mg/kg bodyweight) she conceived in August 2001 in clinical remission and was advised to continue therapy throughout pregnancy. At the time of conception the 33-year-old father has continuously received 6-MP at a dose of 100 mg/d for chronic active disease since March 2001. In the medical history of the parents no spontaneous abortion was noted. After an uneventful pregnancy a healthy baby was delivered in April 2002 at a gestational age of 39 weeks. The female child had a birth weight of 3280 g and a length of 50 cm (50th percentile; Apgar score 9/10/10). During pregnancy clinical remission was maintained. We decided to report this case, because data regarding safety of thiopurines during pregnancy in IBD patients are limited and have been discussed controversially leading to a physicians’ uncertainty whether to recommend cessation or maintenance of this immunosuppressive treatment before conceiving. Rajapakse et al. noted an increased incidence of complications of pregnancies and congenital abnormalities when fathers had received 6-MP within 3 months of fertilization.2Rajapakse R.O. Korelitz B.I. Zlatanic J. Baiocco P.J. Gleim G.W. Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease.Am J Gastroenterol. 2000; 95: 684-688Crossref PubMed Google Scholar Although these data did not provide high evidence, the following report about a baby with a WAGR Syndrome (Wilm’s tumor, Aniridia, Gonadoblastoma, and mental retardation) fathered by an IBD patient receiving AZA intensified precariousness.3Ben-Neriah Z. Ackerman Z. WAGR syndrome in a baby-the result of 6-MP treatment in a father affected by Crohn’s disease?.Am J Gastroenterol. 2001; 96: 251PubMed Google Scholar We experienced uneventful pregnancies and observed 7 healthy children fathered by men with AZA therapy, when assessing male fertility in IBD.4Dejaco C. Mittermaier C. Reinisch W. Gasche C. Waldhoer T. Strohmer H. Moser G. Azathioprine treatment and male fertility in inflammatory bowel disease.Gastroenterology. 2001; 121: 1048-1053Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar The excellent work by Francella et al. provides data based on an adequate patient cohort that treatment with 6-MP in childbearing females and males with IBD may be regarded as safe. So far, discontinuation of AZA and 6-MP treatment seems to be not longer indicated for patients planning to start a family. Our unique case enriches previous knowledge indicating that an uneventful pregnancy and a birth of a healthy offspring is conceivable when even both parents are exposed to thiopurines during conception.