Daniel Mishkin¹, Marc Deschênes²

1Department of Medicine, Jewish General Hospital, ²Department of Medicine Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec, Canada

Interferon alfa-2b and ribavirin combination therapy is now widely recommended for the treatment of chronic hepatitis C. Based on the teratogenic effects in animal models and the persistence of ribavirin in gonadal tissue, it is recommended that woman of childbearing age should not become pregnant while on ribavirin and for at least 6 months post-therapy. Ribavirin is listed as a category X and  Interferon is as a Category C drug by the FDA with regards to pregnancy risk. We report a patient who became pregnant 3 1/2 months after stopping treatment,  with a successful outcome.

The patient was a 29 year old woman diagnosed with chronic hepatitis C. She had briefly experimented with intravenous drugs 12 years prior.  She was treated with interferon (a–2b 3mU three times a week, and ribavirin 1000 mg daily. Treatment was stopped prematurely, after 7 weeks,  because of severe hemolysis. She became pregnant 3 1/2 months after discontinuing treatment and despite medical recommendations, opted to continue the pregnancy. Fetal ultrasounds were normal at the 13th and 19th weeks of gestation. A normal baby boy was born at 41 weeks gestation weighing 9lb 4oz . The child is being followed closely by a pediatrician and is developing normally. At 3 months he is in the 90th percentile for both height and weight.

Our treatment options in hepatitis C disease are currently improving, however, there is little known about safety of the medications used with regards to pregnancy and as a result there is a tendency to err on the side of caution. With regards to ribavirin, limb abnormalities are reported in hamsters whereas craniofacial defects were more predominant in rats. Both defects were seen in mice, in addition to neurological (i.e. exencephaly, encephalocele) and ocular abnormalities (i.e. anopthalmia, micropthalmia).  In the mouse model, a dose of 10 mg/kg, injected intraperitoneally, was found to have no measurable effect at any stage of embryonic development. However, with incremental dosages, higher rates of malformations were observed. The method of administration also appears to be important since oral administration led to more teratogenic effects than intravenous or intraperitoneal routes. This suggests that the metabolite of ribavirin generated in the maternal GI tract and/or liver is potentially a greater teratogen. No data is yet available on humans.

We believe that this is the first report of ribavirin use in proximity to conception. Patients should avoid becoming pregnant while on oral or aerosolized ribavirin. For ethical reasons a controlled study, on this issue, is not possible. Individual case reports, such as this, are therefore essential to evaluate the safety of ribavirin in pregnancy.

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