Does the use of Rebif (interferon beta-1a) during pregnancy pose any risk to the fetus?/nA 30-year-

Fråga: Does the use of Rebif (interferon beta-1a) during pregnancy pose any risk to the fetus? A 30-year-old-woman, pregnant at week 12 (last period 3/5) has been using interferon beta-1a (dose unknown) from May 5th until June 6th.

Sammanfattning: There is some documentation concerning spontaneous abortions but no evidence of increased risk of congenital malformation when using INF beta-1a during pregnancy. In the present case, drug exposure occurred very early in pregnancy. In general, exposure during the first two to three weeks after last menstrual period can be expected to lead to an all - or none effect with an early miscarriage if the fetus has been harmed. If the pregnancy proceeds, the risk of malformations caused by the drug is therefore negligible.

Svar: In a Medline search we could retrieve a case report describing a 24-year-old-woman with retinal necrosis treated with intravenous acyclovir (10 mg/kg) and interferon (INF) beta (1 million units every 8 hours) for two weeks during the 25th and 26th weeks of pregnancy. A healthy child was delivered at 39 weeks of gestation. The authors did not specify which type of interferon beta (-1a or -1b) was used in the study (1). Walther and Hohlfeld have more recently reviewed the adverse effects of INF beta (2). Pre-clinical studies on IFN beta (-1b and -1a) in rhesus monkeys demonstrated that high doses of INF beta were not teratogenic but they had a dose-dependent abortifacient activity. Of 87 documented pregnancies during treatment with INF beta-1b, 33 resulted in live-births. The mean period of fetal exposure was around five weeks. There were six spontaneous and 13 induced abortions. One fetus was stillborn due to rupture of the umbilical cord. The newborns were examined postpartum and for a period of up to three years; all showed normal development. The data on the remaining pregnancies is lacking. Of five pregnancies exposed to INF beta 1-a (22-44 ug three times per week), four resulted in normally developed babies and one in therapeutic abortion due to fetal heart disturbance. In view of these findings, INF beta therapy is not considered an indication for abortion once the drug has been withdrawn (2).

The manufacturer is aware of 15 pregnant women who were exposed to INF beta-1a at a dose of 22 to 44 ug three times weekly. These resulted in 10 normal children, three abortions and two premature babies at 31-32 weeks of gestation. The mothers had been taking the drug for two to four years (3).

No malformations are reported to the Swedish birth register in women treated with INF-beta (4).

In an extensive literature search, we did not find any reports indicating that interferons in general could be teratogenic in humans. However, all major interferons have demonstrated dose-dependent abortifacient activities (5).