Objective: To determine whether interferon therapy during human pregnancy increases reproductive risks in women. Methods: This longitudinal, controlled cohort study consisted of three groups of women: an exposed group, a disease matched unexposed group, and a healthy comparative group. Subjects were selected from women contacting the Motherisk Program regarding maternal beta interferon exposure, mostly for multiple sclerosis during pregnancy, from 1997 to 2004. After delivery all of the women were re-contacted for a follow-up interview regarding maternal health, pregnancy outcome, and neonatal health. Results: The study group (n = 16 women, 23 pregnancies) were exposed to interferon beta-1a (Avonex, Rebif) and interferon-1b (Betaseron). There was a decrease in mean birth weight in the exposed group (3,189 ±416 g) as compared to healthy controls (3,783 ±412 g, p = 0.002). Women exposed to beta interferon had a higher rate of miscarriages and stillbirths (39.1%) vs healthy controls (5%) (p = 0.03), even after correction for potential confounders. There were two major malformations (abnormality in the X chromosome, Down’s syndrome) among exposed fetuses. Conclusions: Beta interferon therapy in the first trimester of pregnancy appears to be associated with an increased risk for fetal loss and low birth weight. Methods: This longitudinal, controlled cohort study consisted of three groups of women: an exposed group, a disease matched unexposed group, and a healthy comparative group. Subjects from women contacting the Motherisk Program regarding maternal beta interferon exposure, mostly for multiple sclerosis during pregnancy, from 1997 to 2004. After delivery all of the women were re-contacted for a follow-up interview regarding maternal health, pregnancy outcome, and neonatal health There was a decrease in mean birth weight in the exposed group (3,189 ± s) (n = 16 women, 23 pregnancies) were exposed to interferon beta-1a (Avonex, Rebif) and interferon- 416 g) as compared to healthy controls (3,783 ± 412 g, p = 0.002). Women exposed to beta interferon had a higher rate of miscarriages and stillbirths (39.1%) vs healthy controls (5% There were two major malformations (abnormality in the X chromosome, Down’s syndrome) among exposed fetuses. Conclusions: Beta interferon therapy in the first trimester of pregnancy appears to be associated with an increased risk for fetal loss and low birth weight.