Immunosuppressive Drugs and Pregnancy: Mycophenolate Mofetil Embryopathy

Abstract

Mycophenolate mofetil (MMF) and its active metabolite mycophenolic acid (MPA) are both very effective immunosuppressive agents widely used for the prevention of organ rejection following transplantation and in the therapy of autoimmune diseases. In experimental studies performed in pregnant animals, MMF exhibited teratogenicity, which later was confirmed in humans, as documented in the United States National Transplantation Pregnancy Registry (NTPR). In 2008, a specific pattern of malformations associated with in utero exposure to MMF was suggested. Subsequently, numerous reports in the scientific literature of newborns having similar patterns of malformations born to mothers who had undergone transplantation and were receiving immunosuppressive therapy provided supporting evidence for the existence of a specific MMF embryopathy. The most consistent characteristics of the MMF embryopathy phenotype include cleft lip and palate, microtia and aural atresia, and ocular anomalies (hypertelorism, arching eyebrows). Perinatal clinicians should be aware of the potential teratogenicity of MMF. Importantly, effective contraception measures should be recommended to fertile women who have received transplants before they become pregnant. Given the cumulative effect of MMF, contraceptive measures should be continued for at least 6 months after discontinuing MMF therapy.