Mycophenolate mofetil embryopathy may be dose and timing dependent

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has now been recognized as teratogenic in humans. A pattern of malformations from in utero exposure to MMF has recently been described, and includes cleft lip and palate, microtia and atresia of the external auditory canal. We present a nulliparous mother who had taken MMF for recurrent erythema multiforme for the first 5 weeks of her pregnancy, and developed a spontaneous miscarriage during the seventh week of pregnancy. For her second pregnancy, she took MMF on her own accord for four days in the seventh week after her last menstrual period. The newborn had bilateral microtia, absence of the external auditory canals, and right iris and chorioretinal coloboma, consistent with the pattern recognized as part of the MMF embryopathy phenotype. As the newborn was not exposed to other immunosuppressive agents in utero, we believe that the phenotype described to be the result of the teratogenic effect of MMF. The spontaneous miscarriage in the first pregnancy may be due to the higher dose and longer duration of MMF exposure. The second pregnancy, with MMF exposure of 4 days, proceeded to term with the resultant phenotype. We conclude that the effect and severity of the embryopathy may be dependent on the dose, timing, and duration of MMF exposure. The manufacturer and the United States Food and Drug Administration have now disseminated information regarding the teratogenic risk of MMF. Women should be fully counseled and advised about contraception during the course of treatment with MMF.

Pregnancy Outcomes in Liver and Cardiothoracic Transplant Recipients: A UK National Cohort Study

“…Congenital anomalies most commonly associated with “mycophenolate embryopathy” include microtia and orofacial cleft defects [30], though there remain questions regarding the role of complex immunosuppressant regimens and interactions. None of these specific anomalies were reported in our cohort.…”

Esophageal atresia and prenatal exposure to mycophenolate

“…In the cases mentioned above, exposure occurred at least until week 8 after LMP in all pregnancies with malformations consistent with a mycophenolate embryopathy except for one [14]. Ang et al [14] described a patient exposure to MMF only for 4 days in week 7 after LMP with bilateral microtia, external auditory canal atresia and unilateral coloboma. In Case 4 the exposure took place until week 6 after LMP.…”

Mycophenolate mofetil in pediatric renal transplantation: A single center experience

“…There are also some long‐term concerns regarding the safety of the MMF. It has recently been recognized in the literature as teratogenic in humans (11, 12). In utero exposure to MMF can lead to phenotypic spectrum of MMF embryopathy, such as cleft lip and palate, microtia with atresia of external auditory canal, micrognathia, and hypertelorism.…”