Mycophenolate mofetil embryopathy may be dose and timing dependent.
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.
Department of Paediatric Ophthalmology, Royal Aberdeen Children's Hospital, Aberdeen, United Kingdom.
Ghee Soon
GS
Ang
Sheila A
SA
Simpson
Aravind R
AR
Reddy
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000015:Abnormalities, Multiple / Q000139:chemically induced*; D000328:Adult; D002675:Child, Preschool; D003103:Coloboma / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004424:Ear Canal / Q000002:abnormalities; D004431:Ear, External / Q000002:abnormalities; D004892:Erythema Multiforme / Q000188:drug therapy; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007498:Iris / Q000002:abnormalities; D018811:Maternal Exposure; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011247:Pregnancy; D013997:Time Factors
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid