thrombocytopenia and leukopenia, and risk of acquired chromosomal breaks.2,5-8 One approach that has been utilized adjusted the azathioprine doses to maintain the maternal leukocyte count within the normal limits for pregnancy, which minimized neonatal effects.8 NTPR data in azathioprine-based renal recipients similarly have not revealed a specific malformation pattern in the newborn.

Among the Category C agents is a range of safety profiles. For several of the agents including daclizumab, orthoclone OKT®3, Thymoglobulin® and ATGAM®, there are no available reproductive data. In reports to the NTPR, rejections during pregnancy have been treated with corticosteroids (prednisone, methylprednisolone) with a few cases using OKT®3. With both cyclosporine (CsA) and tacrolimus, animal reproductive studies have revealed fetotoxicity and fetal resorptions at higher than therapeutic doses. In contrast, animal studies with mycophenolate mofetil (MMF) have suggested teratogenesis at dosages below those causing maternal toxicity and at dosages potentially within the human therapeutic range, thus raising a greater level of concern for the potential for adverse effects on fetal development. NTPR data have not revealed malformations in 5 female renal recipients taking MMF during pregnancy. Animal studies with sirolimus have not revealed teratogenesis.

With combinations of the newer agents, it may be more difficult to identify a specific cause and effect. However, with lowered dosages of these multiple agents, there will be less exposure to each specific drug so theoretically, the potential for teratogenesis may be less. Potentiating effects among drugs as well as unknown interactions in multiple drug regimens may result in adverse fetal effects. These will most likely be discovered only by clinical outcome analyses of viable and non-viable pregnancies.

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