Mycophenolic acid (MPA) products, namely mycophenolate mofetil and mycophenolate sodium, are immunosuppressive medications used to prevent rejection in solid organ transplant recipients and to treat various autoimmune disorders. Mycophenolate therapy is considered to be teratogenic based on observational studies of pregnancies exposed to MPA, which demonstrated an increased incidence of miscarriages in pregnancies exposed to MPA during their first trimester and a pattern of birth defects in the offspring of some pregnancies exposed to MPA. Herein, we have detailed case and series reports in a comprehensive literature review summarizing what is known to date regarding fetal exposure to MPA. Based on evidence from the literature, results of postmarketing surveillance, and information from registries such as the National Transplantation Pregnancy Registry in the United States, it is advised that pregnancy be avoided by women taking MPA. Preconception planning offers the opportunity to explore the alternatives to protect the mother, her transplanted organ, and minimize fetal risk. How to proceed in cases of unplanned pregnancies exposed to MPA in transplant recipients is a complex issue. Research involving large epidemiological studies is expected to be sparse as women heed the warnings about becoming pregnant on MPA. Published recommendations for managing MPA in women of childbearing potential include discontinuing the medication prior to conception, switching the MPA to another medication, or discontinuing the MPA when the pregnancy is discovered.

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, based on a limited subset of our data, which concludes that first-trimester exposure to mycophenolate (MPA) may not be associated with increased fetal risks. We disagree with their interpretation of the data and feel strongly that their conclusions convey false information regarding MPA safety during pregnancy. In contrast, our analysis of these data finds that (1) the significant risks to pregnancies exposed to MPA any time in the first trimester are miscarriage and phenotypic birth defects and (2) no association between discontinuing MPA products <6 weeks preconception and the risk of graft loss at 5 years. We attribute the authors' invalid conclusions to systematic errors in assigning recipients to their comparison groups and missing information. The authors define four MPA discontinuation comparison groups based on when MPA was discontinued relative to conception: group 1: >6 weeks, group 2: 0-6 weeks, group 3: during first trimester, and group 4: "during second trimester or never discontinued." The fourth group combines pregnancies resulting in first-trimester miscarriages where MPA was never stopped with pregnancies that continued to be exposed to MPA into the second or third trimester. An estimated 54 (73%) of the 74 outcomes in the fourth group are first-trimester pregnancy losses that occurred before MPA could be discontinued. This misclassification accounts for the authors' inaccurate conclusions that ".. .contrary to what was previously thought, first-trimester MPA exposure may not be associated with as much risk of miscarriage as second trimester exposure" and "only second-trimester MPA exposure was associated with significant increased rate of birth defects." These assertions contradict conclusive publications (2,3) and are inconsistent with a fundamental principle of teratology that the conceptus is most vulnerable during embryogenesis and organogene-sis, and its susceptibility to teratogens is reduced after the first trimester (4). NTPR analysis has shown that compared to kidney recipients who discontinued MPA before conception (n = 302), those who took MPA in the first trimester (n = 142) have more miscarriages (20% vs. 48%, p < 0.001) and more infants with birth defects (5.7% vs. 11.6%, p = 0.1) (5). Regarding long-term follow-up, the NTPR contacts each participant biannually to ascertain the status of mother and child. When the authors' data set was created, the 5-year postpartum milestone had not been reached for 206 outcomes (n = 382). The data set also lacked potential covariates for graft loss, such as donor source, transplant to conception interval, cause of graft loss, and postpartum events, including acute rejection episodes and whether MPA was resumed. Because the data set was not constructed for this type of analysis , the authors' discussion of 5-year postpartum graft loss is misleading. Especially disconcerting is their conclusion that discontinuing MPA <6 weeks before pregnancy is associated with an increased risk of 5-year graft loss. We encourage continued reporting of pregnanci...

had same diagnosis). At last child follow-up, age 9.6±6.8 yrs, the 20 children were reported otherwise healthy and developing well. Conclusion: Successful pregnancy is possible after lung transplantation, though caution is advised as these are extremely high-risk pregnancies with high incidences of prematurity, low birthweight infants, and maternal mortality. Close surveillance of these recipients is warranted due to the negative impact of rejection during pregnancy on graft and recipient survival.