Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients

Abstract

In 2012, the U.S. Food and Drug Administration issued guidelines advising kidney transplant recipients (KTRs) to discontinue mycophenolate (MPA) in preparation for pregnancy. Little is known about how this guidance has affected pregnancy and graft outcomes. The purpose of this retrospective cohort study was to investigate any association between the discontinuation of MPA and KTR pregnancy and graft outcomes. Data from the National Transplantation Pregnancy Registry included 382 cases in which KTRs managed on MPA became pregnant. Overall, 22 variables, including the time in which a KTR discontinued MPA, were assessed across four end points: miscarriages, birth defects, and 2-and 5-year postpartum graft loss. Birth defects and miscarriages were similar among KTRs who discontinued MPA >6 and <6 weeks prior to pregnancy and during the first trimester. In contrast, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages (odds ratio [OR] 9.35, 95% confidence interval [CI] 4.31-20.00, p < 0.001) and birth defects (OR 6.06, p = 0.002). Discontinuing MPA <6 weeks prior to pregnancy was associated with an increased risk of 5-year graft loss. For the fetus, there is value to discontinuing MPA anytime prior to the second trimester. Adhering to current guidelines does not negatively affect graft survival.

What Is the Teratogenic Risk of Mycophenolate?

“…Ironically, discontinuing MPA during the second trimester or later significantly increased the risk of miscarriages and birth defects. 19 The drug's benefits may outweigh its risks in most people. However, it is important that all women of reproductive potential prior to being treated with MFS or MMF have proper education and counseling about pregnancy prevention.…”

Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II

“…Leukopaenia or thrombocytopenia may also occur. Recent data indicate that MMF should be discontinued 6 weeks before a planned pregnancy …”

Antibody‐mediated rejection due to anti‐HLA‐DQ antibody after pregnancy and delivery in a female kidney transplant recipient

“…In fact, a systematic review showed that as primary immunosuppression, MMF treatment was more effective than AZA in reducing the risk of acute rejection, by approximately 30% . In contrast, a recent study reported the importance of long‐term MMF discontinuation to graft survival postpartum (compared <6 weeks with >6 weeks prior to pregnancy; 5‐year graft loss: odds ratio, 5.56; 95% confidence interval, 1.38–22.22; P = 0.016) . These results not only support the current guideline consensus regarding MMF discontinuation at pregnancy but also raise an issue about the anti‐rejection effects of immunosuppressive agents during pregnancy in kidney transplant recipients.…”

“…Regarding the teratogenic effects of MMF, such as hypoplastic nails, cleft palate, facial malformation, and Tetralogy of Fallot, it is commonly accepted that MMF should be discontinued and changed to another immunosuppressant, such as AZA, more than 6 weeks before a planned pregnancy or upon the desire to bear children . Our patient was switched from MMF to AZA at 3 years before pregnancy; therefore, these changes could have caused the DSA and rejection.…”