Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation

Abstract

Safety of pregnancy in the female transplant recipient population must include consideration of 3 outcomes--mother, baby and transplanted graft. In the majority of female recipients studied, pregnancy does not appear to cause excessive or irreversible problems with graft function, if the function of the transplant organ is stable prior to pregnancy. However, a small percentage of recipients identified within each organ system may develop rejection, graft dysfunction and/or graft loss that may be related to the pregnancy and may occur unpredictably. Outcomes are not entirely similar among all organ systems, and one must consider risks on an individual organ basis. It appears reasonable to advise female recipients to wait one or 2 years after transplantation before attempting pregnancy to insure that function of the transplanted organ is adequate and stable and also to allow for stabilization of immunosuppressive medications. Favorable outcomes, however, have occurred when recipients have become pregnant less than one year from transplant, so cases must be analyzed individually. Immunosuppressive medications may have to be adjusted during pregnancy, and in some cases, rejections occur requiring additional immunosuppressive regimens (steroids and in several cases OKT3). Whether increasing immunosuppressive doses during pregnancy to adjust for falling levels lessens the rejection risk has never been studied prospectively. There is concern based on animal reproductive studies that the risk of birth defects and/or spontaneous miscarriage is increased in women exposed to MMF during pregnancy. Of the 9 pregnancies reported to the registry to date, there have been no birth defects noted among 5 liveborn of female recipients exposed to MMF. Data remain limited. For female recipients, a high incidence of low birth-weight and prematurity compared to the general population has been a consistent outcome, however, there has been no specific pattern of malformation in their newborn or any apparent increase in the incidence of small-for-gestational-age newborn. Long-term follow-up of children to date by the NTPR has been encouraging. A recent report in the literature has suggested impairment of immune function in newborn of CsA-treated mothers. Further study is needed. Some mothers have chosen to breastfeed. The potential risk to the newborn of ingested immunosuppressives compared with the potential benefits of breastfeeding is unknown and options must be discussed with the recipient. From earlier registry reports, recipients with deteriorating graft function, such as liver recipients with recurrent hepatitis C and/or other recipients with deteriorating graft function, appear to be at risk for worsened graft function with pregnancy. Outcomes of male recipient fathered pregnancies have been favorable and appear to be similar to the general population, but this group has not been as well studied as female recipients. No structural problems have been noted in the 38 offspring of males on MMF at the time of conception. Within each organ group, some female recipients have reported more than one pregnancy, sometimes on differing immunosuppressive regimens. If there is stable graft function, additional successful pregnancies are possible. Continued entries to the registry, especially in light of newer immunosuppressives and combinations of agents, are needed to continue to provide guidelines for management. The NTPR acknowledges the cooperation of transplant recipients and over 200 centers nationwide who have contributed their time and information to the registry. The NTPR is supported by grants from Novartis Pharmaceuticals Corp., Fujisawa Healthcare, Inc., Roche Laboratories Inc. and Wyeth-Ayerst Pharmaceuticals, Inc.