Autoimmune and Pregnancy Complications in the Daughter of a Kidney Transplant Patient. Transplantation 2002: 73: 815.

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When confronted with the management of pregnancy after transplantation, concern among practitioners focuses not only on maternal prognosis but also on the potential adverse effects that medications and medical conditions in the recipient may have on the developing fetus. In the article by Scott et al., the authors state that immunosuppressive agents readily cross the placenta during the development of the fetal immune system, but their effects may not become apparent until these offspring become adults themselves. Extrapolating from animal data, remote effects of this exposure may present as autoimmune disorders or reproductive difficulties. A case is presented of a 23-year-old daughter of a renal allograft recipient exposed to azathioprine and prednisone throughout her mother’s pregnancy. The daughter had joint stiffness at age 8 and developed ulcerative colitis at age 16. She went on to have two pregnancies, one complicated by autoantibodies and fetal death, and the other by systemic lupus erythematosus and preeclampsia, but with the birth of a preterm male infant. In raising the question as to whether the next generation pregnancy complications are related to in utero immunosuppressive exposure, the authors have initiated a study to help determine these risks. Contact information including a web site address is given for enrollment of daughters over the age of 18 whose mothers were taking antirejection medications.
This article presents a well-chronicled case with an interesting hypothesis. Adverse pregnancy outcomes from medication exposure might cause the following: 1) embryonic or fetal death, 2) structural malformations in the newborn, 3) growth retardation in a liveborn, or 4) functional problems in a liveborn. These have been concerns in the pregnancies of transplant recipients and have been addressed in case, center, and registry reports over the years, including a detailed case report from Davison and his colleagues in 1976. In that report, the authors questioned whether there might be subtle effects of pregnancy and immunosuppression not only on the kidney transplant but the newborn (1).
Scott et al. state that most, but not all, neonates exposed to these drugs have had an uncomplicated course, progress normally through infancy and childhood, but there are few long-term studies. With the introduction of cyclosporine in the 1980s, early reports raised concern as to the safety of this agent during pregnancy (2,3). In 1991, the National Transplantation Pregnancy Registry (NTPR) was established at Thomas Jefferson University to study the outcomes of pregnancy in female recipients, as well as those pregnancies fathered by male transplant recipients. For most female recipients, pregnancy outcomes have been favorable for the recipient as well as the newborn. Case reports note the potential teratogenicity of immunosuppressive agents, and investigation is ongoing, especially in light of newer agents (4,5). One also has to acknowledge that throughout this literature, there has been a consistent pattern of prematurity and low birthweight, and in some series, intrauterine growth retardation. Although there has not been an increase in the background structural malformation rate of 3–5% and no predominant pattern of malformation in the newborns has been noted, we share with Dr. Scott and colleagues the concern that there might be remote effects on the offspring. Long-term follow-up of the offspring of transplant recipients has been one of the goals of the NTPR and results have been encouraging to date. Specific disorders of the immune system have not been reported in the offspring of cyclosporine- treated kidney recipients. Regarding reproductive problems, the oldest such offspring are only approaching adulthood (6,7).

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