Armenti Vincent T, Daller John A, Constantinescu Serban, Silva Patricio, Radomski John S, Moritz Michael J, Gaughan William J, McGrory Carolyn H, Coscia Lisa A
Department of Surgery, Temple University School of Medicine, Philadelphia, PA, USA.
Clin Transpl. 2006:57-70.
Experience in the field of pregnancy posttransplantation has been gained through continued case reports, center reports, and registry data. The NTPR maintains an ongoing active database to study the safety of pregnancy and includes the outcomes of female transplant recipients as well as male recipients who father pregnancies. Analyses are ongoing and include long-term followup of recipients' graft status and of their offspring. For the most part, guidelines proposed in 1976 for counseling recipients remain applicable (30). While these counseling guidelines were formulated for kidney recipients, they may be extrapolated to other organ recipients as well. Organ-specific issues should also be considered in managing and counseling female transplant recipients. Recipients should be in general good health, and graft function should be stable and, ideally, rejection-free. There should be optimal control of comorbid conditions such as hypertension and diabetes prior to conception. While the shortest safe interval from transplant to conception has not been established, 1 year is a reasonable milestone, given the prerequisites of stable, adequate graft function and maintenance-level immunosuppression. During pregnancy, maintenance-medication regimens should be continued with vigilant monitoring for effective drug levels and drug side effects with appropriate dose adjustment. These pregnancies are high-risk and require close maternal and fetal surveillance through coordinated care among maternal-fetal medicine specialists and transplant personnel. Of the live born reported to the NTPR, a higher incidence of structural malformations has been seen with MMF exposures during pregnancy when compared with the overall kidney transplant recipient offspring group. Three of the four defects included microtia (ear deformity), suggesting a pattern of malformations. However, live-born outcomes without structural malformations have also been noted in the MMF cohort. No structural defects have yet been reported with early pregnancy sirolimus exposures in a limited number of recipients evaluated. Limitations in assessing congenital malformation risk and MMF exposure include methodology and potential reporting bias, small sample size, and our inability to exclude other comorbid factors such as non-immunosuppressive drug effects or other susceptibilities in this population. It is incumbent upon transplant professionals to be aware of any additional risk to the fetus from immunosuppressive medications relative to the potential improvement in maternal graft function/survival conferred by each of these agents. Given the ongoing concerns with the newer immunosuppressive agents, clinicians are responsible for providing pregnancy counseling in all pre- and post-transplant recipients of childbearing age. Centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. Future analyses from the NTPR are directed at potential effects of these newer immunosuppressive regimens, not only from immediate exposure but also from continued exposure that may occur from breastfeeding. As the registry study design allows for contact between registry staff and recipients and their health care providers, efforts are ongoing to analyze the long-term outcomes of parents and children. Continued close collaboration among specialists will help to better identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. The fiftieth anniversary of the first post-transplant pregnancy (reported by Joseph Murray et al.) (31) will be in March 2008. With this important date approaching and with ongoing pregnancy issues concerning post-transplant pregnancy safety, this is an ideal time to raise awareness of the need for continued worldwide cooperation for data collection. Enhanced assessment of pregnancy safety is essential to the development of guidelines for counseling and management of pregnancy in the transplant population.
通过持续的病例报告、中心报告和登记数据,人们积累了移植后妊娠领域的经验。国家移植妊娠登记处(NTPR)维护着一个持续更新的动态数据库,用于研究妊娠安全性,其中包括女性移植受者以及使女性受孕的男性受者的妊娠结局。相关分析正在进行中,包括对受者移植器官状态及其后代的长期随访。在很大程度上,1976年提出的针对受者咨询的指导原则仍然适用(30)。虽然这些咨询指导原则是为肾移植受者制定的,但也可类推应用于其他器官移植受者。在管理和咨询女性移植受者时,还应考虑器官特异性问题。受者总体健康状况应良好,移植器官功能应稳定,理想情况下应无排斥反应。受孕前应优化控制高血压和糖尿病等合并症。虽然尚未确定从移植到受孕的最短安全间隔时间,但考虑到移植器官功能稳定、足够以及维持水平免疫抑制的前提条件,1年是一个合理的时间节点。妊娠期间,应继续维持药物治疗方案,密切监测有效药物水平和药物副作用,并进行适当的剂量调整。这些妊娠属于高危妊娠,需要通过母胎医学专家和移植工作人员的协调护理,对母亲和胎儿进行密切监测。在向NTPR报告的活产儿中,与总体肾移植受者后代群体相比,妊娠期间暴露于霉酚酸酯(MMF)的情况下,结构畸形的发生率更高。报告的四个缺陷中有三个是小耳畸形(耳部畸形),提示存在一种畸形模式。然而,在MMF队列中也注意到了无结构畸形的活产结局。在少数接受评估的受者中,妊娠早期暴露于西罗莫司尚未报告有结构缺陷。评估先天性畸形风险和MMF暴露存在局限性,包括方法学和潜在的报告偏倚、样本量小,以及我们无法排除该人群中的其他合并因素,如非免疫抑制药物的影响或其他易感性。移植专业人员有责任了解免疫抑制药物对胎儿的任何额外风险,以及这些药物对母亲移植器官功能/存活的潜在改善作用。鉴于对新型免疫抑制药物的持续关注,临床医生有责任为所有育龄期移植前后的受者提供妊娠咨询。鼓励各中心向NTPR报告移植受者的所有妊娠暴露情况。NTPR未来的分析将针对这些新型免疫抑制方案的潜在影响,不仅包括即刻暴露的影响,还包括母乳喂养可能导致的持续暴露的影响。由于登记研究设计允许登记工作人员与受者及其医疗服务提供者进行联系,目前正在努力分析父母和子女的长期结局。专家之间持续密切的合作将有助于更好地识别这些人群中潜在的妊娠风险,特别是在开发新型免疫抑制药物时。首例移植后妊娠(由约瑟夫·默里等人报告)(31)的五十周年纪念日将于2008年3月到来。随着这个重要日子的临近,以及移植后妊娠安全性方面持续存在的妊娠问题,这是一个提高人们对全球持续合作进行数据收集必要性认识的理想时机。加强对妊娠安全性的评估对于制定移植人群妊娠咨询和管理指南至关重要。