Armenti V T, Radomski J S, Moritz M J, Philips L Z, McGrory C H, Coscia L A
Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Clin Transpl. 2000:123-34.
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.
女性移植受者群体的妊娠安全性必须考虑三个结果——母亲、婴儿和移植的移植物。在大多数接受研究的女性受者中,如果移植器官在妊娠前功能稳定,妊娠似乎不会对移植物功能造成过度或不可逆转的问题。然而,在每个器官系统中,有一小部分受者可能会发生与妊娠相关的排斥反应、移植物功能障碍和/或移植物丢失,且可能不可预测地发生。所有器官系统的结果并不完全相似,必须根据单个器官来考虑风险。建议女性受者在移植后等待一到两年再尝试妊娠,以确保移植器官的功能足够稳定,同时也能使免疫抑制药物稳定下来,这似乎是合理的。然而,当受者在移植后不到一年就怀孕时,也有出现良好结果的情况,所以必须对每个病例进行单独分析。妊娠期间可能需要调整免疫抑制药物,在某些情况下,会发生排斥反应,需要额外的免疫抑制方案(类固醇,在某些情况下还需要OKT3)。妊娠期间增加免疫抑制剂量以应对水平下降是否能降低排斥风险,从未进行过前瞻性研究。基于动物生殖研究,人们担心妊娠期间接触霉酚酸酯(MMF)的女性出现出生缺陷和/或自然流产的风险会增加。在向登记处报告的9例妊娠中,5例暴露于MMF的女性受者的活产婴儿中未发现出生缺陷。数据仍然有限。与普通人群相比,女性受者低出生体重和早产的发生率一直很高,然而,她们的新生儿没有特定的畸形模式,也没有明显增加小于胎龄新生儿的发生率。国家移植妊娠登记处(NTPR)对儿童的长期随访至今结果令人鼓舞。文献中最近的一份报告表明,接受环孢素A(CsA)治疗的母亲所生新生儿的免疫功能受损。需要进一步研究。一些母亲选择母乳喂养。与母乳喂养的潜在益处相比,摄入免疫抑制药物对新生儿的潜在风险尚不清楚,必须与受者讨论各种选择。从早期的登记处报告来看,移植物功能恶化的受者,如患有复发性丙型肝炎的肝移植受者和/或其他移植物功能恶化的受者,似乎有因妊娠而导致移植物功能恶化的风险。男性受者配偶妊娠的结果良好,似乎与普通人群相似,但对这一群体的研究不如女性受者充分。在受孕时服用MMF的男性所生的38名后代中,未发现结构问题。在每个器官组中,一些女性受者报告了不止一次妊娠,有时采用不同的免疫抑制方案。如果移植物功能稳定,再次成功妊娠是可能的。需要继续向登记处提供信息,特别是鉴于有了更新的免疫抑制药物和联合用药方案,以便继续为管理提供指导方针。NTPR感谢移植受者以及全国200多个中心的合作,他们为登记处贡献了时间和信息。NTPR得到了诺华制药公司、藤泽医疗保健公司、罗氏实验室公司和惠氏-艾尔斯特制药公司的资助。