Pregnancy after lung transplant.

The purpose of this study was to analyze pregnancy outcomes in female lung transplant recipients. Data were collected from the National Transplantation Pregnancy Registry via questionnaires, interviews, and hospital records. Twenty-one female lung recipients reported 30 pregnancies with 32 outcomes (1 triplet pregnancy). Outcomes included 18 live births, 5 therapeutic abortions, and 9 spontaneous abortions. No stillbirths or ectopic pregnancies were reported. Mean (SD) interval from transplant to conception was 3.6 (3.3) years (range, 0.1-11.3 years). Comorbid conditions during pregnancy included hypertension in 16, infections in 7, diabetes in 7, preeclampsia in 1, and rejection in 5 women. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (7 live births, 3 spontaneous abortions, and 2 therapeutic abortions). At last recipient contact, 13 had adequate function, 2 had reduced function, 5 recipients had died (2 with cystic fibrosis), and 1 recipient had a nonfunctioning transplant. Mean gestational age of the newborn was 33.9 (SD, 5.2) weeks, and 11 were born preterm (<37 weeks). Mean birthweight was 2206 (SD, 936) g and 11 were low birthweight (<2500 g). Two neonatal deaths were associated with a triplet pregnancy; one fetus spontaneously aborted at 14 weeks and 2 died after preterm birth at 22 weeks. At last follow-up, all 16 surviving children were reported healthy and developing well. Successful pregnancy is possible after lung transplant, even among recipients with a diagnosis of cystic fibrosis.

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

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling to all pre and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. The NTPR has acquired experience with 2000 pregnancy outcomes in female transplant recipients. For the NTPR's largest group, female kidney recipients, 71-76% of the pregnancies produce a livebirth. For the other organs combined, the livebirth likelihood ranges from 50-86%. The incidence of birth defects in the liveborn appears similar to the general population, except for pregnancies with MPA exposure that have a 23% incidence of birth defects. Long-term follow-up of the offspring of transplant recipients has provided reassurance after 20 years of observation. The continued recording of data in registries such as the NTPR is essential for assessing the safety of pregnancy in solid organ transplant recipients. Key benefits of the NTPR are the personal contact between registry staff and participants, the wide range of pregnancy-related variables that are analyzed, and the opportunity for health-care providers to obtain information that helps them care for transplant recipients on a case-by-case basis.

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

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling in all pre- and post-transplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as 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 long-term outcomes of parent and child. Continued close collaboration among specialists will help to better identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR.

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

With the constant advent of new developments and modifications in immunosuppressive regimens, clinicians are responsible for providing pregnancy counseling in all pre and post-transplant patients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as 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 long-term outcomes of parent and child. Continued close collaboration among specialists will help to identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. The 50th anniversary of the first post-transplant pregnancy (reported by Joseph Murray et al. (32)) that occurred in March of 2008 helped 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.

Nutrition, pregnancy, and transplantation.

One benefit of transplantation, along with the restoration of health, is the opportunity for successful pregnancies. A growing number of pregnancies have been reported among all types of solid-organ recipients. There is an increasing need for practice guidelines that include nutrition information in order to assist practitioners caring for and counseling these high-risk patients. In the transplant community, guidelines for managing pregnancies in transplant recipients have been evolving but lack specific nutrition recommendations. As for all pregnancies, there is a need to optimize nutrition for the mother and her infant, with additional consideration given to the transplant recipient's graft. This article reviews outcomes of posttransplant pregnancies and management guidelines, with special emphasis on nutrition in this unique population.

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

From the first reports of pregnancy in each of the organ groups to the present, concerns varied and were specific to the type of transplant. Organ-specific issues still require additional attention and analyses. Lung recipients appear at greatest risk for poorer pregnancy outcomes. Given these ongoing concerns and the constant advent of new developments, clinicians are responsible for providing pregnancy counseling in all pre- and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as 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 long-term outcomes of parent and child. Continued close collaboration among specialists will help to identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. The 50th anniversary of the first posttransplant pregnancy (reported by Joseph Murray, et al. (11)) was in March 2008. With this important landmark event and with ongoing pregnancy issues concerning posttransplant pregnancy safety, this is an ideal time to raise the 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.

Report from the National Transplantation Pregnancy Registry: outcomes of pregnancy after transplantation.

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.

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

Experience in the field of pregnancy after transplantation 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 follow-up of recipients' graft status and of their offspring. For the most part, guidelines proposed in 1976 for counseling recipients remain applicable. While these counseling guidelines were formulated for kidney recipients, they may be extrapolated for 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. They should have 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, one year is a reasonable milestone, given the prerequisites of stable, adequate graft function and maintenance level immunosupression. During pregnancy, stable medication regimens should be changed as little as possible, and close maternal and fetal surveillance are required. These pregnancies are high-risk and require coordinated care among maternal fetal medicine specialists and transplant personnel. The pregnancy issues that face recipients and caretakers with the current adjunctive therapies and differing combinations of immunosuppressive regimens continue to require further study. The most pressing issue is the question of whether fetal exposure to mycophenolate mofetil or sirolimus confers additional risk, relative to the potential improvement in maternal survival and maternal graft function/survival conferred by these drugs. Given the multiplicity of immunosuppressive regimens, only broad-based registry participation can provide the data needed to analyze such complex questions. Future analyses are directed at potential effects of these newer immunosuppressive regimens, not only from immediate exposure, but also from potential long-term exposures such as may occur from breastfeeding. As the registry study design allows for continuing contact between registry staff and recipients and their health care providers, efforts are in progress to analyze long-term outcomes of parent and child. Continued close collaboration among specialists will help to better identify potential pregnancy risks in these populations, especially as new immunosuppressive agents are developed.

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

The NTPR maintains an ongoing active database to study the safety of pregnancy in transplant recipients and currently includes the outcomes of more than 900 female recipients who became pregnant after their transplant and just over 700 male recipients who fathered one or more pregnancies after receiving a transplant. Analyses include the long-term follow-up of the recipient's graft status and their offspring. Successful pregnancy outcomes have been noted for each solid organ recipient group. The Registry includes information on 1,097 pregnancies in 716 kidney recipients, 187 pregnancies in 111 liver recipients, 56 pregnancies in 38 P/K recipients and smaller numbers for other organs and combinations of organs. There are periodic reports of recipients with graft dysfunction, rejection, or graft loss that may be related to pregnancy events, though the majority of outcomes reported to the NTPR appear favorable for parent and newborn. Organ-specific issues and comorbidities must also be considered in analyzing outcomes. The pregnancy issues that face recipients and caretakers with the current newer adjunctive therapies and newer immunosuppressive regimens require ongoing study. The potential risk of teratogenicity must be weighed against the potential risk of rejection when altering drug regimens before planned conceptions or in making dosage adjustments during pregnancy. Unplanned pregnancies present obvious concerns. Pregnancy safety has not been established for either MMF or sirolimus and all centers are encouraged to report pregnancies with exposures to these agents to the NTPR. Continuing analyses are directed at potential effects of the newer immunosuppressive regimens, not only to identify any risks to the pregnancy from immediate exposure, but also for potential postpartum exposures such as from breastfeeding. As the registry study design allows for continued contact, efforts continue to accrue long-term follow-up of both parent and child.

Pregnancy outcomes in female renal recipients: a comparison of systemic lupus erythematosus with other diagnoses.

This study compares pregnancy outcomes in systemic lupus erythematosus (SLE) patients post renal transplant with recipients with other primary diagnoses, utilizing data from the National Transplantation Pregnancy Registry, Philadelphia, PA. Recipients were referred from transplant centers nationwide. A retrospective analysis was performed using data from questionnaires, hospital records and telephone interviews. Outcomes of pregnancies post renal transplant secondary to lupus nephritis (SLE: n = 38; 60 pregnancies) were compared with the pregnancy outcomes of renal recipients with other diagnoses (non-SLE: n = 247; 374 pregnancies). Drug-treated hypertension during pregnancy was less common in the SLE group than in the non-SLE group (45.0% vs. 62.5%, p = 0.015). There were fewer cesarean sections in the SLE group (30.2 vs. 53.2%, p = 0.008). There was no primary or gestational diabetes in the SLE group. There were no other statistical differences in maternal conditions or pregnancy outcomes between the SLE and non-SLE groups, or in the incidence of post pregnancy graft loss. Female recipients transplanted for renal failure secondary to lupus nephritis can successfully maintain pregnancy. Outcomes are comparable to renal recipients with other diagnoses. Newborns in both groups were often premature and had low birthweight. Overall childhood health was reported to be good; there were no apparent predominant structural malformations among the children.

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

The NTPR continues to maintain an ongoing active database as a resource for health professionals counseling recipients regarding pregnancy and for recipients themselves to contact the registry and request information. This includes female transplant recipients as well as male recipients who father pregnancies. Recipients who consent are entered into a database; analyses are ongoing, including long-term follow-up of the recipient, the graft and the offspring. The safety of pregnancy for parent and child remains the goal of the registry. Guidelines for counseling recipients proposed in 1976 remain applicable. Recipients should be in general good health and graft function should be stable and ideally rejection free. Comorbid conditions should be well controlled, especially hypertension and diabetes. While these counseling guidelines were formulated for kidney recipients, they may be extrapolated for other organ recipients. Analyses this year included pregnancy outcomes of recipients on newer agents, MMF and sirolimus. It remains unclear whether these adjunctive therapies should be altered for pregnancy. The balance of immunosuppression and the prevention of rejection need to be weighed against the potential for teratogenicity when counseling these recipients inquiring about pregnancy. Although there are periodic reports of recipients with graft dysfunction, rejection or graft loss possibly related to pregnancy events throughout all the organ groups, whether transplanted as adults or as pediatric patients, the majority of pregnancy outcomes reported to the NTPR appear favorable for parent and newborn. Whether recipients should breastfeed remains controversial. Recent reports in the literature as well as NTPR data appear favorable. This represents the last report from our initial established location at Thomas Jefferson University. In January of this year, the registry moved to Temple University School of Medicine, Department of Surgery, Philadelphia, PA. The NTPR remains committed to investigating outcomes of pregnancies reported by centers or self-referrals nationwide. Some of the active issues for the upcoming year include the potential for teratogenicity with combinations of newer agents, incidence of viral hepatitis, risk assessment for pregnancy in female lung recipients, and long-term maternal and pediatric follow-up.

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

The NTPR maintains an ongoing database to study the outcomes of pregnancies in female transplant recipients as well as those pregnancies fathered by male transplant recipients. Recipients are entered into the database by completing. a single page questionnaire. There is steady follow-up of recipients and their offspring. While the majority of pregnancy outcomes have occurred in kidney recipients, data continue to accrue in the other types of organ recipients. KIDNEY: A small percentage of pregnancies in female kidney recipients are complicated by rejection with poorer outcomes with respect to both maternal graft function and their newborn. Other analyses this year focused on outcomes of recipients with systemic lupus erythematosus and those with multiple gestations. It was observed that recipients with systemic lupus erythematosus were able to maintain a pregnancy with outcomes that appear to be similar to other diagnoses. In an analysis of multiple gestations in female kidney recipients maintained on calcineurin inhibitors, no multiple gestations higher than triplets have been reported to the NTPR. Successful outcomes have been noted among these recipients. This does require continued surveillance, as there has been an increase in the number of multiple gestations in the general population with the use of adjunctive technologies. OTHER ORGANS: In analyzing outcomes in female liver recipients, no specific graft or newborn outcome differences have been noted when a comparison has been made between different caicineurin inhibitor regimens. Pregnancies in female pancreas-kidney recipients appear to be tolerated with respect to pancreas graft function with no diagnoses of gestational diabetes reported to the NTPR. Data continue to accrue among thoracic recipients. Poorer maternal survival postpartum in lung recipients may be related to higher risks inherent in this population and requires further experience and investigation. OTHER ISSUES: With the recent proliferation of newer immunosuppressive agents, a question that is raised is whether a regimen can be specifically designed with recipients of childbearing age in mind. Extensive data published on azathioprine and cyclosporine treated recipients suggests that while there is a pattern of prematurity among the newborn there has not been an increase in the incidence or pattern of specific malformations noted among the newborn. Less assurance can be given with newer agents such as sirolimus and MMF. Calcineurin inhibitor minimization or steroid withdrawal would require that other agents with less reproductive information be implemented. The unknown risk of teratogenicity must be balanced against the potential risk of rejection or graft dysfunction when deciding which agent to use during pregnancy. Through each of the organ recipient groups, there are sporadic cases of rejection, graft dysfunction, and graft deterioration. Birth defect patterns have not appeared to be specific to any specific regimen as yet. Two newborns with malformations have been noted among a limited series with MMF exposure, but other factors may also be at play. The use of MMF during pregnancy continues to be an unresolved issue in the transplant community. As yet, no one regimen has been identified as superior to another for use during pregnancy. Continued surveillance with the newer agents is necessary. Investigators have taken differing views regarding the safety of breastfeeding in the transplant recipient population, especially with regard to drug exposure to the infant. This issue remains unresolved and some transplant recipient mothers have chosen to breastfeed. Other factors for consideration are the potential long-term effects on offspring of transplant recipients. While there may not be specific structural defects noted at birth, more subtle effects on either immunologic or reproductive function may not manifest until later in life. Scott and his group in Utah have raised this issue with a case report and have initiated a study to focus on the next generation. The safety of pregnancy for parent and child remain the goals of the NTPR. Continued entries to the registry, especially in light of newer combinations of immunosuppressive agents, should assist in developing guidelines needed for management in this era of expanding immunosuppressive agents. All centers are encouraged to participate.