Management of pregnancy in the post-cardiac transplant patient

Over the past 10 years, heart transplantation survival has increased among transplant recipients. Because of improved outcomes in both congenital and adult transplant recipients, the number of male and female patients of childbearing age who desire pregnancy has also increased within this population. While there have been many successful pregnancies in post-cardiac transplant patients reported in the literature, long-term outcome data is limited. Decisions regarding the optimal timing and management of pregnancy in male and female post-cardiac transplant patients are challenging and should be coordinated by a multidisciplinary team of healthcare providers. Pregnant patients will need to be counseled and monitored carefully for complications including rejection, graft dysfunction, and infection. This review focuses on preconception counseling for both male and female cardiac transplant recipients. The maternal and fetal risks during pregnancy and the postpartum period, including risks to the fetus fathered by a male cardiac transplant recipient will be reviewed. It also provides a brief summary of our own transplant experience and recommendations for overall management of pregnancy in the post-cardiac transplant recipient.     

Pregnancy after liver transplantation

There have been great strides in transplant medicine over the past few decades, and hundreds of pregnancies have now been reported in liver transplant recipients. Information on pregnancy in transplant patients has been collected through case reports, retrospective center-specific studies, and voluntary registries. Overall, favorable pregnancy outcomes have been reported for these patients. Pregnancy complications, however, are more common in liver transplant recipients than in the general population. Accordingly, pregnancies in liver transplant recipients should be followed by a multidisciplinary team involving both maternal fetal medicine specialists and transplant physicians. This chapter outlines the available data on the maternal and obstetrical outcomes of pregnancies in liver transplant recipients, and will review guidelines for management of these high-risk pregnancies.     

Pregnancy in transplant recipients

A growing number of transplant recipients are women of reproductive age or children who will reach reproductive age. Thus, menstrual function and pregnancy increasingly are important issues because fertility is restored to women who were previously unable to conceive. To date, successful pregnancies have been reported in female recipients of kidney, liver, heart, pancreas-liver, bone marrow, and lung transplants. Women often become pregnant while being maintained on numerous medications, including immunosuppressive agents, and their care providers must be able to counsel and care for them. Information to date suggests that immunosuppressive medications are safe for use during pregnancy and are important in preventing maternal and fetal complications secondary to graft rejection. Although no formal guidelines have been established due to limited clinical experience, there are a few criteria that are commonly agreed on to improve the probability of a successful pregnancy outcome and the maintenance of graft function in transplant patients. Successful management of the pregnant transplant patient requires a cooperative effort between the obstetrician and transplant team.     

Pregnancy in renal transplant recipients

Women with renal disease face increasing infertility and high-risk pregnancy as they approach end-stage renal disease due to uremia. Renal transplantation has provided these patients the ability to return to a better quality of life, and for a number of women who are of child bearing age with renal disease, it has restored their fertility and provided the opportunity to have children. But, although fertility is restored, pregnancy in these women still harbors risk to the mother, graft, and fetus. Selected patients who have stable graft function can have successful pregnancies under the supervision of a multidisciplinary team involving maternal fetal medicine specialists and transplant nephrologists. Careful observation and management are required to optimize outcome for mother and fetus.     

Pregnancy following renal transplantation

Pregnancy is not contraindicated in renal transplant recipients with stable renal function, and a successful and healthy obstetric outcome can be expected in 95% of such cases. The incidence of both maternal and fetal complications is related to the degree of graft dysfunction and/or hypertension prior to pregnancy. Poorer prognosis is associated with poorer renal function. If complications (usually hypertension, renal deterioration, and/or rejection) occur before 28 weeks, then successful obstetric outcome is reduced by 20%. More information is needed about the intrauterine effects and neonatal consequences of maternal immunosuppression, which appears harmless at maintenance levels. From the data available it seems that pregnancy does not compromise long-term transplant prognosis. In the absence of prospective controlled studies transplant pregnancy registries are the only viable means of providing clinicians with timely and relevant information on pregnancy outcomes on which to base management guidelines.     

Pregnancy outcomes among solid organ transplant recipients in British Columbia

ObjectiveSince 1954, over 14 000 women have given birth after having had an organ transplantation. Unfortunately, some women and physicians remain misinformed about the feasibility and outcomes of pregnancy post transplantation. Our primary objective was to assess their perceptions and difficulties with regard to becoming pregnant. Our secondary objectives were to determine the incidence of pregnancies among transplant recipients in British Columbia and any maternal, graft, or fetal complications.MethodsFrom 1997 to 2007 in British Columbia, there were over 500 female recipients of solid organ transplants. We surveyed recipients in this group who were of child-bearing age.ResultsOne hundred forty of 295 (47%) eligible recipients responded: 44 of these women had attempted pregnancy after transplant, and 31 women gave birth to 47 children. One half of the respondents planned to have children post transplant; 108 of 140 (77%) had no children before transplant. One quarter of the respondents were advised against pregnancy by their physician, and 33% of these women found a new physician to support their pregnancy. Rates of miscarriage (27%), rejection (21%), and prematurity (65%) were higher than expected. Infections were rare, and no birth defects or noteworthy health problems in the offspring were reported.ConclusionOverall, pregnancy appears to be safe following solid organ transplantation, but careful monitoring and counselling are recommended.     

Pregnancy after organ transplant

The frequency and variety of solid organ transplantation in reproductive-age women increases each year. Pregnancy is no longer contraindicated in transplant recipients provided that their graft is functioning well and they are in good general health. Physicians who care for pregnant transplant recipients should be aware of the surmounting data that are available in the literature and through registries of maternal, fetal, and neonatal risks and complications as well as outcome data. Newer immunosuppressive agents preserve graft function and registry data attest to their safety in pregnancy.For optimal maternal and neonatal outcomes, a multispecialty care approach that includes the obstetrician/maternal-fetal specialist,transplant team, anesthesiologist, and neonatal team is prudent when caring for pregnancies after organ transplantation.     

Outcome of pregnancy in renal allograft recipients

Objective  To evaluate risk factors affecting pregnancy, perinatal outcomes and graft condition in women who underwent renal transplantation. Methods  Retrospective study of 34 pregnancies in 28 renal recipients followed in a single tertiary center from January 1989 to January 2007. Main outcome measures  Pregnancy outcome, kidney allograft function, maternal complications and perinatal outcomes were evaluated in these patients. Results  Mean maternal age at time of pregnancy was 27 ± 5.1 years (18–37) and the interval between transplant and pregnancy varied between 1 and 134 months (mean 51.3 ± 34.2). Most pregnant women (25/28) were submitted to triple immunosuppression during the entire pregnancy. The fetal outcome included 27 live births (79.4%), 2 stillbirths (5.9%), 3 spontaneous abortions (8.8%) and 2 therapeutic abortions (5.9%). The most frequent maternal complications were hypertension in 18 pregnancies, 2 of which ended in pre-eclampsia; urinary tract infections in 10 pregnancies; gestational diabetes mellitus in 3, anemia in 3 and 2 acute graft rejections. The major fetal complications observed consisted of four (13. 8%) intrauterine growth restrictions and two (6.9%) stillbirths. Vaginal delivery occurred in 10 women (34.5%); in the other 19 (65.5%), a cesarean section was performed. Of the 27 successful pregnancies, 11 (40.7%) resulted in term deliveries and 16 (59.3%) in preterm deliveries (range 31–39 weeks). The mean birth weight of the offspring was 2,465 g (range 1,300–3,530). There were no major perinatal complications, but two allograft rejections occurred after pregnancy. Conclusions  This series results are in agreement with those in other studies. Even though pregnancy does not seem to adversely affect short-term renal allograft function, risks of obstetric and perinatal complications seem to be increased. Further studies of long term graft function and pediatric follow-up are needed.     

Immunosuppressant therapy in pregnant organ transplant recipients

Transplant recipients are becoming pregnant with increasing frequency, and successful pregnancy outcomes have now been reported for women with all types of solid organ transplants. To prevent rejection of the transplanted organ, these patients are maintained on a life-long immunosuppressive regimen that must also be continued through pregnancy. Controlled human studies of the safety of these drugs have not been conducted, and knowledge regarding the pharmacokinetics of these medications in pregnancy is limited. Significant experience and safety data regarding the use of some of the more common immunosuppressants in pregnancy have, however, been accumulated from large case series and national registries. These observational studies suggest that successful pregnancy outcomes are possible in female organ transplant recipients, although sporadic adverse outcomes have been reported after immunosuppressant use in pregnancy. In this chapter, we will outline the information available regarding the use of immunosuppressive medications in pregnant transplant recipients as well as general concepts regarding fetal exposure to immunosuppressants.     

Nierentransplantation und Schwangerschaft

About 10% of renal transplant patients are in the reproductive age and one out of fifty in that group becomes pregnant. The pregnancy itself does not worsen the prognosis of the transplant function. The main problem is the high rate of preterm deliveries with a mean gestational age of 36 weeks and a mean birth weight of about 2500 g. In 10 to 20% the birth weight is below 1500 g and in 20–30% there is an intrauterine growth restriction, without any focus on one special immunosuppressive regimen. Kreatinine blood levels >1,4 mg/dl and time less than 1–2 years between transplantation and pregnancy as well as preexistent hypertonia are predictive factors for a higher risk for low birth weight, postnatal mortality and postpartum graft rejection. Immunosuppressive therapy has to be maintained during pregnancy to stabilize graft function. Experts in the fields of transplantation, antenatal care, obstetrics and perinatal medicine should together take care of these high risk pregnancies.     

A review on pregnancy after intestinal transplantation

The largest experience of pregnancy after solid organ transplantation is recorded in renal and liver recipients. Intestinal/multivisceral transplantation has shown steady improvements in graft and patient survival over the past 20 years and is rapidly becoming more established: the first pregnancy after this procedure was described 10 years ago, and so far eight cases of pregnancies with 100% successful live births have been reported worldwide. Specifically to this procedure, there are 2 factors to be considered in case of pregnancy: absorptive function of transplanted bowel and higher need of immune-suppressants. Close monitoring of renal function and of the graft by endoscopies and biopsies can be considered during the pregnancy to prevent episodes of rejection or enteritis, preserving the fetus by temporary malnutrition. As more intestinal transplant patients are surviving and regaining reproductive function, it is important to report this option to female recipients and to their health-care professionals.     

Pregnancy and liver transplantation

To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential.     

Risk factors for renal allograft survival in patients receiving cyclosporine immunosuppression.

BACKGROUND AND PURPOSE: Although cyclosporine (CsA) has been widely used in renal transplantation for more than 10 years, no large series of renal transplant patients has been studied in southern Taiwan. The purpose of this retrospective cohort study was to investigate the risk factors for graft survival in renal transplant recipients. METHODS: From August 1987 to January 1998, 101 primary cadaveric renal transplantations were performed. The minimum follow-up period was 1 year. CsA and prednisolone were initially used as immunosuppressive agents in all patients. Use of lower doses of CsA to reduce CsA trough level (50-99 ng/mL) in hepatitis B surface antigen (HBsAg)-positive recipients was attempted at 6 months after transplantation. RESULTS: Graft actuarial survival rates at 1, 5, and 10 years posttransplantation were 89%, 75%, and 57%, respectively. Acute rejection and increased recipient age were found to be significant risk factors (p < 0.05) affecting graft survival, with hazard ratios of 5.20 and 1.74, respectively, by multivariate analysis using a Cox proportional hazards model. Hepatitis B and/or hepatitis C infection had no influence on graft survival. CONCLUSIONS: In this series of cadaveric renal allograft patients, the risk factors affecting allograft survival were acute rejection and recipient age.     

Fertility and reproductive disorders in female solid organ transplant recipients

Solid organ transplantation can prolong the life of individuals with end-stage diseases that affect the kidney, liver, lung, heart, and pancreas. The improved survival of transplant recipients has led to increased attention on quality of life issues, including controlling fertility and having children. Perturbations of the hypothalamic-pituitary-ovarian axis in women with chronic renal failure or severe hepatic dysfunction result in anovulation and reduced fertility. Most often, fertility is restored with successful organ transplantation and good overall health. Although there are case reports of children born subsequent to assisted reproductive technologies (ART) in female transplant recipients, the approach to infertility in this population has not been described. Recognizing the unique medical, ethical, and psycho-social concerns involved in treating infertile female transplant recipients, reproductive endocrinologists must work with a multi-disciplinary team to ensure a successful pregnancy outcome without compromising graft function or maternal health. The primary goal of ART is a singleton pregnancy without complications, such as ovarian hyperstimulation syndrome, that pose greater risks in transplant recipients.     

Pregnancy outcome in liver transplant recipients

OBJECTIVE: To evaluate pregnancy course, complications, and outcomes in liver transplant recipients. METHODS: We conducted a retrospective review of 38 pregnancies conceived between 1992 and 2002 in 29 women who underwent liver transplantation at Mount Sinai Medical Center. RESULTS: The most common primary liver disease was autoimmune hepatitis. All patients were on immunosuppressive regimens that included cyclosporine A or tacrolimus. There were four spontaneous first-trimester abortions and ten first-trimester terminations for worsening liver function. The interval from transplantation to pregnancy was shorter in the group that had abortions and terminations (24.4 +/- 24.3 months) as compared with the group that had live births (47.8 +/- 28.7 months), P =.02. There were 24 live births to 20 patients. The mean gestational age at delivery was 36.4 weeks, and the mean birth weight was 2762 g. Pregnancy complications included preeclampsia (20.8%), chronic hypertension (20.8%), hemolysis, elevated liver enzymes, low platelets syndrome (8.3%), creatinine 1.3 mg/dL or more (25.0%), anemia (33.3%), diabetes (37.5%), cesarean delivery (45.8%), preterm birth less than 37 weeks (29.2%), intrauterine growth restriction (16.7%), and biopsy-proven graft rejection during pregnancy (16.7%). There were no intrauterine or neonatal deaths. All 5-minute Apgar scores were greater than 7. Four minor congenital anomalies were noted. Before 1997, there were five maternal deaths, 10-54 months after pregnancy. Pregnancy complications in our population were more common in those patients who delivered from 1992 to 1997 than in those who delivered from 1998 to 2002. CONCLUSION: Pregnancy planned at least 2 years after liver transplantation with stable allograft function can have excellent maternal and neonatal outcome.     

Pregnancy outcome after renal allograft transplantation: 15 years experience

OBJECTIVE: To present our 15 years' experience in the management of 67 pregnancies in renal allograft recipients in Egypt. METHODS: A retrospective study of 67 pregnancies that occurred in 41 renal allograft recipients over the last 15 years. The study was performed in Department of Obstetrics & Gynecology, and Nephrology & Urology Center at Mansoura University, Egypt. RESULTS: Gestational diabetes occurred in 5.7%, infection in 13.4% and proteinuric hypertension in 19.2% of pregnancies. Graft dysfunction and obstructive uropathy occurred in 30.7% and 9.6% of pregnancies, respectively, but no episodes of graft rejection were reported. Pre-term labour was found in 40.9% and fetal growth retardation occurred in 19.2% of pregnancies. Perinatal mortality was in the order of 9.6%. Pregnancy outcome was better in non-cyclosporine group, in non-proteinuric hypertensive groups and in repeated pregnancies compared to the counter groups. CONCLUSION: Although pregnancy in renal transplant recipients is high-risk, successful outcome is expected for singleton pregnancy and is even better with repeated pregnancies in those cases with stable and good graft function. This satisfactory outcome is generally achieved if the graft is stable and the post-transplant interval is more than 2 years.     

Management of pregnancy in pancreas alone transplant recipient complicated with stage-4 chronic renal insufficiency and superimposed pre-eclampsia: Case report and literature review

Objective

With the prolonged life expectancy in solid organ transplant recipients, their quality of life and fertility desire become of particular concern. Pregnancy in pancreas-alone transplantation, although rare and complicated to manage, is not impossible anymore. We here report such a case with literature review to address this issue.

Successful pregnancy outcome in a lung transplant recipient with tacrolimus immunosuppression. A case report

BACKGROUND: The use of tacrolimus (FK506, PROGRAF) in pregnant lung transplant recipients has been very rarely reported. CASE: A 32-year-old woman, gravida 1, para 0, had previously undergone a unilateral lung transplant secondary to pulmonary fibrosis. Four years later she spontaneously conceived. During pregnancy, she was maintained on an immunosuppressive regimen of tacrolimus and prednisone. Bi-weekly pulmonary function testing remained unchanged until 34 weeks' gestation. At that time, labor was induced due to concern for allograft rejection. A healthy, 2,208-g, female infant was born via an uncomplicated vaginal delivery. Postpartum transbronchial biopsy showed minimal acute cellular rejection. CONCLUSION: Lung transplant recipients may achieve successful pregnancy outcomes with the use of tacrolimus.