Pregnancy after transplant in the older adolescent: Anticipatory guidance for the pediatric provider.

BACKGROUND: Healthcare providers who care for adolescent and young adult transplant recipients should be aware of contraception counseling and potential for pregnancy in this at-risk cohort. METHODS: This paper will review contraceptive options in general for transplant recipients. There will also be a review of common immunosuppressive medications and their risk profile regarding pregnancy after transplantation. Data from the Transplant Pregnancy Registry International were analyzed looking at recipients conceiving under the age of 21 and were compared to overall pregnancy outcomes. RESULTS: Overall pregnancy outcomes in recipients under the age of 21 are like the adult cohort. CONCLUSION: It is imperative to provide contraception counseling to the adolescent and young adult and inform their caregiver that pregnancy can happen if the recipient is sexually active. Pregnant adolescent and young adult transplant recipients should be followed by a multidisciplinary team to assure a positive outcome for the recipient, transplant, and neonate.

Society for Maternal-Fetal Medicine Consult Series #66: Prepregnancy evaluation and pregnancy management of patients with solid organ transplants.

The rate of solid organ transplant in reproductive-aged patients has increased in the past 3 decades. Concurrently, the range of medical immunosuppressive agents has increased, making it safer for reproductive-aged individuals who have received transplants to attempt and continue a pregnancy. In this Consult, we review the general considerations and contemporary approach to medical and obstetrical management of pregnant solid organ transplant recipients, discuss the perinatal outcomes and incidence of graft rejection specific to the most common types of organ transplants, and provide management recommendations based on the available evidence. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend that all solid organ transplant recipients capable of pregnancy be offered prepregnancy counseling as part of the pretransplant evaluation and before any posttransplant pregnancy (Best Practice); (2) we recommend deferring pregnancy for at least 1 year (except for lung transplant recipients in which case a 2-year deferral is recommended) following solid organ transplant or any episode of acute cellular rejection (GRADE 1B); (3) we recommend that solid organ transplant recipients have stable allograft function and optimal control of chronic medical comorbidities before attempting pregnancy (GRADE 1B); (4) we recommend that solid organ transplant recipients of reproductive age use highly effective contraception when on mycophenolate or other immunosuppressive agents with known teratogenic risk (GRADE 1A); (5) we recommend that solid organ transplant recipients contemplating pregnancy transition to an appropriate immunosuppressive regimen before attempting pregnancy to establish stable medication dosing and allograft function (GRADE 1C); (6) we recommend close monitoring of serum drug levels during pregnancy and the postpartum period to guide immunosuppressive therapy dosing (GRADE 1C); (7) we recommend that solid organ transplant recipients who are pregnant or contemplating pregnancy receive all indicated vaccinations before and during pregnancy (GRADE 1C); (8) given the risk of fetal and neonatal sequelae secondary to cytomegalovirus infection in pregnancy, we suggest that solid organ transplant recipients ideally complete any indicated antiviral prophylaxis or treatment before pursuing pregnancy (GRADE 2B); (9) we recommend daily low-dose aspirin prophylaxis to reduce the risk for preeclampsia in pregnant solid organ transplant recipients and to reduce the risk for renal allograft failure in renal transplant recipients (GRADE 1C); (10) as for all pregnant people, we recommend that pregnant solid organ transplant recipients have access to mental health specialists and receive screening for depression during pregnancy and the postpartum period (Best Practice); (11) because of the increased incidence of fetal growth restriction and common coexisting medical morbidities, we recommend serial assessment of fetal growth every 4 to 6 weeks throughout gestation after the anatomic survey (GRADE 1C); (12) we suggest antenatal surveillance from 32 weeks of gestation unless other fetal or maternal factors are identified in which case initiation of surveillance at an earlier gestational age is indicated (GRADE 2C); (13) we recommend that renal function be assessed before pregnancy or in early pregnancy in all solid organ transplant recipients (kidney and non-kidney) (GRADE 1C); (14) we suggest individualized delivery timing for pregnant solid organ transplant recipients and to consider delivery at between 37+0/7 and 39+6/7 weeks of gestation; in the absence of other indications, we suggest delivery by 39+6/7 weeks gestation for pregnant solid organ transplant recipients (GRADE 2B); (15) given that a trial of labor is associated with a high success rate and lower neonatal morbidity without increasing maternal morbidity or compromising graft survival, we recommend that cesarean delivery be reserved for medical obstetrical indications in solid organ transplant recipients (GRADE 1C); (16) we recommend that blood pressure targets in pregnant renal transplant recipients with chronic hypertension follow guidelines for nonpregnant recipients with a target blood pressure of ≤130/80 mm Hg (GRADE 1C); (17) we recommend monthly urine cultures to screen for asymptomatic bacteriuria with treatment if positive to protect the graft in pregnant renal transplant recipients (GRADE 1C); (18) we recommend that pregnancies in pancreas-kidney transplant recipients be managed in a similar way as those of renal transplant recipients alone (GRADE 1C); (19) we recommend characterizing the underlying condition that led to liver transplantation and assessing baseline renal function in pregnant liver transplant recipients. (GRADE 1C); (20) because of the cardiovascular demand of pregnancy and the unique physiological implications of cardiac transplantation, we recommend that pregnant heart transplant recipients receive multidisciplinary care with cardiology, cardiac and/or obstetrical anesthesiology, and maternal-fetal medicine specialists (Best Practice); and (21) we recommend careful delivery planning to minimize hemodynamic stress (including considering operative vaginal delivery to minimize Valsalva) and suggest continuous intrapartum or intraoperative electrocardiographic monitoring for heart transplant recipients (GRADE 1C).

Reproductive health after thoracic transplantation: An ISHLT expert consensus statement.

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.

Promoting safe sexual practices and sexual health maintenance in pediatric and young adult solid organ transplant recipients.

The majority of Americans make their sexual debut during their adolescent years. Preventing pregnancy and STI during this period is vital to ensuring health and safety. As survival has improved after pediatric SOT, chronically immunosuppressed adolescents seek guidance in their medical home on matters of sexual health. Transplant practitioners often do not feel equipped to fully address these needs. This review serves as an introductory sexual preventive care resource for adolescent and young adult (AYA) SOT recipients. First, we review data on safety, efficacy, and use of contraceptive options currently available for transplant recipients with child-bearing potential. Then, we suggest a personalized sexual health discussion focusing on the diagnosis and prevention of STIs in adolescent and young adult transplant recipients. Finally, we present recommendations for STI screening of asymptomatic patients, use of index of suspicion and diagnostic testing in symptomatic patients, and opportunities to optimize STI prevention strategies. Data compiled from studies of adult SOT recipients, general population studies, and published guidelines are often extrapolated for use, as limited data exist in AYA SOT recipients. This informational dearth underscores the need for future research to better characterize the unique needs of AYA SOT recipients.

Pregnancy outcomes in heart transplant recipients.

BACKGROUND: The population of female heart transplant recipients of reproductive age is growing, and counseling regarding reproductive decisions is important. We describe maternal and fetal outcomes of pregnancy in the Transplant Pregnancy Registry International. METHODS: Data regarding pregnancies between 1987 and 2016 were collected via questionnaires, phone interviews, and medical records review. Demographics, comorbidities, changes in immunosuppressive regimens, rejection episodes during pregnancy, data on maternal retransplants, and deaths were recorded. RESULTS: A total of 91 patients reported 157 pregnancies. Mean maternal age at conception was 27 ± 5.6 years. The most common indications for transplant were congenital heart disease (22%) and viral myocarditis (18%). Average transplant to conception interval was 7 ± 6.1 years. Immunosuppression was calcineurin inhibitor-based in almost all patients, with 20% of recipients taking mycophenolic acid (MPA) while pregnant. Complications during pregnancy included pre-eclampsia (23%) and infections (14%). Rejection was reported during 9% of pregnancies and within 3 months postpartum in 7%. Livebirths occurred in 69%, with no neonatal deaths. Miscarriages occurred in 26% of pregnancies, 49% of which had MPA exposure. Mean follow-up post pregnancy was 8.9 ± 6.5 years. At last follow-up, 30 recipients had died, an average of 9.4 ± 6.2 years after pregnancy. The most common causes included allograft vasculopathy and rejection. CONCLUSIONS: This is the largest reported series of pregnancies in heart transplant recipients and demonstrates that two thirds of pregnancies reported are successful. MPA exposure is associated with increased risk of teratogenicity and miscarriage. Pre-pregnancy counseling should include discussions of risk of MPA exposure, rejection, graft dysfunction, and maternal survival.

The 25th Anniversary of the National Transplantation Pregnancy Registry.

The National Transplantation Pregnancy Registry (NTPR) is a unique resource for comprehensive information about parenthood after transplantation. To date, 1461 female solid organ transplant recipients with 2609 pregnancies and 879 male recipients who fathered 1358 pregnancies have participated in the NTPR. Over the first 25 years of the NTPR, pregnancy after transplantation has progressed from a situation where termination was once advised, to a topic of pre-transplant counselling with likelihood for success if established criteria are met. Pregnancy after transplantation remains high-risk; it should be carefully considered, planned, and monitored by a multidisciplinary health care team. Pregnancy and maternal outcomes vary based on multiple factors, especially on the type of organ transplanted and the pre-pregnancy graft function. As an open-ended condition-based study, the NTPR accumulates a vast amount of data that is used for comparisons that measure the reliability and benefits of treatments and for developing state-of-the-art management guidelines based on a review of current practices at participating transplant centers. NTPR data analyses have contributed to quantifying issues surrounding post-transplant parenthood such as location of the transplanted organ in proximity to the developing fetus, the safety of various immunosuppressive regimens for pregnancy and fatherhood, the teratogenicity of maternal exposure to mycophenolate during pregnancy, the advisability and timing of planning a posttransplant pregnancy, the dosing of medications during pregnancy, the incidence and treatment of comorbidities during pregnancy, and the effect of in utero or breast milk exposure to immunosuppressants on the developing child. As the face of transplantation evolves, the NTPR will continue to collect and disseminate information to assist recipients and their healthcare providers in making informed decisions about the advisability of pregnancy and care for those who choose to become parents after a solid organ transplant. To insure the continued success of our study, all transplant centers and recipients are encouraged to contact the NTPR to report any post-transplant pregnancy.

Update on the Teratogenicity of Maternal Mycophenolate Mofetil.

Mycophenolic acid (MPA) products, namely mycophenolate mofetil and mycophenolate sodium, are immunosuppressive medications used to prevent rejection in solid organ transplant recipients and to treat various autoimmune disorders. Mycophenolate therapy is considered to be teratogenic based on observational studies of pregnancies exposed to MPA, which demonstrated an increased incidence of miscarriages in pregnancies exposed to MPA during their first trimester and a pattern of birth defects in the offspring of some pregnancies exposed to MPA. Herein, we have detailed case and series reports in a comprehensive literature review summarizing what is known to date regarding fetal exposure to MPA. Based on evidence from the literature, results of postmarketing surveillance, and information from registries such as the National Transplantation Pregnancy Registry in the United States, it is advised that pregnancy be avoided by women taking MPA. Preconception planning offers the opportunity to explore the alternatives to protect the mother, her transplanted organ, and minimize fetal risk. How to proceed in cases of unplanned pregnancies exposed to MPA in transplant recipients is a complex issue. Research involving large epidemiological studies is expected to be sparse as women heed the warnings about becoming pregnant on MPA. Published recommendations for managing MPA in women of childbearing potential include discontinuing the medication prior to conception, switching the MPA to another medication, or discontinuing the MPA when the pregnancy is discovered.

Breast-feeding after transplantation.

Transplantation affords recipients the potential for a full life and, for some, parenthood. Female transplant recipients must continue to take immunosuppression during pregnancy and breast-feeding. This article reviews case and series reports regarding breast-feeding in those taking transplant medications. Avoidance of breast-feeding has been the customary advice because of the potential adverse effects of immunosuppressive exposure on the infant. Subsequent studies have demonstrated that not all medication exposure translates to risk for the infant, that the exposure in utero is greater than via breast milk and that no lingering effects due to breast-feeding have been found to date in infants who were breast-fed while their mothers were taking prednisone, azathioprine, cyclosporine, and/or tacrolimus. Thus, except for those medications where clinical information is inadequate (mycophenolic acid products, sirolimus, everolimus, and belatacept), the recommendation for transplant recipients regarding breast-feeding has evolved into one that is cautiously optimistic.

Immunosuppressive drugs and fetal outcome.

Successful pregnancies have been reported in all types of solid-organ transplant recipients on a variety of immunosuppressive regimens. Immunosuppression is essential to maintain the transplanted organ and maternal health, thus the safety of these medications continues to be studied. This article reviews information in the literature and data from the National Transplantation Pregnancy Registry (NTPR) in the United States related to immunosuppressive medication and pregnancy. Although most maintenance immunosuppressive regimens have not been shown to affect the outcome of posttransplant pregnancies, mycophenolic acid products are associated with an increased incidence of spontaneous abortion and an increase in the incidence and a specific pattern of birth defects. When counseling transplant recipients about the prospect and safety of pregnancy, the health of the mother, her graft, and the developing fetus must all be taken into account.

Complex chimerism: pregnancy after solid organ transplantation.

Thousands of women with organ transplantation have undergone successful pregnancies, however little is known about how the profound immunologic changes associated with pregnancy might influence tolerance or rejection of the allograft. Pregnant women with a solid organ transplant are complex chimeras with multiple foreign cell populations from the donor organ, fetus, and mother of the pregnant woman. We consider the impact of complex chimerism and pregnancy-associated immunologic changes on tolerance of the allograft both during pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely dynamic during pregnancy and affected by the influx of fetal microchimeric cells, HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T cell tolerance to fetal cells, and fetal minor histocompatibility antigens. Further research is necessary to understand the complex immunology during pregnancy and the postpartum period of women with a solid organ transplant.

Outcomes of pregnancies fathered by solid-organ transplant recipients exposed to mycophenolic acid products.

CONTEXT-In women, exposure to mycophenolic acid products during pregnancy results in an increase in both miscarriages and birth defects in the live born. OBJECTIVE-To describe the outcomes of pregnancies fathered by transplant recipients who were being maintained on mycophenolic acid products at the estimated time of conception and compare these pregnancies with pregnancies in the general population. METHODS- Data were collected by the National Transplantation Pregnancy Registry via questionnaires, telephone interviews, and medical records. RESULTS -One hundred fifty-two male transplant recipients with exposure to mycophenolic acid products fathered 205 pregnancies (208 outcomes, including 3 pairs of twins). Pregnancy outcomes included 194 live births with a prematurity rate of 10.8%, 14 spontaneous abortions, and no therapeutic abortions or stillbirths. Among the live births, 6 malformations were reported, for an incidence of 3.1%. No pattern of malformations was identified. CONCLUSION-The outcomes of pregnancies fathered by transplant recipients treated with mycophenolic acid products appear similar to outcomes in the general population.

Pregnancy after solid organ transplantation: a guide for obstetric management.

Successful pregnancy outcomes are possible among all solid organ transplant recipients. Patients should be fully counseled regarding the potential adverse fetal outcomes, including prematurity and low birth weight. Transplant recipients are at an increased risk for both maternal and neonatal complications and should be seen by a high-risk obstetrician in conjunction with their transplant teams. Ideally, preconception counseling begins during the pretransplantation evaluation process. Initiating contraception early after transplantation is ideal, and long-acting reversible methods such as intrauterine devices and subdermal implants may be preferred. Pregnancy should be avoided for at least 1 year after transplantation to limit the potential risks of early pregnancy that may adversely affect both allograft function and fetal well-being. Hypertension, diabetes, and infection should be monitored and treated to minimize fetal risks during pregnancy. Maintenance of current immunosuppression is usually recommended, with the exception of mycophenolic acid products, which (when possible) should be discontinued before conception and replaced with an alternative medication. Throughout pregnancy, immunosuppression must be maintained at appropriate dosing to avoid graft rejection. During labor and delivery, cesarean delivery should be performed for obstetric reasons only. A multidisciplinary team should manage pregnant transplant recipients before, during, and following pregnancy. Breastfeeding and long-term in utero exposure to immunosuppressants for offspring of transplant recipients continue to require further investigation but have been encouraged by recent reports. Continued reporting of post-transplantation pregnancy outcomes to the National Transplantation Pregnancy Registry is highly encouraged.

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.