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.

Pregnancy after deceased donor vs living donor kidney transplant: associated obstetric and graft outcomes.

BACKGROUND: Outside of pregnancy, recipients of a deceased donor kidney transplant experience worse graft and overall survival compared with recipients of a living donor kidney transplant. In pregnancy, it is unknown whether the type of donor graft modifies either graft health in the peripartum period or pregnancy outcomes. OBJECTIVE: This study aimed to define characteristics and outcomes in pregnancy based on donor type in kidney transplant recipients. STUDY DESIGN: This was a retrospective cohort study of adult kidney transplant recipients who received their graft between 2000 and 2019 with a subsequent pregnancy enrolled in the Transplant Pregnancy Registry International. The primary outcome was graft loss within 2 years of delivery. The secondary outcomes included severe maternal morbidity and neonatal composite morbidity. Univariate, multivariable logistic regression, and Cox proportional-hazards models were constructed for statistical analysis, with recipients of a living unrelated donor as the referent. RESULTS: Overall, 638 pregnant patients after kidney transplant had pregnancy outcomes that met our inclusion criteria. Of these patients, 168 (26.3%) received a graft from a deceased donor, 310 (48.6%) received a graft from a living related donor, and 160 (25.1%) received a graft from a living unrelated donor. Recipients of a deceased donor were more likely to be nulliparous, have an unplanned pregnancy, and self-identify as non-White. Moreover, recipients of a deceased donor were more likely to experience urinary tract infections (deceased donor: 21.8%; living related donor: 10.1%; living unrelated donor: 20.6%; P=.018). Severe maternal morbidity (deceased donor: 3.4%; living related donor: 2.8%; living unrelated donor: 7.2%) and neonatal composite morbidity (deceased donor: 8.4%; living related donor: 17.1%; living unrelated donor: 14.4%) did not differ by donor type. Deceased donor transplant was associated with graft loss within 2 years of delivery (deceased donor: 6.7%; living related donor: 3.7%; living unrelated donor: 1.3%; adjusted odds ratio, 7.52; 95% confidence interval, 1.53-60.8) and long-term graft loss from transplant (adjusted hazard ratio, 2.08; 95% confidence interval, 1.10-3.95). CONCLUSION: Although our study demonstrated an association between deceased donor transplant and graft loss after pregnancy, it did not provide evidence that pregnancy itself causes graft loss. Recipients of a deceased donor kidney transplant should not be discouraged from pursuing pregnancy based on their donor type, but these patients should undergo preconception counseling with a discussion of their individualized obstetrical and graft risks, close intrapartum monitoring for infection and hypertensive disease, and continued surveillance for at least 2 years after delivery with a multidisciplinary obstetrics and transplant team.

Outcomes With Belatacept Exposure During Pregnancy in Kidney Transplant Recipients: A Case Series.

BACKGROUND: Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation confers risks to the recipient, transplant, and fetus, including gestational hypertension, preeclampsia, gestational diabetes, transplant dysfunction, preterm labor, and low birthweight infants. Additionally, mycophenolic acid (MPA) products are teratogenic. Literature evidence regarding belatacept, a selective T-cell costimulation blocker, during pregnancy and while breastfeeding is extremely limited. When female transplant recipients on a belatacept-based regimen are desirous of pregnancy or at the time of conception, transplant providers manage the immunosuppression regimen in 1 of 2 ways: (1) switch both belatacept and MPA to a calcineurin inhibitor-based regimen with or without azathioprine, which is the more common practice but requires several modifications, having potential negative outcomes; or (2) only switch MPA to azathioprine while continuing belatacept. METHODS: This case series includes 16 pregnancies in 12 recipients with exposure to belatacept throughout pregnancy and while breastfeeding. Patient information was obtained from several sources, including Transplant Pregnancy Registry International, providers at Emory University, and Columbia University, as well as literature review. RESULTS: Pregnancy outcomes included 13 live births and 3 miscarriages. No birth defects or fetal deaths were reported in any of the live births. Seven infants were breastfed while their mothers continued belatacept. Outcomes appear comparable to those documented with the administration of calcineurin inhibitors. CONCLUSIONS: This case series provides data supporting the continued administration of belatacept during pregnancy. Additional research will assist in developing better guidelines to counsel female transplant recipients on belatacept desiring to pursue pregnancy.

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.

Emergent prelabor cesarean delivery in solid organ transplant recipients: associated risk factors and outcomes.

BACKGROUND: Pregnancies after solid organ transplant are at a higher risk of antepartum admission and pregnancy complications including cesarean delivery. Emergent prelabor cesarean delivery is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well-understood. OBJECTIVE: This study aimed to characterize the risk factors and outcomes of emergency prelabor cesarean delivery in kidney and liver transplant recipients. STUDY DESIGN: This was a retrospective cohort study of all kidney and liver transplant recipients at >20 weeks gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required emergency prelabor cesarean delivery were compared with those admitted antepartum who underwent nonemergent birth. The primary outcomes were severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity. RESULTS: Of 1979 births, 181 pregnancies (188 neonates) with antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean delivery compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was nonreassuring fetal heart tracing (44 pregnancies /51 emergent deliveries = 86%). Pregnant people who underwent emergent prelabor cesarean delivery were less likely to deliver at a transplant center (37.3% vs 41.5%; P=.04) and had increased rates of chronic hypertension (33.3% vs 16.2%; P=.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%; P=.84), though there was an increase in surgical site infection in the emergent prelabor cesarean delivery cohort (3.9% vs 0%; P=.02). Among those with emergent prelabor cesarean delivery, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%; P<.001) with earlier gestational age at delivery (33.4 vs 34.7 weeks; P=.02), lower birthweight (1899 g vs 2321 g; P<.001), lower birthweight percentile (30.3% vs 40.6%; P=.03), increased neonatal intensive care unit admission (52.8% vs 35.6%; P=.03), and increased neonatal mortality (11.3% vs 1.5%; P=.002). After adjusting for year of conception, race, hypertensive disorders, and fetal malformations, there was a persistent increased risk of neonatal morbidity (adjusted odds ratio, 3.01; 95% confidence interval, 1.50-6.08; P=.002) associated with emergent prelabor cesarean delivery after transplant. CONCLUSION: Almost one-third of kidney and liver transplant recipients admitted antepartum had an emergency prelabor cesarean delivery, and 63% of this cohort delivered outside of a transplant center. Pregnancies after transplantation should involve multidisciplinary transplant-obstetrics collaboration to ensure optimal antepartum disease management, especially for preexisting hypertension, to prevent and mitigate obstetrical and neonatal morbidity in the setting of emergent cesarean delivery.

Counselling, Research Gaps, and Ethical Considerations Surrounding Pregnancy in Solid Organ Transplant Recipients.

Survival after solid-organ transplantation has improved significantly, and many contemporary transplant recipients are of childbearing potential. There are limited data to guide decision-making surrounding pregnancy after transplantation, variations in clinical practice, and significant knowledge gaps, all of which raise significant ethical issues. Post-transplant pregnancy is associated with an increased risk of maternal and fetal complications. Shared decision-making is a central aspect of patient counselling but is complicated by significant knowledge gaps. Stakeholder interests can be in conflict; exploring these tensions can help patients to evaluate their options and inform their deliberations. We argue that uniform, evidence-based recommendations for pregnancy after solid organ transplantation are needed. Conducting research, including patient-engaged studies, in this area should be priority for the transplant community.

Sex and gender disparity in kidney transplantation: Historical and future perspectives.

Sex and gender disparity exist in various stages of kidney transplantation. Females were found to be less likely to be referred for kidney transplant, complete pre-transplant evaluation, be placed on the waitlist, and receive a kidney transplant compared to their male counterparts. Interestingly, females comprise the majority of living kidney donors. This review explores the biological and psychosocial factors that contribute to sex and gender disparity in kidney transplantation and proposes ways to address the disparity.

Acute kidney injury during pregnancy in kidney transplant recipients.

Pregnancy-related acute kidney injury (AKI) is a public health problem and remains an important cause of maternal and fetal morbidity and mortality. The incidence of pregnancy-related AKI has increased in developed countries due to increase in maternal age and higher detection rates. Pregnancy in women with kidney transplants is associated with higher adverse outcomes like preeclampsia, preterm births, and allograft dysfunction, but limited data exists on causes and outcomes of pregnancy-related AKI in the kidney transplant population. Diagnosis of AKI during pregnancy remains challenging in kidney transplant recipients due to lack of diagnostic criteria. Management of pregnancy-related AKI in the kidney transplant population requires a multidisciplinary team consisting of transplant nephrologists, high-risk obstetricians, and neonatologists. In this review, we discuss pregnancy-related AKI in women with kidney transplants, etiologies, pregnancy outcomes, and management strategies.

Mode of Obstetric Delivery in Kidney and Liver Transplant Recipients and Associated Maternal, Neonatal, and Graft Morbidity During 5 Decades of Clinical Practice.

Importance: Rates of cesarean delivery (CD) are increased among transplant recipients. There is a need to define the indications for CD and associated outcomes among transplant recipients to determine the safest mode of obstetric delivery. Objective: To evaluate the association of mode of obstetrical delivery with maternal and neonatal morbidity among pregnant women who have received a kidney or liver transplant. Design, Setting, and Participants: This registry-based retrospective cohort study used data from the Transplant Pregnancy Registry International, which has recruited participants since 1991 from 289 diverse academic and community settings, mainly in North America. Eligible participants were recipients of a kidney or liver transplant who were aged 18 years or older at the time of a live birth at or later than 20 weeks' gestational age and who delivered between 1968 and 2019. The data were analyzed from April 30, 2020, to April 16, 2021. Exposures: Scheduled CD, a trial of labor resulting in CD (TOL-CD), or a TOL resulting in vaginal delivery (TOL-VD). Main Outcomes and Measures: The primary outcomes were severe maternal morbidity and neonatal composite morbidity. Multivariate regression was conducted to calculate odds ratios (ORs) or ß values and 95% CIs with adjustment for differences in maternal comorbidities and gestational age at delivery. Nonmedical indications for CD are those not associated with decreased morbidity or mortality in the obstetric literature. Results: This study included 1865 women, of whom 1435 were kidney transplant recipients and 430 were liver transplant recipients. The age range of the participants was 18 to 48 years; the median body mass index among the participants was in the normal range, and the median transplant-to-conception interval was more than 2 years. Compared with a scheduled CD, a TOL was not associated with increased severe maternal morbidity among kidney transplant recipients (TOL-CD: adjusted odds ratio [aOR], 1.80 [95% CI, 0.77-4.22]; TOL-VD: aOR, 1.22 [95% CI, 0.57-2.62]) (for liver transplant recipients, the numbers were too small for multivariate modeling). In the adjusted model, a TOL was associated with a decrease in neonatal composite morbidity among kidney transplant recipients who underwent TOL-CD (aOR, 0.52; 95% CI, 0.32-0.82) and TOL-VD (aOR, 0.36; 95% CI, 0.24-0.53) and liver transplant recipients who underwent TOL-VD (aOR, 0.41; 95% CI, 0.19-0.87) but not for TOL-CD (aOR, 0.58; 95% CI, 0.21-1.61). The main factors associated with CD after labor were placental abruption (aOR, 12.96; 95% CI, 2.85-59.07) and pregestational diabetes (aOR 5.44; 95% CI, 2.54-11.68). The rate of CD was 51.6% (741 of 1435) among kidney transplant recipients and 41.4% (178 of 430) among liver transplant recipients. In total, 229 of 459 kidney transplant recipients (49.9%) and 50 of 105 liver transplant recipients (47.6%) had scheduled CDs performed for either a nonmedical indication or a repeated indication, although women with these indications are candidates for a TOL. Conclusions and Relevance: In this cohort study, TOL vs a scheduled CD was associated with improved neonatal outcomes among kidney and transplant recipients and not with increased severe maternal morbidity among kidney transplant recipients. These findings may be used to facilitate multidisciplinary decisions regarding the mode of obstetrical delivery.

Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation.

OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10-15.2). CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.

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.

Belatacept during pregnancy in renal transplant recipients: Two case reports.

Impaired fertility is common among patients with chronic organ failure, including end-stage renal disease (ESRD). Women of childbearing age undergoing transplantation may experience rapid return of fertility. Pregnancy posttransplant presents numerous risks for the patient, fetus, and allograft. Maternal risks include hypertension and preeclampsia. Allograft risks include acute rejection and failure of the organ, and fetal risks include miscarriage, birth defects from immunosuppressants, premature delivery, and low birth weight. Belatacept, a selective T cell costimulation blocker, was approved for use in kidney transplant recipients in the United States in 2011. Little is known about the safety of belatacept during pregnancy in humans. We describe 2 cases of successful pregnancy and delivery with the use of belatacept-based immunosuppression. The Transplant Pregnancy Registry International (TPR) is a voluntary registry for transplant recipients who have had pregnancies or fathered a pregnancy posttransplant. To date, these 2 cases are the only known exposures to belatacept that have been reported to the TPR.

Reproductive health in women following abdominal organ transplant.

Fertility is commonly impaired in women with end-stage kidney and liver disease, although most women will have restoration of fertility within 1 year of transplant. Family planning is therefore critical to discuss with reproductive-aged transplant recipients in the early posttransplant period, in order to ensure timely initiation of contraception, and optimal timing for conception. For women seeking pregnancy, the risks to the mother, graft, and baby should be discussed, including evaluation of immunosuppression safety and potential for adjusting medications prior to conception. With an increasing number of transplant patients now breastfeeding, immunosuppression safety in lactation continues to carry great importance.

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.