Objectives: Pregnancy posttransplant remains high risk because of potential maternal, fetal, and graft-related complications. We retrospectively evaluated the clinical course, maternal-fetal outcomes, and graft-related events of pregnancies occurring after liver and kidney transplant at our center.
Materials and Methods: We evaluated 3538 kidney transplants and 760 liver transplants performed at Başkent University between November 3, 1975, and November 3, 2024. Female recipients who became pregnant posttransplant were identified through hospital electronic medical records, the transplant database, and obstetric archives. We performed a subgroup analysis on pediatric transplant recipients who underwent transplant at age <18 years and later became pregnant in adulthood.
Results: Among 41 transplant recipients who experienced pregnancy, 20 were liver transplant and 21 were kidney transplant recipients. Each patient had 1 pregnancy. Mean maternal age at delivery was 31 years (range, 24-38 years), and mean interval between transplant and delivery was 9.9 years (range, 2-22 years). Liver transplant recipients received calcineurin inhibitor-based immunosuppression, whereas kidney transplant recipients received calcineurin inhibitors with prednisone, with azathioprine added in selected patients with history of frequent rejection. One patient delivered vaginally; all others underwent cesarean delivery. Maternal complications included hypertension in 1 patient, gestational diabetes in 3 patients, and lower urinary tract infection in 3 patients. One liver transplant recipient with autoimmune hepatitis developed recurrent disease in the early postpartum period and required retransplant. No other significant maternal complications or graft rejection episodes were observed. Mean gestational age was 35.5 weeks (range, 24-39 weeks). All infants were born healthy except 1, who died at 24 weeks of gestation due to placenta previa.
Conclusions: Pregnancy after liver and kidney transplant can be successfully sustained in most patients under appropriate immunosuppressive management and multidisciplinary follow-up. However, these pregnancies should be considered high risk and managed in experienced centers with close obstetric and transplant surveillance.

Key words : Graft survival, Immunosuppression therapy, Kidney transplantation, Liver transplantation, Teratogenic effects

Introduction
Technical advances in liver transplant (LT) and kidney transplant (KT) surgery and the development of new-generation immunosuppression protocols have led to marked improvements in both patient and graft survival rates. Parallel with these clinical achievements, expectations regarding quality of life have increased among female patients who have received transplants during childhood or young adulthood, and the desire to conceive in the posttransplant period has become a more frequently encountered issue in clinical practice. Nevertheless, in this patient population, the potential teratogenic effects of immunosuppression therapies and the possible adverse effect of the physiological resource load of pregnancy on allograft function still represent a critical clinical challenge that requires careful management.^1,2 Although recently published studies in the literature have indicated that pregnancy after organ transplant is usually successful, it also has been demonstrated that the risk of maternal and perinatal complications is significantly higher compared with the general population. Complications such as preterm birth, preeclampsia, gestational diabetes, anemia, and infections can threaten the health of both the mother and the fetus.^2-5 Immunosuppression management during pregnancy requires a delicate balance. Although evidence suggests that calcineurin inhibitors, azathioprine, and low-dose prednisone can be used relatively safely during pregnancy, it has been established that agents such as mechanistic target of rapamycin inhibitors and mycophenolate mofetil must be discontinued prior to conception due to the teratogenic risks associated with these agents. This complex process necessitates close follow-up by a multidisciplinary team including a perinatologist, a transplant surgeon, and relevant specialists (nephrologist/hepatologist).^2,4,6 In this study, we aimed to retrospectively analyze the clinical course, maternal-fetal outcomes, and graft-related clinical events of pregnancies occurring after LT and KT at our center.

Materials and Methods
In this retrospective, single-center observational study, we evaluated a total of 3538 KT surgeries and 760 LT surgeries performed at Başkent University between November 3, 1975, and November 3, 2024. Among this cohort, female patients who experienced pregnancy after transplant were identified through a systematic review of hospital electronic medical records, the transplant database, and obstetric archives (Figure 1). A specific analysis was conducted on 406 pediatric KT recipients and 370 pediatric LT recipients (<18 years at the time of transplant). From this group, patients who underwent transplant during childhood, subsequently reached adulthood, and became pregnant were included in the study. All transplants were performed from living related donors, who were first-degree or second-degree relatives of the recipients. For each pregnancy, the following variables were recorded: maternal age at delivery, time interval between transplant and pregnancy, maintenance immunosuppression regimen (eg, calcineurin inhibitor, prednisone, azathioprine), mode of birth, and gestational age of the newborn. Maternal complications (eg, preeclampsia, gestational diabetes, infection, rejection), obstetric complications (eg, preterm birth, miscarriage of pregnancy), and neonatal outcomes were systematically assessed.

Results
A total of 41 LT and KT recipients experienced pregnancy. Each patient had only 1 pregnancy. Of these 41 participants, 20 were LT recipients and 21 were KT recipients. The mean maternal age at delivery was 31 years (range, 24-38 years). The mean interval between transplant and delivery was 9.9 years (range, 2-22 years) (Table 1). During pregnancy, LT recipients were maintained on a calcineurin inhibitor. Kidney transplant recipients received a calcineurin inhibitor in combination with prednisone; azathioprine was added to the regimen in patients with a history of frequent rejection. One patient delivered birth vaginally, whereas all remaining patients underwent cesarean birth. Regarding maternal complications, 1 patient developed hypertension, which was controlled with medical therapy. Gestational diabetes was diagnosed in 3 patients and was successfully managed with dietary modification in all cases. One patient who had undergone LT for autoimmune hepatitis developed recurrent autoimmune hepatitis in the early postpartum period and subsequently required a second LT. No other mothers experienced significant complications or organ rejection in the early postpartum period. Three patients developed clinically diagnosed lower urinary tract infection; however, no secondary systemic complications occurred. All pregnancies resulted in healthy newborns except one, which was a miscarriage at 24 weeks of gestation due to placenta previa and resulted in the death of the fetus. The mean gestational age of the newborns was 35.5 weeks (range, 24-39 weeks).

Discussion
The main findings of this study indicate that pregnancy after transplant can be successfully sustained in most patients under appropriate follow-up and immunosuppression management; however, preterm birth and certain maternal complications occur with increased frequency. In our study, the mean maternal age at delivery was 31 years, which is consistent with the age range reported in the literature for posttransplant pregnancies. Deshpande and colleagues reported a mean maternal age of 29 years in their meta-analysis,⁴ whereas Marzec and colleagues reported a mean age of 32 years.⁷ The mean interval of 9.9 years between transplant and delivery suggests that most patients planned pregnancy after achieving stable graft function, and such details support the notion that an adequate waiting period before conception may be important for maternal and fetal safety. Regarding immunosuppression management, the continuation of calcineurin inhibitor-based regimens in LT recipients and the combination of a calcineurin inhibitor with low-dose corticosteroids (with or without azathioprine) in KT recipients is consistent with recommended maintenance strategies during pregnancy.⁸ The addition of azathioprine in KT recipients with a history of frequent rejection can be considered an individualized approach to prioritize maternal safety. The absence of major teratogenic complications associated with these regimens in our cohort suggests that these protocols are tolerable in selected patients. In terms of obstetric outcomes, cesarean birth was the mode of birth in most patients. This finding is consistent with previously published studies that have reported higher cesarean rates in posttransplant pregnancies compared with the general population, largely due to concerns regarding maternal and graft safety.^1,5 The fact that only 1 patient delivered birth vaginally indicates that cesarean birth remains the predominant approach in this patient group in clinical practice. With respect to maternal complications, 1 patient developed hypertension, which was controlled with medical therapy. Gestational diabetes was diagnosed in 3 patients, which was managed with dietary modification in all cases. Marson and colleagues have previously highlighted the increased incidence of hypertensive disorders in posttransplant pregnancies,⁹ whereas Zeevi and colleagues have reported that gestational diabetes could be effectively managed conservatively in most patients.¹⁰ Notably, these types of complications did not result in severe maternal morbidity in our cohort.^9,10 One patient who had undergone LT for autoimmune hepatitis developed recurrent autoimmune hepatitis in the early postpartum period, which required a second LT. This finding suggests that underlying autoimmune disease may reactivate in the postpartum period.^11,12 Accordingly, closer postpartum monitoring is warranted, particularly in transplant recipients with autoimmune etiologies. The absence of significant rejection or serious complications in other mothers supports the notion that pregnancy can be safely sustained in most patients under careful surveillance. Three patients developed clinically diagnosed lower urinary tract infections, but no secondary systemic complications occurred. This finding indicates that although infection risk may be increased in immunosuppressed pregnant patients, early diagnosis and appropriate treatment can prevent severe outcomes. In terms of neonatal outcomes, the mean gestational age was 35.5 weeks, reflecting the tendency toward preterm birth that has been previously reported in posttransplant pregnancies.⁴ One infant in our study died at 24 weeks of gestation due to placenta previa, whereas all other infants were born healthy. Nevertheless, the single-center design and limited sample size of this study restrict the generalizability of these findings. Overall, our results demonstrate that pregnancy after LT and KT is feasible under appropriate immunosuppression management and multidisciplinary follow-up; however, these posttransplant pregnancies carry an elevated risk of preterm birth and certain maternal complications. Therefore, this patient group requires preconception counseling, close obstetric monitoring, and careful postpartum follow-up.

Conclusions
This study demonstrated that pregnancy after LT and KT can be sustained in most patients under appropriate immunosuppression management and multidisciplinary follow-up. However, given the increased frequency of preterm birth and certain maternal complications, pregnancies among this patient group should be considered high-risk pregnancies. Our findings support the need for close obstetric and transplant monitoring of posttransplant pregnancies in experienced centers.