Pregnancy after liver transplantation with tacrolimus immunosuppression: a single center's experience update at 13 years

BACKGROUND: Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. METHODS: All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. RESULTS: Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. CONCLUSION: The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.     

Use of Tacrolimus During Pregnancy After Kidney Transplantaion

PurposeMotherhood is the greatest privilege that nature gives to women. Although pregnancy is a physiological event for women, every pregnancy is a risky pregnancy. During a normal pregnancy, the health of mother and baby are monitored. In post-transplantation pregnancies, the function of the transplanted organ, along with the mother and the infant, must be monitored, since the continuation of pregnancy depends on both the maternal and infant health and an organ functioning within normal limits. The desire is for every baby to be born in due time and at normal weight, but this is not always possible in pregnancies after transplants. Publications about the pharmocokinetics of tacrolimus are very limited. In this study, we wanted to share our experiences with pregnancy in our clinic.Material and methodPatients who used tacrolimus during their pregnancies after renal transplantation (RT) at Antalya Medicapark Organ Transplantation Unit, during November 2008 to July 2018 were included in the study. Patient’s gestational age, pregnancy, drug levels, is charge, and labor creatinine clearances were examined.FindingsFour thousand six hundred thirty-five RT occurred between November 2008 to July 2018; 786 of the patients were female between the ages 18 and 45. Thirty-one pregnancies went full term. Twenty-six pregnant women, who used tacrolimus after RT, were included in the study.Five patients had pre-eclampsia, 1 patient had abortus immines, 2 patients had hypertansion due to pregnancy, and 1 patient had aplated placenta. There was a breech presentation in 1 patient with preeclampsia. Acute rejection developed in 3 postpartum patients, but renal values normalized with medical treatment. All the babies were born alive and healthy; postpartum graft loss was not observed.ConclusionIf planning to become pregnant after RT,our center recommends waiting at least 2 years after the RT, when graft function should be normal and without any signs of HT and proteinuria. Our recommendation regarding the level of tacrolimus after RT is 4.5 to 7 μg.     

Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus

BACKGROUND: The increasing use of tacrolimus as a primary immunosuppressant is paralleled by a growing number of pregnancies occurring in mothers receiving tacrolimus systemically. METHODS: In this retrospective analysis during 1992-1998; data sources were case reports from clinical studies, spontaneous reports from health care professionals, routine surveys by transplant registries, and the published literature. RESULTS: One hundred pregnancies in 84 mothers were recorded. Mean maternal age was 28 years. All except one mother (autoimmune disease) were solid organ transplant recipients (66% liver and 27% kid- ci ney). Mean time from transplantation to conception was 26 months. The mean daily dose of tacrolimus (range 11.7-12.8 mg/day) and the mean tacrolimus whole blood level (range 8.5-11.5 ng/ml) remained fairly constant from preconception through the third trimester. The most frequent maternal complications were graft rejection followed by preeclampsia, renal impairment, and infection. All cases of rejection were successfully treated with corticosteroids and did not result in graft loss. Of 100 pregnancies, 71 progressed to delivery (68 live births, 2 neonatal deaths, and 1 stillbirth), 24 were terminated (12 spontaneous and 12 induced), 2 pregnancies were ongoing, and 3 were lost to follow-up. Mean gestation period was 35 weeks with 59% deliveries being premature (<37 weeks). The birth weight (mean 2573 g) was appropriate for gestational age in 90% of cases. Most common complications in the neonate were hypoxia, hyperkalemia, and renal dysfunction. These were transient in nature. Four neonates presented with malformations, without any consistent pattern of affected organs. CONCLUSION: Pregnancy in tacrolimus-treated transplant recipients resulted in a favourable outcome. Complications of the mother and neonate were similar to those previously described with other immunosuppressants.     

Kidney transplantation for end-stage renal failure in liver transplant recipients with hepatitis C viral infection

BACKGROUND: End-stage renal failure after successful liver transplantation (LTx) has been described in up to 5% of patients. Kidney transplantation (KTx) has been the treatment of choice in these cases. However, in recipients infected with hepatitis C virus (HCV), the augmentation of immunosuppression after KTx may result in an increased viral load. This, in turn, may adversely affect the liver allograft. METHOD: The present study retrospectively examined the outcome in 17 patients (3 females and 14 males, mean age 51.1+/-11.3 years) who received KTx after LTx. The mean interval from LTx to KTx was 57.6+/-32.1 months. The mean follow-up was 41.7+/-20.5 months after KTx, and 99.6+/-37.7 months after LTx. Sixteen of the 17 patients received tacrolimus-based immunosuppression at the time of KTx. RESULTS: During the follow-up period, one patient underwent combined liver and kidney retransplantation 3.7 years after KTx and 12.7 years after LTx. She subsequently died secondary to primary nonfunction. Four other patients died, two of lung cancer, one of pancreatitis/sepsis, and one of severe depression leading to noncompliance. A total of 29 episodes of biopsy-proven acute renal allograft rejection (1.7 episodes/ patient) were encountered and treated with steroids. Seven patients experienced a rise in liver function tests during the period of increased steroid dosage. Four patients received no treatment, and their liver function returned to baseline. The remaining three were treated with interferon. Overall 1- and 3-year actuarial patient and liver allograft survival was 88% and 71% (after renal transplantation); corresponding 1- and 3-year actuarial graft survival was 88% and 61%. Twelve patients are alive with normal liver function. One patient is on dialysis, because of renal allograft loss to noncompliance. CONCLUSION: In this series, LTx recipients with HCV infection were able to undergo KTx with a reasonable degree of success. KTx should be offered for end-stage renal failure after LTx, even in the presence of HCV infection, to individuals with stable liver function and no signs of liver failure.     

Posttransplant diabetes mellitus after kidney transplantation with different immunosuppressive agents

Posttransplant diabetes mellitus (PTDM) is a disturbing side effect of immunosuppression. The aim of this study was to evaluate the effect of different immunosuppressive agents on the development of PTDM in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx. Baseline immunosuppression was azathioprine (AZA), cyclosporine (CSA), or tacrolimus (TAC), or sirolimus in combination with calcineurin inhibitors (SIR). All patients received steroids for both induction and maintenance therapy during the first 6 months posttransplantation. Mean follow-up after KTx was 73 +/- 53.5 months (range 6 months to 16 years). PTDM was defined as two consecutive blood glucose determinations above 126 mg/dL. Thirty-six of 538 (6.7%) recipients experienced PTDM, 31 of whom required insulin treatment and five oral antidiabetic medications. PTDM occurred at 25.3 +/- 38 months posttransplantation in 4.8% of KTx treated with AZA, 4.8% of CSA, 6.5% of KTx treated with TAC and 12.5% of KTx treated with SIR. The time of onset of PTDM was significantly shorter (P =.003) among TAC (2.1 +/- 1.7 months posttransplantation) versus CSA (27.8 +/- 34 months). PTDM disappeared in 6 of 36 patients. We conclude that with current levels of immunosuppression, there is no difference in the incidence of PTDM between TAC- and CSA-treated KTx.     

The outcome of pregnancy following renal transplantation--the experience of a single center.

Many centers still recommend avoidance of pregnancy after renal transplantation because of fears for the safety of both mother and fetus. These fears are in part based on a lack of information concerning the effects of newer immunosuppressive drugs such as cyclosporine on the course and outcome of pregnancy. The present study examines the experience of first pregnancies following renal transplantation in a single center, with emphasis on the role of CsA. Data on the first pregnancies of 22 women transplanted between 1977 and 1988 were studied. The mean age of patients at the time of transplant was 23.4 +/- 3.1 years and interval from transplant to pregnancy was 34.5 +/- 24.5 months (range 1-75 months). Twelve patients received CsA alone or in combination with other immunosuppressives, while the remaining 10 patients received azathioprine and prednisone. Mean serum creatinine fell progressively during pregnancy in both CsA- and azathioprine-treated mothers. Mean CsA dose rose during pregnancy while mean CsA blood concentration fell during the 2nd trimester (P = 0.042). The gestation period ranged from 27 to 40 weeks (35.5 +/- 3.3) with 14 pregnancies ending prematurely prior to 37 weeks. Thirteen deliveries occurred by Caesarian section. Hypertension complicated 10 pregnancies. Birth weight correlated directly with both maternal weight gain (r = 0.57; P less than 0.02) and gestational age (r = 0.9; P less than 0.01). Ten of 23 offspring were below the 10th percentile for weight. Mean birth weight ranged from 0.72 to 3.7 kg (2.3 +/- 0.84 kg). The mean birth weight and gestational age of children born to mothers taking CsA were lower than those in azathioprine treated mothers but these differences were not statistically significant. Successful pregnancy is possible following renal transplantation, although there is a high rate of prematurity, low birth weight, and intrauterine growth retardation. CsA dose requirements may be increased. Maternal risks including hypertension require that such pregnancies be handled by a multidisciplinary team approach.     

Pregnancy and childbearing in a population with biologic valvular prostheses

Long-term performance of biological prostheses and course of pregnancy, labor, and delivery were evaluated in women less than 35 years of age. Between 1975 and 1987, 87 female patients received a porcine (n = 86) or pericardial valve (n = 1); the mean patient age was 26.8 years, with a range of 8 to 35 years. A total of 17 of these patients experienced 37 pregnancies. A total of 25 babies were delivered, of which 19 were babies of normal birth weight born at term and six were born prematurely (two of these were stillborn). There were six spontaneous abortions and five therapeutic abortions. The mean time from primary operation to first delivery was 29 months. Of the 17 pregnant patients, 14 were in normal sinus rhythm and three were in atrial fibrillation. One of those in fibrillation had a therapeutic abortion while receiving warfarin therapy, and another was successfully delivered of her neonate after 7 months of warfarin therapy. The remaining 15 patients were treated through 35 pregnancies without anticoagulants or antiplatelet agents. Of the total population of 87 patients, 32 (36.8%) were treated for valve-related complications. Structural valve deterioration occurred in eight patients (47.1%) of the pregnancy group and 10 patients (14.3%) of the nonpregnancy group (p less than 0.05). The freedom from structural valve deterioration at 10 years was 23.3% +/- 14% for the pregnancy group and 74.2% +/- 8.5% for the nonpregnancy group (p less than 0.05, age as a determinant, p not significant). There were eight valve-related deaths (1.5%/patient-year). Reoperation was performed in 59% of the pregnancy group and 19% of the nonpregnancy group, primarily for structural valve deterioration manifested as valvular obstruction from aggressive calcification (p less than 0.05). The freedom from reoperation at 10 years parallels freedom from structural valve deterioration (20.3% +/- 12.4% and 64.3 +/- 9.1% for the pregnancy and nonpregnancy groups, respectively, with p less than 0.05; with age added as a determinant, p not significant). The overall reoperative mortality was 8.7% (two patients). The biologic prostheses afforded successful pregnancy without fetal wastage or congenital anomalies and without significant maternal morbidity or mortality.     

Successful pregnancies in women on renal replacement therapy: report from the EDTA Registry.

This study reports the geographical incidence of successful pregnancies in women on renal replacement therapy (RRT) and related information on gestation and clinical status of newborns. The impact of successful pregnancy on graft function was assessed by means of a retrospective case-control study. Since 1977 special questionnaires have been sent to each dialysis and transplant centre which reported babies born to mothers on RRT on the yearly centre questionnaire. After 10 years of data collection, a total of 490 pregnancies and 500 babies were available for analysis. A percentage of 88.4 of the babies were born to mothers with a functioning graft, 11.2% to mothers on chronic haemodialysis, and the remaining 0.4% to mothers on CAPD. Almost 50% of all successful pregnancies were reported from the UK. The number of successful pregnancies increased steadily and in parallel with the increasing number of females of childbearing age with a functioning renal transplant. The majority of mothers delivered at age 24-32. For transplanted mothers delivery occurred most commonly during the 3rd and 4th year after successful transplantation. In approximately 85% of cases the duration of pregnancy was shorter than the lower 10th percentile of normal. Birthweight was reduced in accordance with gestational age. Newborn mortality was 1.8%. Fifty-three mothers with a successful pregnancy in 1984-1987 were computer matched with controls according to a number of criteria. The serum creatinine concentration recorded in coded form at the end of each year on the individual EDTA patient questionnaire was used to assess changes in graft function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Results of simultaneous and sequential pediatric liver and kidney transplantation.

BACKGROUND: The indications for simultaneous and sequential pediatric liver (LTx) and kidney (KTx) transplantation have not been well defined. We herein report the results of our experience with these procedures in children with end-stage liver disease and/or subsequent end-stage renal disease. PATIENTS AND METHODS: Between 1984 and 1995, 12 LTx recipients received 15 kidney allografts. Eight simultaneous and seven sequential LTx/KTx were performed. There were six males and six females, with a mean age of 10.9 years (1.5-23.7). One of the eight simultaneous LTx/KTx was part of a multivisceral allograft. Five KTx were performed at varied intervals after successful LTx, one KTx was performed after a previous simultaneous LTx/KTx, and one KTx was performed after previous sequential LTx/KTx. Immunosuppression was with tacrolimus or cyclosporine and steroids. Indications for LTx were oxalosis (four), congenital hepatic fibrosis (two), cystinosis (one), polycystic liver disease (one), A-1-A deficiency (one), Total Parenteral Nutrition (TPN)-related (one), cryptogenic cirrhosis (one), and hepatoblastoma (one). Indications for KTx were oxalosis (four), drug-induced (four), polycystic kidney disease (three), cystinosis (one), and glomerulonephritis (1). RESULTS: With a mean follow-up of 58 months (0.9-130), the overall patient survival rate was 58% (7/12). One-year and 5-year actuarial patient survival rates were 66% and 58%, respectively. Patient survival rates at 1 year after KTx according to United Network of Organ Sharing (liver) status were 100% for status 3, 50% for status 2, and 0% for status 1. The overall renal allograft survival rate was 47%. Actuarial renal allograft survival rates were 53% at 1 and 5 years. The overall hepatic allograft survival rate was equivalent to the overall patient survival rate (58%). Six of seven surviving patients have normal renal allograft function, and one patient has moderate chronic allograft nephropathy. All surviving patients have normal hepatic allograft function. Six (86%) of seven sequentially transplanted kidneys developed acute cellular rejection compared with only two (25%) of eight simultaneously transplanted kidneys (P<0.04). CONCLUSIONS: Simultaneously transplanted kidneys were less likely to develop rejection than sequentially transplanted kidneys in this series. This did not have any bearing on patient or graft survival rates. Mortality correlated directly with the severity of United Network of Organ Sharing status at the time of kidney transplantation. Candidates for simultaneous or sequential LTx/KTx should be prioritized based on medical stability to optimize distribution of scarce renal allografts.     

Renal allograft rejection with normal renal function in simultaneous kidney/pancreas recipients: does dissynchronous rejection really exist?

BACKGROUND: Between July 1, 1994 and December 1, 1998, 147 simultaneous kidney/pancreas transplantations were performed at our center. Of 95 patients who experienced at least one acute renal allograft rejection episode after transplantation, 7 (7.4%) developed rejection in the presence of stable and normal or near-normal renal function. METHODS: The indication for renal allograft biopsy was a rising serum lipase, i.e., suspected pancreatic rejection. All seven patients were treated with steroids and augmentation of the tacrolimus dose, with a fall in the serum lipase and no change in the serum creatinine. RESULTS: The serum creatinine levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1.4+/-0.4, 1.3+/-0.3, 1.2+/-0.2, and 1.2+/-0.2 mg/dl. The serum lipase levels just before, at the time of, 1 week after the biopsy, and at most recent follow-up were 1022+/-1157 mg/dl, 874+/-996 mg/dl, 243+/-260 mg/dl, and 94+/-75 mg/dl. The tacrolimus dosages and levels at the time of the biopsy and 1 week later were 14.9+/-5.0 mg/day and 15.0+/-4.0 ng/ml, and 16.4+/-6.3 mg/day and 15.1+/-6.8 ng/ml. CONCLUSIONS: These findings suggest that, in patients undergoing simultaneous kidney/pancreas transplantation, the entity of dissynchronous pancreatic allograft rejection without renal allograft rejection may not really exist. These data also make an additional fundamental point that acute rejection may occur in patients with normal and stable renal function.     

Parturition in Six Renal Allograft Recipients

Between 1983 and 1994, we studied renal function and neonatal conditions for eight pregnancies and births to six women who had received renal transplants in order to assess the effect of an allograft on pregnancy and its outcome. The gestation period was 34 to 39 weeks (mean 36 weeks and 4 days), and four pregnancies ended before term. All eight babies were delivered by cesarean section. Intrauterine growth retardation (IUGR) was found in both babies of one woman who had been treated with conventional (without cyclosporin) immunosuppression. The serum creatinine level did not change during gestation in any of the women but was elevated after delivery in four. Four mothers suffered from proteinuria (25–364 mg/dl) during gestation, but the proteinuria disappeared after delivery in all but one case. The one exception, persistent proteinuria of 100–200 mg/dl, was assumed to result from the recurrence of the original renal disease (IgA nephropathy). The reduction of creatinine clearance and hydronephrosis of one graft noted during gestation were later reversed. None of the eight babies (four females and four males) was congenitally malformed, and their Apgar scores were 6 to 9 (median 8). They are now 3 months to 11 years old, and seven of them are healthy and show good growth. One of the two IUGR babies has not grown well; her weight and height are more than 1 SD below the mean for her age, and she is mentally retarded and suffers from muscle weakness. Compared with dialysis patients, female renal allograft recipients have a better quality of life because they can safely deliver a child if they observe the criteria for pregnancy established for renal allograft recipients.     

Fertility following solid organ transplantation

Fertility is usually restored in women after solid organ transplantation, and successful pregnancies have been reported in female recipients of kidney, liver, heart, pancreas-liver, and lung transplants. However, women with solid organ allografts have higher incidence of pregnancy complications like hypertension, preeclampsia, preterm delivery. Hypertension appears to be dependent on the type of immunosuppressive agents. The influence of pregnancy on the risk of rejection is poorly known on the basis of available data. Rejection rate appears to be at least similar to the nonpregnant population. In some cases, such as in liver transplant pregnant women, even higher as compared to the nonpregnant population. Maintaining appropriate blood levels of immunosuppressive drugs is currently recommended. Malformation rate in the offsprings of transplanted women appears to not be increased; long-term follow- up of children born to allograft recipients is necessary to investigate possible developmental, immunological, or oncological disorders. We followed 70 pregnancies after kidney transplantation and nine after liver transplantation. All recipients were maintained on immunosuppressive therapy during pregnancy, except one mother who refused immunosuppression and experienced transplant rejection. Hypertension was the most frequent complication during pregnancy: in 23% of kidney transplantated mothers and in one out of nine liver transplant recipients. The only malformation observed in the newborns was the dislocation of the hip in the child of a kidney transplant recipient.     

女性肾移植受者妊娠结果及子代健康状况随访

目的 评价女性肾移植受者妊娠结果及子代健康状况的长期随访结果. 方法 回顾性分析1978年4月至2011年4月妊娠＞5个月的15例肾移植受者资料,并对其子代进行随访.妊娠时年龄(28.5±5.7)岁,妊娠距移植时间(53.4±19.7)个月.产后随访(11.5±6.9)年. 结果 15例受者采用以环孢素或他克莫司为主的免疫抑制剂方案.12例母、子女身体状况及移植肾功能正常;1例产下一男婴2周后因并发肺部感染、心力衰竭,带正常功能移植肾死亡;2例分别于妊娠第21、23周发生移植肾慢性排斥反应,终止妊娠,经治疗无效后摘除移植肾.13例胎儿均经剖宫产娩出后存活,胎龄(35.2±4.0)周,出生体质量(2510 ±68)g,Apgar评分均为10分.13例婴儿出生时无生理缺陷,体格发育无异,出生后以人工喂养.13例儿童智力、体格以及心理发育与同龄者无异常,7例0～2岁时发生反复呼吸道感染,1例诊断为注意力缺陷多动障碍.目前子代年龄3 ～21岁. 结论 严格妊娠指征,肾移植女性受者在术后3年后能够成功妊娠、分娩,长期随访显示患者子代健康状况良好.     

Single-center, open, prospective, randomized pilot study comparing cyclosporine versus tacrolimus in simultaneous pancreas-kidney transplantation

BACKGROUND: Although tacrolimus (Prograf) is the calcineurin inhibitor usually employed in simultaneous pancreas-kidney transplantation (SPKTx), no prospective randomized studies have compared its efficacy to cyclosporine (Neoral), when either drug is used in combination with mycophenolate mofetil (MMF) and the pancreas is drained into the portal vein. METHODS: Between May 2001 and June 2003, 16 SPKTx recipients were randomized to be prescribed Neoral and 17 Prograf in addition to basiliximab, steroids, and MMF. All pancreata were drained into the portal vein. RESULTS: After a median follow-up of 15.6 months, six kidney acute rejection episodes were observed with Prograf (36.5%; one steroid-resistant) and one Neoral (n = 1, 6.2%; P =.04). No pancreas rejection episode was recorded. Two infections occurred in two recipients from each group. No major adverse events were noted other than a severe hematological toxicity (Prograf). Metabolic parameters were equivalent in the two groups, save for higher total cholesterol (212 +/- 39 mg/dL vs 173 +/- 23 mg/dL; P =.008), LDL (129 +/- 33 mg/dL vs 101 +/- 21 mg/dL; P =.029), and triglyceride (191 +/- 86 mg/dL vs 126 +/- 40 mg/dL; P =.028), values with Neoral, although the same differences were already present at baseline. One recipient (Neoral) died with functioning grafts. Patient, pancreas, and kidney survival rates were all 94% for Neoral versus 100% for Prograf. CONCLUSIONS: Although a larger series and a longer follow-up are needed, Neoral and Prograf used in combination with MMF seem to achieve equivalent success rates among primary SPKTx when the pancreas is drained into the portal vein.     

Analysis of 100 pregnancy outcomes in women treated systemically with tacrolimus

Abstract The aim of this paper is to provide a summary of clinical findings regarding the safety of tacrolimus in pregnancy. From 1992 to 1998 data were collected on 100 pregnancies from 84 mothers who received tacrolimus systemically; 83 cases of solid organ transplantation, and 1 case of Behçet's disease. Maternal mean age at conception was 28 years and pregnancy outcome was live birth in 68%, spontaneous abortion in 12%, induced abortion in 12%, stillbirth/perinatal death in 3%, ongoing pregnancy in 2%, and lost to follow up in 3%. Fifty‐nine percent of the neonates were delivered prematurely (< 37 weeks of gestation). Birth weight was appropriate for the gestational age in 90% of the cases. Malformations occurred in 4 neonates: case 1, meningocele and urogenital defects; case 2, alcoholic embryopathy; case 3, ear defect, cleft palate and hypospadia; case 4, multicystic dysplastic kidney. There was no consistent pattern of malformations and 2 mothers subsequently delivered a healthy neonate while on tacrolimus therapy. Nearly 70% of pregnancies following systemic tacrolimus administration resulted in a favourable outcome without any significant effect on intrauterine growth. The incidence of malformations was similar to that reported with other immunosuppressants in transplant recipients.     

Tacrolimus as a rescue immunosuppressant after heart transplantation.

OBJECTIVE: The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance. METHODS: From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations. RESULTS: The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover. CONCLUSIONS: In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.     

Outcome of four high-risk pregnancies in female liver transplant recipients on tacrolimus immunosuppression

Pregnancies in women after liver transplantation are considered high risk due to the greater rate of complications observed in immunosuppressed graft recipients. We report successful outcomes of four high-risk pregnancies in female liver transplant recipients on tacrolimus-based immunosuppression. The patients, aged 23 to 32 years, at the time of conception were 12 to 59 months from transplantation (mean 30 months). Preterm labor was the most important pregnancy complication observed in these patients. One episode of acute graft rejection was observed. A variable demand for tacrolimus was noted during pregnancy. Despite complications all four pregnancies were successful. The mean gestational age at delivery was 34.4 weeks. The birth weight of the newborns varied from 1410 to 3490 g (mean 2303 g) and the mean Apgar score was 8. No structural malformations or early complications were observed in the newborns. Excluding the patient with acute rejection, the remaining three cases showed all liver parameters to remain stable.     

Outcome of pregnancy in renal allograft recipients: SIUT experience

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.     

Pregnancy in kidney transplant recipients

PURPOSE: Our aim was to investigate kidney allograft, obstetric, and maternal outcomes in pregnant women undergoing kidney transplantation in our center. METHODS: Retrospective data on 74 pregnancies in 60 patients were reviewed and completed through phone interviews were compared with information on a control group of female kidney recipients. RESULTS: Mean age of patients at transplantation was 26.55 +/- 4.72 years and the median interval between transplantation and pregnancy was 27.5 months. Gestational period was 8 months. Live birth was the outcome in 43.2% of pregnancies; 9.5% led to still birth, 24.3% were aborted, and obstetrical data of the remaining were unavailable. Among the 11 patients who became pregnant within 12 months after transplantation, we observed seven live births and four abortions. None of pregnancies that were accompanied by acute rejection episodes (ARE) were successful. Twenty-six patients experienced at least one ARE versus 23 patients of the control group (P = NS). However, the first ARE occurred later in the pregnant group (P = .028). Chronic rejection and graft loss were seen in 24 and 18 study group cases and 17 and 17 control cases, respectively (P = NS). One-, 3-, 5-, and 10-year graft survivals were 100%, 96.5%, 94.5%, and 77.1% in the pregnant group versus 93.2%, 85.7%, 81%, and 64.7% in the control group, respectively (P = .07). CONCLUSION: Pregnancy in kidney recipients seems to be safe for kidney allograft recipients even within the first year posttransplant. Nonetheless, the outcomes of pregnancy in this group of patients is not always favorable, especially when rejection occurs simultaneously.     

Outcome of Pregnancies after Biliopancreatic Diversion

Background: Severe obesity has deleterious effects on fertility and pregnancy outcomes. Although surgery is the best long-term treatment for severe obesity, there is a risk of gestational undernutrition in operated mothers because bariatric surgery reduces nutrient availability. This is a follow-up report of our initial findings regarding pregnancy and neonatal outcomes in biliopancreatic diversion (BPD) patients, with addition of a new cohort of children born to mothers after BPD. Methods: All women (n = 916) who had successfully undergone BPD in our hospital were mailed a questionnaire containing multiple-choice and essay questions concerning gynecologic and obstetric history, and pregnancy and neonatal outcomes in both preoperative and postoperative pregnancies. Patients operated between 1984 and 1995 (n = 568) were mailed an additional questionnaire regarding children's weight and height progress, and school performance. Perinatal records from our patients' obstetric clinics were also reviewed. Results: The questionnaire was completed by 783 women (85.5%). 251 postoperative pregnancies in 132 women resulted in 166 infants by 109 mothers. 47.0% of patients who were unable to become pregnant preoperatively were successful postoperatively. 90 out of 109 women (82.6%) reported an appropriate weight gain (9.1 ± 5.9 kg) during postoperative pregnancies. The incidence of fetal macrosomia decreased from 34.8 to 7.7%, with a concomitant increase in normalweight babies from 62.1 to 82.7%. The elevated miscarriage rate (26.0%) in these obese women persisted after surgery. Conclusion: Major weight loss following BPD improves the reproductive function of severely obese women. BPD provides major beneficial effects for both mother and child, including normalization of gestational weight changes, reduction of fetal macrosomia, and normalization of the infant's birth-weight. Our results speak in favor of delaying pregnancy in obese women until after the substantial surgical weight loss has occurred.