tacrolimus and Pre-Eclampsia

We contacted and analyzed the data of 18 lung transplant recipients who had had children. The complications we detected included: hypertension (50%), diabetes mellitus (21%), preeclampsia (13%), infection (21%), rejection (30%), loss of graft function (23%) and a lower percentage of live births than in transplant recipients of other organs. Other aspects to keep in mind are: the potential risk for fetal alterations (caused by drugs used as prophylaxis against rejection crossing the placental barrier); greater risk for infection and alterations in drug levels due to changes in metabolism typical of pregnancy and postpartum period. We describe the two cases in Spain of female lung transplant recipients who have had children after transplantation. Although pregnancy in these cases can have a similar evolution as in non-transplanted women, doctors should recommend their transplanted patients to avoid becoming pregnant, while explaining the high risk of both fetal and maternal morbidity and mortality after transplantation.

Topics: Adult; Cardiomyopathies; Female; Graft Rejection; Heart Defects, Congenital; Heart-Lung Transplantation; Humans; Hypertension; Hypertension, Pulmonary; Immunosuppressive Agents; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases, Interstitial; Lung Transplantation; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, High-Risk; Spain; Survivors; Tacrolimus

Some of obstetrical complications such as unexplained pregnancy loss and preeclampsia (PE) are associated with maternal-fetal immune abnormalities, leading to uteroplacental dysfunction, insufficient fetal immune tolerance, or fetal rejection. Immunosuppressants with calcineurin inhibitors could be useful for the prevention of these complications by modulating the cellular immune balance by directly inhibiting activated T-helper (Th) 1 and natural killer (NK)/NKT cells. We present our experience with the immunosuppressant tacrolimus in five pregnant women who had a previous pregnancy history of unexplained or preeclamptic stillbirth. Th1 and Th2 cell populations and NK cell activities in peripheral blood were measured as clinical parameters during pregnancy. Case 1-3 achieved suppressions of predominant Th1 immunity and live births without pregnancy-related complications. In case 4, increased tacrolimus dose after a miscarriage resulted in her first live birth; however, she developed PE and severe fetal growth restriction with elevated Th1/Th2 cell ratios at 26 weeks of gestation. Case 5 had a previous history of early onset PE and the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and an emergency cesarean section was needed for maternal safety at 20 weeks of gestation. The course of the next pregnancy was stable under tacrolimus treatment; however, the HELLP syndrome recurred after PE at 33 weeks of gestation. Although an imbalance in the Th1/Th2 cell ratio was not observed during pregnancy, NK cell activity was markedly elevated before delivery. In conclusion, tacrolimus is a potential drug candidate for the prevention of unexplained or preeclamptic stillbirth with Th1-dominant immune states.

Topics: Abortion, Spontaneous; Cesarean Section; Female; HELLP Syndrome; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Pharmaceutical Preparations; Pre-Eclampsia; Pregnancy; Stillbirth; Tacrolimus

Transplantation is not only the best method for treating end-stage failure of many organs but also the way to improve the quality of life of patients. For women of childbearing age, an organ transplant often brings a restoration of regular reproductive functions, which means, among other things, the possibility of having biological offspring.. The aim of the study was to analyze the medical records and assess the impact of a liver transplant on the course of pregnancy and labor.. The research was carried out from March to May 2019 in the Nephrology and Transplant Clinic Medical University of Warsaw. The study group consisted of 19 women after liver transplantation. Medical records were analyzed, and laboratory test results routinely performed on patients were also used for the study.. The mean age of conception of the patients following transplantation was 30 ± 4 years old. In the analyzed period, 6 patients gave birth to 2 children each, and 8 patients to 1 child each. Only 3 patients experienced premature birth. Twelve patients gave birth by caesarean delivery. Fourteen patients took tacrolimus.. Pregnancy is possible in patients following a liver transplant and does not appear to have a damaging effect on liver functionality. There is an increased risk of pre-eclampsia, intensified hypertension, and premature birth among patients following a transplant, which is why it is essential for these patients to remain under the care of a specialistic therapeutic team.

Topics: Adult; Female; Humans; Hypertension; Liver Transplantation; Postoperative Complications; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Quality of Life; Tacrolimus; Treatment Outcome

Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported.. In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved.. The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born.. We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor.. Jane and Dan Olsson Foundation for Science.

Topics: 46, XX Disorders of Sex Development; Adrenal Cortex Hormones; Adult; Apgar Score; Azathioprine; Cesarean Section; Congenital Abnormalities; Embryo Transfer; Female; Fertilization in Vitro; Graft Rejection; Gynecologic Surgical Procedures; Humans; Immunosuppressive Agents; Infant, Newborn; Infant, Premature; Live Birth; Living Donors; Male; Mullerian Ducts; Pre-Eclampsia; Pregnancy; Sweden; Tacrolimus; Uterus

Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization.. We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay.. Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (<37 weeks). The median birth weight was 2720 (1040-3730) g. Nine newborns (15%) had low birth weights (<2.5 kg). At least one severe complication occurred in 56% of pregnancies. A high glomerular-filtration rate (GFR) before pregnancy was the sole independent protective factor that avoided a severe complication. Death-censored kidney-allograft survival was 80.4% at 6 years. De novo donor-specific anti-HLA antibodies were detected after only 5.9% of pregnancies: for two women, the father had the same HLA antigens as those from the deceased organ donor. The determination of the HLA of the father before pregnancy can better inform the woman about the possible impact of pregnancy on her kidney-allograft function.. Despite many complications, the outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA alloimmunization was low.

Topics: Adolescent; Adult; Female; Glomerular Filtration Barrier; Graft Rejection; Graft Survival; HLA Antigens; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Tacrolimus; Transplantation, Homologous; Young Adult

To report the pregnancy outcomes in Irish female renal transplant recipients on modern maintenance immunosuppression.. The Republic of Ireland transplant database was accessed to identify the patient cohort in question. All female renal transplant recipients whose transplantation was in Ireland before or during their reproductive years were included. A questionnaire was sent to the identified women. A chart review was performed for those women who reported a pregnancy following renal transplantation.. Two hundred and ten women met the inclusion criteria. There was a response rate of 70% (n = 148). Eighteen women reported 29 pregnancies. The live birth rate was 76%. The mean gestation of the live births was 36.2 weeks with a mean birth weight of 3.0 kg. There were six cases of pre-eclampsia. Twin pregnancies and those entering pregnancy with a creatinine greater than 135 µmol/l had particularly complicated clinical courses. Four women had not conceived post transplant despite actively trying for over 1 year. Two women utilised assisted fertility methods (in vitro fertilisation), one of whom became pregnant.. A significant proportion of women who attempt to conceive following renal transplantation are successful, without the use of assisted fertility. Pregnancy in this setting warrants meticulous multidisciplinary care.

Topics: Abortion, Spontaneous; Adult; Birth Weight; Female; Gestational Age; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Ireland; Kidney Transplantation; Live Birth; Pre-Eclampsia; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted; Tacrolimus; Young Adult

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.. 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.. 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.. 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.

Topics: Abnormalities, Multiple; Adolescent; Adult; Anti-Inflammatory Agents; Birth Weight; Diabetes Mellitus, Type 1; Female; Fludrocortisone; Graft Survival; Humans; Hypertension; Immunosuppressive Agents; Infant, Newborn; Kidney; Liver; Liver Diseases; Liver Transplantation; Pre-Eclampsia; Prednisone; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Pregnancy Outcome; Prospective Studies; Survival Rate; Tacrolimus; Transplantation, Homologous

The increasing use of tacrolimus as a primary immunosuppressant is paralleled by a growing number of pregnancies occurring in mothers receiving tacrolimus systemically.. 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.. 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.. 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.

Topics: Adult; Female; Graft Rejection; Humans; Immunosuppressive Agents; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies; Tacrolimus; Transplantation Immunology