tacrolimus and Stillbirth

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

To assess maternal, neonatal and graft outcomes after pregnancy in patients with kidney transplantation, and to compare the immunosuppressive therapies used.. Review of 29 pregnancies in 23 patients with kidney transplantation, managed at La Fe University Hospital, Valencia. Immunosuppressive therapies with Cyclosporine-A, Tacrolimus, Mycophenolate mofetil and Azathioprine were compared.. No statistical differences were found in perinatal or maternal complications, with respect to the immunosuppressive therapy used. There were no differences between therapy and graft survival. Maternal complications occurred in 25 out of 28 deliveries. The most common were anemia (75%) and hypertension (53.6%). Of the 29 pregnancies, 26 were live deliveries, two were stillbirths and one was a miscarriage. The median birth weight of newborns was 2650 g (900-4350 g). From the 28 deliveries, maternal complications were reported in 25 patients. Perinatal complications were recorded in 55.6% of the patients, with prematurity being the most common (44.4%) type. One malformation was reported, this was a cleft palate in a 25 year old patient who was treated with mycophenolate mofetil.. Pregnancies in patients with kidney transplantation should be considered high-risk pregnancies because of the higher rate of maternal and perinatal complications. Immunosuppressive therapies have not shown differences in maternal or perinatal outcomes.

Topics: Abortion, Spontaneous; Adult; Azathioprine; Cyclosporine; Female; Graft Survival; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Transplantation; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Stillbirth; Tacrolimus; Transplantation Conditioning; Young Adult