mycophenolic-acid and Abortion--Spontaneous

Few data are available on pregnancy in renal transplanted women for lupus nephritis (LN).. Among 38 women with LN who received a renal transplant in our Unit, three had nine pregnancies. During the pregnancies, patients were followed by a multidisciplinary team including gynecologists and nephrologists.. Two patients received a living related and one a deceased kidney transplant. The immunosuppressive therapy consisted of steroids calcinurin inhibithors and mycophenolate mofetil. The last drug was substituted with azathioprine in prevision of pregnancy. All patients had normal renal function and urinalysis. In two patients some signs of immunological activity persisted after transplantation. Five pregnancies ended in miscarriage and four in live births. Two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one case and in a small for gestation age in both cases. And finally, follow-up graft function and urinalysis continued to be normal in all patients.. After renal transplantation our LN women continue to have frequent miscarriages. The other pregnancies ended in live births and, with the exception of pre-eclampsia in a hypertensive patient, no renal or extra-renal complications occurred during or after pregnancy, even in cases with active immunological tests.

Topics: Abortion, Spontaneous; Adult; Anti-Inflammatory Agents; Antibodies, Antinuclear; Antihypertensive Agents; Azathioprine; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Mycophenolic Acid; Pre-Eclampsia; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy 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.

Topics: Abortion, Spontaneous; Female; Fetus; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Mycophenolic Acid; Organ Transplantation; Pregnancy; Risk Factors; Teratogenesis; United States

Myfortic is a new formulation of mycophenolic acid (MPA) utilizing enteric coated mycophenolate sodium (EC-MPS) that may have fewer gastrointestinal side effects.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Contraindications; Delayed-Action Preparations; Female; Gastric Acid; Humans; Hydrogen-Ion Concentration; Immunosuppressive Agents; IMP Dehydrogenase; Intestinal Absorption; Male; Mycophenolic Acid; Pregnancy; Prodrugs; Skin Diseases; Tablets, Enteric-Coated

Successful pregnancy is supported by a healthy maternal-fetal interface (i.e., the decidual tissues) which holds the conceptus and safeguards it against stressors from the beginning of pregnancy. Any disturbance of this interface can presumably lead to the loss of pregnancy. The use of the immunosuppressive drug mycophenolic acid (MPA) should be discontinued in pregnancy given its abortive and embryotoxic effects. Direct teratogenic effects have been observed in mammalian embryos cultured in MPA, but the underlying mechanisms of abortion by MPA are less understood.. Decidual stromal cells isolated from human placentas are cultured in the presence of clinically relevant doses of MPA. Data regarding the effects of MPA on the proliferation and viability of decidua cultures are first analysed and then, molecular pathways contributing to these effects are unravelled.. MPA treatment of decidual stromal cells results in loss of proliferation capacity and a decrease in the viability of decidua cultures. The molecular pathways involved in the effects of MPA on decidual stromal cells are a reduction in pre-rRNA synthesis and subsequent disruption of the nucleolus. The nucleolar stress stabilizes p53, which in turn, leads to a p21-mediated cell cycle arrest in late S and G2 phases, preventing the progression of the decidua cells into the mitosis. Furthermore, MPA does not induce apoptosis but activate mechanisms of autophagy and senescence in decidual stromal cells.. The irreversible growth arrest of decidua cells, whose role in the maintenance of the pregnancy microenvironment is known, may be one cause of miscarriage in MPA treated pregnant women.

Topics: Abortion, Spontaneous; Aging; Decidua; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Placenta; Pregnancy

To evaluate the relative risk of pregnancy loss associated with mycophenolate (MPA) vs azathioprine (AZA) use.. We conducted a retrospective cohort study using the IBM MarketScan Research Databases (2005-2015). Patients with ≥1 MPA or AZA prescription claim during the first trimester were included. The study outcome was pregnancy loss (spontaneous abortion or stillbirth). Potential confounders included age, drug indications, comorbidities, other teratogenic medication use, and gestational age at first MPA or AZA prescription fill. The risk for pregnancy loss was estimated using a generalized estimating equation model with stabilized inverse probability of treatment weighting. In sensitivity analyses, we varied the exposure definition, outcome definition, and the analytical method.. Among 111 pregnancies exposed to MPA, 55 resulted in pregnancy loss (49.5%). Among 471 pregnancies exposed to AZA, 113 had pregnancy loss (24.0%). The unadjusted relative risk for pregnancy loss was 2.0 (95% CI 1.6, 2.6), and the adjusted relative risk was 1.9 (95% CI, 1.6, 2.3) compared to AZA. Relative risk estimates were stable in all sensitivity analyses.. Exposure to MPA during early pregnancy was associated with a 2-fold increase in pregnancy loss risk.

Topics: Abortion, Spontaneous; Adolescent; Adult; Azathioprine; Child; Databases, Factual; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Pregnancy; Retrospective Studies; Risk Assessment; Risk Factors; Stillbirth; Young Adult

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

After maternal exposure to mycophenolate in pregnancy a high number of fetal losses and a specific pattern of birth defects consisting of microtia, cleft lip, and other anomalies have been reported. However, so far, prospective data on pregnancy outcome allowing quantitative risk assessment are missing. We report on 57 prospectively ascertained pregnancies after maternal therapy with mycophenolate (mycophenolate mofetil or mycophenolate sodium) identified by European Teratology Information Services (ETIS) through their risk consultation process. The outcome of these prospective pregnancies was as follows: 16 spontaneous abortions, 12 elective terminations of pregnancy (ETOP) (including two late terminations for multiple malformations consistent with mycophenolate embryopathy), and 29 liveborn infants. The probability of spontaneous abortion was about 45% (95% CI 29 to 66%) estimated using survival analysis technique. Six out of 29 live born infants had major congenital defects: Two with external auditory canal atresia (EACA) (with and without microtia), one with tracheo-esophageal atresia, one with severe hydronephrosis, one with an atrial septal defect (ASD) and one with a myelomeningocele. Thus, at least four fetuses/infants of our prospective case series had a clinical phenotype consistent with mycophenolate embryopathy. Our results confirm a high incidence of major malformations (26%) after first trimester exposure to mycophenolate. Apart from exposure to mycophenololate, the underlying maternal disease and concomitant medication may also have contributed to the other poor pregnancy outcomes such as a high rate of spontaneous abortions, prematurity (62%), and low birth weight (31%).

Topics: Abortion, Spontaneous; Congenital Abnormalities; Europe; Female; Follow-Up Studies; Humans; Infant, Newborn; Mycophenolic Acid; Pregnancy; Pregnancy Outcome; Prospective Studies; Teratogens

About 30% of pregnancies exposed to mycophenolate end in miscarriage. When the pregnancy continues, about 20% of foetuses and newborns have malformations of various types.

Topics: Abortion, Spontaneous; Congenital Abnormalities; Europe; Female; Humans; Immunosuppressive Agents; Infant, Newborn; Mycophenolic Acid; Pregnancy; Pregnancy Outcome; United States