mercaptopurine and Abortion--Spontaneous

Maintaining remission of inflammatory bowel disease (IBD) during pregnancy is critical for positive pregnancy outcomes. Conflicting data exist regarding the association between thiopurine use for IBD treatment in pregnancy and adverse pregnancy outcomes and this meta-analysis aims to clarify this association. A meta-analysis was performed of all original human studies reporting outcomes in pregnancy in patients receiving thiopurines. Nine studies satisfied the inclusion criteria and a total of 494 patients with IBD and 2,782 IBD controls were reported. When compared with healthy women, those receiving thiopurines had an increased risk for congenital malformations (RR 1.45; 95% CI 1.07-1.96; p = 0.02); however, when compared with IBD controls, there was no increased risk (RR 1.37; 95% CI 0.92-2.05; p = 0.1). These data provide support for thiopurines having a minimal risk, if any, to the fetus.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Animals; Azathioprine; Birth Weight; Case-Control Studies; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

Topics: Abnormalities, Multiple; Abortion, Spontaneous; Collagen Diseases; Cyclophosphamide; Female; Gastrointestinal Diseases; Hematologic Diseases; Immune System Diseases; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Leukopenia; Liver Function Tests; Lymphoma; Mercaptopurine; Methotrexate; Nervous System Diseases; Pregnancy

Previous data on inflammatory bowel disease (IBD) relapse during pregnancy mainly originate from retrospective studies. The aim of this study was therefore (i) to evaluate the effect of active disease at conception and IBD disease type on disease relapse during pregnancy and (ii) to study the effects of disease relapse during pregnancy on birth outcomes in a prospective cohort with adequate representation of current treatments.. From 2008 to 2014, IBD women were recruited from an ongoing prospective clinical cohort. All patients with confirmed IBD diagnosis with a pregnancy wish or pregnancy were prospectively followed-up until pregnancy and delivery. Disease relapse was measured at each visit. Birth outcomes were recorded from the obstetrician.. A total of 298 pregnancies were observed in 229 IBD patients (157 Crohn's disease (CD), 66 ulcerative colitis (UC), and 6 IBD unclassified), resulting in 226 live births. Active disease at conception was strongly associated with disease relapse during pregnancy (aOR=7.66, 95% confidence interval (CI): 3.77-15.54). UC patients experienced relapse during pregnancy more often than CD patients, independent of maternal age, smoking, periconceptional disease activity, previous IBD surgery, and the use of immunosuppressives or anti-tumor necrosis factor (TNF) (aOR=3.71, 95% CI:1.86-7.40). Disease relapse was not associated with adverse birth outcomes such as spontaneous abortion, low-birth weight, or preterm birth.. This study confirms that active disease around conception increases the risk of disease relapse during pregnancy. In addition, UC patients relapse more often during pregnancy than CD patients. Birth outcomes were excellent, reflecting the stringent follow-up and treatment of this group of patients.

Topics: Abortion, Spontaneous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Infant, Newborn; Inflammatory Bowel Diseases; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Recurrence; Tumor Necrosis Factor-alpha

6-Mercaptopurine (6-MP) has proven efficacy in the therapy of inflammatory bowel disease. Its teratogenicity is demonstrated in animal studies when used at very high doses, whereas human data suggest that 6-MP at maintenance doses is safe. We report the outcome of 72 pregnancies in patients with inflammatory bowel disease who were previously treated with 6-MP with three different doses of 50, 75, and 100 mg/d, for a median duration of 18 months, along with long-term follow-up of the children.. We have compared the outcome of pregnancies and development of the offspring in the following two groups: group 1, patients with inflammatory bowel disease who conceived 6 months to 22 years after stopping 6-MP (median 72 months); and group 2, patients with inflammatory bowel disease who never received 6-MP prior to conception. All pregnancies were evaluated in terms of outcome: live full-term birth, premature delivery, stillbirth, spontaneous abortion, ectopic pregnancy, and therapeutic dilatation and curettage. Data on children were obtained regarding birth weight, congenital anomalies, and development.. Group 1 included 72 pregnancies carried by 29 women. There were 51 live births (4 premature), 16 spontaneous abortions, 1 stillbirth, 2 therapeutic abortions due to abnormal amniocentesis, and 2 ectopic pregnancies. The total incidence of fetal loss was 29.2%. In group 2, 75 women had 140 pregnancies resulting in 120 live births (8 premature), 18 spontaneous abortions, and 2 stillbirths. There were no cases of ectopic pregnancies or abnormal amniocentesis. The total incidence of fetal loss was 14.3%. There was no increase in the incidence of developmental defects when the mothers had been treated with 6-MP prior to pregnancy.. The incidence of fetal loss is higher in women with inflammatory bowel disease who had been previously treated with 6-MP compared with those who had not. Whether this was related to the older age at conception in 6-MP group, longer duration of disease, initially more severe disease, or use of 6-MP we cannot tell.

Topics: Abortion, Spontaneous; Adult; Case-Control Studies; Child Development; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Embryonic and Fetal Development; Female; Fetal Death; Humans; Infant, Newborn; Infant, Premature; Inflammatory Bowel Diseases; Mercaptopurine; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prevalence; Probability; Reference Values; Risk Assessment

The implantation traces of early embryonal death and abortion in rats induced by some drugs were studied. Early embryonal death and abortion were caused by intraperitoneal injection of 15 mg/kg of busulfan on the 7th day of gestation or 40 mg/kg of 6-mercaptopurine on the 7th and 8th day of gestation. The observation period and staining of the implantation traces were investigated. Early dead embryos and placentas were delivered between the 20th and 24th day of gestation. These were eaten by the dams. The implantation traces of abortion or early embryonal death, and those of normal delivery were able to be identified up to the 120th day and 500th day after extraction, respectively. The implantation traces of abortion were smaller in the three experimental groups. All kinds of implantation traces were stained distinctly with 10% ammonium sulfide, 0.2% sodium hydroxide and 2% potassium ferrocyanide. In this staining method, sodium hydroxide has an excellent effect on the staining of implantation traces. Specimens washed in water after being stained with sodium hydroxide and fixed in formalin can be preserved without discoloration for a long period of time.

Topics: Abortion, Spontaneous; Animals; Busulfan; Embryo Implantation; Female; Fetal Death; Gestational Age; Mercaptopurine; Pregnancy; Rats; Rats, Inbred Strains; Staining and Labeling; Time Factors; Uterus

Eight successful pregnancies and one spontaneous abortion have been observed in 5 women belonging to a group of 212 Nordic children who had their antileukemic therapy discontinued before January 1, 1978. Furthermore a young leukemic man was the father of a healthy child after 4 years of intensive cytostatic therapy. No malformations have been observed in the progeny of these treated individuals.

Topics: Abortion, Spontaneous; Adolescent; Adult; Cyclophosphamide; Female; Follow-Up Studies; Humans; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Prednisone; Pregnancy; Vincristine

The risks of embryonic, fetal, gondal damage of cancer chemotherapy are reviewed. Contrasting with the numerous malformations seen in laboratory animals, the teratogenic risk is low in man. Methotrexate is really dangerous during the first trimester of pregnancy. In malignant haematological diseases and solid tumours, the prognosis of the disease is the essential target but the use of immuno-suppressive drugs in non-malignant diseases is hazardous before 40 years of age. All the investigations show that alkylating agents injure the gonads. Young women should be avised to use contraceptives. The future of children born after administration of anti cancer drugs is uncertain. Sterility, carcinogenic risk, mutation, teratogenetic effects in future generations cannot be ruled out.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Chlorambucil; Cyclophosphamide; Embryo, Mammalian; Female; Fetus; Folic Acid Antagonists; Humans; Infertility; Male; Mercaptopurine; Mice; Neoplasms; Pregnancy; Pregnancy Complications; Rabbits; Rats

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Adult; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Female; Humans; Labor, Induced; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Pregnancy; Pregnancy Complications, Hematologic

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Amides; Animals; Female; Fetal Death; Fetus; Mercaptopurine; Mice; Pregnancy; Pregnancy, Animal