Effect of dual tocolysis with fenoterol and atosiban in human myometrium.

Objectives To measure the tocolytic effect of the combination of the oxytocin receptor antagonist atosiban with the ß-mimetic agent fenoterol on human myometrium of pregnant women. Methods An in vitro study of contractility in human myometrium at the Laboratory of the Department of Obstetrics, University Hospital of Zürich, Switzerland, was performed. Thirty-six human myometrial biopsies were obtained during elective caesarean sections of singleton pregnancies at term. Tissue samples were exposed to atosiban, fenoterol and the combination of atosiban with fenoterol. Contractility was measured as area under the curve during 30 min of spontaneous contractions. The effect of treatment was expressed as the percentage of change from basal activity during 30 min of exposure. Differences were calculated using a paired Wilcoxon signed-rank test. An additive effect of dual tocolysis was assumed when no significant difference was detected between the observed and expected inhibition of dual tocolysis. When inhibition was greater or lower than expected, the dual combination was characterised as "synergistic" or "antagonistic", respectively. Results Atosiban and fenoterol alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The combination of atosiban plus fenoterol was measured at a level of 67.3% inhibition. There was no significant difference in the expected (63.2%) and observed inhibition effect of dual tocolysis (P=0.945). Conclusion This study demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on human myometrium in vitro, but no synergistic or antagonistic effect.

Congenital Lung Lesion: Prenatal Course, Therapy and Predictors of Perinatal Outcome.

Purpose To describe the prenatal course and perinatal outcome, and to define prognostic markers for fetuses with congenital pulmonary airway malformation (CPAM) or bronchopulmonary sequestration (BPS). Materials and Methods A retrospective study was performed at the University Hospital Zurich including pregnancies with either fetal CPAM (n = 26) or BPS (n = 11) between 2000 and 2013. Results Three patients decided for termination of pregnancy. Two intrauterine deaths (CPAM) occurred at 25 weeks. Minimally invasive interventions were performed in 9/37 (24 %) fetuses, post-interventional survival was 8/9 (89 %). Mean gestational age at delivery was 38.1 +/-2.8 and 39.1 +/-2.5 weeks in fetuses with CPAM or BPS, respectively. In fetuses with CPAM the perinatal mortality rate was 4/24 (17 %); the rate of invasive interventions or surgery during the early neonatal period (neonatal morbidity) was 9/22 (41 %). Prenatal diagnosis of hydrothorax and/or increasing cystic volume ratio (CVR) until delivery preceded perinatal death in 3/5 (60 %). Absent mediastinal shift showed a neonatal morbidity rate of 1/8 (13 %) without any perinatal mortality. In fetuses with BPS the perinatal morbidity and mortality were both 1/10 (10 %). Hydrops predicted morbidity and mortality in 100 % of cases. Absent hydrops was followed by uncomplicated perinatal outcome. Conclusion Fetuses with CPAM or BPS have a good outcome under optimal perinatal care including the possibility to perform minimally invasive prenatal interventions. CPAM without mediastinal shift and BPS without hydrops have an excellent prognosis. Hydrothorax, increasing CVR or hydrops indicates a high risk for perinatal morbidity and mortality.

Postponed pregnancies and risks of very advanced maternal age.

QUESTIONS UNDER STUDY: To evaluate pregnancy outcome in pregnant women aged ≥45 years, termed very advanced maternal age (VAMA). METHODS: We retrospectively compared the outcome of pregnancies in VAMA patients with controls aged 30 years at time of delivery. Subgroups of singleton and multiple pregnancies were also analysed. Incidences of maternal and fetal adverse outcomes were measured. Statistical significance was set at p <0.05. Odds ratios (ORs) were adjusted where necessary. RESULTS: One hundred and twenty-seven VAMA pregnancies and 2066 control pregnancies of women aged 30 years were analysed. VAMA pregnancies had a higher rate of maternal complications such as gestational hypertension (3.9% vs 0.6%; OR 6.5), preeclampsia (14.2% vs 3.0%; OR 5.4, adjusted OR 4.4) and gestational diabetes (12.6% vs 3.6%; OR 3.8). Likewise, increased need for blood transfusion (3.2% vs 0.7%; OR 4.8, adjusted OR 4.4) and prolonged hospitalisation >7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight <5th percentile (11.0% vs 5.6%; OR 2.1) were also increased. CONCLUSION: Pregnant women of very advanced maternal age (≥45 years) have significantly increased maternal and fetal risks. Women postponing pregnancy or planning a pregnancy in very advanced age should be informed about these risks, in particular before artificial reproductive technologies are applied or "social freezing".

Position at birth as an important factor for the occurrence of anal sphincter tears: a retrospective cohort study.

OBJECTIVE: This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. STUDY DESIGN: A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. RESULTS: The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). CONCLUSIONS: Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST.

Successful remission of extensive liver metastases in a breast cancer patient with acute liver failure using a combined chemotherapy regimen with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU).

BACKGROUND: Liver failure due to disseminated hepatic secondaries represents a therapeutic dilemma in patients with metastatic breast cancer (MBC). Reduced liver function and non-assessable toxicity are limiting factors in the selection of chemotherapeutic agents. Currently, there is no standard treatment after failure of anthracycline-and taxane-based first-line therapies, although there is a variety of well evaluated drugs such as capecitabine. CASE REPORT: We report on a 45-year-old breast cancer patient with disseminated hepatic metastases. She presented in markedly poor condition, showing substantial ascites and extensive jaundice. Blood chemistry analysis showed increased serum levels of liver enzymes (aspartate aminotransferase 271 U/l, alanine transaminase 101 U/l), bilirubin (7.9 mg/dl), and CA 15-3 (1,459 U/l). We induced a palliative chemotherapy with mitomycin, folinate, and 5-fluorouracil (Mi/Fo/FU). The patient improved impressively after the first cycle of systemic therapy. Liver enzymes stabilized continuously, CA 15-3 returned to normal. The patient was discharged 2 weeks after the treatment start. Chemotherapy was well tolerated under dose escalation, no grade 3/4 toxicity was observed. The progression-free interval was 5 months. CONCLUSIONS: A combination therapy with Mi/Fo/FU appears to be a reasonable and tolerable alternative salvage strategy for patients with liver failure due to hepatic breast cancer metastases.