Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

OBJECTIVE: To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. METHODS: We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-ß=0.8, α=0.05, two-sided). RESULTS: The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. CONCLUSION: Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.

Effect of routine controlled cord traction as part of the active management of the third stage of labour on postpartum haemorrhage: multicentre randomised controlled trial (TRACOR).

OBJECTIVE: To assess the impact of controlled cord traction on the incidence of postpartum haemorrhage and other characteristics of the third stage of labour in a high resource setting. DESIGN: Randomised controlled trial. SETTING: Five university hospital maternity units in France. PARTICIPANTS: Women aged 18 or more with a singleton fetus at 35 or more weeks' gestation and planned vaginal delivery. INTERVENTIONS: Women were randomly assigned to management of the third stage of labour by controlled cord traction or standard placenta expulsion (awaiting spontaneous placental separation before facilitating expulsion). Women in both arms received prophylactic oxytocin just after birth. MAIN OUTCOME MEASURE: Incidence of postpartum haemorrhage ≥ 500 mL as measured in a collector bag. RESULTS: The incidence of postpartum haemorrhage did not differ between the controlled cord traction arm (9.8%, 196/2005) and standard placenta expulsion arm (10.3%, 206/2008): relative risk 0.95 (95% confidence interval 0.79 to 1.15). The need for manual removal of the placenta was significantly less frequent in the controlled cord traction arm (4.2%, 85/2033) compared with the standard placenta expulsion arm (6.1%, 123/2024): relative risk 0.69, 0.53 to 0.90); as was third stage of labour of more than 15 minutes (4.5%, 91/2030 and 14.3%, 289/2020, respectively): relative risk 0.31, 0.25 to 0.39. Women in the controlled cord traction arm reported a significantly lower intensity of pain and discomfort during the third stage than those in the standard placenta expulsion arm. No uterine inversion occurred in either arm. CONCLUSIONS: In a high resource setting, the use of controlled cord traction for the management of placenta expulsion had no significant effect on the incidence of postpartum haemorrhage and other markers of postpartum blood loss. Evidence to recommend routine controlled cord traction for the management of placenta expulsion to prevent postpartum haemorrhage is therefore lacking. TRIAL REGISTRATION: ClinicalTrials.gov NCT01044082.