Atosiban 6.75mg/0.9ml solution for injection pre-filled syringes

ObjectiveTwin pregnancies have a substantial risk of preterm birth, but evidence on tocolytics is limited. We evaluated whether nifedipine or atosiban improves neonatal outcomes compared with placebo.DesignIndividual participant data network meta-analysis (IPD-NMA) of two international multicentre randomised controlled trials (APOSTEL 3 and 8).SettingThe APOSTEL-3 compared nifedipine with atosiban, while the APOSTEL-8 compared atosiban with placebo.PopulationWomen with twin pregnancies and threatened preterm birth between 30+0 and 33+6 weeks.MethodsAnalyses were performed at the infant level using generalised estimating equations to account for clustering within twin pairs.Main outcome measuresAdverse neonatal outcome: composite of neonatal morbidity or mortality.ResultsA total of 179 women were included: 94 allocated to atosiban, 27 to nifedipine, and 58 to placebo. Prolongation beyond 48 h was not significantly increased with nifedipine (RR 0.96, 95% CI 0.68-1.36) or atosiban (RR 1.10, 95% CI 0.88-1.38). The composite adverse neonatal outcome occurred in 3.7% of neonates in the nifedipine group (2/54), 7.5% in the atosiban group (14/188), and 5.2% in the placebo group (6/116). Relative risks were 0.72 (95% CI 0.15-3.43) for nifedipine vs placebo, 1.44 (95% CI 0.57-3.64) for atosiban vs placebo, and 2.01 (95% CI 0.47-8.58) for atosiban vs nifedipine.ConclusionNo clear benefit of nifedipine or atosiban over placebo on neonatal outcomes in twin pregnancies with threatened preterm birth between 30+0 and 33+6 weeks was found.

Abstract licence: CC BY

Abstract Background: Atosiban has shown ameliorative effects in preterm birth (PTB), repeated implantation failure, and breech delivery by suppressing contractions, but its safety profile has not been fully established. Methods: Published randomized controlled trials and observational studies was electronically searched from inception to September 1, 2022. Our primary outcomes were maternal adverse events and neonatal comorbidities. Random effects model was used for data synthesis, and pooled risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Results: 43 studies comprising 11,772 patients were identified eligible. The incidence of maternal adverse events in atosiban group and controls were 4.0% and 12.4%, respectively. Overall, the risk of maternal adverse events and the discontinuation of treatment due to adverse events were significantly lower with atosiban compared with controls (RR 0.38, 95% CI [0.23, 0.61], P < 0.0001; RR 0.11, 95% CI [0.04, 0.29], P < 0.00001; respectively). The incidence of neonatal comorbidities was similar, and a higher risk of neonatal apnoea was observed in atosiban group compared with controls (RR 1.40, 95% CI [1.04, 1.90], P = 0.03). Conclusion: Atosiban has comparable efficacy and substantial better safety profile in the management of PTB, in vitro fertilization-embryo transfer (IVF-ET) and external cephalic version (ECV) compared with controls. Additionally, awareness of the presence of neonatal apnoea is required. In clinical practice, the appropriate treatment regimen needs to be selected according to the local circumstances and the individual patient condition.

Abstract licence: CC BY 4.0