High or low dose oxytocin for nulliparous women delayed in the first stage of labour: the HOLDS RCT.

Background: Delay in the first stage of labour occurs in approximately 20% of nulliparous women. Recommended treatment is intravenous oxytocin, which shortens labour but does not affect the mode of birth. There is some evidence that a higher dose regimen may decrease the need for caesarean section. Objective: The primary objective was to establish if a high-dose regimen of oxytocin compared to the current standard-dose regimen reduced the need for caesarean section for nulliparous women with confirmed delay in the first stage of labour. Design: Multicentre, randomised double-blind controlled trial. Setting: Twenty-one maternity units in the United Kingdom. Participants: Consenting nulliparous women who had a singleton cephalic pregnancy, gestation of 37-41 weeks inclusive, confirmed delay in labour in first stage, ruptured membranes and for whom the clinical decision has been made to prescribe oxytocin. Interventions: Standard-dose regimen of oxytocin (2 mU/min increasing every 30 minutes to a maximum of 32 mU/min) compared with high-dose regimen (4 mU/min increasing every 30 minutes to a maximum of 64 mU/min). Main outcome measures: The primary outcome was the rate of caesarean section. Secondary outcomes included maternal and neonatal birth outcomes and safety. Results: One hundred and eighteen women were successfully randomised via third-party minimisation from an intended sample size of 1500 between 30 June 2017 and 14 November 2022. The caesarean section rate in the standard-dose group was 34% (20/58) and 27% (16/60) in the high-dose group. The intervention was provided as intended in 96% (113/118) of participants. There was no obvious suggestion that the high-dose regime was unsafe (all neonates were discharged home with mother), but this size of sample prohibited any definitive conclusions. Limitations: The trial did not meet its intended sample size due to a number of challenges. It was difficult for busy clinical staff to recruit women in labour in this acute, but not emergency, situation. The legislative requirements of undertaking research using interventional medicinal products imposed further constraints, and we encountered challenges in the production, blinding and monitoring required. Changes in clinical practice since trial design and commencement 10 years ago have resulted in fewer women going into spontaneous labour (reduced from 66% to 47%), and therefore potentially becoming eligible, due to more women having labour induced (22%-33%) or elective caesarean sections (12%-20%). These challenges were further compounded by a falling birth rate and the impact of the COVID-19 pandemic. Conclusions: The question of the optimum dose of oxytocin for nulliparous women delayed in the first stage of spontaneous labour remains an important unanswered clinical question, and the major challenge is how best to address this within the current regulatory framework. Future work: Future studies should consider whether the option of delayed consent would be suitable in this acute, but not emergency, situation. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 14/140/44.