Oral misoprostol for induction of labour in resource-limited settings
Induction of labour is a critical life-saving intervention that has been proven to have an immeasurable impact on reducing maternal and perinatal mortality and morbidity worldwide. Current induction of labour regimes using intravenous oxytocin and prostaglandins, such as dinoprostone, are highly effective but often limited or unavailable in developing countries. dinoprostone, for instance, is widely used in developed countries but its high cost and instability at ambient temperatures limits its usefulness as a cost-effective agent, particularly in developing countries such as Papua New Guinea where the burden of obstetric and perinatal complications are unfortunately the highest in the Pacific region.
Advantages of Misoprostol
Compared to other prostaglandins, misoprostol has several potential advantages. It is stable at room temperature, inexpensive and can be administered through the oral, vaginal, sublingual and buccal routes. Nevertheless, limited data currently exist concerning the safety, efficacy and feasibility of administering oral misoprostol in routine clinical practice in resource-poor settings.
Pilot Observational Study Findings
Prior to the trial, we conducted a pilot observational study to investigate the safety and effectiveness of an oral misoprostol regimen that we have been using in this setting for the past decade. Briefly, in this pilot study, more than 6000 labour ward admissions were screened prior to enrolling 209 women who fulfilled the study inclusion criteria and underwent induction of labour.
The following table presents the key outcomes from the pilot study:
| Metric | Outcome |
|---|---|
| Delivered within 24 hours | 74 per cent |
| Vaginal delivery | 90 per cent |
| Good outcome for mother and baby | 86 per cent |
Overall, 74 per cent of the 209 women delivered within 24 hours. Most (90 per cent) delivered vaginally, with 86 per cent having a good outcome for both the mother and baby. Of the 10 per cent who failed induction of labour and underwent caesarean section, a significant proportion of their babies were admitted to special-care nursery compared to babies delivered vaginally. However, their perinatal mortality rate was not significantly higher. The only maternal death was not study related and occurred in a patient with post-partum haemorrhage that occurred 15 hours after delivery.
Following this study, we concluded that the oral misoprostol regimen for induction of labour, commencing at 25 μg, is safe, effective and logistically feasible to administer in a resource-limited setting. However, questions related to the oral misoprostol dose escalation nature of our study as well as the limited safety data of such a regimen and its potential to cause dose-dependent adverse effects still remained.
Clinical Trial Design and Methodology
With the support of a Global Health Research Scholarship provided by the RANZCOG Foundation, we designed the current trial (trial registration ISRCTN10107246) and hypothesised that a regimen commencing with a lower dose of oral misoprostol administered at 12 μg per dose and gradually increased to a maximum of 50 μg per dose over 24 hours will have a non-inferior efficacy and a better safety profile in inducing labour in a developing country setting.
Study Setting
The clinical trial was conducted at Modilon General Hospital; a provincial hospital on the northern coast of mainland Papua New Guinea. Modilon hospital has an average of 3000 deliveries per year and an average induction rate of three to five per cent. The hospital has two consultant obstetricians, two registrars and nine midwives who assisted in this study, as well as an operating theatre facility that was used to perform emergency caesarean sections and/or other obstetric and gynaecologial operative procedures.
Randomisation Process
After appropriate ethics approvals, trial registration and the formation of a Data Monitoring and Safety Committee, we conducted an open-label randomised controlled trial of a lower dose versus a standard dose of oral misoprostol. Based on computer-generated block randomisation, eligible patients were allocated 1:1 to the standard treatment group commencing at 25 μg or a lower dose of oral misoprostol commencing at 12 μg. Allocated treatments were concealed in sealed numbered envelopes that were opened in sequence by study medical or nursing staff and the specified treatment administered.