Systematic review
Misoprostol for induction of labour
Systematic review
|Updated
Our main findings were that vaginal and oral misoprostol was at least as effective as dinoprostone in inducing labour within 24 hours. However, it may have increased frequency of adverse events such as uterine hyperstimulation both without and with changes in fetal heart rate.
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Background
Approximately 55 000 children are born in Norway each year. It is sometimes necessary to induce labour artificially. With respect to induction with drugs, misoprostol and dinoprostone are used irrespective of whether the cervix is mature or not, while oxytocin only is used when the cervix is mature. The Norwegian Board of Health Supervision asked The Norwegian Knowledge Centre for the health Services to systematically review the efficacy and safety of misoprostol for induction of labour.
Method
This report is an overview of systematic reviews. We performed systematic searches in Cochrane Library, CRD and Ovid Medline and Embase. All included publications were evaluated for quality. In addition, we evaluated the quality of the evidence and the strength of recommendations for selected outcomes.
We also performed an evaluation of legal aspects regarding the use of misoprostol for induction of labour.
Results
Five systematic reviews met our inclusion criteria. In the systematic reviews misoprostol was given vaginally, orally, sublingually or buccally. Misoprostol was used in different dosages and dosage intervals from study to study.
Our main findings were that vaginal and oral misoprostol was at least as effective as dinoprostone in inducing labour within 24 hours. However, it may have increased frequency of adverse events such as uterine hyperstimulation both without and with changes in fetal heart rate.
Conclusion
It may appear that safety is more sensitive to the dose of misoprostol than efficacy. For sublingual and buccal administration of misoprostol the amount of data were limited and we were not able to conclude on efficacy and safety.
Summary
Background
The Norwegian Board of Health Supervision asked The Norwegian Knowledge Centre for the health Services to systematically review the efficacy and safety of misoprostol for induction of labour.
Approximately 55 000 children are born in Norway each year. Around 85 % are delivered vaginally and of these 10-15 % are induced by different methods, including drugs and mechanical or in combination. With respect to induction with drugs, misoprostol and dinoprostone are used irrespective of whether the cervix is mature or not, while oxytocin only is used when the cervix is mature.
Of the drugs used, only dinoprostone holds a marketing authorization in Norway for the indication of induction of labour, and as such only in a dose and formulation for intracervical use. Misoprostol, other forms of dinoprostone and oxytocin are obtained after notification to the Norwegian Medicines Agency or used off-label.
This report deals with induction of labour with misoprostol in different administration forms and in comparison to dinoproston, close to term and of live foetus.
Method
This report is an overview of systematic reviews.
We performed systematic searches in Cochrane Library, CRD and Ovid Medline and Embase. Two employees at the Norwegian Knowledge Centre for the Health Services examined all identified titles and abstracts. Potentially relevant publications were ordered in full-text and evaluated according to predefined criteria. All included publications were evaluated for quality. Study quality was assigned as high, medium or low. Evaluations were performed independently and disagreements were solved by discussion. In addition, we evaluated the quality of the evidence and the strength of recommendations for selected outcomes.
We also performed an evaluation of legal aspects regarding the use of drugs outside the approved indication.
Results
We identified 419 unique titles in the search for systematic reviews. We considered 26 of these to be potentially relevant based on title and/or abstract. Of these, 5 systematic reviews were included based on specific inclusion criteria, Their quality ranged from medium to high.
In the systematic reviews misoprostol was given vaginally, orally, sublingually or buccally. It was used in different dosages and dosage intervals from study to study.
The results indicated that misoprostol was at least as effective as dinoprostone on several outcomes, as vaginal delivery not achieved within 24 hours, cervix unfavourable/unchanged after 12-24 hours and oxytocin augmentation. The results varied according to formulation and dosage. Some adverse events appeared more frequently with misoprostol, such as uterine hyperstimulation without and with changes in fetal heart rate. Differences in more serious adverse events, such as need for neonatal intensive care unit admission were not statistically significant, while data for uterine rupture were too limited to allow for conclusions.
With respect to Norwegian practice the vaginal comparisons seem most relevant. For vaginal misoprostol compared to vaginal dinoprostone, misoprostol had favourable outcomes in vaginal delivery not achieved within 24 hours (RR 0,80 (0,73-0,87)), oxytocin augmentation (RR 0,64 (0,56-0,73)) and cervix unfavourable/unchanged after 12-24 hours (RR 0,52 (0,27-0,98)) while dinoprostone was favoured for hyperstimulation without changes in fetal heart rate (RR 2,93 (2,04-4,2)), hyperstimulation with changes in fetal heart rate (RR 2,32 (1,62-3,32)) and meconium-stained liquor (RR 1,41 (1,05-2,0)). Comparison of vaginal misoprostol with intracervical dinoprostone yielded similar results.
The legal evaluation emphasized on the need of patient information, drug liability and compensation to patients. It further discussed who is to be responsible for harm when drugs are used outside the approved indication
Discussion
The amount of data was surprisingly high considering that induction of labour is “off-label” use of misoprostol.
An overview of systematic reviews has methodological limitations. One possible weakness is that shortcomings in the systematic reviews such as missing studies or limited outcomes are carried on. Further the period of time between performing the literature search to the finished article introduces the possibility of missing out on the latest updates in the area. We have refrained from performing a search for new studies to see if further studies change the conclusions in the systematic reviews. This is a limitation in this report.
The included systematic reviews are based on randomized controlled studies. Studies on misoprostol have included around 20 000 women. This is probably enough women to show effect and examine adverse events that appear relatively frequent, such as uterine hyperstimulation. However, the numbers are not large enough to discover differences in rare adverse events, such as uterine rupture.
Pregnant women and their families are entitled to compensation after treatment with misoprostol for induction of labour just as they would be after other treatments. The condition is that there is a clear link of causation between the use of misoprostol and the adverse event, and that the adverse event also inflict an economic loss for the involved.
Conclusion
Our main findings were:
- vaginal and oral misoprostol were at least as effective as dinoprostone in inducing labour within 24 hours, but may have an increased frequency of adverse events
- It may appear that safety is more sensitive to the dose of misoprostol than efficacy
- For sublingual and buccal administration of misoprostol the amount of data is limited and we are not able to conclude on efficacy and safety.