First author of this new Cochrane Review, 'Low‐dose oral misoprostol for induction of labour', Robert Kerr explains, “Our review found that Misoprostol given orally outperforms the ‘gold-standard’ drug which is much more expensive, and used in preference in many countries. This review has the potential to impact millions of women and babies who have inductions of labour through its comparison of oral misoprostol with other commonly used induction techniques."
Labour inductions are common around the world. Induction rates vary worldwide, but for example in the UK, 1 in 3 women will have labour induced. Induction of labour may be a life-saving intervention and identifying effective and safe methods will help achieve greater positive birth experiences for mothers and their babies.
In this recently published Cochrane review, authors explored the evidence from randomised controlled trials to see if low-dose misoprostol given by mouth is effective in starting labour in women in their third trimester with a live baby. They compared misoprostol with other commonly used methods of inducing labour.
What is the issue?
Artificially starting labour, or induction, is common in pregnancy. Reasons include the mother having high blood pressure in pregnancy or the baby being past the due date. Misoprostol is a type of prostaglandin that can be taken in low doses by mouth to induce labour. Prostaglandins are hormone-like compounds that are made by the body for various functions (including the natural onset of labour). Unlike other prostaglandins such as vaginal dinoprostone, misoprostol does not need to be stored in the refrigerator. Taking a tablet is convenient to mothers and the low-dose tablet sizes are now available (25 µg).
Why is this important?
A good induction method achieves a safe birth for mother and baby. It is effective, results in a relatively low number of caesarean sections, has few side effects, and is highly acceptable to mothers. Some methods of inducing labour may cause more caesarean sections by being ineffective at bringing on labour, other methods may lead to more caesareans as they cause too many contractions (hyperstimulation) that result in the baby becoming distressed (foetal heart rate changes).
What evidence did we find?
We searched for evidence on 14 February 2021 and identified 61 trials involving 20,026 women for inclusion in this review. Not all trials were high quality.
Starting with oral misoprostol immediately may have a similar effect on rates of caesarean section (4 trials, 594 women; low-certainty evidence) to giving no treatment for 12 to 24 hours then starting oxytocin, while the effects of misoprostol on uterine hyperstimulation with foetal heart rate changes are unclear (3 trials, 495 women; very low-quality evidence). All women in theses trials had ruptured membranes.
Oral misoprostol was compared to vaginal dinoprostone in 13 trials (9676 women). Misoprostol use probably decreased the risk of caesarean section (moderate-certainty evidence). When studies were divided by their initial dose of misoprostol, there was evidence that use of 10 µg to 25 µg may be effective in reducing the risk of a caesarean section (9 trials, 8652 women), while the higher 50 µg dose might not reduce the risk (4 trials, 1024 women). There may be very small or no differences between misoprostol and dinoprostone in rates of vaginal births within 24 hours (10 trials, 8983 women; low-certainty evidence) but may be fewer cases of hyperstimulation with foetal heart rate changes with oral misoprostol (11 trials, 9084 women; low-certainty evidence).
Oral misoprostol was compared with vaginal misoprostol in 33 trials (6110 women). Oral use may have resulted in fewer vaginal births within 24 hours (16 trials, 3451 women; low-certainty evidence). Oral use may have caused less hyperstimulation with foetal heart rate changes (25 trials, 4857 women; low-certainty evidence), especially with a dose of 10 µg to 25 µg. There was no clear difference in the number of caesarean sections overall (32 trials, 5914 women; low-certainty evidence) but oral use likely resulted in fewer caesareans being performed because of concerns of the baby being in distress (24 trials, 4775 women).
When oral misoprostol was compared to oxytocin for induction, misoprostol use probably resulted in fewer caesarean sections (6 trials, 737 women). We found no clear difference in vaginal birth within 24 hours (3 trials, 466 women; moderate-certainty evidence) or hyperstimulation with foetal heart rate changes (3 trials, 331 women; very low-certainty evidence).
Oral misoprostol was compared to a balloon catheter inserted in the cervix to mechanically induce labour. The number of vaginal births within 24 hours may have increased with misoprostol (4 trials, 1044 women; low-certainty evidence). Misoprostol probably reduced the risk of caesarean section (6 trials, 2993 women; moderate-certainty evidence) with no difference in risk of hyperstimulation with foetal heart rate changes (4 trials, 1044 women; low-certainty evidence).
Different doses and timings of giving oral misoprostol were explored in three small trials. The certainty of the findings from these trials was either low or very low so we cannot draw any meaningful conclusions from this data.
What does this mean?
Using low-dose (50 µg or less) oral misoprostol to induce labour likely leads to fewer caesarean sections and so more vaginal births than vaginal dinoprostone, oxytocin, and a transcervical Foley catheter. Rates of hyperstimulation with foetal heart rate changes were comparable with these methods. Misoprostol taken by mouth causes less hyperstimulation with foetal heart changes compared to when taken vaginally.
More trials are needed to establish the most effective misoprostol regimen for labour induction, but for now the findings of this review support oral rather than vaginal use, and suggest that commencing oral misoprostol at a dose of 25 µg or less may be safe and effective.
Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours.
Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation.
Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress.
The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.