We would have liked to be more positive about misoprostol in our systematic review because of its known advantages. However, we believe that we should be cautious for the following reasons:
- 1Most published trials have reported cases of clinically significant uterine hyperstimulation with misoprostol.
- 2There have been reports and we are aware of several unreported cases of uterine rupture and fetal loss with and without previous caesarean section following labour induction with misoprostol1. One randomised trial of labour induction with misoprostol in women with a previous caesarean section has been stopped because of 2 cases of uterine rupture in 17 women using very small dosage (25 μg 6-hourly)2.
- 3As misoprostol has not been registered for us in pregnancy, it has not gone through the rigorous testing for safety and dosage that would apply to a registered drug.
- 4There is as yet no agreed dosage or route of administration. Day et al. do not mention the dose and the regimen they use for labour induction with misoprostol. Widely varying doses have been used in the reported trials. Current packaging of misoprostol in 200 mcg tablets in many countries also makes it difficult to use small doses. We have attempted to minimise the risk of overdose and account for individual variations in sensitivity by giving frequent very small oral dosages (initially 20 μg of misoprostol solution), titrated against uterine response3.
- 5The dangers are particularly great in low-income countries where facilities for monitoring the mother and the fetus and emergency caesarean section may be limited. For example, a report from South Africa described labour inductions with vaginal misoprostol in 345 women with live fetuses and 86 with intrauterine deaths. There was one unexplained maternal death; two uterine ruptures, one of which followed a previous caesarean section; eight caesarean sections for fetal distress and one for uterine hyperstimulation; and 10 perinatal deaths4.
We agree that in circumstances in which no alternatives exist, labour induction for serious obstetric problems with misoprostol may be life-saving. Health workers using misoprostol in such cases should be fully aware of the risks and weigh these against potential benefits in each case. However, the widespread use of misoprostol in varying doses as an easy option for routine labour induction, particularly in low-income countries, has become a problem. We maintain that until the optimal dosage and route of administration are established and larger trials reported, misoprostol for labour induction should not be labelled ‘safe’.