British Journal of Obstetrics and Gynaecology April 2000, Vol107, pp. 576-578

CORRESPONDENCE

Misoprostol for induction of labour at term (Received 29 September 1999)

Sic We read with interest the recent randomised comparative trial by Danielian et al. and the systematic review by Hofmeyr et al. (Vol 106, August 1999)’,’ on the use of misoprostol as an agent for induction of labour. We believe that we are one of the few units in the UK to be using this preparation routinely for all women having induction of labour.

We compared the outcomes of 177 women between January and June 1997 whose labours were induced with dinoprostone with 243 women whose labours were induced between January and June 1998 with misoprostol. We demonstrated a significant difference in induc- tion-tkelivery interval when misoprostol was compared with dino- prostone, a significant reduction in the use of oxytocin augmentation and a non-significant reduction in the instrumental delivery rate and caesarean section rate. We also compared umbilical venous pH, umbilical venous base excess, Apgar scores and admission to the spe- cial care baby unit between the two groups and could find no clini- cally important differences. There was a significantly increased rate of tachysystole in the misoprostol group but not of hyperstimulation. There were no untoward maternal or fetal events.

Both articles referred to above and the editorial comment in the same edition of the British Journal of Obstetrics and Gynaecology expressed caution with the use of misoprostol for routine induction of labour. One point made was that the increased pain in the group induced by misoprostol should limit its use but this has to be balanced against the much greater efficacy of the drug and all practising obste- tricians will be familiar with the woman who remains undelivered after several days of dinoprostone. We have found that failed induc- tion is very uncommon when misoprostol is used. Secondly, there are considerable cost savings involved in using this more effective induc- tion agent. We have calculated that on the basis of reduced drug costs and a significantly shorter period of hospital stay our annual savings in a district general hospital with a delivery rate of 4200 was $69,000. Clearly safety concerns must be considered but Hofmeyr et al. and Danielian et al. could find no evidence of clinically adverse events and the latter also referred to two meta-analyses in his paper which came to similar conclusions.

We noticed that one of the authors of the systematic review by Hofmeyr et al. works with the WHO and yet the conclusion of their paper was that it should not be introduced into more widespread use without further controlled trials. We have this luxury in the West but we feel that the potential for the use of misoprostol could have been more positively commented on, particularly its use in the third world. One of the authors of this letter (R.H.) has had experience recently with obstetric units in the former Soviet Union and it is clear that misoprostol which is cheap, effective and does not require refrigera- tion has a powerful capacity to reduce maternal morbidity and mor- tality in countries where standard induction agents (i.e. dinoprostone) cannot be afforded or are in variable supply.

Louise Day, And Tailor & Richard Howard Department of Obstetrics and Gynaecology, King George Hospital, Ilford Stephen Burrell Department of Obstetrics and Gynaecology, University College Hospital, London

References 1 Danielian P, Porter B, Fem N, Summers J, Templeton A. Misoprostol

for induction of labour at term: a more effective agent than dinopros- tone vaginal gel. Br J Obstet Gynaecoll999; 106: 793-797.

2 Hofmeyr GJ, Giilmezoglu AM, Alfirevic Z . Misoprostol for induction of labour: a systematic review. Br J Obstet Gynaecol 1999; 106: 798-803.

AUTHORS’ REPLY Sic 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:

Most published trials have reported cases of clinically significant uterine hyperstimulation with misoprostol. There 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 misoprostol’. 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 Fg 6-hourly)’. As 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. There 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 fre- quent very small oral dosages (initially 20 pg of misoprostol solu- tion), titrated against uterine response3. The 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 cae- sarean sections for fetal distress and one for uterine hyperstimula- tion; 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’. G. J. Hofmeyr Department of Obstetrics and Gynaecology, Coronation Hospital and University of the Witwatersrand, South Africa A. M. Giilmezoglu UK Cochrane Centre Z. Alfirevic Department of Obstetrics and Gynaecology, Liverpool University

References 1 Hofrneyr GJ, Giilmezoglu AM. Vaginal misoprostol for cervical

576 0 RCOG 2000 British Journal of Obstetrics and Gynaecology