G J Hofmeyr1, A M Gulmezoglu. 1. (Director, Effective Care Research Unit, University of the Witwatersrand), Frere/Cecilia Makiwane Hospitals, Private Bag 9047, East London 5200, Eastern Cape, SOUTH AFRICA. gjh@global.co.za
Abstract
BACKGROUND: Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue marketed for use in the prevention and treatment of peptic ulcer disease. It is inexpensive, easily stored at room temperature and has few systemic side effects. It is rapidly absorbed orally and vaginally. Although not registered for such use, misoprostol has been widely used for obstetric and gynaecological indications, such as induction of abortion and of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Date of last search: October 2000. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing vaginal misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. The initial data extraction is done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will then be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. MAIN RESULTS: Compared to placebo, misoprostol was associated with increased cervical ripening (relative risk of unfavourable or unchanged cervix after 12 to 24 hours with misoprostol 0.09, 95% confidence interval 0.03 to 0.24). It was also associated with a reduced need for oxytocin (relative risk 0.52, 95% confidence interval 0.41 to 0.68). Misoprostol was more effective than prostaglandin E2 vaginally for labour induction (relative risk of failure to achieve vaginal delivery in 24 hours 0.70, 95% confidence interval 0.61 to 0.81). Oxytocin augmentation was used less often with misoprostol than with prostaglandin E2 vaginally (relative risk 0.65, 95% confidence interval 0.60 to 0.71). Uterine hyperstimulation and meconium stained liquor were more common with misoprostol than with prostaglandin E2. Lower doses of misoprostol compared to higher doses did not show significant differences except for more need for oxytocin augmentation and less uterine hyperstimulation without fetal heart rate changes. Information on women's views is conspiciously lacking. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective in inducing labour than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. The studies were not large enough to exclude the possibility of rare but serious adverse effects, particularly uterine rupture, which has been reported following misoprostol use in women with and without previous caesarean section. The authors request information on cases of uterine rupture known to readers. Further research is needed to establish safety.
BACKGROUND:Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue marketed for use in the prevention and treatment of peptic ulcer disease. It is inexpensive, easily stored at room temperature and has few systemic side effects. It is rapidly absorbed orally and vaginally. Although not registered for such use, misoprostol has been widely used for obstetric and gynaecological indications, such as induction of abortion and of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Date of last search: October 2000. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing vaginal misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy has been developed to deal with the large volume and complexity of trial data relating to labour induction. This involves a two-stage method of data extraction. The initial data extraction is done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will then be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. To avoid duplication of data in the primary reviews, the labour induction methods have been listed in a specific order, from one to 25. Each primary review includes comparisons between one of the methods (from two to 25) with only those methods above it on the list. MAIN RESULTS: Compared to placebo, misoprostol was associated with increased cervical ripening (relative risk of unfavourable or unchanged cervix after 12 to 24 hours with misoprostol 0.09, 95% confidence interval 0.03 to 0.24). It was also associated with a reduced need for oxytocin (relative risk 0.52, 95% confidence interval 0.41 to 0.68). Misoprostol was more effective than prostaglandin E2 vaginally for labour induction (relative risk of failure to achieve vaginal delivery in 24 hours 0.70, 95% confidence interval 0.61 to 0.81). Oxytocin augmentation was used less often with misoprostol than with prostaglandin E2 vaginally (relative risk 0.65, 95% confidence interval 0.60 to 0.71). Uterine hyperstimulation and meconium stained liquor were more common with misoprostol than with prostaglandin E2. Lower doses of misoprostol compared to higher doses did not show significant differences except for more need for oxytocin augmentation and less uterine hyperstimulation without fetal heart rate changes. Information on women's views is conspiciously lacking. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective in inducing labour than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. The studies were not large enough to exclude the possibility of rare but serious adverse effects, particularly uterine rupture, which has been reported following misoprostol use in women with and without previous caesarean section. The authors request information on cases of uterine rupture known to readers. Further research is needed to establish safety.