G J Hofmeyr1, A M Gülmezoglu. 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 (October 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) and bibliographies of relevant papers. 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 was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will 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: Sixty-two trials have been included. 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 (CI) 0.03 to 0.24). It was also associated with reduced failure to achieve vaginal delivery within 24 hours (relative risk (RR) 0.36, 95% CI 0.19 to 0.68). Uterine hyperstimulation, without fetal heart rate changes, was increased (RR 11.7 95% CI 2.78 to 49). Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol labour induction was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common, with misoprostol and meconium-stained liquor more common. Compared with intracervical prostaglandin E2, unchanged or unfavourable cervix after 12 to 24 hours was less common with misoprostol. Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation, less uterine hyperstimulation, with and without fetal heart rate changes, and a non-significant trend to fewer admissions to neonatal intensive care unit. Use of a gel preparation of misoprostol versus tablet was associated with less hyperstimulation and more use of oxytocin and epidural analgesia. Information on women's views is conspicuously lacking. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. Doses not exceeding 25 mcg four-hourly of concern. Doses not exceeding 25 mcg four-hourly appeared to have similar effectiveness and risk of uterine hyperstimulation to conventional labour inducing methods. The studies reviewed were not large enough to exclude the possibility of rare but serious adverse events, particularly uterine rupture, which has been reported anecdotally 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 the ideal route of administration and dosage, and safety. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances.
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 (October 2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) and bibliographies of relevant papers. 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 was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data will 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: Sixty-two trials have been included. 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 (CI) 0.03 to 0.24). It was also associated with reduced failure to achieve vaginal delivery within 24 hours (relative risk (RR) 0.36, 95% CI 0.19 to 0.68). Uterine hyperstimulation, without fetal heart rate changes, was increased (RR 11.7 95% CI 2.78 to 49). Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol labour induction was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common, with misoprostol and meconium-stained liquor more common. Compared with intracervical prostaglandin E2, unchanged or unfavourable cervix after 12 to 24 hours was less common with misoprostol. Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation, less uterine hyperstimulation, with and without fetal heart rate changes, and a non-significant trend to fewer admissions to neonatal intensive care unit. Use of a gel preparation of misoprostol versus tablet was associated with less hyperstimulation and more use of oxytocin and epidural analgesia. Information on women's views is conspicuously lacking. REVIEWER'S CONCLUSIONS: Vaginal misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. The apparent increase in uterine hyperstimulation is of concern. Doses not exceeding 25 mcg four-hourly of concern. Doses not exceeding 25 mcg four-hourly appeared to have similar effectiveness and risk of uterine hyperstimulation to conventional labour inducing methods. The studies reviewed were not large enough to exclude the possibility of rare but serious adverse events, particularly uterine rupture, which has been reported anecdotally 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 the ideal route of administration and dosage, and safety. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances.
Authors: Gary L Darmstadt; Mohammad Yawar Yakoob; Rachel A Haws; Esme V Menezes; Tanya Soomro; Zulfiqar A Bhutta Journal: BMC Pregnancy Childbirth Date: 2009-05-07 Impact factor: 3.007