Oral misoprostol for induction of labour

Abstract

Background: Misoprostol is an orally active prostaglandin. In most countries misoprostol is not licensed for labour induction, but its use is common because it is cheap and heat stable.

Objectives: To assess the use of oral misoprostol for labour induction in women with a viable fetus.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 January 2014).

Selection criteria: Randomised trials comparing oral misoprostol versus placebo or other methods, given to women with a viable fetus for labour induction.

Data collection and analysis: Two review authors independently assessed trial data, using centrally-designed data sheets.

Main results: Overall there were 76 trials (14,412) women) which were of mixed quality.In nine trials comparing oral misoprostol with placebo (1109 women), women using oral misoprostol were more likely to give birth vaginally within 24 hours (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.05 to 0.49; one trial; 96 women), need less oxytocin (RR 0.42, 95% CI 0.37 to 0.49; seven trials; 933 women) and have a lower caesarean section rate (RR 0.72, 95% CI 0.54 to 0.95; eight trials; 1029 women).In 12 trials comparing oral misoprostol with vaginal dinoprostone (3859 women), women given oral misoprostol were less likely to need a caesarean section (RR 0.88, 95% CI 0.78 to 0.99; 11 trials; 3592 women). There was some evidence that they had slower inductions, but there were no other statistically significant differences.Nine trials (1282 women) compared oral misoprostol with intravenous oxytocin. The caesarean section rate was significantly lower in women who received oral misoprostol (RR 0.77, 95% CI 0.60 to 0.98; nine trials; 1282 women), but they had increased rates of meconium-stained liquor (RR 1.65, 95% CI 1.04 to 2.60; seven trials; 1172 women).Thirty-seven trials (6417 women) compared oral and vaginal misoprostol and found no statistically significant difference in the primary outcomes of serious neonatal morbidity/death or serious maternal morbidity or death. The results for vaginal birth not achieved in 24 hours, uterine hyperstimulation with fetal heart rate (FHR) changes, and caesarean section were highly heterogenous - for uterine hyperstimulation with FHR changes this was related to dosage with lower rates in those with lower doses of oral misoprostol. However, there were fewer babies born with a low Apgar score in the oral group (RR 0.60, 95% CI 0.44 to 0.82; 19 trials; 4009 babies) and a decrease in postpartum haemorrhage (RR 0.57, 95% CI 0.34 to 0.95; 10 trials; 1478 women). However, the oral misoprostol group had an increase in meconium-stained liquor (RR 1.22, 95% CI 1.03 to 1.44; 24 trials; 3634 women).

Authors' conclusions: Oral misoprostol as an induction agent is effective at achieving vaginal birth. It is more effective than placebo, as effective as vaginal misoprostol and results in fewer caesarean sections than vaginal dinoprostone or oxytocin.Where misoprostol remains unlicensed for the induction of labour, many practitioners will prefer to use a licensed product like dinoprostone. If using oral misoprostol, the evidence suggests that the dose should be 20 to 25 mcg in solution. Given that safety is the primary concern, the evidence supports the use of oral regimens over vaginal regimens. This is especially important in situations where the risk of ascending infection is high and the lack of staff means that women cannot be intensely monitored.

Conflict of interest statement

Zarko Alfirevic is one of the principal investigators of a trial included in this review. He acted as an adviser and co‐investigator on the Phase III trials to companies involved in the development of misoprostol products for labour induction, but payments were on a one‐off basis with no regular or long‐lasting personal relationships with any organisation. Neither he, nor his immediate family, hold any shares or stocks in any company. Andrew Weeks runs the www.misoprostol.org website as a service to provide accurate information to women about misoprostol use. He is principal investigator for an MRC funded phase 3 study of oral misoprostol for labour induction. Neither he nor his family have financial interests that would gain from an increased use of misoprostol.

Figures

1

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

2

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

1.1. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 1 Vaginal delivery not achieved in 24 hours.

1.2. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

1.3. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 3 Caesarean section.

1.4. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 4 Serious neonatal morbidity or perinatal death.

1.5. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 5 Serious maternal morbidity or death.

1.6. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 6 Epidural analgesia.

1.7. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 7 Oxytocin augmentation.

1.8. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 8 Uterine hyperstimulation without FHR changes.

1.11. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 11 Instrumental vaginal delivery.

1.12. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 12 Meconium‐stained liquor.

1.13. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 13 Apgar score

1.14. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 14 Neonatal intensive care unit admission.

1.15. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 15 Perinatal death.

1.16. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 16 Nausea.

1.17. Analysis

Comparison 1 Oral misoprostol versus placebo/ no treatment (1): all women, Outcome 17 Vomiting.

2.1. Analysis

Comparison 2 Oral misoprostol versus placebo/ no treatment (1): all women with intact membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

3.1. Analysis

Comparison 3 Oral misoprostol versus placebo/ no treatment (1): all women with ruptured membranes, Outcome 1 Vaginal delivery not achieved in 24 hours.

3.2. Analysis

Comparison 3 Oral misoprostol versus placebo/ no treatment (1): all women with ruptured membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

3.3. Analysis

Comparison 3 Oral misoprostol versus placebo/ no treatment (1): all women with ruptured membranes, Outcome 3 Caesarean section.

3.4. Analysis

Comparison 3 Oral misoprostol versus placebo/ no treatment (1): all women with ruptured membranes, Outcome 4 Serious neonatal morbidity or perinatal death.

3.5. Analysis

Comparison 3 Oral misoprostol versus placebo/ no treatment (1): all women with ruptured membranes, Outcome 5 Serious maternal morbidity or death.

4.1. Analysis

Comparison 4 Oral misoprostol versus placebo/ no treatment (1): all primiparae with ruptured membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

4.2. Analysis

Comparison 4 Oral misoprostol versus placebo/ no treatment (1): all primiparae with ruptured membranes, Outcome 2 Caesarean section.

4.3. Analysis

Comparison 4 Oral misoprostol versus placebo/ no treatment (1): all primiparae with ruptured membranes, Outcome 3 Serious maternal morbidity or death.

5.1. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 1 Vaginal delivery not achieved within 24 hours.

5.2. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

5.3. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 3 Caesarean section.

5.4. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 4 Serious neonatal morbidity or perinatal death.

5.5. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 5 Serious maternal morbidity or death.

5.6. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 6 Cervix unfavourable/unchanged after 12‐24 hours.

5.7. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 7 Oxytocin augmentation.

5.8. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 8 Uterine hyperstimulation without FHR changes.

5.9. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 9 Ruptured uterus.

5.10. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 10 Epidural analgesia.

5.11. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 11 Instrumental vaginal delivery.

5.12. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 12 Meconium‐stained liquor.

5.13. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 13 Apgar score

5.14. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 14 Neonatal intensive care unit admission.

5.15. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 15 Neonatal encephalopathy.

5.16. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 16 Perinatal death.

5.17. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 17 Maternal side effects (all).

5.18. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 18 Nausea.

5.19. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 19 Vomiting.

5.20. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 20 Diarrhoea.

5.21. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 21 Shivering.

5.22. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 22 Postpartum haemorrhage.

5.23. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 23 Serious maternal complications.

5.24. Analysis

Comparison 5 Oral misoprostol versus vaginal PG (2): all women, Outcome 24 Hyperpyrexia.

6.1. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

6.2. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

6.3. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 3 Caesarean section.

6.4. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 4 Serious neonatal morbidity or perinatal death.

6.5. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 5 Serious maternal morbidity or death.

6.6. Analysis

Comparison 6 Oral misoprostol versus vaginal PG (2): all women with intact membranes, Outcome 6 Cervix unfavourable/unchanged after 12‐24 hours.

7.1. Analysis

Comparison 7 Oral misoprostol versus vaginal PG (2): all women with ruptured membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

7.2. Analysis

Comparison 7 Oral misoprostol versus vaginal PG (2): all women with ruptured membranes, Outcome 2 Caesarean section.

8.1. Analysis

Comparison 8 Oral misoprostol versus vaginal PG (2): all women with unfavourable cervices, Outcome 1 Vaginal delivery not achieved within 24 hours.

9.1. Analysis

Comparison 9 Oral misoprostol versus vaginal PG (2): all women with favourable cervices, Outcome 1 Vaginal delivery not achieved within 24 hours.

10.1. Analysis

Comparison 10 Oral misoprostol versus vaginal PG (2): all multiparae, Outcome 1 Vaginal delivery not achieved within 24 hours.

10.2. Analysis

Comparison 10 Oral misoprostol versus vaginal PG (2): all multiparae, Outcome 2 Uterine hyperstimulation with FHR changes.

10.3. Analysis

Comparison 10 Oral misoprostol versus vaginal PG (2): all multiparae, Outcome 3 Caesarean section.

11.1. Analysis

Comparison 11 Oral misoprostol versus vaginal PG (2): all primiparae, Outcome 1 Vaginal delivery not achieved within 24 hours.

11.2. Analysis

Comparison 11 Oral misoprostol versus vaginal PG (2): all primiparae, Outcome 2 Uterine hyperstimulation with FHR changes.

11.3. Analysis

Comparison 11 Oral misoprostol versus vaginal PG (2): all primiparae, Outcome 3 Caesarean section.

12.1. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 1 Vaginal delivery not achieved within 24 hours.

12.2. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

12.3. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 3 Caesarean section.

12.4. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 4 Serious neonatal morbidity or perinatal death.

12.5. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 5 Serious maternal morbidity or death.

12.6. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 6 Cervix unfavourable/unchanged after 12‐24 hours.

12.7. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 7 Oxytocin augmentation.

12.8. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 8 Uterine hyperstimulation without FHR changes.

12.9. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 9 Uterine rupture.

12.10. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 10 Perinatal death.

12.11. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 11 Instrumental vaginal delivery.

12.12. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 12 Meconium‐stained liquor.

12.13. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 13 Apgar score

12.14. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 14 Neonatal intensive care unit admission.

12.15. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 15 Neonatal encephalopathy.

12.16. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 16 Maternal death.

12.17. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 17 Maternal side effects (all).

12.18. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 18 Postpartum haemorrhage.

12.19. Analysis

Comparison 12 Oral misoprostol versus intracervical PG (3): all women, Outcome 19 Women not satisfied.

13.1. Analysis

Comparison 13 Oral misoprostol versus intracervical PG (3): all women with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

13.2. Analysis

Comparison 13 Oral misoprostol versus intracervical PG (3): all women with intact membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

13.3. Analysis

Comparison 13 Oral misoprostol versus intracervical PG (3): all women with intact membranes, Outcome 3 Caesarean section.

13.4. Analysis

Comparison 13 Oral misoprostol versus intracervical PG (3): all women with intact membranes, Outcome 4 Serious neonatal morbidity or perinatal death.

13.5. Analysis

Comparison 13 Oral misoprostol versus intracervical PG (3): all women with intact membranes, Outcome 5 Serious maternal morbidity or death.

14.1. Analysis

Comparison 14 Oral misoprostol versus intracervical PG (3): all women with ruptured membranes, Outcome 1 Vaginal delivery not achieved in 24 hours.

14.2. Analysis

Comparison 14 Oral misoprostol versus intracervical PG (3): all women with ruptured membranes, Outcome 2 Caesarean section.

15.1. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 1 Vaginal delivery not achieved in 24 hours.

15.2. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

15.3. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 3 Caesarean section.

15.4. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 4 Serious neonatal morbidity or perinatal death.

15.5. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 5 Serious maternal morbidity or death.

15.6. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 6 Oxytocin augmentation.

15.7. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 7 Uterine hyperstimulation without FHR changes.

15.8. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 8 Uterine rupture.

15.9. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 9 Epidural analgesia.

15.10. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 10 Instrumental vaginal delivery.

15.11. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 11 Meconium‐stained liquor.

15.12. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 12 Apgar score

15.13. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 13 Neonatal intensive care unit admission.

15.14. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 14 Neonatal encephalopathy.

15.15. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 15 Perinatal death.

15.16. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 16 Nausea.

15.17. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 17 Vomiting.

15.18. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 18 Diarrhoea.

15.19. Analysis

Comparison 15 Oral misoprostol versus oxytocin (4): all women, Outcome 19 Postpartum haemorrhage.

16.1. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 1 Vaginal delivery not achieved in 24 hours.

16.2. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

16.3. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 3 Caesarean section.

16.4. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 4 Serious neonatal morbidity or perinatal death.

16.5. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 5 Serious maternal morbidity or death.

16.6. Analysis

Comparison 16 Oral misoprostol versus oxytocin (4): all women with ruptured membranes, Outcome 6 Meconium‐stained liquor.

17.1. Analysis

Comparison 17 Oral misoprostol versus oxytocin (4): all primiparae, Outcome 1 Uterine hyperstimulation with FHR changes.

17.2. Analysis

Comparison 17 Oral misoprostol versus oxytocin (4): all primiparae, Outcome 2 Caesarean section.

18.1. Analysis

Comparison 18 Oral misoprostol versus oxytocin (4): all primiparae with ruptured membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

18.2. Analysis

Comparison 18 Oral misoprostol versus oxytocin (4): all primiparae with ruptured membranes, Outcome 2 Caesarean section.

19.1. Analysis

Comparison 19 Oral misoprostol versus oxytocin (4): all multiparae, Outcome 1 Caesarean section.

20.1. Analysis

Comparison 20 Oral versus sublingual misoprostol (5): all women, Outcome 1 Caesarean section.

20.2. Analysis

Comparison 20 Oral versus sublingual misoprostol (5): all women, Outcome 2 Meconium‐stained liquor.

20.3. Analysis

Comparison 20 Oral versus sublingual misoprostol (5): all women, Outcome 3 Instrumental delivery.

21.1. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 1 Vaginal delivery not achieved within 24 hours.

21.2. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

21.3. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 3 Caesarean section.

21.4. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 4 Serious neonatal morbidity or perinatal death.

21.5. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 5 Serious maternal morbidity or death.

21.6. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 6 Serious maternal complications.

21.7. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 7 Oxytocin augmentation.

21.8. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 8 Uterine hyperstimulation without FHR changes.

21.9. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 9 Uterine rupture.

21.10. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 10 Epidural analgesia.

21.11. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 11 Instrumental vaginal delivery.

21.12. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 12 Meconium‐stained liquor.

21.13. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 13 Apgar score

21.14. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 14 Neonatal intensive care unit admission.

21.15. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 15 Neonatal encephalopathy.

21.16. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 16 Perinatal death.

21.17. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 17 Maternal side effects (all).

21.18. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 18 Nausea.

21.19. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 19 Vomiting.

21.20. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 20 Diarrhoea.

21.21. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 21 Postpartum haemorrhage.

21.22. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 22 Woman not satisfied.

21.23. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 23 Vaginal delivery not achieved within 24 hours (subgroup by quality).

21.24. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 24 Shivering.

21.25. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 25 Uterine hyperstimulation with FHR changes (subgroup by quality).

21.26. Analysis

Comparison 21 Oral versus vaginal misoprostol (6): all women, Outcome 26 Caesarean section (subgroup by quality).

22.1. Analysis

Comparison 22 Oral versus vaginal misoprostol (6): all women with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

22.2. Analysis

Comparison 22 Oral versus vaginal misoprostol (6): all women with intact membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

22.3. Analysis

Comparison 22 Oral versus vaginal misoprostol (6): all women with intact membranes, Outcome 3 Caesarean section.

22.4. Analysis

Comparison 22 Oral versus vaginal misoprostol (6): all women with intact membranes, Outcome 4 Serious neonatal morbidity or perinatal death.

22.5. Analysis

Comparison 22 Oral versus vaginal misoprostol (6): all women with intact membranes, Outcome 5 Serious maternal morbidity or death.

23.1. Analysis

Comparison 23 Oral versus vaginal misoprostol (6): all primiparae with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

23.2. Analysis

Comparison 23 Oral versus vaginal misoprostol (6): all primiparae with intact membranes, Outcome 2 Serious neonatal morbidity or perinatal death.

23.3. Analysis

Comparison 23 Oral versus vaginal misoprostol (6): all primiparae with intact membranes, Outcome 3 Serious maternal morbidity or death.

24.1. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 1 Vaginal delivery not achieved within 24 hours.

24.2. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 2 Uterine hyperstimulation with FHR changes.

24.3. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 3 Caesarean section.

24.4. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 4 Serious neonatal morbidity or perinatal death.

24.5. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 5 Serious maternal morbidity or death.

24.6. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 6 Oxytocin augmentation.

24.7. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 7 Uterine hyperstimulation without FHR changes.

24.8. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 8 Instrumental vaginal delivery.

24.9. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 9 Apgar score

24.10. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 10 Nausea.

24.11. Analysis

Comparison 24 Oral versus vaginal misoprostol (6): all primiparae, Outcome 11 Vomiting.

25.1. Analysis

Comparison 25 Oral versus vaginal misoprostol (6): all women with ruptured membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

25.2. Analysis

Comparison 25 Oral versus vaginal misoprostol (6): all women with ruptured membranes, Outcome 2 Caesarean section.

26.1. Analysis

Comparison 26 Oral versus vaginal misoprostol (6): all primiparae with unfavourable cervix, Outcome 1 Vaginal delivery not achieved within 24 hours.

26.2. Analysis

Comparison 26 Oral versus vaginal misoprostol (6): all primiparae with unfavourable cervix, Outcome 2 Caesarean section.

26.3. Analysis

Comparison 26 Oral versus vaginal misoprostol (6): all primiparae with unfavourable cervix, Outcome 3 Serious neonatal morbidity or perinatal death.

26.4. Analysis

Comparison 26 Oral versus vaginal misoprostol (6): all primiparae with unfavourable cervix, Outcome 4 Serious maternal morbidity or death.

27.1. Analysis

Comparison 27 Oral versus vaginal misoprostol (6): all multiparae, Outcome 1 Vaginal delivery not achieved within 24 hours.

27.2. Analysis

Comparison 27 Oral versus vaginal misoprostol (6): all multiparae, Outcome 2 Caesarean section.

27.3. Analysis

Comparison 27 Oral versus vaginal misoprostol (6): all multiparae, Outcome 3 Serious neonatal morbidity or perinatal death.

27.4. Analysis

Comparison 27 Oral versus vaginal misoprostol (6): all multiparae, Outcome 4 Serious maternal morbidity or death.

28.1. Analysis

Comparison 28 Oral versus vaginal misoprostol (6): all multiparae with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

29.1. Analysis

Comparison 29 Oral versus vaginal misoprostol (6): all multiparae with unfavourable cervix, Outcome 1 Vaginal delivery not achieved within 24 hours.

29.2. Analysis

Comparison 29 Oral versus vaginal misoprostol (6): all multiparae with unfavourable cervix, Outcome 2 Caesarean section.

29.3. Analysis

Comparison 29 Oral versus vaginal misoprostol (6): all multiparae with unfavourable cervix, Outcome 3 Serious neonatal morbidity or perinatal death.

29.4. Analysis

Comparison 29 Oral versus vaginal misoprostol (6): all multiparae with unfavourable cervix, Outcome 4 Serious maternal morbidity or death.

30.1. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 1 Vaginal delivery not achieved within 24 hours.

30.2. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 2 Caesarean section.

30.3. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 3 Serious neonatal morbidity or perinatal death.

30.4. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 4 Oxytocin augmentation.

30.5. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 5 Uterine hyperstimulation without FHR changes.

30.6. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 6 Uterine rupture.

30.7. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 7 Apgar score

30.8. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 8 Neonatal intensive care unit admission.

30.9. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 9 Nausea.

30.10. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 10 Vomiting.

30.11. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 11 Diarrhoea.

30.12. Analysis

Comparison 30 Hourly 20mcg titrated oral misoprostol versus 4‐hrly oral misoprostol 50mcg (7): all women, Outcome 12 Postpartum haemorrhage.

31.1. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 1 Uterine hyperstimulation with FHR changes.

31.2. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 2 Caesaraean section.

31.3. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 3 Serious maternal morbidity or death.

31.4. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 4 Oxytocin augmentation.

31.5. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 5 Uterine hyperstimulation without FHR changes.

31.6. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 6 Uterine rupture.

31.7. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 7 Meconium‐stained liquor.

31.8. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 8 Neonatal intensive care unit admission.

31.9. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 9 Perinatal death.

31.10. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 10 Nausea.

31.11. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 11 Maternal side effects(all).

31.12. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 12 Nausea.

31.13. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 13 Vomiting.

31.14. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 14 Diarrhoea.

31.15. Analysis

Comparison 31 Oral misoprostol 25 mcg 3‐daily versus 50 mcg 3‐daily (8): all women, Outcome 15 Shivering.

32.1. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 1 Vaginal delivery not achieved within 24 hours.

32.2. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

32.3. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 3 Caesarean section.

32.4. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 4 Uterine hyperstimulation without FHR changes.

32.5. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 5 Oxytocin augmentation.

32.6. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 6 Epidural analgesia.

32.7. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 7 Instrumental vaginal delivery.

32.8. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 8 Meconium‐stained liquor.

32.9. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 9 Apgar score

32.10. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 10 Neonatal intensive care unit admission.

32.11. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 11 Nausea.

32.12. Analysis

Comparison 32 Oral misoprostol 50 mcg versus 100 mcg (9): all women, Outcome 12 Diarrhoea.

33.1. Analysis

Comparison 33 Oral misoprostol 50 mcg versus 100 mcg (9): all women with intact membranes, Outcome 1 Vaginal delivery not achieved within 24 hours.

33.2. Analysis

Comparison 33 Oral misoprostol 50 mcg versus 100 mcg (9): all women with intact membranes, Outcome 2 Uterine hyperstimulation with FHR changes.

33.3. Analysis

Comparison 33 Oral misoprostol 50 mcg versus 100 mcg (9): all women with intact membranes, Outcome 3 Caesarean section.

34.1. Analysis

Comparison 34 Oral misoprostol 50 mcg versus 100 mcg (9): all women with ruptured membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

34.2. Analysis

Comparison 34 Oral misoprostol 50 mcg versus 100 mcg (9): all women with ruptured membranes, Outcome 2 Caesarean section.

35.1. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 1 Uterine hyperstimulation with FHR changes.

35.2. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 2 Caesarean section.

35.3. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 3 Oxytocin augmentation.

35.4. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 4 Uterine hyperstimulation without FHR changes.

35.5. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 5 Instrumental vaginal delivery.

35.6. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 6 Meconium‐stained liquor.

35.7. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 7 Nausea.

35.8. Analysis

Comparison 35 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women, Outcome 8 Diarrhoea.

36.1. Analysis

Comparison 36 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women with intact membranes, Outcome 1 Uterine hyperstimulation with FHR changes.

36.2. Analysis

Comparison 36 Oral misoprostol 3/4‐hourly versus 6‐hourly (10): all women with intact membranes, Outcome 2 Caesarean section.

37.1. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 1 Vaginal delivery not achieved in 24 hours.

37.2. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

37.3. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 3 Caesarean section.

37.4. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 4 Uterine hyperstimulation without FHR changes.

37.5. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 5 Instrumental vaginal delivery.

37.6. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 6 Apgar score

37.7. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 7 Neonatal intensive care unit admission.

37.8. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 8 Postpartum haemorrhage.

37.9. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 9 Diarrhoea.

37.10. Analysis

Comparison 37 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all women, Outcome 10 Vomiting.

38.1. Analysis

Comparison 38 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all primiparae, Outcome 1 Vaginal delivery not achieved in 24 hours.

38.2. Analysis

Comparison 38 Oral miso 3‐hourly vs oral miso x2 then routine oxytocin (11): all primiparae, Outcome 2 Caesarean section.

39.1. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 1 Vaginal delivery not achieved in 24 hours.

39.2. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 2 Uterine hyperstimulation with FHR changes.

39.3. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 3 Caesarean section.

39.4. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 4 Oxytocin augmentation.

39.5. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 5 Uterine hyperstimulation without FHR changes.

39.6. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 6 Instrumental vaginal delivery.

39.7. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 7 Apgar score

39.8. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 8 Neonatal intensive care unit admission.

39.9. Analysis

Comparison 39 Oral misoprostol versus delayed vaginal postaglandins (12): all women, Outcome 9 Nausea.

40.1. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 1 Uterine hyperstimulation with FHR changes.

40.2. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 2 Caesarean section.

40.3. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 3 Serious neonatal morbidity/perinatal death.

40.4. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 4 Oxytocin augmentation.

40.5. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 5 Uterine hyperstimulation without FHR changes.

40.6. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 6 Meconium‐stained liquor.

40.7. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 7 Apgar score

40.8. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 8 Perinatal death.

40.9. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 9 Nausea.

40.10. Analysis

Comparison 40 Oral misoprostol versus dinoprostone vaginal insert, Outcome 10 Vomiting.