BACKGROUND AND PURPOSE:

• Kerr et al. (Cochrane Database of Systematic Reviews, 2021) assessed the efficacy and safety of low-dose oral misoprostol for labor induction in women with a viable fetus in the third trimester of pregnancy

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • RCTs
  • Studies that compared low-dose oral misoprostol (initial dose ≤ 50 µg) with
    • Placebo
    • Vaginal dinoprostone
    • Vaginal misoprostol
    • Oxytocin
    • Mechanical methods
  • Studies that compared oral misoprostol protocols
    • one- to two-hourly vs four- to six- hourly protocols
    • 20 µg to 25 µg vs 50 µg
    • 20 µg hourly titrated vs 25 µg two-hourly static
• Study design
  • Quality of evidence was assessed using GRADE criteria
• Primary outcomes
  • Vaginal birth within 24 hours
  • Cesarean delivery
  • Hyperstimulation with fetal heart rate changes

RESULTS:

• 61 trials | 20,026 women
• Quality of evidence ranged from moderate- to very low-certainty, with downgrading due to imprecision, inconsistency, and study limitations

Oral misoprostol vs placebo/no treatment (4 trials | 594 women)

• Oral misoprostol may make little to no difference in the rate of caesareans
  • Risk ratio (RR) 0.81 (95% CI, 0.59 to 1.11); moderate certainty
• Effect on uterine hyperstimulation is uncertain
  • RR 5.15 (95% CI, 0.25 to 105.31); very low‐certainty
• Vaginal births within 24 hours were not reported
• In all trials, oxytocin could be started after 12 to 24 hours and all women had pre‐labor ruptured membranes

Oral misoprostol vs vaginal dinoprostone (13 trials | 9676 women)

• Oral misoprostol probably results in fewer cesarean deliveries
  • RR 0.84 (95% CI, 0.78 to 0.90); moderate certainty
• Subgroup analysis indicated that this decrease in cesarean deliveries may be limited to 10 µg to 25 µg vs 50 µg dose group
  • 10 to 25 µg: RR 0.80 (95% CI, 0.74 to 0.87)
  • 50 µg: RR 1.10 (95% CI, 0.91 to 1.34)
• Oral misoprostol may decrease
  • Vaginal births within 24 hours
    • RR 0.93 (95% CI, 0.87 to 1.00); low certainty
  • Hyperstimulation
    • RR 0.49 (95% CI, 0.40 to 0.59); low certainty

Oral misoprostol vs vaginal misoprostol (33 trials | 6110 women)

• Oral use may result in
  • Fewer vaginal births within 24 hours: Average RR 0.81 (95% CI, 0.68 to 0.95); low certainty
  • Less hyperstimulation: RR 0.69 (95% CI, 0.53 to 0.92); low certainty
    • Subgroup analysis suggests 10 to 25 µg orally may be superior to 50 µg orally
    • 10 to 25 µg: RR 0.28 (5% CI, 0.14 to 0.57)
    • 50 µg: RR 0.82 (95% CI, 0.61 to 1.11)
• Oral misoprostol probably does not increase cesarean deliveries overall
  • Average RR 1.00 (95% CI, 0.86 to 1.16) low certainty
• Oral misoprostol likely results in fewer cesarean deliveries due to fetal distress
  • RR 0.74 (95% CI, 0.55 to 0.99)

Oral misoprostol vs intravenous oxytocin (6 trials | 737 women, 200 with ruptured membranes)

• Misoprostol may make little or no difference to vaginal births within 24 hours
  • RR 1.12 (95% CI, 0.95 to 1.33); low certainty
• Misoprostol probably results in fewer cesarean deliveries
  • RR 0.67 (95% CI, 0.50 to 0.90); moderate certainty
• The effect on hyperstimulation is uncertain
  • RR 0.66 (95% CI, 0.19 to 2.26); very low certainty

Oral misoprostol vs mechanical methods (6 trials | 2993 women)

• All six trials compared oral misoprostol to transcervical Foley catheter
• Misoprostol may increase vaginal birth within 24 hours
  • RR 1.32 (95% CI, 0.98 to 1.79); low certainty
• Misoprostol probably reduces the risk for cesarean
  • RR 0.84 (95% CI, 0.75 to 0.95); moderate certainty
• There may be little or no difference in hyperstimulation
  • RR 1.31 (95% CI, 0.78 to 2.21); low certainty

Oral misoprostol one‐ to two‐hourly vs four‐ to six‐hourly (1 trial |64 women)

• The evidence on hourly titration was very uncertain due to the low numbers reported

Oral misoprostol 20 µg hourly titrated vs 25 µg two‐hourly static (2 trials | 296 women)

• The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours
  • RR 0.97 (95% CI, 0.80 to 1.16); low certainty
• The evidence is of very low certainty for all other reported outcomes

CONCLUSION:

• Overall, oral misoprostol is probably better than other methods of labor induction
• Compared to vaginal dinoprostone, low-dose oral misoprostol is probably associated with
  • Fewer caesarean deliveries | More vaginal births | Lower rates of hyperstimulation with fetal heart rate changes
  • Time to birth may be increased
• Compared to Foley catheter, low-dose oral misoprostol is associated with
  • Fewer caesarean deliveries
  • Rates of hyperstimulation are similar
• Compared with vaginal misoprostol, oral misoprostol is probably associated with
  • Similar rates of vaginal birth | Rates may be lower within the first 24 hours
  • There are likely fewer cesarean deliveries due to fetal distress, and lower rates of hyperstimulation
• 25 µg starting does appears to be safe and effective
• The authors state

The best available evidence suggests that low dose oral misoprostol probably has many benefits over other methods for labour induction

This review supports the use of low dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally

Learn More – Primary Sources:

Low-dose oral misoprostol for induction of labour

Related ObG Topics:

Oral vs Vaginal Misoprostol for Labor Induction

Single or Multi-Dose Misoprostol for Labor Induction?

Cochrane Review 2017: Outpatient Cervical Ripening and Labor Induction

Cochrane Review Update: Safety and Effectiveness of Mechanical vs Pharmacological Methods of Labor Induction