Grand Rounds

Misoprostol for Retained Placenta: A Recent Meta-analysis Takes Another Look at the Evidence

BACKGROUND AND PURPOSE:

Pharmacologic methods to treat retained placenta have been suggested
Manual extraction is the standard treatment and there is limited data on the whether prostaglandins are a superior alternative compared to other medications
Grillo-Ardila et al. (International Journal of Gynecology and Obstetrics, 2018) assessed the efficacy of prostaglandin analogues for retained placenta

Systematic review and meta-analysis
- Database search of RCTs comparing prostaglandin analogues with any other intervention
- Women age 18-40 years with singleton pregnancy and vaginal delivery
- Trials were independently selected and assessed to eliminate bias
Diagnosis of retained placenta
- ≥30 minutes (5 studies)
- ≥60 minutes (2 studies)
Route of administration included intra-umbilial injection, oral or IV
Intervention
- Prostaglandin analogues vs placebo, no intervention, oxytocin, oxytocin agonists, ergot alkaloids, or any other intervention
- Most common: misoprostol
GRADE methods used to evaluate evidence quality
Primary outcomes
- Maternal mortality | Placenta expulsion | Maternal transfusion | Serious adverse effects

7 randomized controlled trials | 851 patients
Prostaglandins did not increase the placenta expulsion rate
- Relative risk (RR) 1.40; 95% CI, 0.83–2.36 (low quality evidence)
Prostaglandins did not decrease maternal transfusion
- RR 0.72; 95% CI, 0.43–1.22
Compared to oxytocin
- Prostaglandins did not modify expulsion rate (low quality evidence)
  - RR 1.40; 95% CI, 0.83–2.36
- Maternal transfusion
  - RR 1.05; 95% CI, 0.27–4.09
- Time for delivery of placenta
  - Mean difference: −1.56 minutes; 95% CI, −9.25–6.13
Trials comparing prostaglandins with oxytocin agonists, ergometrine, and manual removal reported similar results (moderate quality evidence)

Prostaglandin analogues do not offer an effective alternative for management of retained placenta
Authors acknowledge limited quality of evidence (i.e., little confidence that study results reflect true effect)
Strength of study include inclusion of ‘grey literature’ (i.e., studies that are in different languages or not published)
These results differ from Cochrane reviews
- Intra-umbilical injection: Cochrane demonstrated a decrease in the need to perform manual extraction but only included 2 of the studies presented in this review
- Non-intra-umbilical route: Cochrane results did not meet statistical significance

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