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Grand Rounds

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

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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

METHODS: 

  • 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

RESULTS: 

  • 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)

CONCLUSION: 

  • 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

Learn More – Primary Sources: 

Systematic review of prostaglandin analogues for retained placenta

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Related ObG Topics:

Postpartum Hemorrhage – Medications to Treat Uterine Atony 
How Effective is Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage
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