BACKGROUND AND PURPOSE: 

• Jarde et al. (BJOG, 2018) compared different types and routes of administration of progesterone, cerclage, and pessary for preterm birth prevention 

METHODS: 

• Systematic review and meta-analysis  
  • Included RCTs  
  • Population: At-risk women based on preterm birth, short cervix or other risk factors (as determined by researchers)  
    • Cerclage (any type) | Pessary | Progesterone (any route) 
    • Interventions were compared to controls or other specified interventions  
• Primary outcomes  
  • Preterm birth (PTB) <37 week and preterm birth <34 weeks and overall  
• Secondary outcomes 
  • Neonatal death   
  • Other adverse maternal and newborn outcomes  
• Statistical analysis 
  • Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI) as well as pairwise meta-analyses and confidence intervals (CI)  
• Assessed evidence quality using GRADE methods

RESULTS: 

• 40 trials | 11,311 women 

In at-risk women overall (any risk factor)  

• Vaginal progesterone reduced PTB and risk of neonatal death  
  • PTB <34 weeks: Odds ratio (OR) 0.43 (95% CrI, 0.20–0.81; low quality evidence) 
  • PTB <37 weeks: OR 0.51 (95% CrI, 0.34–0.74; low quality evidence) 
  • Neonatal death: OR 0.41 (95% CrI, 0.20–0.83; moderate quality evidence) 
• IM 17-OHPC reduced PTB 
  • PTB <37 weeks: OR 0.61 (95% CrI, 0.39-0.92; Moderate quality evidence)  
• Pessary reduced risk of PTB  
  • PTB <37 weeks: OR 0.31 (95% CrI, 0.13-0.82 (very low quality evidence)  

Previous PTB 

• Vaginal progesterone reduced PTB  
  • PTB <34 weeks: OR 0.29 (95% CI, 0.12–0.68; moderate quality evidence) 
  • PTB <37 weeks: OR 0.43 (95% CrI, 0.23–0.74; moderate quality evidence) 
  • Appears to be dose dependent with greater reduction when dose was >200 mg/day for PTB<37 weeks (low quality evidence)  
    • OR 0.18 for high dose vs 0.42 for lower dose  
  • No reduction in neonatal death  
• 17OHPC reduced PTB and neonatal death (no studies assessed PTB <34 weeks) 
  • PTB <37 weeks: OR 0.53 (95% CrI, 0.27–0.95; moderate quality evidence) 
  • Neonatal death: OR 0.39 (95% CI, 0.16–0.95; low quality evidence) 
• PO Progesterone 
  • PTB <34 weeks: OR 0.42 (95% CI, 0.22-0.83; low quality evidence)  

Short cervix (≤25 mm) 

• Vaginal progesterone reduced PTB (regardless of history of PTB)  
  • PTB <34 weeks: OR 0.45 (95% CI, 0.24–0.84; low quality evidence) 

CONCLUSION: 

• Authors recognize limitations of this study including  
  • Sparse data for some subgroups (especially short cervix) 
  • Different interventions and outcomes  
• In at-risk women, progesterone and 17-OHPC significantly reduced PTB
  • Pessary reduced PTB <37 weeks and risk of PROM and possibly sepsis  
  • Cerclage increased gestational age at birth and reduced PTB <33 weeks  
• For short cervix, vaginally administered progesterone led to reduced preterm birth in singleton at-risk pregnancies (no/limited data available for other routes)  
• Overall, vaginal progesterone performed well across all groups, but further research is needed to confirm benefit as well as the finding of reduced neonatal death with 17-OHP  

Learn More – Primary Sources: 

Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis 

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