BACKGROUND AND PURPOSE:

• Evidence regarding the efficacy of vaginal progesterone for preterm birth prevention is conflicting
• Conde-Agudelo et al. (AJOG, 2022) assessed the efficacy and safety of vaginal progesterone to prevent recurrent preterm birth and adverse perinatal outcomes in singleton gestations  

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • RCTs
  • Asymptomatic women with a singleton gestation and a history of spontaneous preterm birth
  • Comparison of vaginal progesterone to placebo or no treatment
• Study design
  • Pooled relative risk (RR) were estimated
  • Risk of bias and quality of evidence were assessed
  • Subgroup analyses were performed
• Primary outcomes
  • Preterm birth <37 and <34 weeks
• Secondary outcomes
  • Adverse maternal and perinatal outcomes

RESULTS:

• 10 studies | 2958 women
  • Small studies (sample size <150): 7
    • High risk of bias: 4
  • Large studies (samples size >600): 3
    • High risk of bias: none
• Vaginal progesterone significantly decreased the risk of
  • Preterm birth at 37 weeks
    • RR 0.64 (95% CI, 0.50 to 0.81)
    • 95% prediction interval 0.31 to 1.32
    • Very low-quality evidence
  • Preterm birth <34 weeks
    • RR 0.62 (95% CI, 0.42 to 0.92)
    • 95% prediction interval 0.23 to 1.68
    • Very low-quality evidence
  • NICU Admission
    • RR 0.53 (95% CI, 0.33 to 0.85)
    • 95% prediction interval 0.16 to 1.79
    • Low-quality evidence
• There were no significant differences between the vaginal progesterone and the placebo or no treatment groups for other adverse perinatal and maternal outcomes
• Subgroup analyses revealed that vaginal progesterone decreased the risk of preterm birth in small studies, but not large studies
  • Preterm birth <37 weeks
    • Small studies: RR 0.43 (95% CI, 0.33 to 0.55)
    • Large studies: RR 0.98 (95% CI, 0.88 to 1.09)
  • Preterm birth <34 weeks
    • Small studies: RR 0.27 (95% CI, 0.15 to 0.49)
    • Large studies: RR 0.94 (95% CI, 0.78 to 1.13)
• Analyses restricted to studies at low risk of bias indicated that vaginal progesterone did not reduce the risk of preterm birth
  • Preterm birth <37 weeks: RR 0.96 (95% CI, 0.84 to 1.09)
  • Preterm birth <34 weeks: RR 0.90 (95% CI, 0.71 to 1.15)
• Small-study effects (when small trials report larger benefits of treatment than large trials)
  • Found to be present in the meta-analyses of preterm birth <37 and <34 weeks
• The adjustment for small-study effects resulted in a markedly reduced and nonsignificant effect of vaginal progesterone on preterm birth
  • Preterm birth <37 weeks: RR 0.86 (95% CI, 0.68 to 1.10)
  • Preterm birth <34 weeks: RR 0.92 (95% CI, 0.60 to 1.42)

CONCLUSION:

• Vaginal progesterone did not reduce the risk of recurrent preterm birth for women with singleton gestations and a history of preterm birth
• The authors state

In summary, there is persuasive evidence that small-study effects in the meta-analyses of the effect of vaginal progesterone on preterm birth <37 and <34 weeks of gestation are mainly explained by the poor methodological quality of most small trials

Learn More – Primary Sources:

Does vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis

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