• Romero et al. (Ultrasound in Obstetrics & Gynecology, 2022) updated the 2017 meta-analysis to assess whether vaginal progesterone was associated with a reduced risk of preterm birth in women with twin pregnancies and short cervix 

• Individual patient data meta-analysis 
• Study inclusion criteria 
  • RCTs published from 2017 to 2021 
  • Studies that compared vaginal progesterone (any dose) vs placebo/no treatment for the prevention of preterm birth and/or adverse perinatal outcome in women with a twin gestation and a mid-trimester sonographic cervical length ≤25 mm 
• Study design 
  • Update of a 2017 
    • 1 study removed due to lack of prior approval by ethics committee 
    • Inclusion of 1 new research study  
  • Risk of bias in included studies was assessed with criteria recommended by the Cochrane Handbook for Systematic Reviews of Interventions 
  • Grade criteria used to assess quality of evidence 
  • Adjusted relative risk (RR) used as main estimates to determine effect of vaginal progesterone on primary outcome 
• Primary outcome 
  • Preterm birth <33 weeks 

• Secondary outcomes 
  • Preterm birth < 37, < 36, < 35, < 34, < 32, < 30 and < 28 weeks’ gestation 
  • Spontaneous preterm birth < 33 and < 34 weeks’ gestation 
  • Adverse perinatal outcomes: RDS | NEC | IVH | Proven neonatal sepsis | Retinopathy of prematurity | Fetal death | Neonatal death | Perinatal death | Composite outcome of neonatal morbidity and mortality 

• 6 studies (5 from 2017 study and 1 new study) | 90 women | 195 fetuses 
  • All studies were deemed to be at low risk of bias 
• Vaginal progesterone significantly reduced the risk of preterm birth <33 weeks’ 
  • Vaginal progesterone: 38.5% 
  • Placebo/no treatment: 55.8% 
  • RR 0.60 (95% CI, 0.38 to 0.95); P=0.03 
  • Needed to treat (NNT) for benefit: 5 (95% CI, 3 to 36) 
• Vaginal progesterone group had significantly lower frequencies of  
  • Preterm birth at < 34, < 32, < 30 and < 28 weeks 
  • Spontaneous preterm birth at < 33 and < 34 weeks 
• There was no evidence of an effect of vaginal progesterone on preterm birth < 37, < 36 and < 35 weeks’ gestation 
• Treatment with vaginal progesterone was also associated with a significant decrease in the risk for 
  • Composite neonatal morbidity and mortality 
    • RR 0.59 (95% CI, 0.33 to 0.98) 
  • Birth weight < 1500 g  
    • RR 0.55 (95% CI, 0.33 to 0.94) 

• In this updated individual patient data meta-analysis, vaginal progesterone was still associated with a reduced risk of preterm birth in women with twin pregnancy and short cervix 
• The authors state 

Nevertheless, it should be emphasized that evidence from an ongoing randomized controlled trial (PROSPECT study) is needed to establish whether this promising intervention can be recommended to women with a twin gestation and a short cervix 

Vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations with a short cervix: an updated individual patient data meta-analysis 

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