BACKGROUND AND PURPOSE: 

• Care et al. (BMJ, 2022) performed a network meta-analysis of various treatment options for the prevention of spontaneous preterm birth in at-risk women  

METHODS: 

• Systematic review with Bayesian network meta-analysis
• Study inclusion criteria
  • RCTs
  • Study participants who are at high risk of spontaneous preterm birth due to history of spontaneous preterm birth or short cervical length
  • Data included assessment of treatment options
• Study design
  • Treatments: Bed rest | Cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage) | Cervical pessary | Fish oils or omega fatty acids | Nutritional supplements (zinc) | Progesterone (intramuscular, oral, or vaginal) | Prophylactic antibiotics | Prophylactic tocolytics | Combinations of interventions
  • Controls: Placebo or no treatment
  • Relative treatment effects (odds ratios and 95% credible intervals) and certainty of evidence were calculated for outcomes of preterm birth <34 weeks and perinatal death
• Primary outcome
  • Preterm birth <34 weeks
  • Perinatal death
  • Other maternal and fetal outcomes

RESULTS: 

• 61 studies | 17,273 pregnant women

Preterm Birth <34 weeks

• Compared to placebo or no treatment, vaginal progesterone was associated with fewer women with preterm birth <34 weeks
  • Odds ratio (OR) 0.50 (95% CrI, 0.34 to 0.70); high certainty of evidence
• Effect size of treatment was highest for Shirodkar cerclage, but certainty was low
  • OR 0.06 (95% CrI, 0.00 to 0.84); low certainty of evidence
• The following treatments may also reduce preterm birth <34 weeks
  • 17OHPC (17α-hydroxyprogesterone caproate)
    • OR 0.68 (95% CrI, 0.43 to 1.02); moderate certainty
  • Vaginal pessary
    • OR 0.65 (95% CrI, 0.39 to 1.08); moderate certainty
  • Fish oil or omega 3
    • OR 0.30 (95% CrI, 0.06 to 1.23); moderate certainty

Perinatal death

• Compared to placebo or no treatment, vaginal progesterone was the only treatment that showed clear evidence of benefit for reducing perinatal death
  • OR 0.66 (95% CrI, 0.44 to 0.97); moderate certainty
• The following treatments might reduce perinatal death rates, but credible intervals could not exclude the possibility of harm
  • 17OHPC
    • OR 0.78 (95% CrI, 0.50 to 1.21); moderate certainty
  • McDonald cerclage
    • OR 0.59 (95% CrI, 0.33 to 1.03); moderate certainty
  • Unspecified cerclage
    • OR 0.77 (95% CrI, 0.53 to 1.11); moderate certainty
• Only progesterone treatments are associated with reduction the following neonatal outcomes
  • Neonatal respiratory distress syndrome
  • Neonatal sepsis
  • Necrotizing enterocolitis
  • Admission to neonatal intensive care unit

CONCLUSION: 

• Vaginal progesterone is the best preventative treatment option for asymptomatic women at risk of preterm birth due to short cervix and history of preterm birth 
• The authors suggest that future trials use vaginal progesterone as the ‘gold standard’ comparator group when assessing other treatment options 
  • Administering placebo or no treatment will be difficult to offer 
• The authors state 

Vaginal progesterone is currently the best preterm birth prevention treatment for women with a singleton pregnancy who are asymptomatic but at high risk of preterm birth 

No other treatment can be regarded as superior, but promising results have been observed for alternative routes of administration (oral, intramuscular), and treatments such as cerclage and pessary 

Learn More – Primary Sources: 

Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis 

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