Can universal cervical length screening with vaginal progesterone for a short cervix reduce preterm birth? A systematic review and meta-analyses.

The global rate of preterm birth (PTB) is not declining, resulting in approximately one million deaths annually among children under five due to complications related to PTB. Universal cervical length screening followed by progesterone treatment in women with a short cervix has been proposed as a preventive strategy. We systematically assessed the accuracy of this approach in reducing the incidence of PTB and improving neonatal outcomes. We conducted a systematic literature search and meta-analysis registered in PROSPERO (CRD42024605203). Medline, Embase, and the Cochrane Library were searched in October 2024 and updated in September 2025. Eligible studies included randomized controlled trials (RCTs), cohort studies, and systematic reviews comparing universal cervical length screening with vaginal ultrasound in mid-trimester followed by progesterone treatment versus no screening in asymptomatic women with a singleton pregnancy. Outcomes of interest were any PTB, spontaneous PTB (sPTB), and neonatal outcomes. The certainty of evidence was assessed separately for RCTs and cohort studies using the GRADE approach. Two RCTs (1634 participants) and four cohort studies (425 735 participants) were included. Results from RCTs showed no statistically significant reduction in any PTB, sPTB, peri/neonatal mortality, or morbidity after screening versus no screening. In contrast, meta-analyses of cohort studies demonstrated a significant reduction for any PTB < 37 weeks; adjusted odds ratio 0.87, 95% confidence interval (CI) 0.78-0.98, and sPTB < 37 weeks; relative risk 0.82, 95% CI 0.70-0.96. Meta-analyses of cohort studies also demonstrated a significant reduction in sPTB < 34 and <32 weeks. The cohort studies presented no data on neonatal outcomes. The certainty of evidence from RCTs was rated very low due to limited precision and lack of significant results. Although meta-analyses of cohort studies showed significant associations, the certainty of evidence was also very low because of indirectness and a high risk of bias inherent in observational study designs. It is uncertain, based on very low certainty of evidence, whether universal cervical length screening followed by progesterone treatment for women with a short cervix reduces PTB or affects neonatal outcomes, compared with no screening. More adequately powered trials are needed before a recommendation can be made.