The effectiveness of ultrasound-indicated cerclage for the reduction of extreme preterm birth in twin pregnancies with a short cervix: a systematic review and meta-analysis: Short title: Effectiveness of cerclage in twin pregnancies with a short cervix.

Objective: Evaluate the effectiveness of cervical cerclage in women with a twin pregnancy and a midpregnancy asymptomatic short cervix (≤25mm), in preventing preterm birth (PTB) and improving neonatal outcomes.

Data sources: Systematic searches were conducted in MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to April 17 2023, updated in September and February 2024.

Study eligibility criteria: Included were RCTs, cohort studies and case-control studies comparing cerclage vs. expectant management in twin pregnancies and an asymptomatic short cervix (≤25mm).

Study appraisal and synthesis methods: Risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale and the Risk of Bias 2 (RoB 2) tool. Data was analyzed using RevMan 5.4 using a Random-Effects Model.

Results: Three RCTs and 13 cohort studies, involving 696 cerclage patients and 595 controls, were analyzed. Combined RCT findings (N=49) found no significant difference in PTB occurrence after adjustment for PTB history and gestational age. Neonates from cerclage-treated mothers exhibited significantly higher rates of RDS (aOR 3.88, 95% CI 1.09-21.03) and very low birth weight (aOR 2.22, 95% CI 1.07-5.73). In contrast, pooled cohort data indicated significantly less PTB rates in women with a cerclage: at 34 weeks (RR 0.75, 95% CI 0.63-0.90), 32 weeks (RR 0.67, 95% CI 0.49-0.90), and 28 weeks (RR 0.572, 95% CI 0.39-0.83). Cerclage also reduced risk for infants <1500g, respiratory distress syndrome, admission at the neonatal intensive care unit and sepsis. Women with cervical length <15mm and a cerclage experienced fewer PTB rates at <37 weeks (RR 0.88, 0.81-0.94), 34 weeks (RR 0.70, 95% CI 0.57-0.87), 32 weeks (RR 0.63, 95% CI 0.50-0.80) and 28 weeks (RR 0.43, 95% CI 0.32-0.59). Perinatal mortality risk was significant lower in neonates born to mothers with a cerclage. For women with cervical length between 16 and 25mm, no significant differences in outcomes were observed.

Conclusions: Based on our meta-analysis, cerclage may benefit women with a twin pregnancy with an asymptomatic midpregnancy short cervix <25mm, especially in women with a cervix <15mm, by reducing PTB and improving neonatal outcomes. However, the differences between RCTs and recent cohort studies emphasize the need for well-powered RCTs on neonatal outcomes before introducing cerclage in clinical practice for these women.