Background: Multiple gestation has a higher incidence of preterm birth(PTB), especially in the presence of a short cervix. Objectives: To perform a systematic review and network meta-analysis(NMA) evaluating the effect of progesterone, cerclage, cervical pessary and their combination as treatments for preventing PTB<34 weeks. Search strategy: PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, BVS, Scopus, and grey literature were explored. Selection criteria: We included randomized controlled trials that compared an intervention with a control group or another intervention to prevent PTB in women with a twin pregnancy and a short cervix<40mm. Data collection and Analysis:Studies were checked for trustworthiness. We presented summary relative effect sizes(Odds Ratios) for each possible pair of interventions and we used the surface under the cumulative ranking curves(SUCRA) to rank all interventions. Main Results: A total of 20 studies participated in NMA. We found no evidence that the combined treatment of pessary and vaginal progesterone reduced the risk of spontaneous PTB <34 weeks when compared to no intervention(OR 0.68; 95%CI 0.16 to 2.9). Also, pessary(OR 0.78; 95%CI 0.49 to 1.3), vaginal progesterone(OR 0.79; CI95% 0.45 to 1.4) and injectable 17-OH progesterone alone(OR 0.85; CI95% 0.26 to 2.8) did not show a statistically significant reduction in spontaneous PTB. For overall PTB<34 weeks, findings were similar. Conclusions: We found no evidence that progesterone, cervical pessary, cerclage or their combination reduce PTB<34 weeks. There is an urgent need for randomized trials assessing these treatments in women with a multiple pregnancy and a short cervix.

Objective: To identify the association between cervical length (CL) and gestational age at birth. Design: Prospective cohort study. Setting: Seventeen Brazilian reference hospitals. Population: A cohort of 3139 asymptomatic singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial). Methods: Transvaginal ultrasound (TVU) to measure CL was performed from 18 to 22+6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks’ gestation. Main Outcome Measures: Area under receive operating characteristic curve (AUC), sensitivity, specificity, Kaplan-Meier curves for preterm birth (PTB), number needed to screen (NNS). Results: CL ≤25mm was associated with extremely severe, severe, moderate and late PTB, whereas a CL 25–30mm was directly associated with late sPTB. The AUC to predict sPTB<28 weeks was 0.82 and for sPTB<34 weeks was 0.67. Almost half of the sPTB occurred in nulliparous women and CL ≤30mm was associated with sPTB <37 weeks (OR = 7.84; 95%CI = 5.5–11.1). The NNS to detect one sPTB <34 weeks in women with CL ≤25mm is 121 and 248 screening tests are necessary to prevent one sPTB <34 weeks using vaginal progesterone prophylaxis. Conclusions: CL measured by TVU is associated with sPTB <34 weeks. Women with CL ≤30mm are at increased risk for late sPTB. Funding: Bill & Melinda Gates Foundation [OPP1107597], the Brazilian Ministry of Health, and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. Keywords: cervical length; number needed to screen; preterm birth; short cervix.