by Kelly Hughes, David Nguyen, Mason Aberoumand, Heather Ford, Erin Clarke, Nuria Banos Lopez, Margaret Dziadosz, Richard Fischer, Renato T. Souza, Jose Guilherme Cecatti, Kelly Orzechowski, Courtney Olson-Chen, Alberto Borges Peixoto, Vorapong Phupong, Joshua Rosenbloom, Moeun Son, Athena Souka, Liu Du, Michael Sean Esplin, Roberta Granese, Simi Gupta, Brenda Kazemier, Lindsay Kindinger, Pihla Kuusela, Jeanine Van der Ven, Omer Weitzner, Evelyn Minis, Alba Farras Llobet, Heather Frey, Rashmi Bagga, Siddhidatri Mishra, Elizabeth Patberg, Philip Bennett, Megan Hall, Andrew Shennan, Shaun Brennecke, Shakila Thangaratinam, Anna Lene Seidler, Ben Willem Mol, Rui Wang
Background
Spontaneous preterm birth (SPTB) is the leading cause of perinatal and early childhood mortality worldwide. Studies have generally suggested that mid-trimester transvaginal sonographic cervical length <25 mm is an important predictor of SPTB. Aggregate data meta-analyses are limited by data availability and reporting in the primary literature. The purpose of this individual participant data meta-analysis (IPDMA) was to quantify the prognostic value of mid-trimester cervical length for SPTB in asymptomatic women with singleton pregnancy, and to assess other factors which may modify this association.
Methods and findings
The project was prospectively registered with PROSPERO (CRD42020146987). We searched Medline, Embase, CINAHL, LILACS, Database of Abstracts of Reviews of Effects (DARE), Cochrane database, JBI Database of Systematic Reviews, ClinicalTrials.gov, and Google Scholar. We included cohort studies and non-treatment arms of randomized controlled trials which assessed an association between mid-trimester transvaginal sonographic cervical length and SPTB in asymptomatic women with singleton pregnancy. The search was performed on 30/9/2020, with an update performed on 4/11/2025. The primary outcome was STPB <37 weeks. Two reviewers screened all studies for inclusion and performed risk of bias assessments using QUIPS. We performed a two-stage IPDMA in a logistic regression model using cervical length as a continuous variable (the primary analysis) with restricted cubic splines to explore non-linear associations.IPD of 27 eligible studies were obtained and included (n = 91,404). Mean cervical length was 40 mm (standard deviation [SD] 9 mm) at about 20 weeks’ gestation. SPTB <37 weeks occurred in 4,442 (5.2%) participants. An L-shape non-linear association between cervical length and SPTB was observed. A longer cervical length was associated with steeply lower odds of SPTB until it reached 40 mm, beyond which the odds of SPTB became stable. This means that compared to a woman with a cervical length of 40 mm, those with a cervical length of 20 and 30 mm were associated 6.22 and 2.10 higher odds of SPTB (95% confidence intervals [4.76, 8.13] and [1.85, 2.38]), respectively. Limitations included suboptimal data retrieval rate (51% of all eligible participants) and a lack of comprehensive co-predictors of SPTB across all datasets.
Conclusion
We found a non-linear association between cervical length and SPTB. We found a non-linear association between cervical length and SPTB. Shorter cervix is associated with progressively higher risk of SPTB when length is less than 40 mm, but probability of term birth is high when cervical length is over 40 mm.
Rui Wang
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