Risk Factors for Spontaneous Preterm Birth are Mediated through Changes in Cervical Length

Although short cervical length in the mid-trimester of pregnancy is a one of the strongest predictors of preterm birth (i.e., parturition before 37 completed weeks), there is limited understanding of how the dynamics of cervical remodeling (i.e., changes in cervical length) leading up to labor and delivery can inform obstetrical risk. In this study, latent growth curve analysis was applied to serial cervical length measurements across pregnancy (median of 6; IQR = 3-8) to quantify characteristics of cervical change in a cohort of 5,111 singleton pregnancies consisting predominantly of Black women from Detroit, Michigan. A conditional mediation model including nine common maternal risk factors for spontaneous preterm birth as exogenous predictors accounted for 26.5% of the variability in gestational age at delivery (P < 0.001). This model provides insight into distinct mechanisms by which specific maternal risk factors influence preterm birth. For instance, effects of maternal parity and smoking status were fully mediated through cervical change parameters, whereas the influence of previous preterm birth was only partially explained, suggesting alternative pathways could be involved. This study provides the first account of the intermediary role of cervical dynamics in associations between known maternal risk factors and gestational age at delivery. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, by federal funds from NICHD/NIH/DHHS (Contract No. HHSN275201300006C). RR has contributed to this work as part of his official duties as an employee of the United States Federal Government. ALT and SSH were also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Boards of Wayne State University and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/National Institutes of Health/U.S. Department of Health and Human Services (Detroit, MI, USA) approved the study. Participants were enrolled under the protocols Biological Markers of Disease in the Prediction of Preterm Delivery, Preeclampsia and Intra-Uterine Growth Restric- tion: A Longitudinal Study (WSU IRB#110605MP2F and NICHD/NIH# OH97-CH-N067). All participants provided written informed consent for the collection of cervical length data and blood samples for future genetic research studies. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.