Risk Factors of Marginal Cord Insertion in Singleton Pregnancies: A Systematic Review and Meta-Analysis

Background: Marginal cord insertion (MCI) is increasingly recognized as a pathological variation that necessitates early diagnosis. Identifying the risk factors associated with MCI is essential for improving prenatal screening and optimizing management strategies. Our meta-analysis systematically and quantitatively synthesizes the current evidence on various potential risk factors for MCI. Methods: This systematic review and meta-analysis adhered to the PRISMA and MOOSE guidelines. Comprehensive searches were performed in three databases up until 6 May 2024, identifying observational cohort and case-control studies that examined risk factors for MCI in singleton pregnancies compared with central or eccentric cord insertion. Quality and risk of bias assessment were performed using the Newcastle-Ottawa Scale and the Quality In Prognosis Studies tool, respectively. Statistical analyses employed random-effects models to calculate relative risks (RR) and mean differences with their 95% confidence intervals (95% CI). Heterogeneity was assessed via Cochran's Q and I² statistics. Results: A total of 18 studies (14 cohort and 4 case-control), encompassing 51,463 MCI cases and 901,020 control cases, were included. The meta-analysis revealed a prevalence of MCI at 5.71% among singleton pregnancies. Significant risk factors for MCI included the use of assisted reproductive technology (RR = 1.55; 95% CI: 1.34-1.78), chronic hypertension (RR = 1.47; 95% CI: 1.11-1.95), placenta previa (RR = 1.83; 95% CI: 1.62-2.08), and nulliparity (RR = 1.18; 95% CI: 1.08-1.30). No significant associations were found for smoking, maternal age, prior Cesarean section, preexisting diabetes, or Caucasian ethnicity. Sensitivity analyses corroborated the robustness of these findings. Conclusions: This meta-analysis identified assisted reproductive technology, chronic hypertension, placenta previa, and nulliparity as significant risk factors for marginal cord insertion in singleton pregnancies. These findings can inform the development of prenatal screening protocols and enable targeted screenings for high-risk populations.