Abstract
BACKGROUND: Velamentous cord insertion (VCI) complicates 0.9-1.9% of singleton pregnancies and is associated with adverse perinatal outcomes due to unprotected fetal vessels traversing the membranes. Color Doppler ultrasound enables prenatal diagnosis, yet systematic evaluation of diagnostic performance and risk factor association models remains limited. We hypothesized that systematic second-trimester screening achieves superior diagnostic accuracy before 28 weeks, and that identification of clinical risk factors associated with VCI would enhance understanding of its etiology and inform screening strategies. METHODS: This retrospective case-control study included 240 singleton pregnancies (120 confirmed VCI cases and 120 age-matched controls) between 2022-2025. All underwent systematic second-trimester color Doppler ultrasound evaluating cord insertion site, membranous vessel length, and vasa previa. Multivariate logistic regression was used to identify independent risk factors associated with VCI and to develop a risk factor association model; model discrimination was assessed using C-index with 1,000-bootstrap internal validation. RESULTS: Color Doppler ultrasound achieved 94.2% sensitivity and 100% specificity for VCI detection, with superior accuracy before 28 weeks (97.3% vs. 85.7%, p = 0.008). Three independent risk factors were identified: Three independent clinical risk factors were identified: ART (aOR = 2.87), maternal anemia (aOR = 2.15), and short cervical length (aOR = 2.34). Placenta previa demonstrated a strong association with VCI (OR = 3.92), likely reflecting a shared spectrum of abnormal trophoblast implantation. The multivariate model demonstrated moderate discrimination (C-index = 0.713, 95% CI: 0.648-0.778) for distinguishing VCI from controls. The VCI cohort was associated with significantly higher rates of adverse outcomes: preterm delivery 22.5% vs. 8.3% (p = 0.002), FGR 18.3% vs. 6.7% (p = 0.004), and perinatal mortality 3.3% vs. 0% (p = 0.042). CONCLUSION: In tertiary referral settings with experienced operators, targeted color Doppler ultrasound demonstrates high diagnostic accuracy for VCI detection, particularly during second-trimester evaluation. The developed risk factor model demonstrated moderate discrimination in this cohort; external validation in independent populations is required before clinical implementation.