ABSTRACT
BACKGROUND: Imbalance of circulating factors related to angiogenesis plays a central role in the pathogenesis of preeclampsia (PE). OBJECTIVE: The aim of this study was to discover and validate a cutoff value of pigment epithelium-derived factor (PEDF)/vascular endothelial growth factor (VEGF) ratio for early prediction of PE before 20â¯weeks of gestation. STUDY DESIGN: This prospective multicenter study was performed in mainland China, and was divided into 3 phases to discover, develop, and validate a cutoff value of PEDF/VEGF ratio that could predict PE prior to diagnosis in pregnant women at high risk of PE (12â¯weeks 0â¯days to 19â¯weeks 6â¯days of gestation). We estimated PEDF/VEGF ratio at 5 visits: from visit 0 (baseline) to the postpartum visit. RESULTS: In the discovery phase (200 women), we found that antiangiogenic PEDF was higher and angiogenic VEGF was lower in the PE group than in the control group before 20â¯weeks of gestation. In the development phase (650 women), we found that a cutoff value of 800 for PEDF/VEGF ratio demonstrated a preferably predictive value. Subsequently, in the validation phase (additional 900 women), we found that the negative predictive value of PEDF/VEGF ratio ≤800 at the visit 1 was 98.6% (95% CI, 97.3-99.4), at the visit 2 was 96.9% (95% CI, 95.1-98.1) and at the visit 3 was 95.1% (95% CI, 93.0-96.7). ORs were 4.40, 6.27, and 5.73, respectively. CONCLUSIONS: PEDF/VEGF ratio ≤800 may have some predictive value for early diagnosis of PE. Further multicenter studies with larger sample sizes are necessary to confirm our findings.