Pigment epithelium-derived factor/vascular endothelial growth factor ratio for early prediction of preeclampsia: A prospective multicenter study in China.

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 20 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 (12 weeks 0 days to 19 weeks 6 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 20 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.