Abstract
Imbalance between angiogenesis-related factors is closely related to the development of preeclampsia. The objective was to estimate the most effective and accurate predictive biomarker among levels and ratios of angiogenesis-related factors, including soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin, placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1), in women who subsequently developed preeclampsia. A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-beta1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women. Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-beta1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-beta1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-beta1) were significantly higher than in normotensive women (P<.001) and even greater in severe preeclampsia with preterm delivery compared with mild preeclampsia with term delivery (P<.05). At equivalent sensitivity (85%), the false-positive rate was 45% for sFlt-1, 41% for soluble endoglin, 33% for sFlt-1/PlGF, 21% for soluble endoglin/TGF-beta1, and 10% for the combined ratio. After adjusting for potential confounding factors, the risks for developing preeclampsia were as follows: odds ratio (OR) 6.9 [95% confidence interval 2.3-20.7] for sFlt-1 level, 7.1 [2.3-21.7] for soluble endoglin level, 6.8 [2.4-19.4] for sFlt-1/PlGF, 38.8 [9.8-154.3] for soluble endoglin/TGF-beta1, and 74.8 [17.6-316.7] for the combined ratio. The combined ratio of angiogenesis-related factors showed the lowest false-positive rate and the highest OR for prediction of preeclampsia, indicating that it may provide more effective prediction of development of preeclampsia. II.
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