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Obstetrics & Gynecology 2008;111:1403-1409
© 2008 by The American College of Obstetricians and Gynecologists
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ORIGINAL RESEARCH

Effective Prediction of Preeclampsia by a Combined Ratio of Angiogenesis-Related Factors

Ji Hyae Lim, MS1, Shin Young Kim, MS1, So Yeon Park, PhD1, Jae Hyug Yang, MD, PhD2, Moon Young Kim, MD, PhD2 and Hyun Mee Ryu, MD, PhD1,2

From the 1Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women’s Healthcare Center, Seoul, Korea; and the 2Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, KwanDong University College of Medicine, Seoul, Korea.

OBJECTIVE: 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-β1 (TGF-β1), in women who subsequently developed preeclampsia.

METHODS: A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-β1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women.

RESULTS: Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-β1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-β1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-β1) 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-β1, 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-β1, and 74.8 [17.6-316.7] for the combined ratio.

CONCLUSION: 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.

LEVEL OF EVIDENCE: II






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