Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors.
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-beta1 (TGF-beta1), 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-beta1 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-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.


CONCLUSIONS
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.


METHODS
II.
Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
Ji Hyae
JH
Lim
Shin Young
SY
Kim
So Yeon
SY
Park
Jae Hyug
JH
Yang
Moon Young
MY
Kim
Hyun Mee
HM
Ryu
D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D015703:Antigens, CD / Q000097:blood*; D016001:Confidence Intervals; D000071063:Endoglin; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D016017:Odds Ratio; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000175:diagnosis*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011262:Pregnancy Trimester, Second; D011956:Receptors, Cell Surface / Q000097:blood*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1