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

Kim SY, et al. J Korean Med Sci. 2007 Oct;22(5):873-877. http://dx.doi.org/10.3346/jkms.2007.22.5.873

Non-invasive prenatal testing of trisomy 21 (T21) is being actively investigated using fetal-specific epigenetic markers (EPs) that are present in maternal plasma. Recently, 12 EPs on chromosome 21 were identified based on tissue-specific epigenetic characteristics between placenta and blood, and demonstrated excellent clinical performance in the non-invasive detection of fetal T21. However, the disease-specific epigenetic characteristics of the EPs have not been established. Therefore, we validated the disease-specific epigenetic characteristics of these EPs for use in non-invasive detection of fetal T21.

Kim SY, et al. J Korean Med Sci. 2004 Oct;19(5):688-692. http://dx.doi.org/10.3346/jkms.2004.19.5.688