Plasma biomarkers for early prediction of preeclampsia
David Carty, Lesley Anderson, Jim Mcculloch, Anna Dominiczak & Christian Delles
Introduction: Several biomarkers are elevated in late pregnancy in women with preeclampsia (PET), but none have been sensitive or specific enough to be used routinely in early pregnancy to predict the condition. We measured plasma levels of the anti-angiogenic peptides FMS-like tyrosine kinase 1 (sFLT-1), soluble endoglin (sENG), placental growth-factor (PGF), and an array of cytokines and adhesion molecules in early and mid pregnancy to assess their ability to predict PET.
Methods: Two thousand women were recruited at gestational week 1216 (booking); 36 (1.9%) developed PET, and were matched for age and BMI to 74 women who had normotensive pregnancies. 50 women with ≥2 risk factors were sampled again at gestational week 28, of whom 11 developed pre-eclampsia. sFLT-1, sENG and PGF levels were measured using ELISA kits (R&D Systems); levels of cytokines and adhesion-molecules were determined by immunoassay using biochip technology (Randox Laboratories).
Results: Systolic blood pressure was not different, but diastolic blood pressure higher (74±10 vs 69±9 mmHg; P=0.022) at booking in women who developed PET. sENG was higher (6.96±3 vs 5.72±2.1 ng/ml, P=0.025), and PGF lower (25.8±27 vs 37.4±30 pg/ml, P<0.001) at booking in affected women. sFLT-1 was not different between the 2 groups at booking (P=0.52), but higher in affected women at week 28 (1979±1118 vs 1230±624 pg/ml, P=0.009.) Of the cytokines and growth factors, E-Selectin was higher in women who developed PET, both at booking (15.1±4.9 vs 12.9±4.5 ng/ml, P=0.022) and week 28 (14.4±5.6 vs 10.73±3.5 ng/ml, P=0.01). There was no difference between the 2 groups at either timepoint in levels of VCAM-1, ICAM-1, P-Selectin, L-Selectin, Interleukins 1-α, 1-β, 2, 4, 6, 8 or 10, VEGF, TNF-α, interferon-γ, MCP-1 and EGF.
Conclusion: When measured in early pregnancy, along with maternal risk factors, sENG, PGF and E-Selectin may provide additional prognostic information about future risk of pre-eclampsia.