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Purpose: The aim of this nested case-control study was to investigate the association between hepatocyte growth factor (HGF)concentrations in maternal plasma and the risk of developing preeclampsia. Materials and Methods: Plasma HGF concentration were measured in 52 women who subsequently developed preeclampsia and 104 normal pregnant women at the time of genetic amniocentesis (15-20 weeks) by enzyme-linked immunosorbent assay. Results: Maternal plasma HGF concentrations were significantly higher in women with subsequent preeclampsia (median:737.8 ng/mL vs. 670.4 ng/mL, P=0.003) than in normal controls. However, HGF concentrations were not significantly different between subgroups by preeclamptic complications. After adjusting for potential confounding factors, women with HGF concentrations ≥702.5 ng/mL had a 3.2-fold increased risk (95% CI 2.7-5.4, P<0.001) of subsequent development of preeclampsia compared with women with HGF concentrations <702.5 ng/mL. Conclusion: Elevated maternal plasma HGF concentrations in the early second-trimester are associated with an increased risk of developing preeclampsia.