Maternal serum-soluble vascular endothelial growth factor receptor-1 in early pregnancy ending in preeclampsia or intrauterine growth retardation

Context: Vascular endothelial growth factor (VEGF) promotes placental vascularization, which is inadequate in preeclampsia and intrauterine growth retardation (IUGR). The soluble receptor of VEGF(sVEGFR-1), also known as soluble fms-like tyrosine kinase-1, is produced in the placenta and reduces VEGF activity. Therefore, elevated sVEGFR-1 could contribute to the development of preeclampsia and IUGR. Objective: The objective of this study was to study maternal serum sVEGFR-1 concentration in early pregnancy ending in preeclampsia and IUGR. Design: This was a case-control study. Setting: This study was conducted at Helsinki University Central Hospital (Helsinki, Finland), a tertiary referral center. Patients: Patients included 124 pregnant women, of whom 49 developed preeclampsia, 16 gave birth to IUGR infants without preeclampsia, and 59 remained normotensive and gave birth to normal-sized infants. Serum samples were collected at 12-15 and 16-20 gestational weeks. Main Outcome Measures: Serum sVEGFR-1 concentrations were determined by ELISA. Results: Women with subsequent preeclampsia had higher [median; interquartile range (IQR)] concentrations of sVEGFR-1 at 16-20 wk gestation (436 and 282-699 ng/liter; P=0.005) than the controls (296 and 184-508 ng/liter). The conclusion was the same if women with mild (340 and 285-750 ng/liter; P=0.043) or severe (497 and 235-699 ng/liter; P=0.022) preeclampsia were analyzed separately. An elevated sVEGFR-1 concentration at 16-20 wk gestation is associated with an increased risk of preeclampsia but not of isolated IUGR. Soluble VEGFR-1 concentration decreased by 15% from the first to the second sampling in the controls but not in women with preeclampsia or IUGR. Conclusion: Elevated sVEGFR-1 concentrations at 16-20 wk gestation precede the clinical manifestations of preeclampsia. By neutralizing VEGF, sVEGFR-1 may contribute to inadequate placental vascularization.