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First-trimester placental growth factor, SFLT-1, and risk for preeclampsia

      Objective

      Angiogenesis is a critical component of normal placental development, and an imbalance of angiogenic growth factors and their inhibitors may lead to an increased risk for preeclampsia. We investigated whether serum levels of placental growth factor, a potent angiogenic factor, and its inhibitor, soluble fms-like tyrosine kinase 1 (sFlt1) , identified women at risk for preeclampsia, isolated gestational hypertension, or delivering a small for gestational age newborn.

      Study design

      We performed a prospective nested case-control study of 40 women who developed preeclampsia (PE), 40 who developed gestational hypertension (GH), 40 who delivered a small for gestational age newborn (SGA), and 80 contemporaneous randomly selected controls. Blood samples were collected on or before 12 weeks of gestation, stored at −80°C until testing, and tested for PlGF and sFlt1 within 18 months of collection.

      Results

      Compared with controls, first-trimester serum levels of PlGF were lower among women who subsequently developed PE (23±24 pg/mL vs 63±145 pg/mL, P<0.01), developed GH (27±19 pg/mL, P = 0.03), or delivered SGA newborns (21±16 pg/mL, P<0.01). First-trimester serum levels of sFlt-1 were slightly but not significantly elevated in women who developed PE (1048±657 pg/mL) or who delivered SGA newborns (1011±479 pg/mL), compared to women who developed GH (942±437 pg/mL) or to normal controls (973±490 pg/mL). Multivariable analysis demonstrated that compared to normotensive controls, there was a 3.7-fold (95% CI 1.2-12.5) increase in risk for PE for every one log unit decrease in serum levels of PlGF. Similar analyses for risk for GH or SGA were not significant.

      Conclusion

      Our data suggest the combination of first-trimester serum levels of PlGF and sFlt-1 strongly identifies women at high risk for subsequent preeclampsia, and distinguishes these women from those at risk for developing gestational hypertension, delivery of a small for gestational age infant, or having a normal pregnancy outcome.