First Trimester Placental Growth Factor and Soluble Fms-Like Tyrosine Kinase 1 and Risk for Preeclampsia

Abstract

An imbalance of pro- and antiangiogenic factors may lead to preeclampsia (PE). In this prospective nested case-control study, we investigated whether first trimester serum levels of placental growth factor (PlGF), a potent angiogenic factor, and its soluble inhibitor, soluble fms-like tyrosine kinase 1 (sFlt1), distinguished women who developed PE (n = 40) from those who developed gestational hypertension (n = 40), delivered a small for gestational age (SGA) newborn (n = 40), or completed a full term normal pregnancy (n = 80). Compared with controls, serum PlGF levels were lower among women who developed PE (23 +/- 24 pg/ml vs. 63 +/- 145 pg/ml; P < 0.01) or gestational hypertension (27 +/- 19 pg/ml; P = 0.03), or who delivered a SGA newborn (21 +/- 16 pg/ml; P < 0.01). In contrast, serum sFlt1 levels did not markedly differ between the groups: PE, 1048 +/- 657 pg/ml; gestational hypertension, 942 +/- 437 pg/ml; SGA newborns, 1011 +/- 479 pg/ml; and normal controls, 973 +/- 490 pg/ml. Multivariable analysis adjusting for potential confounders and serum sFlt1 levels demonstrated a 3.7-fold (95% confidence interval, 1.2-12.5) increase in risk for PE for every log unit decrease in serum levels of PlGF compared with controls. Analyses for gestational hypertension and SGA were not significant. Examined in tertiles, the risk for PE was increased 28.7-fold (95% confidence interval, 2.3-351.0) in the third (<12 pg/ml) compared with the first (>39 pg/ml) PlGF tertile. First trimester serum levels of PlGF and sFlt1 may identify women at high risk for PE.

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis

“…19 The undetectable levels of VEGF and PlGF in the pregnant rats in the current study were in agreement with other investigators, who failed to detect these angiogenic factors in a large population of pregnant women regardless of the end result of pregnancy. [20][21][22] Furthermore, low PlGF in the presence of high sFlt-1 levels, as observed in the PRE group in the current study, increased the risk of PE in a prospective nested control study. 21 The decrease in circulating VEGF and PlGF in PE could be due to decreased placental production.…”

“…[20][21][22] Furthermore, low PlGF in the presence of high sFlt-1 levels, as observed in the PRE group in the current study, increased the risk of PE in a prospective nested control study. 21 The decrease in circulating VEGF and PlGF in PE could be due to decreased placental production. 23 Moreover, increased sFlt-1 is suggested to bind to these angiogenic factors and decrease their free fractions.…”

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

“…In agreement with the existing literature on early pregnancy, [23][24][25][26][27] we found that low levels of PiGF at 10-15 weeks of gestation predict the subsequent development of pre-eclampsia. However, we found no significant link between sFlt-1 or sEng and pre-eclampsia during this gestational period, in keeping with the results from other authors.…”

“…However, we found no significant link between sFlt-1 or sEng and pre-eclampsia during this gestational period, in keeping with the results from other authors. 3,[23][24][25]28 It would appear that women who develop pre-eclampsia begin to show higher levels of sFlt-1 and sEng only well into the second trimester of pregnancy. 2,3,28 In contrast, elevations of Bb occur much earlier.…”

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

“…In humans, low levels of PlGF have been associated with pre-eclampsia (25)(26)(27)(28)(29)(30), and endometrial PlGF is reported to be an exclusive product of uNK cells in the late menstrual cycle. PlGF is also found in uNK cells from early, elective pregnancy terminations (5).…”