Total and Free Placental Growth Factor Levels During Preeclampsia and Fetal Growth Restriction

BACKGROUND: The objective of this study was to evaluate total circulating PlGF (placental growth factor) and free PlGF concentrations to provide insights into the mechanisms of decreased PlGF noted in preeclampsia and fetal growth restriction. METHODS: We conducted a retrospective single-center study in pregnant women receiving care for suspected preeclampsia and/or fetal growth. Serum angiogenic proteins (sFLT1 [soluble fms-like tyrosine kinase] and free PlGF) were measured on an automated platform as part of standard-of-care. Total PlGF concentrations in the serum were directly measured using a validated biochemical procedure that dissociated circulating sFLT1 and PlGF complexes. Small for gestational age (SGA) was defined by birthweight ≤10th percentile. RESULTS: Of the 407 women studied, 155 women did not develop preeclampsia or SGA (control group), 111 women developed SGA without preeclampsia (SGA group), 71 women developed preeclampsia without SGA (preeclampsia group), and 70 developed preeclampsia and SGA (preeclampsia+SGA group). Despite reductions in free PlGF levels (229 [158–321] pg/mL), total PlGF levels were not reduced in the preeclampsia group (1020 [738–1444] pg/mL) compared with the control group (1077 [763–1595] pg/mL). In contrast, the total PlGF levels were significantly reduced in the SGA group (744 [462–1161] pg/mL; P <0.0001) and the preeclampsia +SGA group (616 [349–917] pg/mL; P <0.0001) compared with the control group (1077 [763–1595] pg/mL). CONCLUSIONS: Placental dysfunction associated with preeclampsia, characterized by reduced free PlGF levels but unchanged total PlGF, is driven by excessive placental production of sFLT1. Placental dysfunction associated with SGA, marked by reductions in both free and total PlGF, is mediated by decreased placental PlGF production.