Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis

In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p < 0.0001 ) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p < 0.05 ) ( n = 18 ) was compared to controls ( n = 12 ). PAI-1 was increased (~10-fold, p < 0.001 ) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen ( r = - 0.68 , p < 0.0001 ). The plasma’s angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels ( r = 0.65 , p < 0.01 ). This association was attenuated by PAI-1 inhibiting antibody ( p < 0.001 ). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies.