First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome

Background: Hypertensive disorders, fetal growth restriction and preterm birth are major obstetrical complications and are related to impaired placentation. Early identification of impaired placentation can advance clinical care by preventing or postpone adverse pregnancy outcome. Objectives: Determine whether sonographic assessed placental vascular development and concomitant changes in inflammation- and/or angiogenesis-related serumproteins differ in the first trimester between uncomplicated pregnancies and pregnancies with adverse outcome. Study design: This prospective longitudinal study defines adverse pregnancy outcome as conditions associated with impaired placentation; fetal growth restriction, hypertensive disorder, preterm birth and placental abruption. The vascularization index, flow index, vascularization flow index and placental volume were determined at 8, 10 and 12 weeks pregnancy from 64 women using 3D power Doppler. Serum levels were analyzed for Angiopoetin-1 and -2, Leptin, VEGF-R, VEGF, and EGF. Results: The vascularization index and vascular flow index increased in uneventful pregnancies with almost 50% between 8 and 12 weeks, resulting in a ∼50% higher vascularization index at 12 weeks compared to women with an adverse pregnancy outcome. Women with an adverse pregnancy outcome (n = 13) had significantly lower indices and placental volumes at all time points measured and these indices did not increase between 8 and 12 weeks. Reduced vascular development was associated with increased Angiopoietin-1 levels at 8 and 12 weeks and increased Leptin levels at 8 weeks. Conclusions: Pregnancies with an adverse outcome caused by conditions associated with impaired placentation differ from uneventful pregnancies in having reduced placental vascularization accompanied by elevated circulating levels of Angiopoietin-1 and Leptin already in the first trimester.