Uteroplacental blood flow and placental vascular endothelial growth factor in normotensive and pre‐eclamptic pregnancy

OBJECTIVE: To determine whether placental vascular endothelial growth factor (VEGF) is increased in pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Royal Prince Alfred Hospital, Sydney, Australia. SAMPLE: Eleven normotensive women and eight women with pre-eclampsia matched for age and gestation. METHODS: Uterine artery Doppler ultrasound flow velocity profiles were recorded in the third trimester and resistance index calculated as (Vs-Vd)/Vs (Vs = peak systolic flow velocity, Vd = end diastolic flow velocity). Placental tissue at delivery was examined for VEGF distribution with avidin-biotin-peroxidase immunohistochemistry. RESULTS: Uterine resistance index [median (range)] was significantly increased in pre-eclamptic women (normotensive: 0.42 (0.36-0.51); pre-eclampsia: 0.59 (0.40-0.75); P = 0.005). Notching of the uterine artery waveform, consistent with a high resistance circulation, was evident in early diastole in five women with pre-eclampsia but only one normotensive woman (P = 0.013). Placental VEGF was increased in women with pre-eclampsia in the decidual trophoblast (normotensive: 34% (4-59) cells stained for VEGF; pre-eclampsia: 58% (15-95); P = 0.033) and in the villous syncytiotrophoblast (normotensive: VEGF count 1.4 arbitrary units (1.1-2.1); pre-eclampsia: 1.8 arbitrary units (1.4-2.2); P = 0.041). Analysis indicated that uterine artery resistance index was directly correlated with placental VEGF staining, mean arterial pressure and birthweight. CONCLUSIONS: Abnormal uterine artery Doppler ultrasound flow velocity profiles in pre-eclampsia indicate increased uteroplacental resistance. The associated increase in placental VEGF may represent a compensatory mechanism attempting to restore blood flow towards normal.