Plasma concentrations of angiogenic/anti-angiogenic factors have prognostic value in women presenting with suspected preeclampsia to the obstetrical triage area: a prospective study

Abstract

Objective To prospectively determine the prognostic value of maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng) and soluble vascular endothelial growth factor receptors-1 and −2 (sVEGFR-1 and −2) in identifying patients with suspected preeclampsia (PE) who require preterm delivery (PTD) or develop adverse outcomes. Study design This prospective cohort study included 85 consecutive patients who presented to the obstetrical triage area at 20–36 weeks with a diagnosis of ‘rule out PE’. Patients were classified as: 1) those who remained stable until term (n=37); and 2) those who developed severe PE and required PTD (n=48). Plasma concentrations of PlGF, sEng and sVEGFR-1 and −2 were determined by ELISA. Results Patients with PlGF/sVEGFR-1 ≤0.05 multiples of the median (MoM) or PlGF/sEng ≤0.07 MoM were more likely to deliver preterm due to PE [adjusted odd ratio (aOR) 7.4 and 8.8], and to develop maternal (aOR 3.7 and 2.4) or neonatal complications (aOR 10.0 and 10.1). Among patients who presented <34 weeks of gestation, PlGF/sVEGFR-1 ≤ 0.035 MoM or PlGF/sEng ≤0.05 MoM had a sensitivity of 89% (16/18), specificity of 96% (24/25) and likelihood ratio for a positive test of 22 to identify patients who delivered within two weeks. The addition of the PlGF/sVEGFR-1 ratio to standard clinical tests improved the sensitivity at a fixed false-positive rate of 3% (p=0.004) for the identification of patients who were delivered due to PE within two weeks. Among patients who had a plasma concentration of PlGF/sVEGFR-1 ratio ≤ 0.035 MoM, 0.036–0.34 MoM and ≥ 0.35 MoM, the rates of PTD < 34 weeks were 94%, 27% and 7%, respectively. Conclusions The determination of angiogenic/anti-angiogenic factors has prognostic value in patients presenting to the obstetrical triage area with suspected preeclampsia for the identification of those requiring preterm delivery and at risk for adverse maternal/neonatal outcomes.

Angiogenic Factors in Preeclampsia

“…Several recent studies have confirmed that levels of sFlt1 and PlGF in the triage setting can be used as a robust prognostic test and these levels correlate with the duration of pregnancy. [74][75][76][77] In addition, we have also provided evidence that women with clinically diagnosed preeclampsia, but who have normal angiogenic profile have no adverse maternal or fetal outcomes.…”

Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study

“…There is a growing body of evidence indicating that an imbalance in maternal plasma concentrations of angiogenic and anti-angiogenic factors is characteristic of a substantial fraction of women who have or will develop preeclampsia [44, 97–107, 110, 111, 130–168], fetal death [114, 115, 169–173], SGA [64, 102–104, 117, 173–178], massive perivillous fibrin deposition [115, 178], twin-to-twin transfusion syndrome [118, 179, 180], and mirror syndrome [181]. We have also found significant differences in angiogenic marker distributions among uncomplicated pregnancies and those who are or will be affected by spontaneous PTL with intact membranes [112].…”

Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study

“…We recently added to the limited information available about the levels of these factors in other forms of hypertension in pregnancy [21-24] and found that free PlGF measured before 35 weeks of pregnancy may predict preterm delivery in all forms of hypertensive disorders of pregnancy [25]. There is still little information to date on their ability to predict fetal outcomes such as intrauterine growth restriction through their assessment of placental function [26]. …”