Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor

Abstract

Objective: Preeclampsia has been proposed to be an antiangiogenic state that may be detected by the determination of the concentrations of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor (PlGF) in maternal blood even before the clinical development of the disease. The purpose of this study was to determine the role of the combined use of uterine artery Doppler velocimetry (UADV) and maternal plasma PlGF and sVEGFR-1 concentrations in the second trimester for the identification of patients at risk for severe and/or early onset preeclampsia.

Study design: A prospective cohort study was designed to examine the relationship between abnormal UADV and plasma concentrations of PlGF and sVEGFR-1 in 3348 pregnant women. Plasma samples were obtained between 22 and 26 weeks of gestation at the time of ultrasound examination. Abnormal UADV was defined as the presence of bilateral uterine artery notches and/or a mean pulsatility index above the 95th percentile for the gestational age. Maternal plasma PlGF and sVEGFR-1 concentrations were determined with the use of sensitive and specific immunoassays. The primary outcome was the development of early onset preeclampsia (< or = 34 weeks of gestation) and/or severe preeclampsia. Secondary outcomes included preeclampsia, the delivery of a small for gestational age (SGA) neonate without preeclampsia, spontaneous preterm birth at < or = 32 and < or = 35 weeks of gestation, and a composite of severe neonatal morbidity. Contingency tables, chi-square test, receiver operating characteristic curve, and multivariate logistic regression were used for statistical analyses. A probability value of < .05 was considered significant.

Results: (1) The prevalence of preeclampsia, severe preeclampsia, and early onset preeclampsia were 3.4% (113/3296), 1.0% (33/3296), and 0.8% (25/3208), respectively. UADV was performed in 95.4% (3146/3296) and maternal plasma PlGF concentrations were determined in 93.5% (3081/3296) of the study population. (2) Abnormal UADV and a maternal plasma PlGF of < 280 pg/mL were independent risk factors for the occurrence of preeclampsia, severe preeclampsia, early onset preeclampsia, and SGA without preeclampsia. (3) Among patients with abnormal UADV, maternal plasma PlGF concentration contributed significantly in the identification of patients destined to develop early onset preeclampsia (area under the curve, 0.80; P < .001) and severe preeclampsia (area under the curve, 0.77; P < .001). (4) In contrast, maternal plasma sVEGFR-1 concentration was of limited use in the prediction of early onset and/or severe preeclampsia. (5) The combination of abnormal UADV and maternal plasma PlGF of < 280 pg/mL was associated with an odds ratio (OR) of 43.8 (95% CI, 18.48-103.89) for the development of early onset preeclampsia, an OR of 37.4 (95% CI, 17.64-79.07) for the development of severe preeclampsia, an OR of 8.6 (95% CI, 5.35-13.74) for the development of preeclampsia, and an OR of 2.7 (95% CI, 1.73-4.26) for the delivery of a SGA neonate in the absence of preeclampsia.

Conclusion: The combination of abnormal UADV and maternal plasma PlGF concentration of < 280 pg/mL in the second trimester is associated with a high risk for preeclampsia and early onset and/or severe preeclampsia in a low-risk population. Among those with abnormal UADV, a maternal plasma concentration of PlGF of < 280 pg/mL identifies most patients who will experience early onset and/or severe preeclampsia.

Figure 1

Maternal plasma PlGF concentration (solid line) contributed significantly to the prediction of patients destined to develop A, early onset preeclampsia (PE; P < .001) and B, severe preeclampsia (P < .001). In contrast, maternal plasma sVEGFR-1 concentration (dotted line) was of limited use in the prediction of A, early onset preeclampsia (area under the curve [AUC], 0.49; P = .9) and B, severe preeclampsia (area under the curve, 0.54; P = .5;).

Figure 1

Maternal plasma PlGF concentration (solid line) contributed significantly to the prediction of patients destined to develop A, early onset preeclampsia (PE; P < .001) and B, severe preeclampsia (P < .001). In contrast, maternal plasma sVEGFR-1 concentration (dotted line) was of limited use in the prediction of A, early onset preeclampsia (area under the curve [AUC], 0.49; P = .9) and B, severe preeclampsia (area under the curve, 0.54; P = .5;).

Figure 2

Flow diagram for the identification of patients at risk for early onset and/or severe preeclampsia (PE), with the use of, sequentially, UADV measurement and the determination of maternal plasma PlGF concentration.

Figure 3

Simplified flow diagram for the identification of patients at risk for early onset and/or severe preeclampsia (PE), with the use of UADV followed by maternal plasma PlGF determinations. The asterisk denotes that data for patients with normal UADV were combined, regardless of the plasma PlGF concentration.

Figure 4

Flow diagram for the identification of patients at risk for early onset and/or severe preeclampsia (PE), with the use of maternal plasma PlGF determination followed by UADV.

Figure 5

Cumulative hazard ratios for the clinical presentation of preeclampsia (PE) according to the UADV and maternal plasma PlGF concentrations among study groups (only patients with preeclampsia were included in this analysis). The examination-to-diagnosis interval in patients with abnormal UADV and plasma PlGF of ≤280 pg/mL (median, 69 days; interquartile range, 58-88 days) was significantly shorter than in patients with abnormal UADV and plasma PlGF concentration of >280 pg/mL (median, 94 days; interquartile range, 84-106 days) and patients with normal UADV (median, 99 days; interquartile range, 91-107 days) who had preeclampsia (log rank, 37.9; P< .001)