Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies

Abstract

BackgroundDifferences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome.MethodsThis study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF.ResultsThe odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia.ConclusionsThe pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women.

Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study

“…In this context, PlGF concentration in maternal blood has been suggested as a predictor of placenta-related pathologies such as preeclampsia, [8,26]. Nevertheless, the utility of PlGF as a marker to predict these conditions has been questioned [27], mainly due to the significant heterogeneity that is observed in its concentration in the circulation of pregnant women that do not exhibit placental abnormalities. Considering that the underlying reason for the heterogeneity is not known, it is possible that factors other than primary placental disorders influence PlGF concentration in maternal blood.…”

The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia

“…Perni et al demonstrated in a longitudinal study of women with chronic hypertension that alterations in sFlt-1, PlGF, sFlt-1/ PlGF, and sEng were dramatically altered as early as 20 weeks of gestation in women who developed subsequent early onset preecalmpsia (51 ). Results have been more modest in other studies using angiogenic markers in high-risk populations (52,53 ). However, in the high-risk population the diagnosis of preeclampsia may not be straightforward, and therefore it may be important to study the utility of these biomarkers in the context of preeclampsia-related adverse maternal and fetal outcomes.…”

Angiogenic Factors in Superimposed Preeclampsia

“…14 -16 Alterations in the levels of circulating factors in women with chronic hypertension are beginning to be appreciated primarily after crosssectional analyses of subgroups. [17][18][19] The current investigation was designed to characterize the levels of circulating sFlt1, sEng, and PlGF in women with preexisting hypertension and to investigate whether longitudinal profiling can help distinguish chronically hypertensive pregnant women who develop SPE from those who do not develop SPE. In this study, we have leveraged and performed a secondary analysis of the peripheral blood specimens originally collected longitudinally in the context of a placebocontrolled, double-blinded randomized trial of calcium supplementation in chronically hypertensive pregnant women and demonstrate significant alterations in sFlt1, sEng, and PlGF before the clinical diagnosis of early onset (Ͻ34 weeks) SPE and at the time of diagnosis in women with both early and late-onset SPE.…”