Maternal plasma-soluble ST2 concentrations are elevated prior to the development of early and late onset preeclampsia – a longitudinal study

Romero, Roberto; Chaemsaithong, Piya; Tarca, Adi L.; Korzeniewski, Steven J.; Maymon, Eli; Pacora, Percy; Panaitescu, Bogdan; Chaiyasit, Noppadol; Dong, Zhong; Erez, Offer; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn

doi:10.1080/14767058.2017.1286319

Cited by 25 publications

(20 citation statements)

References 183 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of interest, even when only patients with lesions consistent with MVM were compared to those with a normal pregnancy, proteins of placental origin (e.g., PlGF and siglec-6) were still the most predictive of early preeclampsia, but only after 22 weeks of gestation. This finding is consistent with our earlier study in late preeclampsia [72] and with previous longitudinal studies of angiogenic and anti-angiogenic factors [35,46,151]. Moreover, the data presented herein also support our previous systems biology study in early preeclampsia showing that siglec-6 expression in the placenta increased in the second half of pregnancy due to a hypoxic-ischemic trophoblastic response to placental malperfusion [258].…”

Section: Discussionsupporting

confidence: 93%

“…Current prediction models for preeclampsia combine maternal risk factors, Doppler velocimetry of the uterine arteries, and maternal blood proteins [32,37,42–46]. Although the detection rate of these models [12,47–50] for the identification of patients at risk for early/preterm preeclampsia is sufficient to enable preventive strategies [40], the contribution of biochemical markers in these models is limited.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The prediction of early preeclampsia: Results from a longitudinal proteomics study

et al. 2019

Self Cite

View full text Add to dashboard Cite

Objectives To identify maternal plasma protein markers for early preeclampsia (delivery <34 weeks of gestation) and to determine whether the prediction performance is affected by disease severity and presence of placental lesions consistent with maternal vascular malperfusion (MVM) among cases. Study design This longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8–16, 16.1–22, 22.1–28, 28.1–32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap. Results We found that 1) multi-protein models at 16.1–22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1–28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1–32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1–28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1–22 weeks; 87% versus 81% at 22.1–28 weeks; and 90% versus 85% at 28.1–32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1–22 weeks). Conclusion We have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease an...

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The prediction of early preeclampsia: Results from a longitudinal proteomics study

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Characterized by quick onset and rapid progression, ES-PE can cause organ failure, fetal distress and asphyxia (4). ES-PE poses a big threat to the safety of both the mother and the baby (21) and therefore, its treatment is a hot topic in clinical research. Magnesium sulfate is the preferred drug for ES-PE treatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of magnesium sulfate combined with labetalol on serum sFlt‑1/PlGF ratio in patients with early‑onset severe pre‑eclampsia

2020

View full text Add to dashboard Cite

The aim of the present study was to investigate the therapeutic effect of magnesium sulfate combined with labetalol on the early-onset severe pre-eclampsia (ES-PE) and explore the role of soluble fms-like tyrosine kinase-1 (sFlT-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in the treatment. A total of 164 ES-PE patients admitted to the Maternity and Child Health Care Hospital of Hubei (Wuhan, China) were assigned to this observational study. Among them, 83 patients were enrolled in group A and treated with magnesium sulfate combined with labetalol hydrochloride, and 81 patients were enrolled in group B and treated with magnesium sulfate. The therapeutic effect, adverse reactions and pregnancy outcomes in the two groups were analyzed. Serum sFlt-1 and PlGF concentrations, before and after treatment, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of pre-treatment serum sFlt-1/PlGF ratio for the clinical outcome. The effective rate was significantly higher in group A than that in group B. Group A presented superior pregnancy outcomes over group B. The serum sFlt-1 concentration and sFlt-1/PlGF ratio after treatment were significantly lower than those before treatment in groups A and B, whereas PlGF concentration was significantly higher after treatment in both groups. After treatment, group A had markedly lower serum sFlt-1 concentration and sFlt-1/PlGF ratio than group B, and markedly higher PlGF concentration than group B. The area under curve (AUC) of serum sFlt-1/PlGF ratio before treatment for the prediction of the clinical efficacy was 0.737. In conclusion, magnesium sulfate combined with labetalol could be effectively used for the treatment of ES-PE. The results of ELISA revealed that the balance of sFlT-1 and PlGF was improved after treatment and the sFlT-1/PlGF ratio was decreased. The assessment of sFlt-1/PlGF ratio before treatment was shown to have a certain predictive value for the efficacy of ES-PE treatment.

show abstract

“…Thus, pro-inflammatory molecules and cytokines may play a role in the pathogenesis of PE. IL-33 exerts its inflammatory action through its receptor interleukin-1 receptor-like 1 (22), which is expressed in the nuclei of endothelial cells of both large and small vessels, as well as in the placental endothelium and smooth muscle cells (23). In a previous study, an inverse correlation between IL-33 and PlGF was found both in PE and control groups, suggesting that cytokines were released when PlGF levels decreased (24).…”

Section: Discussionmentioning

confidence: 95%

Doppler ultrasound and photoplethysmographic assessment for identifying pregnancy‑induced hypertension

Sun

Chen

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

The current study investigated whether placentation and systemic inflammation are associated with pregnancy-induced hypertension (PIH) or pre-eclampsia (PE), and evaluated some measurable indexes for assessment of maternal factors contributing to high-risk pregnancy. Photoplethysmographic reflection index (PPG RI), uterine artery (UtA) pulsatile index (PI) and reflection index (RI), as well as maternal serum placental growth factor (PlGF) and soluble endoglin (sEng) were measured in pregnant women with singleton pregnancy at the gestational age of 22 to 23 weeks. Study subjects were women with normal pregnancy (NP, n=24), PIH (n=14) and PE (n=16). It was found that individuals in the PIH group exhibited higher UtA RI and UtA PI values, as well as PPG RI values compared with individuals in the NP group. Individuals in the PE group had the highest UtA RI, UtA PI and PPG RI values among these 3 groups. UtA and PPG results were significantly different in PIH and PE groups compared with the NP group. Significant differences were found in both PlGF and sEng levels between PIH and PE groups. A strong inverse across-subject correlation was found between PlGF and sEng levels. A weak inverse correlation was found between PlGF and UtA RI, and PlGF and UtA PI. A moderate inverse correlation was found between PlGF and PPG RI. A moderate positive correlation was found between either sEng and UtA RI or sEng and UtA PI. A very strong positive correlation was found between sEng and PPG RI. Taken together, the current results indicated that maternal effects related to cardiovascular adaptation to placentation and systemic inflammation exhibited significant differences between NP and PIH or PE groups. Therefore, assessment of UtA and PPG could be used for identifying high-risk pregnancy.

show abstract

Maternal plasma-soluble ST2 concentrations are elevated prior to the development of early and late onset preeclampsia – a longitudinal study

Abstract: Maternal plasma sST2 concentrations are elevated 6 weeks prior to the clinical diagnosis of preeclampsia. An increase in the maternal plasma concentration of sST2 may contribute to an exaggerated intravascular inflammatory response and/or the Th1/Th2 imbalance in some cases.

Cited by 25 publications

References 183 publications

The prediction of early preeclampsia: Results from a longitudinal proteomics study

The prediction of early preeclampsia: Results from a longitudinal proteomics study

Effect of magnesium sulfate combined with labetalol on serum sFlt‑1/PlGF ratio in patients with early‑onset severe pre‑eclampsia

Doppler ultrasound and photoplethysmographic assessment for identifying pregnancy‑induced hypertension

Contact Info

Product

Resources

About