PlGF Ratio Research Articles

VP37.18: The role of sFLT‐1/PLGF ratio for predicting placental dysfunction in pregnant women hospitalised for non‐placental dysfunction disorders

VP37.18: The role of sFLT‐1/PLGF ratio for predicting placental dysfunction in pregnant women hospitalised for non‐placental dysfunction disorders

P-008. Predictive efficacy of sFlt-1/PlGF ratio in risk stratification on Indian hypertensive pregnant population

P-008. Predictive efficacy of sFlt-1/PlGF ratio in risk stratification on Indian hypertensive pregnant population

P-010. Short-term prediction of preeclampsia using the sFlt-1/PlGF ratio in pregnant women with suspected preeclampsia

Short-carbon-fiber-reinforced polyetherimide (SCF/PEI) composites have good mechanical properties and are expected to have wide applications including components serving under water lubrication conditions. However, no work has been reported on the tribological behaviors of SCF/PEI composites under water lubrication conditions. This work attempts to explore the practicality of the SCF/PEI composite from a tribological point of view under water lubrication conditions. SCFs are coated by polydopamine (PDA) to enhance the interfacial interaction between fibers and matrix. The tribological performances of SCF/PEI composite are systematically investigated by sliding wear tests under tap and sea water lubrication conditions. Experimental results show that the SCF/PEI composite has a better friction performance in water lubrications than that under dry sliding because of the separation effects formed by a water molecule film and a transfer film. However, no remarkable differences of wear resistance are found between water lubrication and dry contact conditions, and the magnitude of specific wear rate under these conditions is around 1 × 10−6 mm3/N·m. It is found that contact surface hardness of the SCF/PEI composite is reduced after a sliding test in water due to the plasticization phenomenon, especially sea water can accelerate the diffusion of water molecules into matrix, making the specific wear rate in sea water is ten times of that in tap water for highly-loaded conditions. Meanwhile, the abrasive wear is observed to be the dominated wear mode in boundary lubrication regime, and the adhesion wear occurs around the transition position from the boundary to mixed lubrication regime. It is also found that pressure has a significant effect on the temperature rise within the contact surface than the speed does. Finally, the tribological performance of the SCF/PEI composite under water is exhibited to be better than that of most of polymers and composites reported previously.

P-013. Negative predictive value of sFlt-1/PlGF ratio ≤ 38 for ruling out preeclampsia within 1–4 weeks of testing: A secondary analysis of the INSPIRE trial

The objective of this systematic review was to evaluate the efficacy of non-surgical periodontal therapy on rheumatoid arthritis activity.Articles published until April 2019 were electronically searched and screened using PubMed / MEDLINE, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). This study was recorded in the international PROSPERO database (CRD42019132205). The PICO question (population, intervention, comparison, results) was: in adult patients with rheumatoid arthritis and periodontitis (P), does non-surgical periodontal treatment (I), as compared to no treatment (C), provides better outcomes in rheumatoid arthritis activity (O).After searching the databases, seven articles were selected for qualitative and five for quantitative analysis. The total number of participants included was 292, with an average age of 50.5 years. All patients had rheumatoid arthritis and periodontal disease. Non-surgical periodontal treatment significantly reduced Disease Activity Score 28 (P = 0.004; I2 = 92%) and erythrocyte sedimentation rate (P = 0.01; I2 = 78%), but with no significant effect on C-reactive protein (P = 0.34; I2 = 92%).It can be concluded that non-surgical periodontal treatment can benefit patients with rheumatoid arthritis.

P-012. The association of sFlt-1: PlGF ratio with systematic damage in patient at increased risk of hypertensive disorders during pregnancy

P-012. The association of sFlt-1: PlGF ratio with systematic damage in patient at increased risk of hypertensive disorders during pregnancy

P-016. Sub-analysis of the Japanese population from PROGNOSIS Asia study assessing the sFlt-1/PlGF ratio for short-term prediction of preeclampsia

P-016. Sub-analysis of the Japanese population from PROGNOSIS Asia study assessing the sFlt-1/PlGF ratio for short-term prediction of preeclampsia

P-017. The Elecsys sFlt-1/PlGF ratio for short-term prediction of preeclampsia in the Japanese cohort of the PROGNOSIS Asia study: Economic evaluation

P-017. The Elecsys sFlt-1/PlGF ratio for short-term prediction of preeclampsia in the Japanese cohort of the PROGNOSIS Asia study: Economic evaluation

SFlt-1/PlGF Ratio in Prediction of Short-Term Neonatal Outcome of Small for Gestational Age Neonates.

Background: Small for gestational age is a pregnancy complication associated with a variety of adverse perinatal outcomes. The aim of the study was to investigate if sFlt-1/PlGF ratio is related to adverse short-term neonatal outcome in neonates small for gestational age in normotensive pregnancy. Methods: A prospective observational study was conducted. Serum sFlt-1/PlGF ratio was measured in women in singleton gestation diagnosed with fetus small for gestational age. Short-term neonatal outcome analyzed in the period between birth and discharge home. Results: Eighty-two women were included. Women with sFlt-1/PlGF ratio ≥33 gave birth to neonates with lower birthweight at lower gestational age. Neonates from high ratio group suffered from respiratory disorders and NEC significantly more often. They were hospitalized at NICU more often and were discharged home significantly later. sFlt-1/PlGF ratio predicted combined neonatal outcome with sensitivity of 73% and specificity of 82.2%. Conclusions: sFlt-1/PlGF ratio is a useful toll in prediction of short-term adverse neonatal outcome in SGA pregnancies.

Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker.

BackgroundWe investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia.Methods and ResultsIn 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF‐15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt‐1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF‐15×sFlt‐1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF‐15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF‐15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14).ConclusionsWe conclude circulating GDF‐15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt‐1/PlGF ratio.

The role of sFlt1/PlGF ratio in the assessment of preeclampsia and pregnancy-related hypertensive disorders.

Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Early recognition of the disease may be challenging. Complications may precede the onset of clinical symptoms and medical intervention is often delayed. Moreover, in the absence of specific clinical signs, many patients will present symptoms mimicking the disease without ever being diagnosed with preeclampsia. This situation may, however, lead to medical interventions and cause unnecessary stress for the patient. For many years, research tried to evaluate the significance of serum biomarkers as early indicators of preeclampsia. Among many, the sFlt-1/PlGF ratio, given its performance, aroused the greatest interest. This article reviews current knowledge on the subject, focusing on a Swiss perspective.

Model for Early Prediction of Preeclampsia: A Nested Case Controlled Study in Indian Women.

Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, (n = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20weeks in women with optimal sensitivity and specificity.

The sFlt-1 to PlGF ratio in pregnant women with rheumatoid arthritis: impact of disease activity and sulfasalazine use.

An elevated sFlt-1/PlGF ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with RA. We explored whether the sFlt-1/PlGFratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since SSZ has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether SSZ could affect sFlt-1 or PlGF levels. Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21-42 years, were included, with a median gestational age of 30 + 3 weeks. No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (P = 0.07 and P = 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r = -0.01 and r = -0.05, respectively). Four (2%) women with a sFlt-1/PlGF ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. SSZ users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-SSZ users (n = 164, P = 0.91 and P = 0.11). Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, SSZ use did not affect sFlt-1 or PlGF levels in this population.

Therapeutic plasma exchange and dextran-sulfate plasma adsorption as extracorporeal treatments of extremely preterm preeclampsia with fetal growth restriction.

To evaluate effectiveness and safety of therapeutic plasma exchange (TPE) and dextran-sulfate plasma adsorption (DSA) for extracorporeal removal of soluble Fms-like tyrosine kinase-1 (sFlt-1) as part of expectant management of preeclampsia at extremely preterm gestational age. Retrospective case series of six patients with preeclampsia at <28 weeks of gestation, treated with DSA or TPE. Laboratory results, clinical characteristics and neonatal outcomes were collected from charts and National Perinatal Information System. Fetal growth restriction (FGR) was diagnosed in all cases. Pregnancy was prolonged for a median of 14 (range 5-74) days from admission and 10 (3-73) days from first apheresis. A mixed effects model showed a decrease in sFlt-1 and sFlt-1/PlGF ratio during DSA/TPE (significant effect of time [before/after]), which was comparable between DSA and TPE (no effect of procedure type). Median absolute reduction in sFlt-1 was 42% (inter-quartile range [IQR] 13%-57%) during DSA and 34% (16%-40%) during TPE; for sFlt-1/PlGF ratio it was 29% (22%-36%) and 38% (29%-42%), respectively. All procedures were well tolerated by fetuses. Anaphylactoid reaction, often with angioedema, occurred in 4/6 patients undergoing DSA and was attributed to bradykinin activation. One patient developed wound hematoma after cesarean section, possibly attributed to depletion coagulopathy. As potential novel treatment of early preeclampsia, a non-selective and widely available TPE was comparable to DSA regarding sFlt-1 reduction but was associated with fewer side-effects. Both seem to allow maternal stabilization and pregnancy prolongation even when early preeclampsia is complicated by FGR.

Extremely early intrauterine growth restriction with dramatic sFlt-1/PlGF ratio

Extremely early intrauterine growth restriction with dramatic sFlt-1/PlGF ratio

Prenatal serum sFlt-1/PlGF ratio predicts the adverse neonatal outcomes among small-for-gestational-age fetuses in normotensive pregnant women: A prospective cohort study.

We investigated the predictive value of the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio for poor neonatal outcomes of SGA neonates in the absence of preeclampsia.This prospective cohort study included 530 singleton pregnant women who attended a prenatal screening program at a single institution. The sFlt-1/PlGF values at 24 to 28+6 weeks and 29 to 36+6 weeks of gestation were analyzed and compared between control and SGA group (subdivided as with normal neonatal outcomes and with poor neonatal outcomes).After 22 preeclampsia cases were excluded, 47 SGA neonates and 461 control neonates were included. In the SGA group, 17 neonates had adverse neonatal outcomes (36.1%, 17/47). The mean (±D) sFlt-1/PlGF ratio of early third trimester was significantly higher in SGA with averse neonatal outcome group than in the control group (14.42 ± 23.8 vs 109.12 3.96, P = .041) and the ratio retained an independent and significant association with SGA with adverse neonatal outcomes (odds ratio = 1.017, P = .01). A sFlt-1/PlGF ratio cut-off of 28.15 at 29 to 36+6 weeks significantly predicted adverse outcomes among SGA neonates (sensitivity = 76.9%, specificity = 88%).In this study, sFlt-1/PlGF ratio at 29 to 36 + 6wks of SGA with adverse neonatal outcome group was significantly higher than control group. This study suggests the feasibility of the sFlt-1/PlGF ratio as helpful objective measurement for predicting the adverse SGA neonatal outcome by providing sFlt-1/PlGF cut-off value.

Applying the concept of uncertainty to the sFlt-1/PlGF cut-offs for diagnosis and prognosis of preeclampsia.

Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) assays and the corresponding ratios (sFlt-1/PlGF) have been proposed to aid in the diagnosis by exclusion and/or prognosis of preeclampsia (PE). A method for evaluating ratio uncertainties (RUs), based on the theory of error propagation, was applied to the sFlt-1/PlGF ratio. RUs were calculated using data derived from sFlt-1 and PlGF Internal Quality Control (IQC) results collected from four centers using Elecsys (Roche) or Kryptor (Thermo Fisher) sFlt-1 and PlGF assays. The corresponding ratio uncertainties were defined for each ratio value. The RUs increased linearly with the sFlt-1/PlGF ratio values. The Elecsys RUs were lower than the Kryptor RUs. Although RUs cannot eliminate differences in ratio values observed among various immunoassays, it can affect interpretation of the sFlt-1/PlGF ratio, especially when results are within the range of predefined PE diagnosis or prognosis cut-offs. Since RUs are only a function of PlGF and sFlt-1 precision, they can be calculated for each assay from each laboratory to adjust the interpretation of sFlt-1/PlGF ratio results in the context of PE.

Economic evaluation of the sFlt-1/PlGF ratio for the short-term prediction of preeclampsia in a Japanese cohort of the PROGNOSIS Asia study

The PRediction of short-term Outcomes in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) Asia validated the use of the soluble fms-like tyrosine 1/placental growth factor (sFlt-1/PlGF) ratio cutoff value of ≤38 to rule out the occurrence of preeclampsia in the short term in Asian women. We assessed the economic impact of the introduction of the sFlt-1/PlGF ratio test for predicting preeclampsia in Japan using data from the Japanese cohort of PROGNOSIS Asia. The cost analysis was developed with estimates in either a no-test scenario, with clinical decisions based on standard diagnostic procedures alone, or a test scenario, in which the sFlt-1/PlGF ratio test was used in addition to standard diagnostic procedures. For both scenarios, rates of hospitalization and other test characteristics were obtained from the results for the Japanese cohort in PROGNOSIS Asia. The total cost per patient was the main outcome of this cost analysis model. Introduction of the sFlt-1/PlGF ratio test using a cutoff value of 38 resulted in a reduced hospitalization rate compared with the rate in the no-test scenario (14.4% versus 8.7%). The reduction in the rate of hospitalizations led to an estimated 16 373 JPY reduction in healthcare costs per patient. The sFlt-1/PlGF ratio test is likely to reduce the unnecessary hospitalization of women at low risk of developing preeclampsia in the short term while also identifying high-risk individuals requiring appropriate management. Reducing unnecessary hospitalizations would result in significant cost savings in the Japanese healthcare system.

1072 Early pregnancy BMI and angiogenesis-related biomarkers (sFlt-1/PlGF): a pathway for adverse pregnancy outcomes?

Obesity is a risk factor for adverse pregnancy outcomes, but it is unclear whether this is mediated through placental angiogenic factors. We examined the relationship between early pregnancy body mass index (BMI) and 1st- and 2nd-trimester concentrations of sFlt-1/PlGF as a potential biologic pathway for placental insufficiency. We conducted secondary analyses of data and samples from a large, multi-site prospective cohort study of nulliparous pregnant women conducted in the U.S. First- and 2nd-trimester blood samples, 1st-trimester BMI, demographic, lifestyle, and pregnancy data were gathered for all participants. sFlt-1 and PlGF concentrations were measured for a subsample of 1,502 cases (delivery<37weeks, preeclampsia or eclampsia, birthweight for gestational age <5th%, or stillbirth) and 911 controls. We used one-way ANOVA and multivariable linear and logistic regression models to test the association of BMI and sFlt-1/PlGF ratio, using a previously published ratio cutoff of ≥38 in logistic regression. We identified potential confounders a priori and used backward elimination to determine the best-fit model. Plots of mean sFlt-1/PlGF ratios by BMI category and gestational week showed lower ratios in overweight and obese groups in the 1st trimester, which reversed to higher ratios among overweight and obese groups in the 2nd trimester (Fig. 1). After controlling for clinical and demographic factors, women in all high BMI groups had significantly lower mean sFlt-1/PlGF ratios than normal weight women in the 1st trimester (Table 1). In the 2nd trimester, women with BMI ≥35 had a 35% higher mean sFlt-1/PlGF ratio than normal weight women (p=0.009). Logistic regression suggested increased odds of a 2nd-trimester ratio ≥38 among women with BMI ≥35, though not statistically different from 1.0 (OR 2.59, 95% CI 0.95-7.08). Early pregnancy BMI is associated with alterations in first- and second-trimester sFlt-1/PlGF ratios. Findings suggest a potential physiologic pathway between obesity and placental insufficiency.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Association study of hypertension susceptibility genes ITGA9, MOV10, and CACNB2 with preeclampsia in Chinese Han population

Objective Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes ITGA9, MOV10 and CACNB2 with PE in Chinese Han population. Methods A case–control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci (ITGA9 rs155524, MOV10 rs2932538 and CACNB2 rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF. Results Our study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with ITGA9 rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed ITGA9 rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between MOV10 and CACNB2 with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level. Conclusion This study has identified ITGA9 is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.

Expert consensus: Indication criteria and screening strategy for preeclampsia using the serum sFlt-1/PlGF ratio at 18–36 weeks of gestation in women at imminent/basal risk of preeclampsia under insurance coverage

Expert consensus: Indication criteria and screening strategy for preeclampsia using the serum sFlt-1/PlGF ratio at 18–36 weeks of gestation in women at imminent/basal risk of preeclampsia under insurance coverage