Placental Growth Factor Research Articles

External validation of the Fetal Medicine Foundation model for preterm pre-eclampsia prediction at 11-14 weeks in an Australian population.

Pre-eclampsia causes adverse maternal and perinatal complications and is preventable through early screening and aspirin treatment. This study evaluates the predictive performance of the Fetal Medicine Foundation first-trimester preterm pre-eclampsia competing risks model in an Australian population. This was a retrospective cohort study of prospectively collected multisite screening data and pregnancy outcomes between 2014 and 2017 in Australia. Individualized risk for preterm pre-eclampsia was calculated using the Fetal Medicine Foundation model at 11-14 weeks by using maternal factors, biophysical biomarkers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI)), and serum biochemical biomarkers (placental growth factor (PlGF) and/or pregnancy-associated plasma protein A (PAPP-A)). The predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUC) and calibration. The detection rates for delivery with preterm pre-eclampsia were calculated at a 10% fixed false-positive rate. Decision curve analysis of the model was evaluated. Of 29 609 women screened, 132 (0.45%) experienced preterm pre-eclampsia. The median age (interquartile range) was 34 (30-38) years. Women with pre-eclampsia had higher multiple of the median values of MAP and UtA-PI and lower values of PIGF and PAPP-A compared to those without pre-eclampsia. Combined screening by maternal factors, biophysical, and biochemical biomarkers yielded an AUC of 0.87 (95% CI 0.79-0.92), detecting 71% of preterm pre-eclampsia cases at 10% fixed false-positive rate, with the addition of PlGF improving the detection rate by 31% over sole PAPP-A use. Preterm pre-eclampsia screening using maternal factors with all biomarkers showed better clinical net benefit at preference thresholds between 1% and 12% compared to default strategies. The Fetal Medicine Foundation model, combining maternal factors with biophysical and biochemical biomarkers, demonstrated similar predictive performance in the Australian population compared to previous validation studies in other settings, detecting 71% of preterm pre-eclampsia cases at 10% fixed false-positive rate. The clinical utility analysis showed that early screening and intervention strategies based on a risk-based screening approach is more beneficial than universal or no intervention strategies.

The role of maternal age, markers of ultrasound, sFlt-1 and CA125 serum levels in the prediction of miscarriage: Study acronym: MIS-CARE (markers of ultrasound, immunologic and serum factors in the comprehensive analysis of the risks for early pregnancy loss).

The role of maternal age, markers of ultrasound, sFlt-1 and CA125 serum levels in the prediction of miscarriage: Study acronym: MIS-CARE (markers of ultrasound, immunologic and serum factors in the comprehensive analysis of the risks for early pregnancy loss).

Hypoxia-induced histone lactylation promotes pulmonary arterial smooth muscle cells proliferation in pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Glycolysis plays a crucial role in PH pathogenesis, but the epigenetic mechanisms linking glycolysis to PASMCs proliferation remain unclear. Histone lactylation, a novel post-translational modification derived from glycolytic lactate, may regulate PASMCs proliferation. Primary rat PASMCs were cultured under hypoxia and treated with sodium L-lactate (NaLa) to assess glycolytic activity and histone lactylation. RNA sequencing, RT-qPCR, and Western blotting identified differentially expressed genes (DEGs), while ChIP-qPCR evaluated histone lactylation enrichment at gene promoters. In vivo, a hypoxia-induced PH rat model was used to examine the effect of glycolysis inhibition using oxamate. Mendelian randomization (MR) analysis assessed the causal relationship between placental growth factor (PGF) and PH. Hypoxia and NaLa treatment significantly increased glycolytic activity, lactate production, and histone lactylation, promoting PASMCs proliferation. Transcriptomic analysis identified 157 DEGs, with five key genes (Gbe1, Pgf, Mt2A, Ythdf2 and Gys1) upregulated in response to histone lactylation. ChIP-qPCR confirmed H3K18la enrichment at their promoters. Glycolysis inhibition with oxamate effectively reduced histone lactylation, PASMCs proliferation, and vascular remodeling in hypoxic PH rats. MR analysis identified PGF as a causal factor contributing to PH risk, suggesting a potential therapeutic target. This study reveals that glycolysis-induced histone lactylation drives PASMCs proliferation and vascular remodeling in PH. Targeting lactate metabolism and histone lactylation may provide a novel therapeutic approach.

Updates on Preeclampsia: Pathogenesis, Biomarkers, Diagnosis, and Management.

Preeclampsia complicates 2-4% of pregnancies globally and contributes significantly to maternal and fetal morbidity and mortality. Early-onset preeclampsia (<34 weeks gestation) is primarily characterized by abnormal placentation and defective remodeling of uterine spiral arteries, while late-onset preeclampsia (>34 weeks gestation) often involves a mismatch between normal maternal perfusion and increasing placental metabolic demands. Angiogenic imbalance, featuring elevated antiangiogenic factors [soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin] and decreased proangiogenic factors [placental growth factor (PlGF)], plays a pivotal role in disease manifestation. Diagnostic criteria include hypertension with new-onset proteinuria, maternal end-organ damage, or uteroplacental dysfunction. The addition of sFlt-1/PlGF ratio has been Food and Drug Administration approved for risk assessment for preeclampsia. Prevention strategy includes mainly low-dose aspirin for high-risk women. While delivery remains the definitive treatment, novel therapies targeting the pathophysiology of preeclampsia are being investigated, including therapeutic apheresis, siRNA therapies, metformin, proton pump inhibitors, statins, and complement inhibitors. Women with a preeclampsia history face significantly increased long-term risks of cardiovascular disease, stroke, renal dysfunction, and metabolic disorders, emphasizing the need for comprehensive postpregnancy follow-up and preventive strategies. This review comprehensively examines the pathogenesis, diagnosis, biomarkers, and management strategies of preeclampsia.

Soluble FMS-like tyrosine kinase-1/Pro- angiogenic placental growth factor (sFlt- 1/PlGF) ratio as an early predictor for oxygenation impairment in preeclampsia

Preeclampsia is a major cause of maternal mortality worldwide, with angiogenic imbalance playing a central role in its pathophysiology. This study aimed to investigate the relationship between the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio and oxygenation impairment in preeclamptic patients. A cross-sectional observational study was conducted on 47 women with singleton pregnancies diagnosed with preeclampsia at a gestational age beyond 34 weeks who underwent cesarean delivery. Data were obtained from medical records, including sFlt-1 and PlGF serum levels, sFlt-1/PlGF ratio, and arterial blood gas analysis for calculating PaO₂/FiO₂ (P/F) ratios. A significant negative correlation was found between the sFlt-1/PlGF ratio and the P/F ratio (r = -0.514, p &lt; 0.001), indicating that a higher angiogenic imbalance is associated with poorer oxygenation status. Receiver operating characteristic (ROC) curve analysis revealed a cut-off value of 138.58 for the sFlt-1/PlGF ratio, with 83.33% sensitivity and 80% specificity for predicting oxygenation impairment. These findings suggest that the sFlt-1/PlGF ratio may serve as an early biomarker for detecting oxygenation disturbances in preeclampsia, supporting timely clinical interventions.

Role of Fetal Medicine Foundation (FMF) Instrument as a Screening Pre-eclampsia: A Cohort Study

Maternal death is still a problem among pregnant women. One of the most prevalent causes of maternal death is preeclampsia. Preeclampsia contributes not only to maternal death, but also increases fetal morbidity. Early screening for preeclampsia is a key factor to managing the condition. The Fetal Medicine Foundation (FMF) has developed an algorithm to predict preeclampsia during the first trimester of pregnancy. However, there has been lack of studies done in Indonesia its usage. Therefore, this study aims to examine the accuracy of the FMF algorithm as a screening tool to identify preeclampsia in women in the first trimester of pregnancy. //Prospective cohort study done in Obstetrics and Gynecology Department of Mohammad Hoesin Hospital Palembang in January-December 2023. Sixty subjects that met the inclusion criteria were followed from 11 to 13+6 weeks to birth. All subjects undergo history taking for maternal and obstetrics history, physical examination, in particular mean arterial pressure (MAP) measurement, ultrasonography examination to evaluate mean uterine artery pulsatility index (UtA-PI), crown-rump length (CRL), and laboratory testing for pregnancy-associated plasma protein-A [PAPP-A] and placental growth factor [PlGF]. The outcome of this study is the incidence of preeclampsia as well as the detection rate (accuracy rate), false positive rate, positive predictive value (PPV), and negative predictive value (NPV) of the FMF algorithm. Data were analyzed using SPSS version 25.0 with a significance level of p &lt;0.05 and a 95% CI. Kolmogorov Smirnov test was used for data homogeneity, Chi-square or Fisher test for categorical data, One way anova and Kruskal wallis test for numerical data. Sixty subjects were enrolled. Among these, 30 subjects subsequently developed preeclampsia, with 18 (30%) experiencing early-onset preeclampsia, 12 (20%) experiencing late-onset preeclampsia, and 30 (50%) not developing preeclampsia (normotension). There was no significant difference in maternal characteristics and obstetric history among the three groups. MAP is found to be significantly different, with the highest found in the early onset preeclampsia group (p=0.021). Uterine artery pulsatility index (UtA-PI) was significantly higher in early-onset and late-onset preeclampsia subjects (p=0.019). There was no significant difference among the three groups in CRL. Serum PIGF was significantly lower in early onset and late-onset preeclampsia subjects (p-0.0001). Serum PAPP-A is also significantly lower in the early-onset preeclampsia subjects (p=0.0002). The combination of FMF/MAP, UtA-PI, yields the highest accuracy in predicting preeclampsia with 100% values for sensitivity, specificity, PPV, and NPV (p=0,000). The other combinations show lower accuracy, but quite good values of specificity and sensitivity. The FMF algorithm is an accurate screening tool to identify preeclampsia in the first trimester of pregnancy.

Placental Syncytium-on-Chip (PSoC)-Comparison of Forskolin or Mechanical Induced-Syncytialization.

The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts and differentiated syncytiotrophoblats, whose maturation and function are influenced by wall shear stress (WSS) from the maternal blood circulation. Most in vitro placenta models rely on cyclic adenosine monophosphate inducer forskolin (FSK) to establish a placental syncytium. Here a trophoblastic BeWo cell line is used to systematically compare the effect of FSK treatment in static culture with WSS stimulation in a pumpless, recirculating organ-on-chip. It is shown that BeWo cells undergo a similar differentiation under WSS exposure to FSK treatment. A WSS of 0.1 dyn cm-2 leads to cell fusion, polarization, barrier functions, human chorionic gonadotropin (β-hCG) secretion, and increased expression of key transporters. Moreover, WSS induces favorable changes in the levels of FMS-like tyrosine kinase-1 (FLT-1) and Placental Growth Factor (PlGF) suggesting the development of a physiologically relevant placental syncytium-on-chip (PSoC) without the need for FSK. The platform is further expanded to a syncytiotrophoblast/endothelial co-culture showing physiological vascular functions under WSS. The forskolin-free PSoC presented here represents the first pumpless recirculating and scalable platform for physiological placental studies and drug testing.

Efficacy of switching from existing anti-vascular endothelial growth factor drugs to ranibizumab biosimilar in neovascular age-related macular degeneration.

This study evaluated the clinical outcomes and aqueous humor cytokine levels in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept to ranibizumab biosimilar (BS). Prospective observational study. Thirty-eight eyes of 38 patients with nAMD who received aflibercept under a treat-and-extend (TAE) regimen were prospectively switched to ranibizumab BS. Eight eyes with cataracts undergoing surgery served as controls for aqueous humor cytokine analysis. Best-corrected visual acuity (BCVA) and anatomical outcomes were assessed over one year. The aqueous humor levels of vascular endothelial growth factor (VEGF)-A, angiopoietin-2 (Ang-2), and placental growth factor (PlGF) were measured before and after switching in eyes with nAMD and at surgery in controls. Disease activity remained controlled in 94.3% of patients with nAMD for over one year. No significant changes were observed in the BCVA (P=0.65) after one year. Ang-2 levels remained unchanged (P=0.66) and were not significantly different between eyes with nAMD and controls both before (P=0.64) and after switching (P=0.30). PlGF levels also remained stable (P=0.12) but were significantly higher in eyes with nAMD than in controls both before (P<0.01) and after switching (P=0.03). VEGF-A levels significantly increased after switching (P<0.01) but remained lower than in the controls both before (P<0.01) and after switching (P=0.02). Switching from aflibercept to ranibizumab BS effectively maintained disease stability and cytokine balance in eyes with nAMD. These findings support ranibizumab BS as a viable and cost-effective alternative for long-term treatment.

Cardiovascular risk assessment in women at high risk for pre-eclampsia in first half of pregnancy.

Women diagnosed with pre-eclampsia (PE), especially those with early-onset and severe forms, are at heightened risk of future cardiovascular disease. However, it is uncertain if women at high risk for PE present cardiovascular impairment at the beginning of pregnancy. The aim of this study was to assess cardiovascular biomarkers and cardiac function in the first half of pregnancy in women at high risk for PE. This was a prospective cohort study including women attending first-trimester screening for PE at a single center in Spain, between July 2020 and April 2023. The risk of PE in the first trimester was calculated using a previously validated model that includes maternal factors and biophysical markers. A cut-off of 1 in 250 was used to classify high risk for developing PE. Maternal echocardiographic function and morphometry were evaluated, and peripheral blood samples were obtained to assess hematological and biochemical variables, including lipid profile and cardiovascular and angiogenic factors. Findings were compared between women at high risk and those at low risk for PE. A total of 349 pregnant individuals were included, 257 at high risk and 92 at low risk for PE. Maternal echocardiography was performed at a mean ± SD gestational age of 14.9 ± 1.3 weeks and blood sampling at 16.3 ± 1.9 weeks. The high-risk PE group exhibited a worse lipid profile (significantly lower levels of high-density lipoprotein (69.7 ± 14.2 vs 74.0 ± 14.6 mg/dL; P = 0.020), significantly lower placental growth factor multiples of the median (0.89 ± 0.63 vs 1.15 ± 0.58; P < 0.001) and significantly lower levels of N-terminal pro B-type natriuretic peptide (51.0 ± 2.1 vs 52.1 ± 2.0 ng/L; P = 0.008)). Echocardiographic evaluation indicated concentric remodeling along with an altered diastolic pattern in the high-risk group. Women at high risk of developing PE exhibit differences in lipid profile, angiogenic factors and echocardiographic parameters, indicative of cardiac maladaptation or impairment during the first half of pregnancy. These findings suggest a link between subclinical cardiovascular dysfunction, PE development and later cardiovascular disease risk. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Advances in Molecular Imaging of VEGFRs: Innovations in Imaging and Therapeutics.

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful strategy for non-invasive imaging of VEGFR expression and distribution in vivo. Through positron emission tomography (PET) and single-photon emission computed tomography (SPECT), these targeted tracers enable real-time visualization of angiogenic and lymphangiogenic activity, providing insights into disease progression and therapeutic responses. This review explores the current advances in VEGFR-targeted imaging, focusing on the development of novel tracers, radiolabeling techniques, and their in vivo imaging characteristics. We discuss the preclinical and clinical applications of VEGFR imaging, highlight existing challenges, and provide perspectives on future innovations that could further enhance precision diagnostics and therapeutic monitoring in angiogenesis and lymphangiogenesis-driven diseases.

KCNK2-mediated regulation of MMP-2/9 by PlGF influences uterine artery function in pregnancy-induced hypertension

BackgroundPregnancy induced hypertension (PIH) is characterized by aberrant uterine arterial remodeling, a process tightly associated with an imbalance between placental growth factor (PlGF) and soluble fms like tyrosine kinase 1 (sFlt 1) as well as the down regulation of matrix metalloproteinases 2/9 (MMP 2/9). This study investigated the regulatory effect of PlGF on the two pore domain potassium channel KCNK2 and its downstream targets MMP 2/9, and explored the role of the PlGF KCNK2 MMP 2/9 axis in PIH related uterine arterial dysfunction.MethodsIn vitro, human aortic endothelial cells (HAECs) were assessed for proliferation and migration using CCK 8 and Transwell assays. Nitric oxide (NO) and endothelin 1 (ET 1) levels were quantified by ELISA, while KCNK2 and MMP 2/9 expression was analyzed by Western blotting. In vivo, a Sprague Dawley rat PIH model was established to monitor blood pressure and 24 h urinary protein. Hematoxylin–eosin staining was used to measure uterine arterial intimal thickness; endothelial nitric oxide synthase (eNOS) and ET 1 localization was determined by immunohistochemistry, and KCNK2 as well as MMP 2/9 expression was quantified by immunohistochemistry and Western blotting.Results2,2,2 Trichloroethanol and PlGF significantly enhanced endothelial cell proliferation and migration, increased NO, decreased ET 1, and up regulated KCNK2 and MMP 2/9 expression (P < 0.05); ropivacaine produced opposite effects. PIH rats exhibited markedly elevated blood pressure and urinary protein, intimal thickening, reduced eNOS and elevated ET 1, together with diminished MMP 2/9 expression. Combined treatment with PlGF and 2,2,2 trichloroethanol lowered blood pressure and urinary protein, attenuated intimal thickness, increased eNOS and decreased ET 1, and up regulated KCNK2 and MMP 2/9 (P < 0.05).Conclusion2,2,2 Trichloroethanol activates KCNK2, elevates MMP 2/9, and improves uterine arterial endothelial function, while PlGF synergizes with KCNK2 signaling to potentiate these effects. The PlGF KCNK2 MMP 2/9 axis plays a pivotal regulatory role in the vascular pathology of PIH, highlighting its potential as a therapeutic target for PIH related vascular dysfunction.

Using vascular biomarkers to assess heart failure event risk in hospitalized patients with and without AKI

BackgroundPatients with AKI experience higher rates of heart failure (HF). This study seeks to identify criteria to assess the risk of heart failure post-hospitalization, with a special focus on AKI patients. We hypothesized that the combined use of 9 vascular biomarkers would predict future heart failure events after AKI. Using a study of 1497 hospitalized patients with and without AKI, we found that these 9 vascular biomarkers successfully stratified patients into different risk groups for HF, and were able to improve prediction of HF when added to routine clinical variables.MethodsUsing the ASSESS-AKI cohort, we performed an unsupervised spectral cluster analysis with 9 plasma biomarkers measured at 3 months post-hospitalization [Angiopoietin (angpt)-1, angpt-2, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-d, VEGF receptor 1 (R1), solubleTie-2 (sTie-2), placental growth factor (PlGF), and basic fibroblast growth factor (bFGF)] in 1,497 patients, half of whom had AKI. We used a Cox regression analysis to evaluate the associations between the clusters and HF. Models were adjusted for demographics, cardiovascular disease risk factors, medications, ICU status, lung disease, sepsis, clinical center, and 3-month post-discharge serum creatinine and proteinuria. We calculated change in the area under the curve (AUC) for the prediction of HF or death at 3 years by adding the biomarkers to a clinical model selected by a penalized regression with LASSO. We also calculated a net reclassification index for the addition of the biomarkers to the clinical model.ResultsThree biomarker-derived clusters were identified: Cluster 1 [n = 302, Vascular Injury (Injury) Phenotype] had higher levels of injury markers, whereas Cluster 2 [n = 728, Vascular Repair (Repair) Phenotype] had higher levels of repair markers. Cluster 3 (n = 467) had lower levels of all markers (Dormant Phenotype). Across the entire cohort, those with the Injury Phenotype had twofold higher risk of a HF event compared to the Repair Phenotype [aHR 2.24 (95% CI: 1.57–3.19)] and noted in both participants with AKI [aHR 2.12 (95% CI: 1.35–3.34)] and without AKI [aHR 2.94 (95%CI: 1.57–5.50)]. The Dormant Phenotype was associated with higher risk of HF events only in participants without AKI. The AUC for the prediction of HF event or death at 3 years by the biomarkers was 0.76 (95% CI: 0.73–0.80), 0.77 (95% CI: 0.73–0.80) for the clinical model, and 0.80 (95% CI: 0.77–0.83) for the combined model. The addition of the biomarkers significantly improved reclassification of HF event or death.ConclusionsVascular biomarkers can be used to derive phenotypes capable of stratifying future risk of HF events in recently hospitalized patients with or without AKI.

The role of placental growth factor as a biomarker in patients with resectable gastric cancer.

The role of placental growth factor as a biomarker in patients with resectable gastric cancer.

P-503 Assessment of serum soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF) as biomarkers of early pregnancy failure

Abstract Study question Can serum sFLT-1 and PlGF be used to differentiate between ectopic pregnancy and miscarriage in early pregnancy? Summary answer SFLT-1 and PlGF have shown significant promise in identifying ectopic pregnancy from miscarriage, but further research with intrauterine pregnancy samples is required. What is known already Approximately 8-24% of pregnancies end in miscarriage and 2% are ectopic. Typically, diagnoses require ultrasound imaging, which can be inconclusive in up to 40% of cases. Serial serum human chorionic gonadotrophin aids in diagnosis, but requires repeated measurements, prolonging diagnostic uncertainty during a potentially distressing time. sFLT-1 is a variant of vascular endothelial growth factor that prevents abnormal angiogenesis whilst PlGF is an angiogenic signalling protein. These angiogenic growth factors have shown promise as potential serum biomarkers of early pregnancy failure for reliable and rapid diagnosis in existing studies. Study design, size, duration This is a retrospective case-control study: serum samples (n = 359) collected from pregnant women presenting with vaginal bleeding in early pregnancy with a final diagnosis of ectopic pregnancy (n = 99) or miscarriage (n = 260). All samples were stored at -80 °C. Participants/materials, setting, methods Serum sFLT1 and PlGF were measured using Elecsys sFLT-1 and PlGF immunoassays run on the Cobas e411. Receiver operating characteristic (ROC) curves for each biomarker, as well as the ratio between them, were then calculated using R easyROC version 1.3.1. A cut-off point was identified from these using the Youden index. Subsequent sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were then calculated using the cut-off point. Main results and the role of chance Our results showed significant promise for using serum sFLT-1, and also the ratio between sFLT-1 and PlGF, to distinguish between ectopic pregnancy and miscarriage. The results for PlGF alone were less convincing, but still showed potential. Using a cut-off point of 165.8pg/mL, sFLT-1 was able to determine ectopic pregnancy from miscarriage with a PPV of 99% and an NPV of 75% (area under curve (AUC) of 0.95). With a cut-off point of 12.78pg/mL, PlGF could identify ectopic pregnancy from miscarriage with a PPV of 93% and an NPV of 46% (AUC 0.79). The ratio between sFLT-1 and PlGF could determine ectopic pregnancy from miscarriage with a PPV of 97% and an NPV of 73% when using a cut-off point of 14.69 (AUC of 0.93). All p-values were &amp;lt;0.05. Limitations, reasons for caution Our study does not currently include women with intrauterine pregnancies, so further research is needed with samples from viable pregnancies to aid use in clinical practice. Additionally, further research is needed to better understand how levels of biomarkers vary with gestational age, as this would be valuable for reliable interpretation. Wider implications of the findings The possibility of a blood test to differentiate ectopic pregnancy and miscarriage in early pregnancy failure would provide a novel tool to enable more rapid and reliable diagnosis of women with early pregnancy failure, in what can be a distressing time for patients. Trial registration number No

Effect of aspirin on biomarker profile in women at high-risk for preeclampsia

Effect of aspirin on biomarker profile in women at high-risk for preeclampsia

Assessment of a salivary cfRNA biomarker panel to predict preeclampsia.

Assessment of a salivary cfRNA biomarker panel to predict preeclampsia.

Correlation between first trimester placental growth factor levels and skin microvascular reactivity assessed by laser speckle contrast imaging - a cross-sectional study.

Correlation between first trimester placental growth factor levels and skin microvascular reactivity assessed by laser speckle contrast imaging - a cross-sectional study.

Vascular endothelial growth factor receptors 1 and 3 mediate placental trophoblast leptin production in preeclampsia, inducing vascular dysfunction

Heightened soluble FMS-like tyrosine kinase-1 (sFlt-1) levels is a hallmark of preeclampsia patients and induces a state of angiogenic imbalance by sequestering free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The receptors for VEGF and PlGF, membrane-bound VEGFR, are expressed in placental trophoblast cells, but their functions are largely unknown. Placenta production of leptin significantly increases in preeclampsia, and we recently showed leptin induces placental and vascular endothelial dysfunction in pregnancy. We hypothesized that there is a mechanistic link in which inappropriately high sFlt-1 in preeclampsia leads to an increase in trophoblast leptin production. We treated human placental explants and trophoblast cells with sFlt-1 and show an increase in leptin peptide production, which is ablated by coadministration with either VEGF or placental growth factor (PLGF). We further demonstrate that VEGFR1 and 3, not R2, expressions are predominant in human trophoblasts and that reducing activation of these receptors mediates trophoblast leptin production. In pregnant mice, we show that sFlt-1 infusion induces vascular endothelial dysfunction in association with significantly elevated plasma leptin levels. In pregnant sFlt-1-infused mice treatment with leptin receptor antagonist significantly ablated vascular endothelial dysfunction. Collectively, these data indicate that angiogenic imbalance in preeclampsia impacts placental trophoblast endocrine function by suppressing VEGFR1 and 3 activation, resulting in leptin overproduction. Furthermore, sFlt-1 induces vascular endothelial dysfunction in mice dependent on leptin receptor activation.

Perinatal Outcomes of Fetal Growth Restriction (FGR) and Small for Gestational Age (SGA) Defined by Delphi Criteria and Placental Growth Factor (PlGF): Preliminary Retrospective Data [ID 1303

INTRODUCTION: The objective was to investigate the associations between placental growth factor (PlGF) levels and adverse perinatal outcomes in pregnant patients diagnosed with fetal growth restriction (FGR)/small for gestational age (SGA) by Delphi criteria. METHODS: Data were collected between June 2022 and August 2024. Placental growth factor levels were interpreted based on gestational age. Data were analyzed using Delphi criteria: early-onset FGR (less than 32-week estimated fetal weight [EFW], less than 3%); late-onset FGR (greater than 32-week EFW, less than 3%); early-onset SGA (less than 32-week EFW, 4–10%); late-onset SGA (greater than 32-week EFW, 4–10%). Perinatal outcomes were defined as abnormal placental morphology (ultrasound), preeclampsia, intrauterine fetal demise (IUFD), cesarean birth rates, admission to neonatal intensive care unit (NICU), and confirmed maternal/fetal malperfusion (placental pathology). The study was approved by REB-USask #Bio3702. RESULTS: Seventy-six patients met the Delphi criteria for FGR/SGA. Low PlGF levels were more frequent in late-onset FGR (66%). There was a significant association between PLGF levels and the presence of FGR/SGA (P=.01). Abnormal placental morphology was more frequent in early-onset (53%) and late-onset (56%) FGR. Preeclampsia was more frequent in late-onset FGR (44%) and late-onset SGA (56%). Intrauterine fetal demise was more frequent in late-onset SGA (11%). Cesarean birth rates were higher in all four categories of FGR/SGA (56–71%). Admission to NICU was 59% in early-onset FGR and 78% in late-onset FGR. Confirmed placental pathology findings were present in greater than 50% of early/late-onset FGR. CONCLUSIONS/IMPLICATIONS: Low PlGF levels were associated with diagnosis of FGR/SGA (Delphi criteria). Early/late-onset FGR were associated with low PLGF levels, abnormal placental morphology, preeclampsia, cesarean birth, admission to NICU, and confirmed fetal/maternal vascular malperfusion. Late-onset SGA was associated with preeclampsia, IUFD, and cesarean birth.

Rule-in and rule-out of pre-eclampsia using a novel point-of-care placental growth factor test.

Rule-in and rule-out of pre-eclampsia using a novel point-of-care placental growth factor test.