Placental Growth Factor Levels Research Articles

Плацентарні фактори у вагітних з ізольованими вадами серця в плода

The placenta, as a unique and transient organ in humans, ensures the development and protection of the fetus, the expression of angiogenic and antiangiogenic factors and their receptors. The integrity of the fetoplacental endothelial barrier is critical for the development of fetal organs, especially the cardiovascular system. Placental growth factor (PLGF) regulates the morphologic and functional development of the uteroplacental vasculature and can vary with gestational age and in various pathologic conditions of the pregnant woman. Since there is a differential expression of PLGF and soluble form of fms-like tyrosine kinase (sFlt-1) at different gestational ages and their competitive interaction, it is advisable to study their level in the blood of a pregnant woman as indicators of regulation of the placental vascular system in pathological conditions of the woman and fetus. Purpose - to determine the levels of placental factors, namely PLGF and sFlt-1, in the serum of pregnant women with isolated congenital heart disease (CHD) in the fetus to increase the effectiveness of diagnostics and the ability to predict heart diseases. Materials and methods. The work was based on a prospective clinical study of a hospital sample, using the case-control study method, with the evaluation of some clinical and laboratory data in 30 pregnant women with isolated fetal CHD (study group) and 60 pregnant women with a healthy fetus (control group). In order to minimize the influence of various risk factors for fetal heart disease, the criteria for selecting pregnant women with non-syndromic forms of CHD and the control group were defined. Clinical, laboratory and statistical methods were used in the study. The level of angiogenesis indicators in blood serum of pregnant women of both groups was determined by enzyme-linked immunosorbent assay in units of pg/ml in the third trimester of pregnancy. The statistical analysis was carried out using the R software package. ROC analysis and AUC (area under the ROC curve) were used for quantitative interpretation. Differences with p<0.05 were considered statistically significant. Results. According to the results of the study, the age of the women in the study group ranged from 17 to 39 years with a mean of 28.36±5.12, and the age of the women in the control group was 29.63±5.39 (p=0.239). The mean gestational age of women in the study group at enrollment was 28.26±8.45 weeks. The mean PLGF level was 93.73±77.32 pg/mL in the study group and 198.63±168.27 pg/mL in the control group (p=0.002). The average level of sFlt-1 in the blood serum of the women in the study group was 9779.44±5407.53 pg/ml, while in the pregnant women in the control group it was 3124.6±1624.53 (p<0.001). The sFlt/PlGF ratio was 180.9±151.1 in the study group and 15.76±14.7 in the control group (p<0.001). Conclusions. The obtained results in the form of a decrease of the placental growth factor in the blood of pregnant women with congenital heart defects in the fetus and an increase of the antiangiogenic factor in this group in the III trimester compared to a healthy fetus indicate a violation of angiogenesis in the fetoplacental system. Analysis of data on the age of pregnant women of both groups did not reveal a statistically significant difference between them. Due to the usage of multifactor logistic regression model, was created the CHD “risk calculator” which, using the placental factors of the pregnant woman, calculates the probability of the occurrence of a heart defect in fetus. The study was conducted in accordance with the tenets of the Declaration of Helsinki. The local ethics committee approved the study protocol for all participants. Informed consent was obtained from patients. No conflict of interests was declared by the author.

Clinical efficacy and changes of serum VEGF-A, VEGF-B, and PLGF after conbercept treating neovascular age-related macular degeneration.

To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PLGF) levels after intravitreal injections for the neovascular age-related macular degeneration (AMD). Thirty-five patients (35 eyes) with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were detected before the intravitreal injection and at 1, 3, and 12mo after conbercept treatment. The levels of serum VEGF-A, VEGF-B, and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments. At baseline, the mean BCVA score was 39.89±14.64 letters. The mean BCVA scores were 51.03±15.78, 56.71±14.38, and 52.49±10.16 letters at 1, 3, and 12mo after conbercept treatment, and the BCVA improvements were all significant, respectively (P<0.05). At baseline, the mean CRT was 436.7±141.9 µm. At 1, 3, and 12mo after conbercept treatment, the mean CRT values were 335.1±147.8, 301.1±116.5, and 312.2±98.22 µm, and the CRT improvements were all significant, respectively (P<0.05). At baseline, 1 and 12mo after conbercept treatment, the mean levels of serum VEGF-A were 1013.8±454.3, 953.1±426.4, and 981.5±471.7 pg/mL, the mean levels of serum VEGF-B were 46.93±24.76, 42.99±19.16, and 45.32±18.76 pg/mL, the mean levels of serum PLGF at these points were 251.7±154.9, 241.3±166.7, and 245.6±147.2 pg/mL, respectively. Compared with the baseline, the levels of serum VEGF-A, VEGF-B, and PLGF did not significantly change at 1 and 12mo after conbercept treatment, respectively (P>0.05). Conbercept intravitreal injection leads to BCVA and CRT improvement, however, it does not significantly affect systemic serum VEGF-A, VEGF-B, and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.

Role of First Trimester Screening Biochemical Markers to Predict Hypertensive Pregnancy Disorders and SGA Neonates-A Narrative Review.

Early recognition of high-risk pregnancies through biochemical markers may promote antenatal surveillance, resulting in improved pregnancy outcomes. The goal of this study is to evaluate the possibilities of using biochemical markers during the first trimester of pregnancy in the prediction of hypertensive pregnancy disorders (HPD) and the delivery of small-for-gestational-age (SGA) neonates. A comprehensive search was conducted on key databases, including PubMed, Scopus, and Web of Science, for articles relating to the use of biochemical markers in the prediction of HPD and SGA. The findings show that changes in the levels of biomarkers in the early pregnancy phases could be an important indicator of adverse pregnancy outcomes. The literature shows that low PAPP-A (pregnancy-associated plasma protein A) and PlGF (placental growth factor) levels, low alkaline phosphatase (AP), higher sFlt-1 (soluble fms-like Tyrosine Kinase-1) levels, higher AFP (alfa fetoprotein) levels, and elevated levels of inflammatory markers such as β-HGC (free beta human chorionic gonadotropin), interferon-gamma (INF-γ), and tumor necrosis factor-α (TNF-α) may be associated with risks including the onset of HPD, fetal growth restriction (FGR), and delivery of SGA neonates. Comparatively, PAPP-A and PlGF appear to be the most important biochemical markers for the prediction of SGA and HPD.

Oleuropein attenuates placental growth factor expression by regulating oxidative stress and apoptosis in acrylamide hepatotoxicity

The liver is susceptible to toxic effects, as it is the main site of acrylamide biotransformation and detoxification. Researchers have claimed that placental growth factor (PlGF) and its pathway are potentially involved in numerous diseases, including liver fibrosis and angiogenesis. Oleuropein is a natural phenolic compound with potent antioxidant effects. The purpose of this study was to examine the role of PlGF and the potential protection provided by oleuropein in acrylamide hepatotoxicity. Wistar albino rats were assigned into control, acrylamide (ACR) (5 mg/kg), oleuropein (OLE) (4.2 mg/kg), and ACR+OLE groups. Acrylamide and oleuropein were administered for 21 days. The control group received only physiological saline. Liver tissues were evaluated histologically and immunohistochemically. Histological examinations revealed significant enlargement of the sinusoidal vessels and abundant hepatocytes with pyknotic nuclei in the ACR group. Acrylamide toxicity resulted in elevated PlGF, accumulation of 8-hydroxydeoxyguanosine (8-OHdG), and increased Caspase-3 immunoreactivity in the liver. Oleuropein treatment reduced the increased expression of PlGF, 8-OHdG, and Caspase-3 against these deleterious effects observed in the ACR group. A positive correlation was observed between PlGF levels as well as oxidative stress and apoptosis markers in acrylamide toxicity. Oleuropein probably counteracted this mechanism by exhibiting antioxidant activity.

Anti-Vascular Endothelial Growth Factor Therapy with or Without Initial Steroid Therapy for Macular Edema in Branch Retinal Vein Occlusion.

In branch retinal vein occlusion (BRVO), administering steroid injections to inhibit expression of inflammatory factors in the first phase of macular edema may reduce recurrence of the edema. The purpose of our study was to investigate the functional and morphological prognosis and frequency of recurrence after injection of an anti-vascular endothelial growth factor (VEGF) with and without initial steroid therapy to treat macular edema with BRVO. Patients with BRVO and macular edema (41 eyes) received intravitreal ranibizumab injection (IRI) alone (IRI group, 21 eyes) or subtenon triamcinolone (STTA) injection and IRI (combination group, 20 eyes). Patients in both groups with recurrent macular edema received further IRI as appropriate. A laser flare meter was used to assess aqueous flare values, and an optical coherence tomography device was used to measure central macular thickness (CMT). Before the first treatment, we obtained samples of aqueous humor and analyzed them by the suspension array method to evaluate VEGF, placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). The two groups were not significantly different with regard to levels of VEGF, PlGF, PDGF-AA, sICAM-1, MCP-1, IL-6, IL-8, or IP-10. Best-corrected visual acuity, CMT, and aqueous flare value (IRI group, baseline 8.69 ± 4.55 photon counts/ms; combination group, baseline 9.21 ± 3.72 photon counts/ms) improved significantly in both groups without significant intergroup differences. Analyses showed no significant intergroup differences in the mean number of IRIs during the 12-month follow-up, but the proportion of patients without recurrence (ie, who received only one IRI) was significantly higher in the combination group than in the IRI group (P = 0.032). Furthermore, the time to initial recurrence was significantly longer in the combination group than in the IRI group (P = 0.003). These findings suggest that initial STTA injection and IRI may have a synergistic effect in patients with BRVO and macular edema in that they increase the time between anti-VEGF treatments.

Sex differences in placenta-derived markers and later autistic traits in children

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1st (mean= 13.5 [SD = 2.0] weeks gestation) and 2nd trimesters (mean=20.6 [SD = 1.2] weeks gestation), as part of the Generation R Study, Rotterdam, the Netherlands. Subsequent assessment of autistic traits in the offspring at age 6 was performed with the 18-item version of the Social Responsiveness Scale (SRS). Associations of placental protein concentrations with autistic traits were tested in sex-stratified and cohort-wide regression models. Cases with pregnancy complications or a later autism diagnosis (n = 64) were also assessed for differences in placenta-derived markers. sFlt-1 levels were significantly lower in males in both trimesters but showed no association with autistic traits. PlGF was significantly lower in male pregnancies in the 1st trimester, and significantly higher in the 2nd trimester, compared to female pregnancies. Higher PlGF levels in the 2nd trimester and the rate of PlGF increase were both associated with the occurrence of higher autistic traits (PlGF-2nd: n = 3469,b = 0.24 [SE = 0.11], p = 0.03) in both unadjusted and adjusted linear regression models that controlled for age, sex, placental weight and maternal characteristics. Mediation analyses showed that higher autistic traits in males compared to females were partly explained by higher PlGF or a faster rate of PlGF increase in the second trimester (PlGF-2nd: n = 3469, ACME: b = 0.005, [SE = 0.002], p = 0.004). In conclusion, higher PlGF levels in the 2nd trimester and a higher rate of PlGF increase are associated with both being male, and with a higher number of autistic traits in the general population.

Comprehensive Analysis for Anti-Cancer Target-Indication Prioritization of Placental Growth Factor Inhibitor (PGF) by Use of Omics and Patient Survival Data.

The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the PGF target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included PGF gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with PGF. The overall evaluation was conducted given the totality of evidence, to target the PGF gene to treat the cancer where the PGF level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. PGF showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for PGF inhibitors, due to their potential effects on PGF, are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma.

#3885 KIDNEY TRANSPLANTATION IN EARLY PREGNANCY-ASSOCIATED ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims Clinical differentiation of pregnancy-associated thrombotic microangiopathies is challenging and can occur in conjunction with or mimic conditions including hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, pre-eclampsia (PET), thrombotic thrombocytopenia purpura (TTP) and atypical HUS (aHUS). aHUS that occurs during pregnancy classically presents in the third trimester. When kidney transplantation is performed in aHUS patients, disease recurrence is high and can be associated with transplant failure. Here, we report a unique case of aHUS that presented early during pregnancy where the patient subsequently underwent kidney transplantation. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 30 year old G2P0A1 diabetic African American woman presents at 9 weeks gestation with new hypertension. At 18 weeks, she developed acute kidney injury and proteinuria. Further investigations revealed hemoglobin 68 g/L, platelets 120 x 109/L, increased LDH 588 U/L, undetectable haptoglobin and schistocytes on blood smear. Creatinine was 88 umol/L, increased from a baseline of 50 umol/L, and proteinuria greater than 1 g/day. Pre-eclampsia was ruled out as her presentation began at 9 weeks gestation, prior to placental implantation. Placental growth factor levels at 24 and 28 weeks remained &amp;gt;100 pg/mL. HELLP syndrome was excluded given the timing in pregnancy and normal liver enzymes. TTP was excluded with a normal ADAMTS13. Complement Factor H autoantibody was negative. Complement studies revealed grossly elevated soluble C5b-9 level (sC5b-9) of 1.05 (normal &amp;lt;0.3 mg/L). aHUS was diagnosed and she began treatment with eculizumab (ECU). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed and was severely abnormal pre-treatment with ECU (activated 223%, normal &amp;lt;150%), and normalized with ECU therapy (activated 123%, normal &amp;lt;150%). Genetic testing eventually revealed a Complement Factor I mutation, NM_000204.3:c.550G/A, p. Vall84Met reported as likely pathogenic and confirming primary aHUS. Due to worsening renal function, she delivered a healthy boy at 30 weeks gestation by Caesarean section. A renal biopsy performed 3 weeks post-partum demonstrated features of TMA, mainly chronic (i.e. treated) and severe diabetic nephropathy with advanced glomerular sclerosis. Six months post-partum, she required dialysis. She remained on ECU and had an unrelated living kidney transplantation 1.5 years later. Her kidney transplantation included basiliximab and methylprednisolone induction. Calcineurin inhibitors were prescribed in standard fashion. Given severity of original multiorgan aHUS and CFI mutation, she was treated with eculizumab 1200 mg the day prior to surgery and another 1200 mg on post operative day 1. Subsequently she was given eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks. Eculizumab drug level for adequacy of complement blockade was measured on day 4 post transplant and was 279 (therapeutic &amp;gt;100 mcg/mL) and sC5b-9 was 1504 (normal &amp;lt; 244). Repeated ECU level pre 900 mg dose was 189 and sC5b-9 was 392. 6 months post transplant she has excellent graft function without proteinuria (urine ACR 2.2 mg/mmol) or evidence of aHUS recurrence. Conclusion aHUS, although described to occur late in pregnancy or post-partum, presented here during the first trimester. Thus, TMA in pregnancy is not always PET or HELLP. aHUS is a treatable condition in pregnancy, and should be considered as a possibility particularly for presentations occurring prior to 20 weeks gestation. Complement function studies may aid in aHUS diagnosis. Despite extra ECU dosing and therapeutic ECU levels for this patient post kidney transplantation, she had evidence of massive C5 release (grossly elevated sC5b-9 level). sC5b-9 measurement post transplantation may be useful to guide ECU dosing.

TNF ALPHA INHIBITOR USE AFFECTS BIRTHWEIGHT INDEPENDENTLY OF THE SOLUBLE FMS-LIKE TYROSINE KINASE 1 / PLACENTAL GROWTH FACTOR RATIO IN PREGNANT WOMEN WITH RHEUMATOID

Objective: The use of tumor necrosis factor ↑ (TNF↑) inhibitors in pregnant women with rheumatoid arthritis (RA) improves birthweight, while in women with preeclampsia high levels of soluble fms-like tyrosine kinase 1 (sFlt-1) result in a reduction in birthweight, possibly because binding of placental growth factor (PlGF) to sFlt-1 reduces its activity. Here we studied whether the beneficial effect of TNF↑ inhibitors on birthweight involves a reduction in sFlt-1 and an improved sFlt-1/PlGF ratio. Design and method: Levels of sFlt-1 and PlGF were retrospectively determined in each trimester for 158 women enrolled in a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Results: Half (52.5%) of the women used TNF↑ inhibitors during (part of) their pregnancy. There was no significant difference in the levels of sFlt-1 and PlGF or their ratio between TNF↑ inhibitor users and non-users when comparing the biomarker values per trimester. Correction for parity, other drug use (sulfasalazine, prednisone, hydroxychloroquine), trimester, and disease activity score (DAS28CRP) did not alter this outcome. The well-known negative correlation between sFlt-1 and birthweight was observed in women not using TNF↑ inhibitors and became stronger in each subsequent trimester. Remarkably, this association was entirely absent in all trimesters in women using TNF↑ inhibitors. Conclusions: TNF↑ inhibitor use by pregnant women with RA does not alter the levels of sFlt-1 and PlGF or their ratio, although it did annihilate the negative correlation between sFlt-1 and birthweight. This indicates that TNF↑ inhibitor use improves birthweight independently of the sFlt-1/PlGF ratio.

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features.

Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34week's gestation) severe preeclampsia. 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.

Reduced Endothelial Progenitor Cells: A Possible Biomarker for Idiopathic Fetal Growth Restriction in Human Pregnancies.

Circulating endothelial progenitor cells (EPCs) may be necessary throughout pregnancy by ensuring proper placentation and embryonic growth. The lack of standardized EPC quantification techniques has prevented conclusive proof of an increase in EPC during pregnancy. The purpose of this study was to determine whether EPC levels change for healthy and idiopathic fetal growth restriction (FGR) pregnancies. The study population consisted of 48 healthy pregnant females with no previous history of IUGR (10 in the first trimester, 15 in the second, and 23 in the third), 48 women with pregnancy complicated by idiopathic FGR, and 15 non-pregnant women. By using flow cytometry, EPCs in maternal blood were recognized as CD45dim/CD34/KDR cells. ELISA was used to measure plasmatic cytokines. We ascertained a progressive rise in EPCs in healthy pregnancies that was apparent in the first but more pronounced in the third trimester. At comparable gestational ages, FGR-complicated pregnancies had impaired EPC growth. Placental growth factor and stromal-derived factor-1 levels in the blood were significantly lower in FGR than in healthy pregnancies, which may have contributed to the degradation of the EPCs. The count in EPCs might hold considerable promise toward developing a peculiar authentication marker for observing pregnancies, and could be the focus of cutting-edge tactics for the prognosis and treatment of FGR pregnancies.

Associations of cortisol with neuroinflammation biomarkers in a memory clinic cohort

AbstractBackgroundCortisol, one of the most important mediators of stress in humans, is often found increased in Alzheimer’s disease (AD) patients and correlates with disease severity. Stress response and inflammation are two systems that are tightly associated to one another. Several lines of evidence suggest that cortisol can promote inflammation. However, less is known on the interaction of cortisol with neuroinflammation in the context of AD, and to the best of our knowledge there are no human studies that have systematically explored the association of these two systems in AD patients so far. The aim of this study was to investigate levels of cerebrospinal fluid (CSF) biomarkers of neuroinflammation and their relationship to salivary cortisol in a memory clinic cohort.MethodA total of 108 memory clinic patients with subjective cognitive decline (SCI, n = 40), mild cognitive impairment (MCI, n = 39) and AD (n = 29), from the Karolinska University Hospital in Stockholm, Sweden, were included in this study. Salivary cortisol was collected at six timepoints during the day on two days, to quantify awakening cortisol, cortisol awakening response (CAR), bedtime cortisol and total cortisol. CSF levels of 37 neuroinflammation and cerebrovascular dysfunction biomarkers were determined by a multiplex immunoassay. Associations among cortisol and neuroinflammation markers were assessed by linear regression models adjusting for age and diagnosis. ANCOVA tests were used to compare biomarker levels between the diagnostic groups.ResultAwakening cortisol was significantly elevated in the AD group compared to the SCI and MCI participants. Higher IP‐10 and placental growth factor (PlGF) levels were associated with decreased CAR independent of age and diagnosis. Thymus and activation‐regulated chemokine (TARC), CRP, intracellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1) levels were upregulated in MCI participants compared to SCI and AD.ConclusionWe provide evidence that the HPA axis is altered in AD. Moreover, salivary cortisol is associated to neuroinflammation in an age and diagnosis independent manner. Finally, neuroinflammatory and vascular dysfunction regulators are increased in CSF during MCI stages followed by a drop in their levels in AD participants, presumably reflecting a more active role of neuroinflammation at an early state.

High Serum Ratio of Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) to Placental Growth Factor (PIGF) and High Level of Low-Density Lipoprotein (LDL) as Risk Factors of Preeclampsia

Preeclampsia is an obstetric disease that is a health problem worldwide, including in Indonesia. Several studies have shown that changes in the maternal spiral arteries are thought to lead to preeclampsia. Preeclampsia in this decade has been associated with changes in angiogenesis regulatory proteins originating from the placenta and circulating in the mother's blood circulation, namely soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). The author was interested in examining the ratio of sFlt-1/PIGF and low-density lipoprotein (LDL) to the incidence of preeclampsia in pregnant women. This study used a case control analytic observational design. The research sample was selected by consecutive sampling of 20 cases and 20 controls. Univariate analysis was used to describe patient characteristics descriptively, and bivariate analysis was used to determine the relationship between the 2 variables There is no significant difference in the characteristics of the research subjects. Low PIGF levels are a risk factor for preeclampsia (OR 4.33; p 0.0302) with a cut-off value of 24.5. High sFlt-1 levels are a risk factor for preeclampsia (OR 4.33; p 0.027) with a cut-off value of 869.5. A high sFlt-1/PIGF ratio is a risk factor for preeclampsia (OR 4.33 p 0.030) with a cut-off value of 38. High LDL levels are a risk factor for preeclampsia (OR 6.0; p 0.013) with a cut-off value of 150 ,2. Low placental growth factor (PIGF), high levels of soluble FMS-like tyrosine kinase 1 (sFlt-1), and high levels of LDL are risk factors of preeclampsia in pregnant women.

Evaluation of the angiogenic factors sFlt-1, PlGF, and the sFlt-1/PlGF ratio in preeclampsia and associated features.

Soluble Fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF) were previously reported to play a key role in the pathogenesis of preeclampsia (PE). We tested the link between altered PlGF and sFLT-1 levels, and their ratio (sFlt-1/PlGF) with PE and PE-associated featured in Tunisian PE cases and age- and BMI-matched normotensive women. Peripheral blood specimens from 88 women with PE, and 60 control women were tested for PlGF and sFLT by commercially available ELISA. Significant increases in sFlt-1 levels and in the sFlt-1/PlGF ratio, more than changes in PlGF levels were noted in PE subjects when compared to control women. Elevation in sFlt-1 and sFlt-1/PlGF ratio was observed at different percentile values in PE cases. The receiver operating characteristic (ROC) area under the curve (AUC) for sFlt-1, PlGF, and sFlt-1/PlGF ratio were 0.869±0.031, 0.463±0.048, and 0.759±0.039, respectively. A systematic shift in sFlt-1, but not in PlGF, distributions for higher values occurred in PE subjects. A progressive increase in the adjusted OR paralleled increased sFlt-1 and the sFlt-1/PlGF ratio percentile values; no similar trend was noted for the PlGF percentiles. Increased sFlt-1 levels and sFlt-1/PlGF ratio were significantly correlated with dysmenorrhea, hypertension, baby weight, and C-section. In contrast, no correlation was found between PlGF and the PE-associated features tested. Increased sFlt-1 levels and corresponding sFlt-1/PlGF ratio, but not circulating PlGF levels, constitute an independent risk factor for PE.

Extended combined screening for preeclampsia prediction in women with diabetes mellitus

BACKGROUND:Early screening for preeclampsia has shown high efficiency for low-risk groups, however, the presence of systemic vascular disease in patients with diabetes mellitus complicates their use and requires the development of additional approaches to predicting preeclampsia in this group of patients.&#x0D; AIM:The aim of this study was to evaluate the effectiveness of early prediction of preeclampsia with extended combined screening in patients with pregestational types of diabetes mellitus.&#x0D; MATERIALS AND METHODS:This study included 75 pregnant women: 40 patients with type 1 diabetes mellitus, and 35 patients with type 2 diabetes mellitus. To determine the risk of further preeclampsia development, we evaluated biochemical, biophysical and anamnestic factors, along with the serum levels of placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin at 11+0to 13+6gestational weeks. The main outcome assessed was the development of preeclampsia.&#x0D; RESULTS:In patients with further development of preeclampsia (35% in type 1 and 40 % in type 2 diabetic women), we observed higher soluble fms-like tyrosine kinase 1 / placental growth factor ratios, as well as elevated serum soluble endoglin (type 1 diabetes mellitus) and soluble fms-like tyrosine kinase 1 (type 2 diabetes mellitus) levels. Isolated determination of placental growth factor showed no significant differences in the levels of this angiogenic factor in preeclampsia. A multivariate predictive model for preeclampsia demonstrated high prognostic parameters: for patients with type 1 diabetes mellitus, area under the curve was 0.96 (95% confidence interval 0.931.00), with positive predictive value 76.7% and negative predictive value 90.1%; for patients with type 2 diabetes mellitus, area under the curve was 0.94 (95% confidence interval 0.861.00), with positive predictive value 88.5% and negative predictive value 97.1%.&#x0D; CONCLUSIONS:Specific biochemical and biophysical markers of preeclampsia combined with maternal risk factors and assessment of carbohydrate metabolism can increase the predictive value of early screening studies for preeclampsia in women with pregestational diabetes mellitus.

Prognostic value of anti- and proangiogenic factors in severe preeclampsia

BACKGROUND:Over the years, preeclampsia has remained a common pathology of pregnancy. Its severe form poses a significant threat to the health of the woman and the fetus. To assess the risk of developing preeclampsia, biochemical screening for placental growth factor and soluble tyrosine kinase-1 is carried out. The soluble glycoprotein endoglin, which regulates angiogenesis by influencing cell activation, adhesion, and migration, can supplement the idea of the imbalance of vascular factors in severe preeclampsia. A holistic study of anti- and proangiogenic factors can significantly complement the diagnosis of preeclampsia at the preclinical stage and a look at the course and treatment of this pregnancy complication.&#x0D; AIM:The aim of this work was to evaluate the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin, soluble tyrosine kinase-1, placental growth factor) and compare the obtained data with the clinical manifestations of severe preeclampsia.&#x0D; MATERIALS AND METHODS:This case-control study included 81 pregnant women. The main group consisted of patients with severe preeclampsia (n= 41), while the control group comprised individuals with normal pregnancy (n= 40). To determine soluble glycoprotein endoglin levels in biological fluids, we used a new ELISA kit developed in the Laboratory of Hybridoma Technology, Academician A.M. Granov Russian Research Center for Radiology and Surgical Technologies (Saint Petersburg, Russia). placental growth factor and soluble tyrosine kinase-1 concentrations were assessed by electrochemiluminescence immunoassay using commercial Roche Diagnostics kits. Statistical analysis was performed using the StatTech v.3.0.6 program (Stattech Ltd., Russia).&#x0D; RESULTS:When analyzing the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin in the blood serum and urine, soluble tyrosine kinase-1, placental growth factor and the ratio of these factors), depending on the study group, statistically significant results were obtained (p 0.05). The diagnostic significance of serum and urine soluble glycoprotein endoglin levels in predicting the probability of severe preeclampsia was assessed by the method of ROC curve analysis. Statistically significant differences (p 0.05) were found in the analysis of the concentrations of anti- and pro-angiogenic factors depending on the clinical manifestations such as systolic blood pressure 160 mm Hg (except for placental growth factor level), a multiple increase in urine soluble glycoprotein endoglin level with massive proteinuria, an increase in soluble glycoprotein endoglin levels in biological fluids with an increase in edematous syndrome. Correlation analysis revealed a significant relationship between anti- and proangiogenic factors and the term of delivery, as well as urine soluble glycoprotein endoglin level and the duration of the treatment.&#x0D; CONCLUSIONS:The data obtained complement the concept of severe preeclampsia. Knowing the concentrations of soluble glycoprotein endoglin in the blood serum and urine allows for predicting the timing of delivery and the possible duration of treatment, which is critical in the management of patients with severe preeclampsia.

Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy.

Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case-control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 µmol/L vs. 177.40 µmol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy.

Predictive Value of Sflt-1/Plgf Ratio for Occurrence of Preeclampsia in Singleton Pregnancies: A Retrospective Study

Introduction: Preeclampsia is multisystem disorder of pregnancy, characterized by endothelial and placental dysfunction. It is classified as an early onset (which occurs &lt; 34 weeks) and late onset (which occurs ≥ 34 weeks). There is an increase of level of antiangiogenic factor of soluble form similar to tyrosine kinase 1 (sFlt-1) and decrease of level of proangiogenic placental growth factor (PlGF) at preeclampsia. High ratio sFlt-1/PlGF is connected to occurrence of preeclampsia. Materials and Methods: There was a retrospective study of the Clinic for Gynecology and Obstetrics of the University Clinical Center of Republic of Srpska (KGA UKC RS), which was implemented in period January 1st, 2020 – December 31st, 2021 and which included 224 patients hospitalized at the Department of Perinatology for suspected preeclampsia development, from 26+0 weeks of gestation until birth. One of the key criteria for the inclusion of patients in the study is the use of the sFlt-1/PlGF ratio as a marker for the onset of preeclampsia, and the determination of protein values in 24-hour urine (biuret). The antenatal state of the fetus was also monitored by ultrasound measurement of the flow resistance ratio (Ri) through the middle cerebral artery and the umbilical artery (C/U), as well as the values of the newborn’s Apgar score in the first and fifth minute of life (AS 1 and 5). The patients included in the study were divided into two groups according to gestational age: group 1 (&lt;33+6 NG) and group 2 (≥34NG). For the purposes of the research, data from patient protocol books for the specified period, as well as corresponding data from the Clinical Information System (KIS), were used. Results: Calculated values for cut off 38 for group 1 are: NPV= 76.9%, PPV=72.0%, sensitivity=85.7%, specificity=58.8%, and for group 2 are: NPV= 89 ,1%, PPV=40.8%, sensitivity=72.1%, specificity=68.5%. For cut off 85, the calculated values for group 1 are: NPV= 82.4%, PPV=85.7%, sensitivity=85.7%, specificity=82.4%, and for group 2 they are: NPV= 84.9 %, PPV=70.4%, sensitivity=44.2%, specificity=94.4%. For cutt off 110, the calculated values for group 1 are: NPV= 77.8%, PPV=85%, sensitivity=81%, specificity=82.4%, and for group 2 they are: NPV= 83.5 %, PPV=72.7%, sensitivity=37.2%, specificity=95.8%. The measured value of protein in 24h urine (biuret) in comparison with the measured values of the sFlt-1/PlGF ratio have statistical significance for predicting the onset of preeclampsia. Statistical data processing obtained by examining the measured values of the sFlt-1/PlGF ratio and the antenatal and natal condition of the fetus (C/U and AS 1 and 5) showed statistical significance, except for C/U for group 2, where p=0.32. Conclusion: Determination of the sFlt-1/PlGF ratio as well as biuret and monitoring of the antenatal and postnatal state of the fetus significantly contributes to the timely diagnostic of preeclampsia, which impacts reducing the incidence of undesirable outcomes for the mother and the fetus.

Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia.

An imbalance between angiogenic and anti-angiogenic factors plays a fundamental role in the pathogenesis of preeclampsia (PE). Studies have shown a dysregulation of sFlt-1 and placental growth factor (PlGF) in PE. However, there are differing reports on the levels of these pro-/antiangiogenic factors in HIV-infected preeclamptic and normotensive pregnancies, possibly due to highly active antiretroviral therapy (HAART) and its immune reconstitution effect. The study aimed to investigate the effect of hypertension and ARVs on circulating and placental pro- and antiangiogenic factors in HIV-infected PE. The level of sFlt-1 expression is elevated in PE compared to normal pregnancies. PlGF was altered by placental dysfunction. Antiretroviral therapy does not impact the angiogenic shift in PE development. The angiogenic imbalance evident in the circulatory system by higher sFlt-1 compared to PlGF levels is replicated in the placenta by reduced expression of PlGF receptors in comparison to sFlt-1 receptors. However, there is a lack of data that explore the relationship between HAART and anti-angiogenic factors in the placenta and the circulation of PE comorbid with HIV infection.

Decreased serum placental growth factor levels in adult atopic dermatitis: a preliminary study.

Decreased serum placental growth factor levels in adult atopic dermatitis: a preliminary study.