Serum Levels Of Placental Growth Factor Research Articles

The Predictive Value of sFlt-1/PlGF Ratio for Postpartum Preeclampsia

Abstract Background Preeclampsia (PE) is a leading cause of maternal mortality, affecting 5% to 8% of pregnancies worldwide. Postpartum PE typically develops within the first 48 hours and can occur up to 6 weeks after childbirth and requires immediate clinical management. However, overdiagnosis may lead to unnecessary hospital admissions and overuse of medical resources. The ratio of soluble fms like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) has been evaluated as a tool to predict PE, but its utility in the postpartum setting is yet to be established. Methods In this study, we conducted a non-interventional, prospective study at NewYork-Presbysterian-Weill Cornell Hospital, measuring serum sFlt-1 and PlGF levels using Elecsys® and cobas e411 analyzer. The primary aim was to determine the predictive accuracy of the sFlt-1/PlGF ratio in postpartum PE, focusing on its sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) using a cutoff 38, as established in the PROGNOSIS study. Results Among 47 participants, 9 (19.1%) developed postpartum PE. The sFlt-1/PlGF ratio was significantly higher for the women who developed PE (55.9, IQR, 48.6-196.2) than for women without PE (19.9, IQR, 5.8-29.1). There was no significant difference in age, first-trimester body-mass index (BMI), gestational week of delivery, smoking status and nulliparous between PE and non-PE groups. Moreover, the sFlt-1/PlGF ratio at 38 cutoff point had a sensitivity of 77.8% (95% CI, 45.0-93.7) and a specificity of 81.6% (95% CI, 66.6-90.8), with a PPV of 50.0% (95% CI, 33.9-66.1). Notably, it demonstrated a high NPV of 93.9% (95% CI, 80.4-98.3). Conclusion Our findings suggest that the sFlt-1/PlGF ratio may be used as a predictor of postpartum PE, highlighting its significance in managing postpartum PE.

Discussion on the evaluation of the therapeutic efficacy of uterine artery blood flow parameters and serum PLGF and sFlt-1 in patients with recurrent spontaneous abortion

ObjectiveTo investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes.MethodsThis retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio.Results1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 2. Serum PLGF levels and the sFlt-1/PLGF ratio at gestational weeks 30-31+6 were significantly lower in the non-drug group than in the aspirin group, combined drug group, and control group, while serum sFlt-1 levels were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 3. Serum PLGF, sFlt-1, and sFlt-1/PLGF had lower diagnostic efficiency for predicting hypertensive disorders during pregnancy than the combined diagnostic efficiency of serum PLGF, sFlt-1, and sFlt-1/PLGF with uterine artery blood flow parameters at gestational weeks 30-31+6.ConclusionAspirin and aspirin combined with LMWH can upregulate serum PLGF and decrease serum sFlt-1 levels in patients with recurrent spontaneous abortion, reduce the miscarriage rate, and significantly improve pregnancy outcomes. The combination of serum PLGF, sFlt-1, sFlt-1/PLGF, and uterine artery blood flow parameters can effectively predict hypertensive disorders during pregnancy.

Research on the Improvement of Endothelial Cell Function and Trophoblast Apoptosis in Rats with Preeclampsia by Tanshinone IIA

Background Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the kidneys. Recent studies suggest that endothelial dysfunction and trophoblast apoptosis are involved in the pathogenesis of preeclampsia. Purpose To investigate the effects of tanshinone IIA (TIIA) on clinical symptoms, vascular endothelial function, and placental trophoblast apoptosis in preeclampsia rats. Materials and Methods Twenty-four pregnant Sprague-Dawley rats, between 8 and 10 weeks old, were randomly divided and allocated into three groups: Control, model, and treatment, with each group consisting of 8 rats. The control group received normal saline injections via the tail vein; the model group received NG-nitro-l-arginine methyl ester (l-NAME) to induce preeclampsia, followed by normal saline injections; and the treatment group received TIIA (10 mg/kg) via tail vein injection after preeclampsia induction with l-NAME. Various parameters were measured, including tail artery systolic pressure, 24-hour proteinuria, offspring and placental weight, levels of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) in serum, and expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-related X protein (Bax) in placental trophoblasts. Results TIIA treatment led to decreased tail artery systolic pressure and 24-hour urine protein levels, increased body and placental weights of offspring, and favorable changes in serum levels of ET-1, sFlt-1, eNOS, and PLGF. Moreover, TIIA treatment resulted in decreased Bax levels and apoptosis in placental trophoblasts, along with increased Bcl-2 levels. Conclusion TIIA can improve the clinical symptoms of preeclampsia in rats induced by l-NAME, alleviate the apoptosis of placental trophoblast cells, and improve vascular endothelial function.

Placental growth factor deficiency initiates obesity- and aging-associated metabolic syndrome

Obesity often leads to inadequate angiogenesis in expanding adipose tissue, resulting in inflammation and insulin resistance. We explored the role of placental growth factor (PlGF) in metabolic syndrome (MS) using mice models of type 2 diabetes, high-fat diet, or aging. Reduced serum PlGF levels were associated with decreased insulin sensitivity and development of MS features. PlGF was localized within endothelial cells and pericytes of adipose tissue. In vitro, low PlGF levels in hypoxic conditions worsened oxidative stress, apoptosis, and reduced autophagy. This was associated with a reduction in expression of vascular endothelial growth factor (VEGF)-A/VEGF-R1/−R2, which was influenced by a decrease and increase in PlGF/pAMPK/PI3K-pAkt/PLCγ1-iCa++/eNOS and PTEN/GSK3β axes, respectively. PlGF-knockout mice exhibited MS traits through alterations in the same signaling pathways, and these changes were mitigated by recombinant PlGF and metformin. These enhanced angiogenesis and lipid metabolism, underscoring PlGF's role in age-related MS and its potential as a therapeutic target.

Clinical Analysis of Serum Soluble Tyrosine Kinase Receptor-1 and Placental Growth Factor in Pre-eclampsia

Objective: To study the clinical application effect of using serum soluble tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) in pre-eclampsia. Methods: From September 2021 to September 2023, 58 cases of pre-eclampsia patients who underwent physical examination during pregnancy and eventually gave birth in Xinghua People’s Hospital were the observation group of this study and 795 cases of healthy pregnant women who underwent pregnancy examination in this hospital during the same period of time were the control group of this study; 38 cases of mild pre-eclampsia in the observation group were treated as the mild group and 20 cases of severe pre-eclampsia patients were treated as the severe group and the serum sFlt-1 and PlGF were used to compare the results of the observation group and the control group. Compare the serum sFlt-1 and PlGF levels between the observation and control groups; compare the serum sFlt-1 and PlGF levels between the mild and severe groups. Results: The serum PlGF level of the observation group was lower than that of the control group, and the sFlt-1 level was higher than that of the control group, P &lt; 0.05; the serum PlGF level of the mild group was higher than that of the severe group, and the sFlt-1 level was lower than that of the control group, P &lt; 0.05; the results showed that the serum and urine sFlt-1 and PlGF levels of pregnant women of all the three groups were elevated with the aggravation of the condition of pre-eclampsia, and the sFlt-1/PlGF ratio also increased. The differences of sFlt-1/PlGF in serum and urine of the three groups were compared, with P &lt; 0.05; the above ratios of the patients in the mild group were higher than those of the control group and those of the severe group were higher than those of the mild group, with P &lt; 0.05. Conclusion: Serum sFlt-1 level was high in preeclamptic patients, while serum PlGF was low in preeclamptic patients.

Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1/creatinine ratio improves the prediction value

ObjectivesTo evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. Study DesignThis case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. ResultsUrine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). ConclusionsUrinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.

Placental growth factor and fetoplacental Doppler indices in combination predict preterm birth reliably in pregnancies complicated by fetal growth restriction.

To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR). This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB (< 37 weeks). Multivariable Cox regression models were used with biomarkers as time-varying covariates. The study cohort included 320 singleton pregnancies, comprising 179 (55.9%) affected by FGR, defined according to a Delphi consensus, and 141 (44.1%) with an AGA fetus. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio were associated with significantly shorter time to PTB. Low PlGF was a better predictor of PTB than was either sFlt-1/PlGF ratio or a combination of PlGF and sFlt-1/PlGF ratio (Harrell's C, 0.81, 0.78 and 0.79, respectively). Although both Doppler indices were significantly associated with time to PTB, in combination they were better predictors of PTB than was either UA-PI > 95th centile or UtA-PI > 95th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF < 100 ng/L, UA-PI > 95th centile and UtA-PI > 95th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32). Low maternal serum PlGF level (< 100 ng/L) and abnormal fetoplacental Doppler indices (UA-PI > 95th centile and UtA-PI > 95th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association of Low Levels of Placental Growth Factor With Abnormal Fetal Doppler Assessment [ID 2683423

INTRODUCTION: Placental growth factor (PlGF) is involved in placental angiogenesis and maturation. Low maternal serum PlGF levels predict placental dysfunction and associated conditions, such as preeclampsia, and fetal growth restriction. These pregnancy complications can lead to abnormal fetal Doppler assessment, indicating progressive fetal deterioration prompting preterm delivery. METHODS: We collected retrospective data from laboratory results of PlGF levels and fetal Dopplers (umbilical artery [UA], middle cerebral artery [MCA], and ductus venosus [DV]) from patients who had clinical indication for PlGF testing. Over 100 patients were identified to have results of all assessments between 2021 and 2023. Levels of PlGF were stratified in five categories according to gestational age and compared with normal and abnormal doppler results. For comparisons, the values were aggregated in normal and low PlGF. RESULTS: There were statistically significant associations between PlGF levels and Dopplers. Patients with low PlGF (less than 5th percentile for gestational age) were more likely to have abnormal dopplers than patients with normal PlGF (UA, P&lt;.001; MCA, P&lt;.001; DV, P&lt;.001). A normal PlGF had a high negative predictive value (NPV) for normal dopplers (UA, 88%; MCA, 94.3%; DV, 98.6%). CONCLUSION: The results show that normal PlGF is highly associated with normal Dopplers. Additional data will be required to account for confounding factors; however, our preliminary data suggest that PlGF could be a useful tool for patients in rural and remote locations, as normal PlGF has a statistically and clinically significant negative predictive value for normal Doppler assessment.

Association of Low Levels of Placental Growth Factor and Fetal Growth Restriction in a Setting With a High Prevalence of Diabetes [ID 2683431

INTRODUCTION: Placental growth factor (PlGF) is a glycosylated protein from the vascular endothelial growth factor (VEGF) family that is involved in placental angiogenesis. In cases of placental dysfunction, decreased maternal serum PlGF levels predict the development of pregnancy complications such as preeclampsia, fetal growth restriction (FGR), and stillbirth. METHODS: Datasets from 114 high-risk patients who had clinical indication for PlGF testing from 2021 to 2023 were collected retrospectively. The anonymized dataset comprises PlGF test results categorized by gestational age-specific ranges and FGR categorized by percentile. Chi-squared analysis of 114 patients was used to assess the association between PlGF levels and FGR (less than 10th percentile). This study was approved by REb-USask #Bio3702. RESULTS: Of the 114 patients, 21 (18.4%) with low/very low PlGF and 8 (7.1%) with borderline/normal PlGF had fetuses with FGR less than 10th percentile. There was a significant difference between groups with a low/very low PlGF and normal PlGF levels (P&lt;.001). The negative predictive value (NPV) for development of FGR less than 10% was 97.54%. CONCLUSION: Data collection is ongoing; however, in our patient population with a high prevalence of diabetes, preliminary data from 114 patients suggest that gestational age-stratified maternal serum PlGF levels have high NPV value for development of FGR less than 10th percentile. The implementation of this simple laboratory test in rural and remote communities would allow for earlier identification of pregnancies that require more intensive surveillance at a high-risk center of care.

Predictive value of maternal serum placental growth factor levels for discordantfetal growthin twins: a retrospective cohort study.

Accurate prenatal recognition of discordantfetal growth in twins is critical for deciding suitable management strategies. We explored the predictive value of the level of maternal second-trimester placental growth factor (PLGF) as a novel indicator of discordantfetal growth. A total of 860 women pregnant with twins were enrolled, including 168 women with monochorionic twins (31 cases of discordant fetal growth and 137 without) and 692 with dichorionic twins (79 cases of discordant fetal growth and 613 without). Maternal second-trimester PLGF concentrations were measured via immunofluorescence. Maternal second-trimester PLGF levels were significantly lower in women pregnant with twins who subsequently developed discordant fetal growth than in those who did not (monochorionic twin pregnancy: P < 0.001; dichorionic twin pregnancy: P < 0.001). A 3-4 fold difference in median PLGF concentrations was detected between the two groups with both monochorionic and dichorionic twin pregnancies. Maternal second-trimester PLGF levels were significantly correlated with birth weight differences (monochorionic twin pregnancy: r = - 0.331, P < 0.001; dichorionic twin pregnancy: r = - 0.234, P < 0.001). A receiver operating characteristic curve was used to evaluate the predictive efficiency. In monochorionic twin pregnancies, the area under the curve (AUC) was 0.751 (95% confidence interval [CI]: 0.649-0.852), and the cutoff value was 187.5pg/mL with a sensitivity of 77.4% and specificity of 71.0%. In dichorionic twin pregnancies, the AUC was 0.716 (95% CI; 0.655-0.777), and the cutoff value was 252.5pg/mL with a sensitivity of 65.1% and specificity of 69.6%. Based on the above cutoff values, univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (OR) for the PLGF levels. After adjustment for potential confounding factors, low PLGF concentrations still significantly increased the risk of discordant fetal growth (monochorionic twin pregnancy: adjusted OR: 7.039, 95% CI: 2.798-17.710, P < 0.001; dichorionic twin pregnancy: adjusted OR: 4.279, 95% CI: 2.572-7.120, P < 0.001). A low maternal second-trimester PLGF level is considered a remarkable risk factor and potential predictor of discordant fetal growth. This finding provides a complementary screening strategy for the prediction of discordant fetal growth and offers a unique perspective for the subsequent research in this field.

Effects of different physical exercise types on health outcomes of individuals with hypertensive disorders of pregnancy: a prospective randomized controlled clinical study

Objective To explore the impacts of different types of physical exercise on health outcomes of individuals with hypertensive disorders of pregnancy (HDPs). Methods Forty individuals with HDPs admitted to a tertiary hospital providing maternal and pediatric care between July 2023 and March 2024 were enrolled in this prospective randomized controlled clinical study and completed a ≥4-week intervention. Data were collected before the intervention and before delivery. Participants were assigned randomly to control (no exercise intervention), aerobic exercise (AE), resistance training (RT), and AE + RT groups. All participants downloaded a mobile health-education app for gestational hypertension developed by our research group. Exercise videos in the app guided participants’ performance of different types of exercise. General information; physical activity and sleep quality data; morning blood pressure, lipid profiles, and urinary micro-albumin/creatinine ratios; serum soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and advanced oxidation protein product (AOPP) concentrations; and pregnancy outcome data were collected and compared among groups. Results After the intervention, the physical activity status, sleep quality, morning blood pressure, lipid profiles, urinary micro-albumin/creatinine ratios, and pregnancy outcomes differed significantly among all groups comparing with control (all p < .05). In the three exercise groups, the serum sFlt-1, PlGF, and AOPPs levels improved significantly (all p < .05). All differences were most pronounced in the AE + RT group. Limitations The study period was relatively short. The further long-term follow-up research is needed. A larger sample size study is also needed. Conclusions The study results suggest that AE + RT interventions are beneficial for individuals with HDPs in clinical settings, and could be implemented with careful consideration of individuals’ specific conditions.

Automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation predicts preterm preeclampsia: a retrospective cohort study.

Our aims were to obtain the gestational-age-specific median of common logarithmic placental growth factor (PlGF) values in the first trimester in women with a singleton pregnancy in order to generate the gestational-age-specific multiple of the median (MoM) of log10PlGF at 9-13 weeks of gestation, to evaluate screening parameters of MoM of log10PlGF at 9-13 weeks of gestation to predict preterm preeclampsia (PE), and to construct an appropriate prediction model for preterm PE using minimum risk factors in multivariable logistic regression analyses in a retrospective sub-cohort study. Preterm PE occurred in 2.9% (20/700), and PE in 5.1% (36/700). Serum PlGF levels were measured using Elecsys PlGF®. MoMs of log10PlGF at 9-13 weeks of gestation in Japanese women with a singleton pregnancy followed a normal distribution. We determined the appropriate cut-off value of MoM of log10PlGF to predict preterm PE at around a10% false-positive rate (0.854). The MoM of log10PlGF < 0.854 yielded sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (95% confidence interval [CI]), and negative likelihood ratio (95% CI) of 55.0%, 91.9%, 17.5%, 98.5%, 6.79 (4.22-10.91), and 0.49 (0.30-0.80), respectively. The combination of MoM of log10PlGF and presence of either chronic hypertension or history of PE/gestational hypertension (GH) yielded sensitivity and specificity of 80.0 and 85.7%, respectively, to predict preterm PE. In conclusion, the automated electrochemiluminescence immunoassay for serum PlGF levels in women with singleton pregnancy at 9-13 weeks of gestation may be useful to predict preterm PE.

Reference range of placental growth factors at 11–14 weeks’ gestation in Indonesia

ObjectivesTo develop a reference chart for placental growth factor (PLGF) value during 11–14 weeks’ gestation in Indonesian population. MethodsThis was an observational study observing women in their first trimester. Maternal characteristics, biophysical tests, and serum PLGF levels were collected during the visit. PLGF Multiple of Median (MoM) was adjusted for maternal characteristics including age, parity, smoking habits, diabetes mellitus, weight, height, body mass index, gestational age, and crown-rump length (CRL) utilizing the linear regression analysis. Plot distributions of PLGF level and PLGF MoM adjusted to CRL were developed using logistic regression technique. ResultsOut of 2.062 consecutive women undergoing 11–14 weeks’ gestation ultrasound screening, the median of PLGF level and PLGF MoM were 50.38 pg/ml (1.09–265.20 pg/ml) and 1.00 (0.02–4.80), respectively. In the multivariate analysis, PLGF MoM was not significantly influenced by maternal factors such as age, parity, smoking habit, diabetes mellitus, height, weight, and BMI. The adjusted PLGF MoM reference chart according to the CRL was developed using quadratic linear regression. ConclusionPLGF levels at 11–14 weeks’ gestation were notably influenced by CRL but not by maternal characteristics. The usefulness of this parameter in combining with other established markers as a screening tool for the Indonesian population basis requires further investigation.

Effects of sirtuin 1 deficiency on trophoblasts and its implications in the pathogenesis of pre-eclampsia

Background Sirtuin 1 (SIRT1) is mainly localised in syncytiotrophoblasts and cytotrophoblasts, and is involved in pregnancy regulation. However, data on the association between SIRT1 and pre-eclampsia (PE) remains limited. This study aimed to investigate the role of SIRT1 in PE pathophysiology. Methods Placental SIRT1 expression, as well as serum SIRT1, placental growth factor (PlGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) levels, were measured using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assays in 40 healthy pregnant women (NP group) and 40 women with severe PE (PE group). Additionally, the effects of SIRT1 on the migration, invasion, PlGF, and sFlt-1 secretion of HTR-8/SVneo cells were analysed. Results SIRT1 expression was significantly reduced in the placenta of patients with severe PE compared with that in healthy pregnant women. Compared with the NP group, serum SIRT1 and PlGF expression was significantly lower in the PE group; however, the expression of serum sFlt-1 was significantly higher in the PE group. Correlation analysis showed that in the PE group, placental SIRT1 protein levels positively correlated with serum PlGF levels (r = 0.468, P = .002) and negatively correlated with serum sFlt-1 levels (r = −0.542, P < .001). Cells with downregulated SIRT1 had a significantly shorter migration distance and a prominently reduced number of invasive cells compared with the corresponding negative control group, suggesting that SIRT1 deficiency may inhibit the migration and invasive ability of HTR-8/SVneo cells. The opposite results were observed after transfection with lentivirus overexpressing SIRT1. Compared with the corresponding controls, cells with downregulated SIRT1 had significantly reduced PlGF levels and significantly increased sFlt-1 levels in the cell culture supernatants, whereas SIRT1 overexpression produced the opposite results. Conclusions SIRT1 deficiency may contribute to the pathogenesis of pre-eclampsia by reducing trophoblastic migration, invasion, and PlGF secretion and increasing sFlt-1 secretion.

Abstract 11949: Novel First-Trimester Serum Biomarkers for Early Prediction of Preeclampsia

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable biomarkers. Research questions: Could potential imbalances in cytokines and autoimmune antibodies be detectable in the first trimester of pregnancy in women who later develop PE? Goals: Our study aims to discover novel biomarkers within the first trimester and construct an efficient predictive model to enhance early PE screening strategies. Methods: Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, we measured the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously identified PE biomarkers—including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A—in 34 women diagnosed with PE and 34 matched normotensive controls. Results: Our analysis revealed that the PE group exhibited significantly elevated first-trimester serum levels of hepatocyte growth factor (HGF), interleukin (IL)-2Rα, IL-9, RANTES, tumor necrosis factor-β (TNF-β), total IgM, and total IgG, and aPS IgG optical density (OD) value, in addition to decreased first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value compared to the control group. The combination of the top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value [area under the curve (AUC) and 95% confidence interval (CI): 0.983 (0.952-1.000)] for PE development compared to PlGF and PlGF/sFlt-1 independently [AUC and 95% CI: 0.825 (0.726-0.924) and 0.670 (0.539-0.800), respectively]. Conclusion: We identified novel first-trimester serum biomarkers and developed an effective prediction model integrating immune-related factors and PlGF for early PE detection, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.

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.

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.

Placental Growth Factor and Pregnancy-Associated Plasma Protein-A as Potential Early Predictors of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and one of the main causes of adverse pregnancy outcomes. An early diagnosis of GDM is of fundamental importance in clinical practice. However, the major professional organizations recommend universal screening for GDM, using a 75 g oral glucose tolerance test at 24-28 weeks of gestation. A selective screening at an early stage of pregnancy is recommended only if there are maternal risk factors for diabetes. As a result, the GDM diagnosis is often delayed and established after the appearance of complications. The manifestation of GDM is directly related to insulin resistance, which is closely associated with endothelial dysfunction. The placenta, the placental peptides and hormones play a pivotal role in the manifestation and progression of insulin resistance during pregnancy. Recently, the placental growth factor (PlGF) and plasma-associated protein-A (PAPP-A), have been shown to significantly affect both insulin sensitivity and endothelial function. The principal function of PAPP-A appears to be the cleavage of circulating insulin-like growth factor binding protein-4 while PlGF has been shown to play a central role in the development and maturation of the placental vascular system and circulation. On one hand, these factors are widely used as early predictors (11-13 weeks of gestation) of complications during pregnancy, such as preeclampsia and fetal aneuploidies, in most countries. On the other hand, there is increasing evidence for their predictive role in the development of carbohydrate disorders, but some studies are rather controversial. Therefore, this review aims to summarize the available literature about the potential of serum levels of PlGF and PAPP-A as early predictors in the diagnosis of GDM.

Combination of Maternal Serum ESM-1 and PLGF with Uterine Artery Doppler PI for Predicting Preeclampsia.

This study aimed to determine whether the combination of pregnancy-associated endothelial cell-specific molecule 1 (ESM-1), the placental growth factor (PLGF) in the first- and second-trimester maternal serum, and the uterine artery Doppler pulsatility index (PI) in the second trimester can predict preeclampsia (PE). The serum levels of ESM-1 and PLGF in 33 severe preeclampsia (SPE) patients, 18 mild preeclampsia patients (MPE), and 60 age-matched normal controls (CON) were measured. The Doppler ultrasonography was performed, and the artery pulsatility index (PI) was calculated for the same subjects. The 2nd PLGF level was significantly lower and the 2nd PI was higher than those in the MPE group. Combining the 2nd PLGF with the 2nd PI yielded an AUC of 0.819 (83.33% sensitivity and 70.00% specificity). In the SPE group, the 1st ESM-1 level and the 2nd PLGF level were significantly lower, and the 2nd ESM-1 level and the 2nd PI were significantly higher in the SPE group. The combination of the 1st ESM-1, the 2nd PLGF, and the 2nd PI yielded an AUC of 0.912 (72.73% sensitivity and 95.00% specificity). The 1st ESM-1 and the 2nd PLGF levels and the 2nd PI were associated with PE. The combination of serum biomarkers and the PI improved the screening efficiency of the PE prediction, especially for SPE.

First trimester screening and prediction of preeclampsia by Application of Fetal Medicine Foundation Algorithm at Tanta University

Background: Preeclampsia (PE) is a complex illness linked to conception that affects a variety of bodily functions and is usually connected with perinatal morbidity and deaths. Early PE anticipation will reduce this linked morbidity and death by allowing for routine maternal and foetal monitoring and the use of preventative measures. Aim of the work: the goal of this study is to investigate whether the measurement of maternal serum placental growth factor (PlGF) combined with uterine artery Doppler ultrasound, are useful in early predicting PE and to examine the diagnostic accuracy of the Fetal Medicine Foundation (FMF) Algorithm for the early screening and anticipation of the high- risk PE at 11-13 weeks conception in a group of pregnant women. Patients and Methods: one hundred and twenty primigravida women with living, singleton fetus at 11-13 weeks conception without risk factors other than being primigravida attending antenatal care clinic at the Department of Obstetrics and Gynecology at Tanta University Hospitals. All cases were subjected to ; A signed informed written consent, proper history taking, full clinical examination, estimation of body mass index (BMI), blood pressures and determination of mean arterial blood pressure (MAP), ultrasound, Uterine artery doppler ultrasound examination with the determination of the mean Pulsatility index (PI) of the uterine arteries. Maternal serum levels of PlGF were also measured by specific immunoassay (ELISA). The measured values of MAP, mean uterine artery pulsatility index (PI) and PlGF were converted into multiples of the median (MoM). Then the FMF model was used for the determination of patient-specific risk of PE at 11-13 weeks conception in each case. Results: The main results of the present study revealed that; Only 11 of 120 normal pregnant women were categorized as a high PE risk with a percentage of 9.2% and the rest 109 cases were low PE risk with a percentage of 90.8% by application of FMF algorithm. There was a significant difference between the high and low risks regarding the mean uterian UtA-Pi and PIGF levels at 11–13 weeks. Receiver operating characteristic curve (ROC) demonstrate to what extent it can be depended on PlGF, mean UtA-PI and MAP as a predictor for PE denoting the significant diagnostic performance for PIGF and mean uterine artery pulsatility index (PI). The optimal cutoff value of PlGF value using the ROC curve was ≤40 leading to a sensitivity of 90.91%, a specificity of 96.33%, a PPV of 71.4, a NPV of 99.1% and an accuracy of 95.83%. While the optimal cutoff measure of mean uterine artery PI value using the ROC curve was >1.91 leading to a sensitivity of 90.91%, a specificity of 96.33%, PPV of 71.4, NPV of 99.1% and an accuracy of 95.83%. Conclusion: On the basis of these results, it could be concluded that the combined measurement of maternal serum PlGF concentrations and mean PI of the uterine arteries at 11–13 weeks of conception may help to predict the high-risk PE in primigravida when other parameters of PE anticipation are normal. And The FMF screening algorithm for the high-risk PE group performing satisfactorily. PE estimated by the competing risk model incorporated in the FMF algorithm may be applicable locally, and the earlier screening in conception would allow women at a higher risk to be monitored accordingly, participate in early intervention trials, and commence prophylactic therapy.